buprenorphine and Neonatal-Abstinence-Syndrome

The use and misuse of opioids in pregnancy have been increasing and are a major public health issue. Opioid use in pregnancy and during lactation has been associated with increased maternal and neonatal morbidity and mortality.. This review aims to summarize the existing literature and current recommendations for opioid use while pregnant or lactating.. A PubMed, Cochrane Library, and Google Scholar literature search using the following terms was performed to gather relevant data: "opioids," "opioid maintenance therapy," "opioid use disorder," "suboxone," "buprenorphine," "methadone," "medication for opioid use disorder," "fetal outcomes," "perinatal outcomes," "pregnancy," "lactation," and "neonatal abstinence syndrome.". Available studies on opioid use in pregnancy and during lactation were reviewed and support association with increased odds of maternal death, placental insufficiency, cardiac arrest, preterm birth, neonatal intensive care unit admission, low birth weight, and small for gestational age infants. Studies were also reviewed on pharmacotherapy options in pregnancy and promising prenatal care models.. There is a critical need for research on the effects of opioid use and related pharmacotherapy options in pregnancy. Once the adverse perinatal effects of opioid exposure are identified and well-characterized, patient education, intervention, and antenatal surveillance can be developed to predict and mitigate its impact on maternal and fetal health.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Lactation; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Parturition; Placenta; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth

Neonates born to mothers taking opioids during pregnancy are at risk for neonatal opioid withdrawal syndrome (NOWS), for which there is no recognized standard approach to care. Nonpharmacologic treatment is typically used as a first-line approach for management, and pharmacologic treatment is added when clinical signs are not responding to nonpharmacologic measures alone. Although morphine and methadone are the most commonly used pharmacotherapies for NOWS, buprenorphine has emerged as a treatment option based on its pharmacologic profile and results from initial single site clinical trials. The objective of this report is to provide an overview of NOWS including a summary of ongoing work in the field and to review the state of the science, knowledge gaps, and practical considerations specific to the use of buprenorphine for the treatment of NOWS as discussed by a panel of experts during a virtual workshop hosted by the National Institutes of Health.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy

Chronic intrauterine exposure to psychoactive drugs often results in neonatal opioid withdrawal syndrome (NOWS). When nonpharmacologic measures are insufficient in controlling NOWS, morphine, methadone, and buprenorphine are first-line medications commonly used to treat infants with NOWS because of in utero exposure to opioids. Research suggests that buprenorphine may be the leading drug therapy used to treat NOWS when compared with morphine and methadone. Currently, there are no consensus or standardized treatment guidelines for medications prescribed for NOWS. Opioids used to treat NOWS exhibit large interpatient variability in pharmacokinetics (PK) and pharmacodynamic (PD) response in neonates. Organ systems undergo rapid maturation after birth that may alter drug disposition and exposure for any given dose during development. Data regarding the PK and PD of opioids in neonates are sparse. Pharmacometric methods such as physiologically based pharmacokinetic and population pharmacokinetic modeling can be used to explore factors predictive of some of the variability associated with the PK/PD of opioids in newborns. This review discusses the utility of pharmacometric techniques for enhancing precision dosing in infants requiring opioid treatment for NOWS. Applying these approaches may contribute to optimizing the outcome by reducing cumulative drug exposure, mitigating adverse drug effects, and reducing the burden of NOWS in neonates.

Topics: Buprenorphine; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Methadone; Models, Biological; Morphine; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders

To critically review and summarize current knowledge regarding the assessment of newborns with neonatal abstinence syndrome (NAS).. We searched the following databases for articles on the assessment of newborns with NAS that were published in English between January 2014 and June 2020: PubMed, CINAHL, and PsycINFO. Keywords and Medical Subject Heading terms used to identify relevant research articles included neonatal abstinence syndrome; Finnegan Scale; eat, sleep, console; epigenetics; genetics; pharmacokinetics; and measurement. We independently reviewed articles for inclusion.. We retrieved 435 articles through database searches and 17 through manual reference searches; 31 articles are included in the final review. Excluded articles were duplicates, not relevant to NAS, qualitative studies, and/or of low quality.. We used the methodology of Whittemore and Knafl to guide this integrative review. We extracted and organized data under the following headings: author, year and country, purpose, study design, participants, measurement, biomarker (if applicable), results, limitations, recommendations, and intervention.. The Finnegan Neonatal Abstinence Scale is the most widely used instrument to measure symptoms of NAS in newborns, although it is very subjective. Recently, there has been a transition from the Finnegan Neonatal Abstinence Scale to the eat, sleep, console method, which consists of structured assessment and intervention and has been shown to decrease length of hospital stay and total opioid treatment dose. Researchers examined biomarkers of NAS, including genetic markers and autonomic nervous system responses, on the variation in incidence and differential severity of NAS. In the included articles, women with opioid use disorder who were treated with naltrexone during pregnancy gave birth to newborns without NAS diagnoses. However, most women who were treated with buprenorphine gave birth to newborns with NAS diagnoses.. NAS negatively affects newborns in a multitude of ways, and the objective assessment and measurement of the newborn's response to withdrawal remains understudied and needs further investigation.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Length of Stay; Neonatal Abstinence Syndrome; Pregnancy

Neonatal abstinence syndrome (NAS) due to opioid withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss, seizures and neurodevelopmental problems.. To assess the effectiveness and safety of using an opioid for treatment of NAS due to withdrawal from opioids in newborn infants.. We ran an updated search on 17 September 2020 in CENTRAL via Cochrane Register of Studies Web and MEDLINE via Ovid. We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for eligible trials.. We included randomised controlled trials (RCTs), quasi- and cluster-RCTs which enrolled infants born to mothers with opioid dependence and who were experiencing NAS requiring treatment with an opioid.. Three review authors independently assessed trial eligibility and risk of bias, and independently extracted data. We used the GRADE approach to assess the certainty of evidence.. We included 16 trials (1110 infants) with NAS secondary to maternal opioid use in pregnancy. Seven studies at low risk of bias were included in sensitivity analysis. Opioid versus no treatment / usual care: a single trial (80 infants) of morphine and supportive care versus supportive care alone reported no difference in treatment failure (risk ratio (RR) 1.29, 95% confidence interval (CI) 0.41 to 4.07; very low certainty evidence). No infant had a seizure. The trial did not report mortality, neurodevelopmental disability and adverse events. Morphine increased days hospitalisation (mean difference (MD) 15.00, 95% CI 8.86 to 21.14; very low certainty evidence) and treatment (MD 12.50, 95% CI 7.52 to 17.48; very low certainty evidence), but decreased days to regain birthweight (MD -2.80, 95% CI -5.33 to -0.27) and duration (minutes) of supportive care each day (MD -197.20, 95% CI -274.15 to -120.25). Morphine versus methadone: there was no difference in treatment failure (RR 1.59, 95% CI 0.95 to 2.67; 2 studies, 147 infants; low certainty evidence). Seizures, neonatal or infant mortality and neurodevelopmental disability were not reported. A single study reported no difference in days hospitalisation (MD 1.40, 95% CI -3.08 to 5.88; 116 infants; low certainty evidence), whereas data from two studies found an increase in days treatment (MD 2.71, 95% CI 0.22 to 5.21; 147 infants; low certainty) for infants treated with morphine. A single study reported no difference in breastfeeding, adverse events, or out of home placement. Morphine versus sublingual buprenorphine: there was no difference in treatment failure (RR 0.79, 95% CI 0.36 to 1.74; 3 studies, 113 infants; very low certainty evidence). Neonatal or infant mortality and neurodevelopmental disability were not reported. There was moderate certainty evidence of an increase in days hospitalisation (MD 11.45, 95% CI 5.89 to 17.01; 3 studies, 113 infants), and days treatment (MD 12.79, 95% CI 7.57 to 18.00; 3 studies, 112 infants) for infants treated with morphine. A single adverse event (seizure) was reported in infants exposed to buprenorphine. Morphine versus diluted tincture of opium (DTO): a single study (33 infants) reported no difference in days hospitalisation, days treatment or weight gain (low certainty evidence). Opioid versus clonidine: a single study (31 infants) reported no infant with treatment failure in either group. This study did not report seizures, neonatal or infant mortality and neurodeve. Compared to supportive care alone, the addition of an opioid may increase duration of hospitalisation and treatment, but may reduce days to regain birthweight and the duration of supportive care each day. Use of an opioid may reduce treatment failure compared to phenobarbital, diazepam or chlorpromazine. Use of an opioid may have little or no effect on duration of hospitalisation or treatment compared to use of phenobarbital, diazepam or chlorpromazine. The type of opioid used may have little or no effect on the treatment failure rate. Use of buprenorphine probably reduces duration of hospitalisation and treatment compared to morphine, but there are no data for time to control NAS with buprenorphine, and insufficient evidence to determine safety. There is insufficient evidence to determine the effectiveness and safety of clonidine.

Topics: Buprenorphine; Chlorpromazine; Clonidine; Diazepam; Humans; Hypnotics and Sedatives; Infant, Newborn; Methadone; Morphine; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Opium; Phenobarbital; Randomized Controlled Trials as Topic

Pregnant and postpartum women with opiate use disorder present a challenge in perinatal care. It is important for health care teams to provide sensitive and compassionate evidence-based care for these women, who often are stigmatized during the prenatal, delivery, and postpartum periods. Women with opiate use disorder are at risk for inadequate prenatal and postpartum care and for complications. Infants are at risk for neonatal abstinence syndrome and are expected to require neonatal intensive care. Pain management during labor and for cesarean delivery requires consultation and collaboration with providers who have expertise in management of addiction. Postpartum follow-up is essential.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cesarean Section; Female; Humans; Infant, Newborn; Labor, Obstetric; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Perinatal Care; Postpartum Period; Pregnancy; Pregnancy Complications

Opioid use during pregnancy has serious consequences for mother and baby. The true extent of the problem is unknown and there is a need for better screening. Existing guidelines with respect to the management of pregnant women with opioid use are based on limited evidence. To improve recommendations for optimal identification, management, and treatment, publications on opioids in pregnancy were reviewed. Published literature from 2007 to 2017 was searched in PubMed, Cochrane and Embase databases. The review employed 60 publications from 210 studies identified, that were of varying quality and included randomized controlled trials, systematic reviews, meta-analyses, and Cochrane reviews. The prevalence of opioid use in pregnancy is underestimated. Screening by urine testing and self-reporting is acceptable to identify fetal exposure. To minimize risk, opioid agonist pharmacotherapy should replace the continued use of opioids or detoxification. Current guidelines recommend methadone and buprenorphine equally. However, recent studies indicate that buprenorphine has advantages over methadone. Accordingly, we suggest buprenorphine as first-line therapy. Future studies should elaborate on better objective screening methods to prevent the consequences of fetomaternal opioid exposure.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Maternal-Fetal Exchange; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications

The incidence of neonatal abstinence syndrome owing to prenatal opioid exposure has grown rapidly in recent decades and it disproportionately affects rural, non-white, and public insurance-dependent populations. Treatment consists of pharmacologic and nonpharmacologic interventions with wide variability in approaches across the United States. Standardizing clinical assessment, minimizing unnecessary interruptions, and prioritizing nonpharmacologic and family-centered care seems to improve hospital outcomes. Neonatal abstinence syndrome may have long-term developmental and biological effects, but understanding is limited owing in part confounding biosocial factors. Early intervention and longitudinal support of the infant and family promote better outcomes.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Methadone; Morphine; Neonatal Abstinence Syndrome; Nurseries, Hospital; Opiate Substitution Treatment; Opioid-Related Disorders; Parents; Phenobarbital; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rooming-in Care; Severity of Illness Index; Treatment Outcome

Perinatal opioid use is a major public health problem and is associated with a number of deleterious maternal and fetal effects. We review recent evidence of perinatal outcomes and treatment of opioid use disorder (OUD) during pregnancy.. Opioid exposure in pregnancy is associated with multiple obstetric and neonatal adverse outcomes, with the most common being neonatal opioid withdrawal syndrome (NOWS). Treatment with buprenorphine or methadone is associated with NOWS, but neither medication appears to have significant adverse effects on early childhood development. Buprenorphine appears to be superior to methadone in terms of incidence and severity of NOWS in exposed infants. The long-term effects of opioid exposure in utero have been inconclusive, but recent longitudinal studies point to potential differences in brain morphology that may increase vulnerability to future stressors. Maintenance therapy with methadone or buprenorphine remains the standard of care for pregnant women with OUD given its consistent superiority to placebo in terms of rates of illicit drug use and pregnancy outcomes. New non-pharmacologic management options for NOWS appear promising. Future research is needed to further evaluate the effects of opioid exposure in utero and determine the optimal delivery model for maintenance therapy.

Topics: Buprenorphine; Child Development; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome

We sought to compare the efficacy and safety of detoxification from opioids compared with opioid replacement therapy (ORT) during pregnancy.. We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to June 2017 for English-language randomized-controlled trials or cohort studies that compared detoxification with ORT. We sought studies with outcomes data on maternal abstinence at the time of delivery, neonatal abstinence syndrome (NAS), stillbirth, and preterm birth (PTB). We calculated pooled relative risks (RRs) with a random-effects model, assessed heterogeneity using the chi-square test for heterogeneity, and quantified heterogeneity using the. Three cohort studies met the inclusion criteria; eligible studies included 235 women with opioid use disorder in pregnancy. Maternal detoxification was associated with increased risk of relapse (RR = 1.91; 95% confidence interval [CI] = 1.14-3.21); however, no treatment differences were observed for the rates of NAS (RR = 0.99; 95% CI = 0.38-2.53) or PTB (RR = 0.39; 95% CI = 0.10-1.60).. Our findings suggest an increased risk of relapse with detoxification treatment compared with ORT; however, detoxification does not alter the risk of PTB or NAS. Further studies should confirm our findings and explore mechanisms to fight the current opioid epidemic.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Recurrence

Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.. To compare pharmacological therapies for neonatal abstinence syndrome.. Systematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018).. Randomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.).. Data extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis.. The primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.. Eighteen trials (N = 1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision.. The current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Network Meta-Analysis; Treatment Outcome

Neonatal abstinence syndrome is defined by signs and symptoms of withdrawal that infants develop after intrauterine maternal drug exposure. All infants with documented in utero opioid exposure, or a high pre-test probability of exposure should have monitoring with a standard assessment instrument such as a Finnegan Score. A Finnegan score of >8 is suggestive of opioid exposure, even in the absence of declared use during pregnancy. At least half of infants in most locales can be treated without the use of pharmacologic means. For this reason, symptom scores will drive the decision for pharmacologic therapy. Nevertheless, all infants, regardless of initial manifestations, should be first be managed with non-pharmacologic approaches which in turn, should not be considered as the sole alternative to drug therapy, but rather, as the base upon which all patients are treated. Those who continue to have symptoms despite supportive care should be pharmacologically treated, which in the most severe cases, is life-saving.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Humans; Infant, Newborn; Methadone; Morphine; Neonatal Abstinence Syndrome

When opioid misuse rises in the United States, pregnant women and their neonates are affected. This article summarizes the use of Food and Drug Administration-approved products, including methadone, buprenorphine, and the combination formulation of buprenorphine and naloxone to treat adult opioid use disorder during the perinatal period. All labels include pregnancy, neonatal, and lactation information and note the accepted use of these medications during the perinatal period if the benefits outweigh the risks. A summary of the neonatal abstinence syndrome definition, its assessment tools, treatment approaches, and future genetic directions are provided.

Topics: Analgesia, Obstetrical; Analgesics; Analgesics, Opioid; Breast Feeding; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Clonidine; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Kangaroo-Mother Care Method; Maternal-Fetal Exchange; Methadone; Neonatal Abstinence Syndrome; Occupational Therapy; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Patient Education as Topic; Phenobarbital; Physical Therapy Modalities; Pregnancy; Pregnancy Complications; Rooming-in Care

Neonatal abstinence syndrome (NAS) which is observed in 55-94% of the newborns from opioids-taking mothers produces deleterious neurological symptoms. Various pharmacological therapies have been investigated in neonates with NAS. This article reviews all studies on NAS treatment to analyze the duration of treatment, length of hospitalization and possible drug adverse effects. The search was limited to the randomized clinical trials which examined the treatments of neonates with NAS. Scientific databases including PubMed, Cochrane Library, ISI Web of Science, Embase and Scopus were systematically searched. Retrieved articles were reviewed by two researchers and evaluated using the JADAD scoring system. Finally, the treatment duration, hospitalization length and drug side-effects were extracted. Methadone, buprenorphine and clonidine were found more effective than morphine. Diluted tincture of opium (DTO) in combination with phenobarbital or clonidine was significantly more effective than DTO alone. Clonidine was a significantly better adjunctive therapy than phenobarbital in reducing morphine treatment days. No significant difference was observed between morphine and DTO effectiveness. Deciding the optimal regimen to manage symptomatic NAS, as a single or an adjunct therapy is not possible based on the literature, due to the low quality, small size and short-term treatment considered in the published studies. Graphical abstract Process of selecting trials included in the present systematic review.

Topics: Analgesics, Opioid; Buprenorphine; Clonidine; Drug Therapy, Combination; Humans; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

To compare short-term treatment outcomes of opioid pharmacotherapy for neonatal opioid withdrawal syndrome (NOWS).. PubMed/MEDLINE, Embase, PsycINFO, and The Cochrane Library were searched from inception through September 30, 2018. Primary outcome was treatment duration (LOT). Secondary outcomes included hospitalization duration (LOS) and rate of adjunct drug needed (RAD).. Of 753 publications, 11 studies met inclusion criteria. There was no difference in LOT (WMD -1.39 [-5.79 to -3.01] days, I. Methadone had superior primary treatment success compared with morphine. Buprenorphine was associated with the shortest overall durations of treatment and hospitalization.

Topics: Analgesics, Opioid; Buprenorphine; Humans; Infant, Newborn; Length of Stay; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment

Infants exposed in utero to opioids will demonstrate a withdrawal syndrome known as neonatal abstinence syndrome (NAS). Buprenorphine is a long-acting opioid with therapeutic use in medication-assisted treatment of opioid dependency in adults and adolescents. Emerging data from clinical trials and treatment cohorts demonstrate the efficacy and safety of sublingual buprenorphine for those infants with NAS who require pharmacologic treatment. Pharmacometric modeling will assist in defining the exposure-response relationships and facilitate dose optimization.

Topics: Buprenorphine; Drug Dosage Calculations; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Treatment Outcome

Opioid neonatal abstinence syndrome (NAS) refers to signs of withdrawal observed in infants experiencing intrauterine opioid exposures. Early identification of at-risk infants allows for the prompt initiation of nonpharmacologic supportive care. When withdrawal symptoms are severe despite these interventions, pharmacologic therapy including opioid weaning is initiated. Consistency with standardized nonpharmacologic approaches as well as stringent weaning protocols are important in minimizing the length of stay and length of pharmacologic treatment for these vulnerable patients.

Topics: Buprenorphine; Clinical Protocols; Humans; Infant, Newborn; Length of Stay; Morphine; Neonatal Abstinence Syndrome; Risk Assessment; Substance Withdrawal Syndrome

Neonatal abstinence syndrome, which occurs as a result of in utero opioid exposure, affects between 6.0 and 20 newborns per 1000 live US births. There is substantial variability in how neonatal abstinence syndrome is diagnosed and managed.. To summarize key studies examining the diagnosis and management (both pharmacologic and nonpharmacologic) of neonatal abstinence syndrome published during the past 10 years.. PubMed, Web of Science, and CINAHL were searched for articles published between July 1, 2007, and December 31, 2017. Abstracts were screened and included in the review if they pertained to neonatal abstinence syndrome diagnosis or management and were judged by the authors to be clinical trials, cohort studies, or case series.. A total of 53 articles were included in the review, including 9 randomized clinical trials, 35 cohort studies, 1 cross-sectional study, and 8 case series-representing a total of 11 905 unique opioid-exposed mother-infant dyads. Thirteen studies were identified that evaluated established or novel neonatal abstinence syndrome assessment methods, such as brief neonatal abstinence syndrome assessment scales or novel objective physiologic measures to predict withdrawal. None of the new techniques that measure infant physiologic parameters are routinely used in clinical practice. The most substantial number of studies of neonatal abstinence syndrome management pertain to nonpharmacologic care-specifically, interventions that promote breastfeeding or encourage parents to room-in with their newborns. Although these nonpharmacologic interventions appear to decrease the need for pharmacologic treatment and result in shorter hospitalizations, the interventions are heterogeneous and there are no high-quality clinical trials to support them. Regarding pharmacologic interventions, only 5 randomized clinical trials with prespecified sample size calculations (4 infant, 1 maternal treatment) have been published. Each of these trials was small (from 26 to 131 participants) and tested different therapies, limiting the extent to which results can be aggregated. There is insufficient evidence to support an association between any diagnostic or treatment approach and differential neurodevelopmental outcomes among infants with neonatal abstinence syndrome.. Evidence pertaining to the optimal diagnosis and treatment strategies for neonatal abstinence syndrome is based on small or low-quality studies that focus on intermediate outcomes, such as need for pharmacologic treatment or length of hospital stay. Clinical trials are needed to evaluate health and neurodevelopmental outcomes associated with objective diagnostic approaches as well as pharmacologic and nonpharmacologic treatment modalities.

Topics: Acupuncture Therapy; Analgesics; Breast Feeding; Buprenorphine; Clonidine; Female; Humans; Infant, Newborn; Methadone; Morphine; Mothers; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Rooming-in Care

Opioid abuse and dependence continues to rise in both the general population and pregnancy, with opioid overdose deaths having quadrupled in the last 15 years. Illicit drug use in last 30 days of pregnancy was over 4% with almost 0.6% documented maternal opiate use at time of birth. The management of the opioid-tolerant, buprenorphine-dependent or methadone-dependent patient in the peripartum period is reviewed. Options for treatment of opioid dependence, acute pain management, and perioperative multimodal analgesia are discussed. The effects of maternal management on neonatal abstinence syndrome are also reviewed.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Humans; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Peripartum Period; Pregnancy; Pregnancy Complications; Treatment Outcome

Substance use among pregnant women is a major public health issue. Both prescription opioid use and illicit opioid abuse have increased dramatically in recent years. Prolonged in utero drug exposure may result in neonatal abstinence syndrome (NAS), an acute multisystemic clinical entity that occurs in the first days of life. This syndrome is caused by abrupt discontinuation of fetal exposure to licit or illicit drugs chronically consumed by the mother during pregnancy and transmitted to the fetus through the placenta. It usually requires prolonged hospitalization and may have long-term effects. The interplay of many factors contributes to its clinical heterogeneity, and its pathophysiology has not been fully unveiled. The first step in NAS management consists of nonpharmacologic interventions and includes promoting breastfeeding when not contraindicated. If withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring system supports care providers across the pharmacotherapy process from initiation through the monitoring phase, until weaning and discontinuation. However, a standardized approach to pharmacotherapy is still lacking. Morphine is usually the first-line agent to treat NAS. Methadone is a valid option, but its safety profile is not completely known. Phenobarbital, despite its lack of effect on gastrointestinal symptoms and unfavorable pharmacologic features, has been identified as a second-line agent to be used in infants unresponsive to opiates. Although buprenorphine and clonidine seem promising, their use requires further validation. Long-term developmental effects of NAS therapy call for more-comprehensive, longitudinal assessments. In this article, key points for use of recommended therapies are outlined, and directions for future research are suggested.

Topics: Analgesics, Opioid; Antidepressive Agents; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Neurodevelopmental Disorders; Opiate Substitution Treatment; Pregnancy

Pregnant women with opioid use disorder can be treated with methadone, buprenorphine, or naltrexone to reduce opioid use and improve retention to treatment. In this review, we compare the pregnancy outcomes of methadone, buprenorphine, and naltrexone in clinical trials and discuss the potential behavioral and developmental effects of these agents seen in offspring in animal studies. Important clinical considerations in the management of opioid use disorder in pregnant women and their infants are also discussed. Outside of pregnancy, buprenorphine is used in combination with naloxone to reduce opioid abuse and diversion. During pregnancy, however, the use of buprenorphine as a single agent is preferred to prevent prenatal naloxone exposure. Both methadone and buprenorphine are widely used to treat opioid use disorder; however, compared with methadone, buprenorphine is associated with shorter treatment duration, less medication needed to treat neonatal abstinence syndrome (NAS) symptoms, and shorter hospitalizations for neonates. Despite being the standard of care, medication-assisted treatment with methadone or buprenorphine is still underused, making it apparent that more options are necessary. Naltrexone is not a first-line treatment primarily because both detoxification and an opioid-free period are required. More research is needed to determine naltrexone safety and benefits in pregnant women. Animal studies suggest that changes in pain sensitivity, developmental processes, and behavioral responses may occur in children born to mothers receiving methadone, buprenorphine, or naltrexone and is an area that warrants future studies.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Naltrexone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome

Perioperative management of patients receiving opioid addiction therapy presents a unique challenge for the anesthesiologist. The goal of pain management in this patient population is to effectively manage postoperative pain, to improve patient satisfaction and outcomes, and to reduce the cost of health care. Multimodal analgesics, including nonsteroid anti-inflammatory drugs, intravenous acetaminophen, gabapentanoid agents, and low-dose ketamine infusions, have been used to improve postoperative pain and to reduce postoperative opioid use. Patients on long-term opioid management therapy with methadone and buprenorphine require special considerations. Recommendations and options for treating postoperative pain in patients on methadone and buprenorphine are outlined below. Other postoperative pain management options include patient-controlled analgesia, intravenous, and transdermal, in addition to neuraxial and regional anesthesia techniques. Special patient populations include the parturient on long-term opioid therapy. Recommendations for use of opioids in these patients during labor and delivery and in the postpartum period are discussed.

Topics: Buprenorphine; Drug Administration Schedule; Female; Humans; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pain, Postoperative; Postpartum Period; Practice Guidelines as Topic; Pregnancy; Pregnancy Outcome

Although there is an abundance of interventional studies to increase breastfeeding rates, little is known about how to support and promote breastfeeding among mothers on opioid maintenance treatment (OMT). The studies on maternal OMT mainly focus on medication excreted in breast milk and breastfeeding benefits for infants with neonatal abstinence syndrome (NAS). We aim to review interventions to improve breastfeeding outcomes among mothers on OMT to make recommendations for practice and future research. We searched CINAHL, PubMed, PsycINFO, and the Cochrane Database of Systematic Reviews for articles, preferably experimental/quasi-experimental studies published within the past 10 years, that examined interventions to increase rates of breastfeeding initiation and duration among mothers on OMT. Nine studies met our inclusion criteria, comprising 5 categories: 4 combined obstetric and addiction care, 1 rooming-in, 1 Baby-Friendly hospital, 2 inpatient/outpatient NAS treatment, and 1 divided methadone dose. Breastfeeding rates were relatively higher for divided methadone dose (81% initiated any breastfeeding) and rooming-in (62% initiated any breastfeeding); lower in Baby-Friendly hospital (24%) and inpatient/outpatient NAS treatment (45% and 24%, respectively); and mixed in combined obstetric and addiction care programs (2 studies reported 70% and 76%; 2 studies reported 17% and 28%). Studies that included both methadone and buprenorphine did not specify breastfeeding results by medication. We recommend future research to differentiate breastfeeding types and duration by OMT medication. Qualitative studies are needed to explore maternal view on breastfeeding regarding need, barrier, and motivating factors in order to develop effective interventions to promote breastfeeding among mothers on OMT.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Female; Health Promotion; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders

To evaluate maternal and neonatal safety outcomes for methadone and buprenorphine in the obstetric population.. A literature search of PubMed (1966 to March 2016) and EMBASE (1973 to March 2016) was completed using the search terms buprenorphine, methadone, pregnancy, opioid, and neonatal abstinence syndrome Priority was given to randomized controlled trials and trials directly comparing buprenorphine and methadone during pregnancy. The bibliographies were reviewed for other relevant articles.. All human studies published in English, that compared methadone and buprenorphine use in pregnancy were evaluated. Because of the limited number of obstetric studies, only 5 critical studies were found.. Buprenorphine significantly improved or had similar outcomes to methadone for development of neonatal abstinence syndrome (NAS), percentage of infants requiring treatment for NAS (20%-47% vs 45.5%-57%, respectively), total amount of morphine used to treat NAS (0.472-3.4 vs 1.862-10.4 mg, respectively), duration of NAS (4.1-5.6 vs 5.3-9.9 days, respectively), peak NAS (3.9-11 vs 4.9-12.8 score, respectively), infant hospital stay (6.8-10.6 vs 8.1-17.5 days, respectively), and gestational age at delivery (38.8-39.7 vs 37.9-38.8 weeks, respectively). No difference was found with other neonatal or maternal outcomes.. Both methadone and buprenorphine are effective agents, with improved safety compared with continued nonmedical opioid use during pregnancy. There is evidence to suggest that buprenorphine should be considered as an equivalent option to methadone for use in pregnancy; however, larger studies are still needed to fully evaluate buprenorphine safety and advantages over methadone in the obstetric population.

Topics: Buprenorphine; Female; Humans; Infant; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic

Neonatal abstinence syndrome (NAS) from in utero opioid exposure has reached epidemic levels in the United States. Although nonpharmacologic therapies form the foundation of care, many neonates require pharmacotherapy. Morphine represents the most widely used first-line agent and effectively treats the symptoms of withdrawal. However, methadone or buprenorphine may facilitate earlier discharge. Although phenobarbital is traditionally used when opioids fail, clonidine may be a more appropriate adjunctive agent to minimize negative neurodevelopmental impact. Consideration of the available data allows hospitals to generate effective pharmacologic strategies to manage NAS while further research continues.

Topics: Analgesics; Buprenorphine; Clonidine; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Infant, Newborn; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Phenobarbital

Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians.

Topics: Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Female; Humans; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnant Women; Prenatal Exposure Delayed Effects; Substance-Related Disorders; Treatment Outcome

Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Female; Humans; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Risk Factors; Substance-Related Disorders; United States

Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Models, Statistical; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome

Neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure is an increasing problem. Variability in assessment and treatment of NAS has been attributed to the lack of high-quality evidence to guide management of exposed neonates. This systematic review examines available evidence for NAS assessment tools, nonpharmacologic interventions, and pharmacologic management of opioid-exposed infants. There is limited data on the inter-observer reliability of NAS assessment tools due to lack of a standardized approach. In addition, most scales were developed prior to the prevalent use of prescribed prenatal concomitant medications, which can complicate NAS assessment. Nonpharmacologic interventions, particularly breastfeeding, may decrease NAS severity. Opioid medications such as morphine or methadone are recommended as first-line therapy, with phenobarbital or clonidine as second-line adjunctive therapy. Further research is needed to determine best practices for assessment, nonpharmacologic intervention, and pharmacologic management of infants with NAS in order to improve outcomes.

Topics: Breast Feeding; Buprenorphine; Clonidine; Female; Humans; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects

Pregnancy in opioid users poses a number of problems to treating physicians. Most guidelines recommend maintenance treatment to manage opioid addiction in pregnancy, with methadone being the gold standard. More recently, buprenorphine has been discussed as an alternate medication. The use and efficacy of buprenorphine in pregnancy is still controversial. This article reviews the current database on the basis of a detailed and critical literature search performed in MEDLINE (206 counts). Most of the relevant studies (randomised clinical trials and one national cohort sample) were published in the last 2 years and mainly compared buprenorphine with methadone. Some studies are related to maternal outcomes, others to foetal, neonatal or older child outcomes. With respect to maternal outcomes, most studies suggest that buprenorphine has similar effects to methadone. Very few data from small studies discuss an effect of buprenorphine on neurodevelopment of the foetus. Neonatal abstinence syndrome is common in infants of both buprenorphine- and methadone-maintained mothers. As regards neonatal outcomes, buprenorphine has the same clinical outcome as methadone, although some newer studies suggest that it causes fewer withdrawal symptoms. Since hardly any studies have investigated the combination of buprenorphine with naloxone (which has been suggested to possibly have teratogenic effects) in pregnant women, a switch to buprenorphine monotherapy is recommended in women who become pregnant while receiving the combination product. These novel findings indicate that buprenorphine is emerging as a first-line treatment for pregnant opioid users.

Topics: Animals; Buprenorphine; Child; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications

This review will summarize the symptoms, evaluation, and treatment of neonatal and iatrogenic withdrawal syndromes.. Buprenorphine is emerging as the drug of choice for maintaining opioid-dependent women during pregnancy, because of its association with less severe withdrawal symptoms. Recent findings suggest it may be the drug of choice for treating the opioid-exposed neonate as well.. Healthcare workers should be cognizant of the risk factors for neonatal abstinence syndrome (NAS), as well as its symptoms, so that nonpharmalogic and pharmacologic therapies can be initiated. With increased emphasis on pain control in children, it is likely that iatrogenic withdrawal will continue to be a concern, and healthcare workers should understand the similarities and differences between this and NAS.

Topics: Analgesics, Opioid; Buprenorphine; Diagnosis, Differential; Evidence-Based Medicine; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Risk Factors; Substance Withdrawal Syndrome

Current trends in the United States suggest that chronic narcotic use has increased in reproductive aged women over the past 10 years. Regular exposure to such substances during pregnancy has maternal and fetal implications. Appropriate prenatal care is critical to optimizing outcomes. Management options for narcotic dependence should be patient-specific and may include discontinuation of narcotics with careful observation, limitation of prescription dispensing, or substitution therapy with methadone or buprenorphine. A multidisciplinary, collaborative approach is highly recommended. This review discusses usage of narcotic medications, associated maternal and fetal risks, and management strategies for the antepartum, intrapartum, and postpartum periods.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Care

Most infants at risk for neonatal abstinence syndrome have opioid plus another drug exposure; polypharmacy is the rule rather than the exception. Scales for evaluation of neonatal abstinence syndrome are primarily based for opioid withdrawal. A standard protocol to treat neonatal abstinence syndrome has not been developed. Institute nonpharmacologic strategies for all neonates at risk. The American Academy of Pediatrics recommends mechanism-directed therapy (treat opioid withdrawal with an opioid) as the first-line therapy. Second-line medications are currently under evaluation.

Topics: Analgesics, Opioid; Buprenorphine; Feeding Methods; Humans; Infant Care; Infant, Newborn; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pacifiers; Treatment Outcome

Substance misuse in pregnancy is not a new problem, but although impaired foetal growth and the risk of developing neonatal abstinence syndrome are widely appreciated, relatively little attention has been paid to longer term consequences for the infant. Available evidence indicates that prenatal exposure to opioids and other drugs of misuse is detrimental to the developing foetal brain; consistent with this, poor in utero head growth, delayed infant visual maturation and impaired general neurodevelopmental progress independent of social confounders are increasingly being recognised. This review considers current evidence and discusses best practice in the neonatal management and follow-up of affected babies. More studies are required to explore alternatives to methadone maintenance in pregnancy and to define optimal treatment for neonatal abstinence syndrome. All infants born to drug-misusing mothers must be considered vulnerable, even if they have not required treatment for neonatal abstinence syndrome.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Mothers; Narcotic Antagonists; Neonatal Abstinence Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Substance-Related Disorders

Managing opioid dependence in pregnant women is a complex and potentially challenging task. Drug-dependent women may be difficult to engage in antenatal care and opioid substitution requires careful dose titration. Pregnancy, however, can be an opportune time to effect behaviour change, and supporting an opioid-dependent woman through pregnancy can be a rewarding clinical experience.. This article provides an overview of treatment principles for managing opioid dependence in pregnancy, and reviews current treatment guidelines for use of opioid-substitution therapy in pregnant women.. The management of opioid dependence during pregnancy requires holistic and comprehensive assessment and referral to specialist services is often appropriate. Specific issues that may need to be addressed include decision-making regarding the choice of opioid-substitution therapy and the potential for neonatal abstinence syndrome in the newborn. General practitioners are often well placed to support and coordinate care of their opioid-dependent pregnant patients.

Topics: Adult; Buprenorphine; Female; General Practice; Humans; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Prenatal Care; Young Adult

The present paper considers naltrexone to treat opioid dependence during pregnancy. The public health problem of opioid dependence and its treatment during pregnancy is reviewed first. Next, the naltrexone and opioid dependence treatment literature is summarized, with overviews of the pre-clinical and clinical research on prenatal naltrexone exposure. Finally, considerations and recommendations for future medication research for the treatment of opioid dependence in pregnant women are provided. The efficacy of long-acting injectable naltrexone relative to placebo, its blockade of opioid agonist euphoric effects, its lack of abuse and tolerance development and its modest adverse effect profile make it a potential medication for opioid-dependent pregnant women. However, it is not without seriously concerning potential drawbacks, including the difficulty surrounding medication induction that may lead to vulnerability with regard to relapse, physical dependence re-establishment, increased risk behaviors, treatment dropout and resulting opioid overdose. Before embarking on future research with this medication, the benefits and risks for the mother-embryo/fetus/child dyad should be weighed carefully. Should future research be conducted, a multi-level commitment to proactive ethical research is needed to reach the ultimate goal of improving the lives of women and children affected by opioid dependence.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Risk Assessment; Risk Factors; Treatment Outcome

The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care in maternal and fetal/neonatal (M-F/N) medicine. The standard of care for illicit or prescription opioid dependence during pregnancy is opioid agonist (methadone or buprenorphine) substitution therapy, which are also frequently abused. The next generation of pharmacotherapies for the treatment of illicit or prescription opioid addiction in the M-F/N interactional dyad must take into consideration the interplay between genetic, epigenetic, and environmental factors. Addiction to illicit drugs during pregnancy presents unique challenges to effectively treat the mother, and the developing fetus and infant after delivery. New pharmacotherapies should be safe to the developing fetus, effective in treating the physical and psychological consequences of addiction in the mother, and reduce the incidence and severity of NAS in the infant after birth. More pharmacotherapeutic options should be available to the physician such that a more individualized rather than a one-drug/strategy-fits-all approach can be used. A myriad of new and exciting pharmacotherapeutic strategies for the treatment of opioid dependence and addiction are on the horizon. This review focuses on such three strategies: (i) pharmacotherapeutic targeting of the serotonergic system; (ii) mixed opioid immunotherapeutics (vaccines); (iii) pharmacogenomics as a therapeutic strategy to insure personalized care. We review and discuss how these strategies may offer additional treatment modalities for the treatment of M-F/N during pregnancy and the treatment of the infant after birth.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Immunotherapy; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pregnancy; Selective Serotonin Reuptake Inhibitors

This review will discuss the complex nature of maternal and other factors that can affect the infant's display of neonatal abstinence syndrome (NAS), clinical presentation and treatment of NAS, and the impact of recent findings on future directions for research.. NAS has traditionally been described as a constellation of signs/symptoms displayed by the neonate upon withdrawal of gestational opioid exposure; however, recent research has advanced our understanding of this disorder. Other psychoactive substances, such as increasingly prescribed serotonin reuptake inhibitors, may produce an independent or synergistic discontinuation syndrome. The wide variability in NAS presentation has generated interest in the interplay of prenatal and postnatal environmental and genetic factors that may moderate or mediate its expression. Finally, recent advances in the treatment of opioid-dependent pregnant women have suggested buprenorphine as an alternative treatment to methadone during pregnancy, largely due to reduced NAS severity in exposed neonates.. Physicians should be aware of the complexity of the maternal, fetal, and infant factors that combine to create the infant's display of NAS, and incorporate these aspects into comprehensive assessment and care of the dyad. Further research regarding the pathophysiology and treatment of NAS is warranted.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects

This article provides an overview and discussion of the collective maternal, fetal and neonatal outcome research on women maintained on methadone or buprenorphine during pregnancy. Its focus is on an assessment of the comparative effectiveness of methadone and buprenorphine pharmacotherapy, with particular attention given to recent findings from the literature. Recommendations for clinical practice are outlined, and directions for future research are presented. Findings from comparative studies of methadone and buprenorphine underscore the efficacy of both medications in preventing relapse to illicit opioid use in the treatment of opioid-dependent pregnant patients, as well as the simplicity of induction onto methadone and patient retention while receiving such therapy. Fetal monitoring suggests that buprenorphine results in less fetal cardiac and movement suppression than does methadone. The clinical implications of these findings need future exploration. For the neonate, evidence from studies using a wide range of designs, including retrospective chart reviews, prospective observational studies, and randomized clinical trials, show consistent results, with prenatal exposure to buprenorphine resulting in less severe neonatal abstinence syndrome relative to methadone. Any medication given to pregnant women should be prescribed only after considering the risk : benefit ratio for the maternal-fetal dyad. Medication choices for each opioid-dependent patient during pregnancy need to be made on a patient-by-patient basis, taking into consideration the patient's opioid dependence history, previous and current treatment experiences, medical circumstances and treatment preferences. Moreover, for a full remission of opioid addiction to be sustainable, both post-partum and across the lifespan, treatment providers must not rely solely on medication to treat their patients but should also utilize women-specific comprehensive treatment models that address the underlying multifaceted complexities of their patient's lives.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic

This paper reviews the published literature regarding outcomes following maternal treatment with buprenorphine in five areas: maternal efficacy, fetal effects, neonatal effects, effects on breast milk and longer-term developmental effects.. Within each outcome area, findings are summarized first for the three randomized clinical trials and then for the 44 non-randomized studies (i.e. prospective studies, case reports and series and retrospective chart reviews), only 28 of which involve independent samples.. Results indicate that maternal treatment with buprenorphine has comparable efficacy to methadone, although difficulties may exist with current buprenorphine induction methods. The available fetal data suggest buprenorphine results in less physiological suppression of fetal heart rate and movements than methadone. Regarding neonatal effects, perhaps the single definitive conclusion is that prenatal buprenorphine treatment results in a clinically significant less severe neonatal abstinence syndrome (NAS) than treatment with methadone. The limited research suggests that, like methadone, buprenorphine is compatible with breastfeeding. Data available thus far suggest that there are no deleterious effects of in utero buprenorphine exposure on infant development.. While buprenorphine produces a less severe neonatal abstinence syndrome than methadone, both methadone and buprenorphine are important parts of a complete comprehensive treatment approach for opioid-dependent pregnant women.

Topics: Buprenorphine; Child Development; Female; Fetus; Humans; Infant, Newborn; Length of Stay; Methadone; Milk, Human; Morphine; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Patient Dropouts; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Randomized Controlled Trials as Topic; Substance Abuse Detection; Treatment Outcome

The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current--and single most comprehensive--research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine.. The MOTHER study design is outlined, and its basic features are presented.. At least seven important lessons have been learned from the MOTHER study: (i) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (ii) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment, patient populations and hospital practices that, in turn, differentially impact recruitment rates, treatment compliance and attrition; (iii) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (iv) staff turnover needs to be addressed with a proactive focus on both hiring and training; (v) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (vi) timely tracking of data in a multi-site trial is both demanding and unforgiving; and (vii) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results.

Topics: Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Selection; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Treatment Outcome; United States

The purpose of this review is to discuss the incidence, risks, pregnancy complications, and maintenance options for treatment of opioid addiction in pregnancy.. Opioid dependence in pregnancy carries clear identifiable maternal and fetal risk. Providing care for patients with dependence is best done in a multidisciplinary care model addressing the particular needs of this population. There are limited data on maternal detoxification, with data still emerging surrounding the safety profile of this practice. Historically, methadone has been the recommended maintenance treatment; however, recent data on buprenorphine identify this as a safe and effective option. The majority of births from women with opioid dependence result in neonatal abstinence syndrome requiring prolonged neonatal hospitalization. Intrapartum pain management should not differ from the general obstetric population. Postpartum pain is magnified in this population, and particular attention should be focused on this issue. Breast-feeding is recommended regardless of maintenance dose, unless other conditions restricting breast-feeding are present. Comprehensive postpartum care and transition of care to addiction specialists are highly recommended.. Obstetricians and gynecologists, family physicians, addiction specialists.. After completing this CME activity, physicians should be better able to assess the treatment options available to patients with opioid addiction during pregnancy, compare the risk/safety profiles of methadone and buprenorphine, and evaluate the recommendations and current data surrounding breast-feeding while on opioid maintenance treatment.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pregnancy; Pregnancy Complications

Although a statement on Neonatal Drug Withdrawal was published in 1998 by the American Academy of Pediatrics, pharmacologic management of neonatal abstinence syndrome (NAS) remains a challenge. Published clinical trials are limited, restricting treatment decision making to practitioner's experience and preference rather than evidence-based medicine. To optimize withdrawal symptom prevention, drug selection is often based on the offending agent (opioids versus polysubstance exposure), clinical presentation, mechanism of action (agonist versus partial agonist/antagonist, receptor effects), pharmacokinetic parameters and available drug formulations. This review addresses risk factors and pathophysiology of NAS, summarizes parameters of common drugs used for the management of NAS, and reviews published literature of standard therapies as well as newer agents. Based on the current literature, paregoric is no longer recommended and oral morphine solutions remain the mainstay of therapy for opiate withdrawal. Other potential therapies include methadone, buprenorphine, phenobarbital and clonidine with the latter two agents as adjunctive therapies.

Topics: Benzodiazepines; Buprenorphine; Clonidine; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Phenobarbital; Pregnancy

The number of opiate addicted patients treated with opioid replacement therapy is continuously increasing. In Germany, 57.7% of these patients are treated with methadone and 18.6% with buprenorphine. This maintenance therapy provides several advantages while addicted pregnant women and their foetus have a high benefit from appropriate replacement therapy. However, the recommendations concerning breast feeding during an opioid replacement therapy are discussed controversially, because methadone as well as buprenorphine accumulate in breast milk. This accumulation might cause damages to the newborn's health; so, child benefits of breast feeding have to be balanced with possible health risks.This review provides an overview of a selective literature search based on the PubMed-database and german consensus recommendations. Used search terms included: (methadone*) AND (breastfeeding OR lactation), (methadone*) AND (human milk), (buprenorphine*) AND (breastfeeding OR lactation) and (buprenorphine*) AND (human milk).According to the available literature, addicted women, substinated with methadone or buprenorphine are allowed to breast feed their newborns. The advantages of breast feeding prevail the risks of an infant opiate intoxication caused by methadone or buprenorphine.

Topics: Analgesics, Opioid; Breast Feeding; Buprenorphine; Contraindications; Dose-Response Relationship, Drug; Female; Germany; Humans; Infant; Infant, Newborn; Male; Metabolic Clearance Rate; Methadone; Milk, Human; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy

This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has long been regarded as the standard of care in pregnancy, and buprenorphine, which is increasingly being investigated and prescribed as an alternative to methadone. Controlled studies comparing methadone at high and low doses, as well as those comparing methadone with buprenorphine, are highlighted and the diagnosis and management of neonatal abstinence syndrome is discussed. Over the past two decades, attention of the scientific and lay communities has also been focused on the potential adverse effects of cocaine and crack cocaine, especially during the height of the cocaine epidemic in the United States. Herein, the findings are summarized from prospective studies comparing cocaine-exposed with non-cocaine-exposed infants and toddlers with respect to anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development. The potentially stigmatizing label of the so-called "crack baby" preceded the evidence now accumulating from well-designed prospective investigations that have revealed less severe sequelae in the majority of prenatally exposed infants than originally anticipated. In contrast to opioids, which may produce neonatal abstinence syndrome and infant neurobehavioral deficits, prenatal cocaine exposure appears to be associated with what has been described as statistically significant but subtle decrements in neurobehavioral, cognitive, and language function, especially when viewed in the context of other exposures and the caregiving environment which may mediate or moderate the effects. Whether these early findings may herald more significant learning and behavioral problems during school-age and adolescence when the child is inevitably confronted with increasing social and academic challenges is the subject of ongoing longitudinal research.

Topics: Buprenorphine; Child Development; Child, Preschool; Cocaine; Cocaine-Related Disorders; Female; Heroin; Humans; Infant; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Substance-Related Disorders

Through a novel synthesis of the literature and our own clinical experience, we have derived a set of evidence-based recommendations for consideration as guidance in the management of opioid-dependent pregnant women and infants.. PubMed literature searches were carried out to identify recent key publications in the areas of pregnancy and opioid dependence, neonatal abstinence syndrome (NAS) prevention and treatment, multiple substance abuse and psychiatric comorbidity.. Pregnant women dependent on opioids require careful treatment to minimize harm to the fetus and neonate and improve maternal health. Applying multi-disciplinary treatment as early as possible, allowing medication maintenance and regular monitoring, benefits mother and child both in the short and the long term. However, there is a need for randomized clinical trials with sufficient sample sizes.. Opioid maintenance therapy is the recommended treatment approach during pregnancy. Treatment decisions must encompass the full clinical picture, with respect to frequent complications arising from psychiatric comorbidities and the concomitant consumption of other drugs. In addition to standardized approaches to pregnancy, equivalent attention must be given to the treatment of NAS, which occurs frequently after opioid medication.. Methodological flaws and inconsistencies confound interpretation of today's literature. Based on this synthesis of available evidence and our clinical experience, we propose recommendations for further discussion.

Topics: Buprenorphine; Diagnosis, Dual (Psychiatry); Female; GABA Modulators; Humans; Infant, Newborn; Mental Disorders; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Phenobarbital; Pregnancy; Pregnancy Complications

Topics: Analgesics, Opioid; Buprenorphine; Female; Fetus; Humans; Infant, Low Birth Weight; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Prenatal Care; Substance Withdrawal Syndrome; Substance-Related Disorders

It is estimated that 55-94% of infants born to opioid-dependent mothers in US will show signs of opioid withdrawal. Buprenorphine has been reported to produce little or no autonomic signs or symptoms of opioid withdrawal following abrupt termination in adults. To date, there have been 21 published reports representing approximately 15 evaluable cohorts of infants exposed to buprenorphine in utero. Of approximately 309 infants exposed, a neonatal abstinence syndrome (NAS) has been reported in 62% infants with 48% requiring treatment; apparently greater than 40% of these cases are confounded by illicit drug use. The NAS associated with buprenorphine generally appears within 12-48 h, peaks at approximately 72-96 h, and lasts for 120-168 h. These results appear similar to or less than that observed following in utero exposure to methadone. From a review of the literature, buprenorphine appears to be safe and effective in both mother and infant with an NAS that may differ from methadone both qualitatively and quantitatively.

Topics: Buprenorphine; Disease Management; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects

Buprenorphine, a long-acting opioid with both agonist and antagonist properties, binds to mu-opioid (OP(3)), kappa-opioid (OP(2)), delta-opioid (OP(1)), and nociceptin (ORL-1) receptors. Its actions at these receptors have not been completely characterized, although buprenorphine is generally regarded as a mu-opioid receptor partial agonist and a kappa-opioid receptor antagonist. Its pharmacology is further complicated by an active metabolite, norbuprenorphine. Although buprenorphine can be used as an analgesic agent, it is of greater importance in the treatment of opioid abuse. Because of its partial agonist activity at mu-opioid receptors and its long half-life, buprenorphine has proven to be an excellent alternative to methadone for either maintenance therapy or detoxification of the opioid addict. Although buprenorphine may ultimately prove to be superior to methadone in the maintenance of the pregnant addict, its effects on the developing fetus must be carefully evaluated.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu

In this review of the literature, we collected 102 case reports of newborns exposed in utero to buprenorphine between 1996 and 2000. Reported data show that infants born to a mother taking buprenorphine are delivered at term and have a birth weight close to infants not exposed to these substances. The published data also showed that observations have varied concerning the frequency, intensity, and duration of the withdrawal syndrome in newborns exposed in utero to buprenorphine.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Substance-Related Disorders

Methadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent.. Participants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child's life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined.. Tests of mean differences between children prenatally exposed to methadone vs. buprenorphine over the three-year period yielded 2/37 significant findings for children. Similarly, tests of mean differences between children treated for NAS relative to those not treated for NAS yielded 1/37 significant finding. Changes over time occurred for 27/37 child outcomes including expected child increases in weight, head and height, and overall gains in cognitive development, language abilities, sensory processing, and temperament. For mothers, significant changes over time in parenting stress (9/17 scales) suggested increasing difficulties with their children, notably seen in increasing parenting stress, but also an increasingly enriched home environment (4/7 scales) CONCLUSIONS: Findings strongly suggest no deleterious effects of buprenorphine relative to methadone or of treatment for NAS severity relative to not-treated for NAS on growth, cognitive development, language abilities, sensory processing, and temperament. Moreover, findings suggest that prenatal opioid agonist exposure is not deleterious to normal physical and mental development.

Topics: Adult; Buprenorphine; Child Development; Child, Preschool; Cognition; Female; Humans; Infant, Newborn; Male; Methadone; Mothers; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Parenting; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Temperament

Neonatal abstinence syndrome (NAS) is a constellation of withdrawal symptoms in infants born to mothers with chronic opioid use during pregnancy. A proportion of infants will need pharmacotherapy in addition to non-pharmacological interventions. In this article, we reviewed a clinical trial comparing the use of sublingual buprenorphine to oral morphine (the most widely used pharmacotherapy for NAS) in term infants. The primary end point was the duration of treatment, and secondary end points were the length of hospital stay, the proportion of infants who needed supplemental phenobarbital, and safety.

Topics: Administration, Oral; Administration, Sublingual; Buprenorphine; Clinical Decision-Making; Female; Humans; Infant, Newborn; Length of Stay; Male; Morphine; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy, High-Risk; Prognosis; Risk Assessment; Severity of Illness Index; Term Birth; Time Factors; Treatment Outcome

Neonatal abstinence syndrome (NAS) is a condition affecting newborns that are exposed to an opioid in utero. In a randomized, controlled trial assessing the efficacy of buprenorphine and morphine in NAS, blood samples were analyzed from a subset of patients receiving buprenorphine along with NAS scores. The data were used to validate and adapt an existing model of buprenorphine in neonates and to identify relationships between buprenorphine or norbuprenorphine pharmacokinetics (PK) and efficacy or safety. The time to NAS stabilization was found to decrease with increasing buprenorphine exposure. This pharmacokinetic-pharmacodynamic (PK-PD) relationship was able to be quantified and adequately described with a mathematical model. The findings confirm a previous PK model of buprenorphine and extend the model to describe the PK of norbuprenorphine and to identify a novel PK-PD relationship of buprenorphine in NAS. This model will allow optimization of dosing strategies in future clinical trials.

Topics: Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Male; Metabolic Clearance Rate; Morphine; Neonatal Abstinence Syndrome; Respiratory Rate

Current pharmacologic treatment of the neonatal abstinence syndrome with morphine is associated with a lengthy duration of therapy and hospitalization. Buprenorphine may be more effective than morphine for this indication.. In this single-site, double-blind, double-dummy clinical trial, we randomly assigned 63 term infants (≥37 weeks of gestation) who had been exposed to opioids in utero and who had signs of the neonatal abstinence syndrome to receive either sublingual buprenorphine or oral morphine. Infants with symptoms that were not controlled with the maximum dose of opioid were treated with adjunctive phenobarbital. The primary end point was the duration of treatment for symptoms of neonatal opioid withdrawal. Secondary clinical end points were the length of hospital stay, the percentage of infants who required supplemental treatment with phenobarbital, and safety.. The median duration of treatment was significantly shorter with buprenorphine than with morphine (15 days vs. 28 days), as was the median length of hospital stay (21 days vs. 33 days) (P<0.001 for both comparisons). Adjunctive phenobarbital was administered in 5 of 33 infants (15%) in the buprenorphine group and in 7 of 30 infants (23%) in the morphine group (P=0.36). Rates of adverse events were similar in the two groups.. Among infants with the neonatal abstinence syndrome, treatment with sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than treatment with oral morphine, with similar rates of adverse events. (Funded by the National Institute on Drug Abuse; BBORN ClinicalTrials.gov number, NCT01452789 .).

Topics: Administration, Oral; Administration, Sublingual; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Length of Stay; Male; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Phenobarbital

The present study examined the psychometric characteristics of the Neonatal Abstinence Scoring System (NASS; "Finnegan Scale") and the MOTHER NAS Scale (MNS).. Secondary analysis of data from 131 neonates from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a randomized trial in opioid-dependent pregnant women administered buprenorphine or methadone.. Both the NASS and MNS demonstrated poor psychometric properties, with internal consistency (Cronbach's αs) failing to exceed .62 at first administration, peak NAS score, and NAS treatment initiation.. Findings support the need for development of a NAS measure based on sound psychometric principles.. This study found that two frequently used measures of neonatal abstinence syndrome suffer inadequacies in regard to their basic measurement characteristics. (Am J Addict 2016;25:370-373).

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Neonatal Screening; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Psychometrics; Reproducibility of Results

Compare duration of treatment of neonatal abstinence syndrome between methadone and morphine.. A prospective, double-masked, randomized trial at a single site. Randomization of methadone or morphine was stratified for maternal treatment with methadone or buprenorphine. Inclusion criteria were (i) maternal treatment with prescribed methadone or buprenorphine, (ii) withdrawal treatment criteria, (iii) adjusted gestational age ⩾35(0/7) weeks and (iv) medically stable. Primary outcome was length of opioid treatment.. From January 2011 through October 2012, 78 infants were eligible for the study: 41 methadone-exposed and 37 buprenorphine-exposed. Consent was obtained from 31 mothers, 13/41 (32%) methadone-treated and 18/37 (49%) buprenorphine-treated. Length of opioid treatment was significantly shorter for methadone than morphine treatment, median 14 versus 21 days (P=0.008).. Methadone had a shorter length of neonatal withdrawal treatment compared with morphine. Owing to the smaller sample size and single site, a larger randomized study is needed.

Topics: Analgesics, Opioid; Birth Weight; Buprenorphine; Double-Blind Method; Female; Gestational Age; Humans; Infant, Newborn; Length of Stay; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Prospective Studies; Treatment Outcome

Buprenorphine pharmacotherapy for opioid-dependent pregnant women is associated with maternal and neonatal outcomes superior to untreated opioid dependence. However, the literature is inconsistent regarding the possible existence of a dose-response relationship between maternal buprenorphine dose and neonatal clinical outcomes.. The present secondary analysis study (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5 min, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women receiving buprenorphine as participants in a randomized clinical trial.. (1) Analyses failed to provide evidence of a relationship between maternal buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48) and (2) significant mean differences between the untreated (n=31) and treated (n=27) for NAS groups were found for duration of neonatal hospital stay and NAS peak score (both p-values<.001).. (1) Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising.

Topics: Buprenorphine; Double-Blind Method; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects

In recent years, the U.S. has experienced a significant increase in the prevalence of pregnant opioid-dependent women and of neonatal abstinence syndrome (NAS), which is caused by withdrawal from in-utero drug exposure. While methadone-maintenance currently is the standard of care for opioid dependence during pregnancy, research suggests that buprenorphine-maintenance may be associated with shorter infant hospital lengths of stay (LOS) relative to methadone-maintenance. There is no "gold standard" treatment for NAS but there is evidence that buprenorphine, relative to morphine or methadone, treatment may reduce LOS and length of treatment.. Point-of-care clinical trial (POCCT) designs, maximizing external validity while reducing cost and complexity associated with classic randomized clinical trials, were selected for two planned trials to compare methadone to buprenorphine treatment for opioid dependence during pregnancy and for NAS. This paper describes design considerations for the Medication-assisted treatment for Opioid-dependent expecting Mothers (MOMs; estimated N = 370) and Investigation of Narcotics for Ameliorating Neonatal abstinence syndrome on Time in hospital (INFANTs; estimated N = 284) POCCTs, both of which are randomized, intent-to-treat, two-group trials. Outcomes would be obtained from participants' electronic health record at three participating hospitals. Additionally, a subset of infants in the INFANTs POCCT would be from mothers in the MOMs POCCT and, thus, potential interaction between medication treatment of mother and infant could be evaluated.. This pair of planned POCCTs would evaluate the comparative effectiveness of treatments for opioid dependence during pregnancy and for NAS. The results could have a significant impact on practice.

Topics: Adult; Birth Weight; Buprenorphine; Female; Humans; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Research Design

Topics: Adolescent; Adult; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Treatment Outcome; Young Adult

The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current--and single most comprehensive--research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine.. The MOTHER study design is outlined, and its basic features are presented.. At least seven important lessons have been learned from the MOTHER study: (i) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (ii) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment, patient populations and hospital practices that, in turn, differentially impact recruitment rates, treatment compliance and attrition; (iii) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (iv) staff turnover needs to be addressed with a proactive focus on both hiring and training; (v) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (vi) timely tracking of data in a multi-site trial is both demanding and unforgiving; and (vii) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results.

Topics: Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Selection; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Treatment Outcome; United States

To identify factors that predict the expression of neonatal abstinence syndrome (NAS) in infants exposed to methadone or buprenorphine in utero.. Multi-site randomized clinical trial in which infants were observed for a minimum of 10 days following birth, and assessed for NAS symptoms by trained raters.. A total of 131 infants born to opioid dependent mothers, 129 of whom were available for NAS assessment.. Generalized linear modeling was performed using maternal and infant characteristics to predict: peak NAS score prior to treatment, whether an infant required NAS treatment, length of NAS treatment and total dose of morphine required for treatment of NAS symptoms.. Of the sample, 53% (68 infants) required treatment for NAS. Lower maternal weight at delivery, later estimated gestational age (EGA), maternal use of selective serotonin re-uptake inhibitors (SSRIs), vaginal delivery and higher infant birthweight predicted higher peak NAS scores. Higher infant birthweight and greater maternal nicotine use at delivery predicted receipt of NAS treatment for infants. Maternal use of SSRIs, higher nicotine use and fewer days of study medication received also predicted total dose of medication required to treat NAS symptoms. No variables predicted length of treatment for NAS.. Maternal weight at delivery, estimated gestational age, infant birthweight, delivery type, maternal nicotine use and days of maternal study medication received and the use of psychotropic medications in pregnancy may play a role in the expression of neonatal abstinence syndrome severity in infants exposed to either methadone or buprenorphine.

Topics: Adolescent; Adult; Analgesics, Opioid; Birth Weight; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Length of Stay; Linear Models; Methadone; Morphine; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk Factors; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Smoking; Young Adult

To compare the profile of signs of neonatal abstinence syndrome (NAS) in methadone- versus buprenorphine-exposed infants.. Secondary analysis of NAS data from a multi-site, double-blind, double-dummy, flexible-dosing, randomized clinical trial. Data from a total of 129 neonates born to opioid-dependent women who had been assigned to receive methadone or buprenorphine treatment during pregnancy were examined.. For 10 days after delivery, neonates (methadone = 72, buprenorphine = 57) were assessed regularly using a 19-item modified Finnegan scale. Data from neonates who required pharmacological treatment (methadone = 41, buprenorphine = 27) were included up to the time treatment was initiated. The incidence and mean severity of the total NAS score and each individual sign of NAS were calculated and compared between medication conditions, as was the median time until morphine treatment initiation among treated infants in each condition.. Two NAS signs (undisturbed tremors and hyperactive Moro reflex) were observed significantly more frequently in methadone-exposed neonates and three (nasal stuffiness, sneezing, loose stools) were observed more frequently in buprenorphine-exposed neonates. Mean severity scores on the total NAS score and five individual signs (disturbed and undisturbed tremors, hyperactive Moro reflex, excessive irritability, failure to thrive) were significantly higher among methadone-exposed neonates, while sneezing was higher among buprenorphine-exposed neonates. Among treated neonates, methadone-exposed infants required treatment significantly earlier than buprenorphine-exposed infants (36 versus 59 hours postnatal, respectively).. The profile of neonatal abstinence syndrome differs in methadone- versus buprenorphine-exposed neonates, with significant differences in incidence, severity and treatment initiation time. Overall, methadone-exposed neonates have a more severe neonatal abstinence syndrome.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Double-Blind Method; Female; Humans; Incidence; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Severity of Illness Index; Symptom Assessment; Time Factors; Treatment Outcome

To determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior.. Three sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial participated in this substudy.. Medical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria.. Thirty-nine full-term infants.. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14-15 and 28-30.. While neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress-abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over-aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self-regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone-exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self-regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03).. While neurobehavior improves during the first month of postnatal life for in utero agonist medication-exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Infant Behavior; Infant, Newborn; Linear Models; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Severity of Illness Index; Young Adult

More than half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacological therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS.. Randomized, Phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine.. Large, urban, tertiary care hospital.. Twenty-four term infants requiring pharmacological treatment for NAS.. Outcomes were neonatal safety, length of treatment and length of hospitalization.. Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (P = 0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (P = 0.05).. Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine.

Topics: Administration, Sublingual; Adult; Birth Weight; Buprenorphine; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Humans; Hypnotics and Sedatives; Infant, Newborn; Length of Stay; Male; Morphine; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Phenobarbital; Pregnancy; Severity of Illness Index; Treatment Outcome

Chronic medical conditions such as opioid dependence require evidence-based treatment recommendations. However, pregnant women are under-represented in clinical trials. We describe the first within-subject comparison of maternal and neonatal outcomes for methadone- versus buprenorphine-exposed pregnancies. Although methadone is the established treatment of pregnant opioid-dependent women, recent investigations have shown a trend for a milder neonatal abstinence syndrome (NAS) under buprenorphine. However, it is not only the choice of maintenance medication that determines the occurrence of NAS; other factors such as maternal metabolism, illicit substance abuse and nicotine consumption also influence its severity and duration and represent confounding factors in the assessment of randomized clinical trials. CASE SERIES DESCRIPTION: Three women who were part of the European cohort of a randomized, double-blind multi-center trial with a contingency management tool [the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study], each had two consecutive pregnancies and were maintained on either methadone or buprenorphine for their first and then the respective opposite, still-blinded medication for their second pregnancy. Birth measurements, the total neonatal abstinence score, the total amounts of medication used to treat NAS and the days of NAS treatment duration were assessed.. Both medications were effective and safe in reducing illicit opioid relapse and avoiding preterm labor. Methadone maintenance yielded to a significantly higher neonatal birth weight. Data patterns suggest that buprenorphine exposure was associated with lower neonatal abstinence syndrome (NAS) scores. Findings from this unique case series are consistent with earlier reports using between-group analyses.. Buprenorphine has the potential to become an established treatment alternative to methadone for pregnant opioid-dependent women. Under special consideration of ethical boundaries, psychopharmacological treatment during pregnancy must be addressed as an integral part of clinical research projects in order to optimize treatment for women and neonates.

Topics: Adult; Analgesics, Opioid; Birth Weight; Buprenorphine; Double-Blind Method; Female; Humans; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Severity of Illness Index; Smoking; Treatment Outcome; Young Adult

In order to investigate the effects of exposure to buprenorphine compared with methadone during pregnancy, a prospective multicenter study was conducted in collaboration with maternity hospitals, maintenance therapy centers, and general practitioners involved in addiction care. Ninety pregnant women exposed to buprenorphine and 45 to metadone were selected for the study.. During pregnancy, some women were exposed to illicit agents: cannabis (42% in the buprenorphine group vs. 58% in the methadone-treated group), heroin (17% vs. 44%), or cocaine (3% vs. 11%). Pregnancies ended in 85 vs. 40 live births, one vs. two stillbirths, two vs. one spontaneous abortion, two vs. one voluntary termination, and one vs. one medical termination in the buprenorphine and the methadone groups, respectively. Newborns had a birth weight of 2,892 ± 506 g (buprenorphine) vs. 2,731 ± 634 g (methadone) and a body length of 47.6 ± 2.5 cm vs. 47.1 ± 3 cm. 18.8% vs. 10% of newborns were delivered before 37 weeks of amenorrhea. Neonatal withdrawal syndrome occurred more frequently in the methadone group (62.5% vs. 41.2, p = 0.03). After adjustment for heroin exposure in late pregnancy, rates of neonatal withdrawal were no longer different between the methadone and buprenorphine groups. Twenty-one babies (84%) in the methadone group and 20 (57%) in the buprenorphine group (p = 0.03) required opiate treatment.. We did not observe more frequent malformations or cases of withdrawal syndrome in the buprenorphine group than in the methadone-treated group. Buprenorphine appears to be as safe as the currently approved substitute methadone considered to date as the reference treatment for pregnant opioid-dependent women.

Topics: Adult; Analgesics, Opioid; Birth Weight; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies

The purpose was to explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure.. Subjects comprised 19 opioid-dependent pregnant women from 2 clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared with those in placenta and meconium, and urine specimens collected throughout gestation.. Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the third trimester, and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score, and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine- and opiate-positive specimens than did umbilical cord.. Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict the NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Meconium; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Placenta; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pyrrolidines; Umbilical Cord

The objective of this study is to compare maternal and neonatal outcome of opioid-dependent women maintained on buprenorphine or methadone throughout pregnancy in a randomized double-blind double-dummy clinical trial (CT) with a comparison group undergoing a structured standard protocol (SP) at the Medical University of Vienna, Austria.. One hundred and fourteen subjects were included in the analysis, with 77 in SP (n = 51 methadone, n = 26 buprenorphine), and 37 in CT (n = 19 methadone, n = 18 buprenorphine), comparing maternal concomitant consumption during third trimester, demographic birth data, duration of treatment for neonatal abstinence syndrome (NAS), morphine dose for NAS treatment and length of hospital stay (LOS).. Both study groups yielded healthy neonates with no significant demographic differences and equivalently low rates of positive maternal urine toxicologies. However, NAS parameters were significantly better in CT regarding total medication dose administered to neonates (p = 0.014) and LOS (p = 0.015). Superior results were achieved in buprenorphine compared with methadone-exposed neonates regarding gestational age at birth (p = 0.003), birth weight (p = 0.011), total morphine dose administered (p = 0.008), NAS treatment duration (p = 0.008) and LOS (p = 0.001).. Comparably favorable outcome for mothers and infants and efficacy and safety of opioid medications were shown in both treatment approaches. Neonatal care could benefit from transferring successful CT procedures into clinical practice.

Topics: Adult; Austria; Birth Weight; Buprenorphine; Double-Blind Method; Female; Gestational Age; Humans; Infant, Newborn; Length of Stay; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Third; Prospective Studies; Time Factors; Young Adult

Prior studies have shown an increased vulnerability among males to adverse outcomes during the postnatal period. Most children exposed to opioids and other medications in utero develop neonatal abstinence syndrome (NAS), yet individual predisposition for NAS is poorly understood.. This investigation examined the role of neonatal sex in the postnatal period for neonates exposed to standardized opioid maintenance treatment in utero with a focus on NAS regarding severity, medication requirements, and duration.. This was a secondary analysis of data collected in a prospective randomized, double-blind, double-dummy, multicenter trial (MOTHER study) that examined the comparative safety and efficacy of methadone and buprenorphine during pregnancy. A total of 131 neonates born to opioid-dependent women randomized at 6 US sites (n = 74) and 1 European site (n = 37) were analyzed. Sex-based differences in birth weight, length, head circumference, NAS duration, NAS severity, and treatment parameters of full-term neonates were assessed.. Males had a significantly higher birth weight (P = 0.027) and head circumference (P = 0.017) compared with females, with no significant sex difference in rates of preterm delivery. No significant sex-related differences were found for NAS development, severity, or duration, or medication administered, and there were no significant differences in concomitant drug consumption during pregnancy (P = 0.959).. This unique prospective study shows similar postnatal vulnerability for both sexes, suggesting that factors other than sex are the major determinants of clinically significant NAS. ClinicalTrials.gov identifier: NCT 00271219.

Topics: Birth Weight; Buprenorphine; Double-Blind Method; Female; Humans; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Factors; Severity of Illness Index; Sex Distribution; Sex Factors

Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.. We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference.. Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events.. These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Head; History, Ancient; Humans; Infant, Newborn; Length of Stay; Logistic Models; Methadone; Morphine; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu-opioid agonist used for treatment of adult detoxification and maintenance but has never been administered to neonates with opioid abstinence syndrome. The primary objective of this study was to demonstrate the feasibility and, to the extent possible in this size of study, the safety of sublingual buprenorphine in the treatment of neonatal abstinence syndrome. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered.. We conducted a randomized, open-label, active-control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to receive sublingual buprenorphine 13.2 to 39.0 mug/kg per day administered in 3 divided doses and 13 to receive standard-of-care oral neonatal opium solution. Dose decisions were made by using a modified Finnegan scoring system.. Sublingual buprenorphine was largely effective in controlling neonatal abstinence syndrome. Greater than 98% of plasma concentrations ranged from undetectable to approximately 0.60 ng/mL, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants who received buprenorphine and 1 infant who received standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for those in the neonatal-opium-solution group was 32 compared with 22 days for the buprenorphine group. The mean length of stay for the neonatal-opium-solution group was 38 days compared with 27 days for those in the buprenorphine group. Treatment with buprenorphine was well tolerated.. Buprenorphine administered via the sublingual route is feasible and apparently safe and may represent a novel treatment for neonatal abstinence syndrome.

Topics: Administration, Sublingual; Buprenorphine; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Gestational Age; Humans; Inactivation, Metabolic; Infant, Newborn; Male; Narcotic Antagonists; Neonatal Abstinence Syndrome; Retrospective Studies; Treatment Outcome

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS.

Topics: Adult; Buprenorphine; Cocaine; Double-Blind Method; Female; Humans; Infant, Newborn; Male; Maternal Behavior; Maternal-Fetal Exchange; Meconium; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Nicotine; Opiate Alkaloids; Opioid-Related Disorders; Pregnancy; Smoking

The aim of the study was to evaluate the effect of substitution therapy in heroin addicted pregnant women on the course of pregnancy, perinatal outcomes and course of the neonatal abstinence syndrome.. A five-year randomised prospective comparative study. The study was carried out in the period of 2002-2007. The group of patients included 147 i.v. heroin-addicted pregnant women. All of them were outpatients of our Perinatal Care Unit. Their daily dose of heroin was approximately lg. Later, 30 women were disqualified from the study for breaking the randomised criteria engagement. The substitution therapy in women who agreed to undergo it, started during the I. trimester of pregnancy. Finally, 47 heroin, 32 methadone and 38 buprenorphine addicted women were enrolled in the study. Birthweight of newborns was compared with the national birthweight tables. Severity and duration of neonatal abstinence syndrome (NAS) were evaluated by Finnegan s score scale.. None of the women delivered before the end of 34th gestational week. We did not encounter any perinatal death or developmental defect. The lowest birthweight, the highest number of newborns with IUGR and the most numerous placental changes were found in the group of heroin-addicted women. The differences compared to the two groups receiving substitution therapy were statistically significant (p < 0.05). The severity and course of NAS were the most severe (p < 0.001) in newborns of women from the methadone group.. Comparison of the groups of outpatients is in many ways questionable because of the restricted possibility of the patients' control. The lifestyle of addicted women has the same impact as the drug use alone. This is probably the main reason for differences in some of the monitored parameters between individual groups. Based on our results we can state that substitution therapy provides pregnant women with the possibility of social stabilization and adequate prenatal care. substitution therapy decreases the street heroin consumption. Methadone notably protracts the newborn's abstinence syndrome. With regard to this fact, attention has been recently focused on substitution with buprenorphine that seems to be from this viewpoint a more considerate option.

Topics: Adult; Birth Weight; Buprenorphine; Female; Fetal Growth Retardation; Heroin; Heroin Dependence; Humans; Infant, Newborn; Life Style; Methadone; Narcotics; Neonatal Abstinence Syndrome; Outpatients; Postpartum Period; Pregnancy; Pregnancy Outcome; Prospective Studies; Severity of Illness Index

To evaluate the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women.. Randomized, double-dummy, double-blind, flexible-dosing comparison study.. Addiction Clinic at the Medical University of Vienna, Austria.. Eighteen women were assigned randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six in the methadone and eight in the buprenorphine group).. Sublingual buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day), with matched placebos.. Mothers: retention in treatment, urine toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence syndrome (NAS) in severity and duration.. There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group (P = 0.047).Neonates: There was earlier onset of NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); 43% did not require NAS-treatment with short treatment duration in both groups (mean 5 days).. This preliminary study had limited power to detect differences but the trends observed suggest this kind of research is practicable and that further studies are warranted.

Topics: Buprenorphine; Double-Blind Method; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant women and their neonates. Treatment involved daily administration of either sublingual buprenorphine or oral methadone using flexible dosing of 4-24 mg or 20-100 mg, respectively. Primary a priori outcome measures were: (1) number of neonates treated for NAS; (2) amount of opioid agonist medication used to treat NAS; (3) length of neonatal hospitalization; and (4) peak NAS score. Two of 10 (20%) buprenorphine-exposed and 5 of 11 (45.5%) methadone-exposed neonates were treated for NAS (p=.23). Total amount of opioid-agonist medication administered to treat NAS in methadone-exposed neonates was three times greater than for buprenorphine-exposed neonates (93.1 versus 23.6; p=.13). Length of hospitalization was shorter for buprenorphine-exposed than for methadone-exposed neonates (p=.021). Peak NAS total scores did not significantly differ between groups (p=.25). Results suggest that buprenorphine is not inferior to methadone on outcome measures assessing NAS and maternal and neonatal safety when administered starting in the second trimester of pregnancy.

Topics: Administration, Sublingual; Adult; Buprenorphine; Double-Blind Method; Female; Heroin Dependence; Humans; Infant, Newborn; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Severity of Illness Index

Perinatal prognosis of pregnant drug abusers is better with intensive prenatal care and substitution maintenance programs. There is a large body of data in the literature on methadone (MTD), but very little on high-dose buprenorphine (HDB). The objective of this study was to compare 2 groups of pregnant women maintained on MTD or HDB for perinatal events.. Prospective multicentric study; all neonates (NN) whose mothers has been maintained during pregnancy on MTD or HDB were included by 34 French perinatal centers with specialized staff for care of these pregnant drug abusers.. Two hundred and forty-six pregnant women were included: 93 (38%) MTD and 153 (62%) HDB. Social and perinatal data, prenatal care and factors correlated with poor prenatal care are reported. Forty-six percent of the pregnant women had good prenatal care; 88% had peridural analgesia; mean birthweight=2838g; mean gestational age=38.7 weeks; prematurity<37 weeks=13; intra-uterine growth retardation=32%. Sixty-five percent neonates had withdrawal neonatal syndrome (WNNS) at a mean age of beginning at H40, mean highest Lipsitz score was 8.2 at H78. Half of the neonates with WNNS received treatment, mainly with morphine chlorhydrate. Neonatal mortality was 0/246. Discharge of the neonates was 60% with their father and their mother, and 32% with their mother alone; 4% were placed in foster homes by judicial decision. The only statistically significant differences between the MTD and HDB groups were: maintenance program was more frequently initiated before this pregnancy for the HDB vs MTD group (p<0.03); MTD maintenance was more often supervised by maintenance specialized centers and HDB by general practitioners (p<0.001); prematurity was 18% for MTD group vs 9% for HDB group (p<0.04); mean age of maximum Lipsitz score was H92 for MTD group vs H70 for HDB group (p<0.001).. The perinatal medical and social prognosis of these 246 pregnant drug abusers and of their neonates appeared to be improved by the specialized prenatal care, comparatively with literature data. Perinatal impact of substitution program during pregnancy would be similar with MTD or HDB.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Morphine; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Prenatal Care; Prognosis; Prospective Studies; Substance-Related Disorders

Neonatal opioid withdrawal syndrome (NOWS) is a growing public health problem associated with complex and prolonged medical care and a significant resource utilization burden. The objective of this study was to compare the cost of different convalescent care settings for infants with NOWS.. Retrospective comparison study of infants with NOWS discharged directly from NICU, transferred to an acute care pediatric floor (PPCU) or rehabilitation hospital (PRH). Primary outcomes were length of stay (LOS) and cost of stay (COS).. Infants had 1.3 (95% CI: 1.1,1.6) times and 2.5 (95% CI: 2.1,3.1) times significantly longer mean LOS for PPCU and RH discharges compared to NICU discharges. NICU discharged infants had the lowest mean COS ($25,745.00) and PRH the highest ($60,528.00), despite PRH having a lower cost per day. PRH discharged infants had higher rates of methadone and benzodiazepine and less buprenorphine exposure than NICU/PPCU discharged. Infants born to mothers on marijuana and buprenorphine had a 28% lower mean COS compared to unexposed infants. Median treatment cumulative morphine doses were six-fold higher for PRH than NICU discharge.. Infants transferred to convalescence care facilities had longer and more costly admissions and received more medication. However, there may be a role for earlier transfer of a subset of infants at-risk for longer LOS as those exposed to methadone and/or benzodiazepines. Further studies exploring differences in resource utilization, convalescent care delivery and cost expenditure are recommended.

Topics: Analgesics, Opioid; Buprenorphine; Child; Hospitalization; Humans; Infant; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Retrospective Studies

Receipt of opioid agonist treatment during early and late pregnancy for opioid use disorder may relate to varying perinatal risks. We aimed to assess the effect of time-varying prenatal exposure to opioid agonist treatment using buprenorphine or methadone on adverse neonatal and pregnancy outcomes.. We conducted a retrospective cohort study of pregnant women with opioid use disorder using Rhode Island Medicaid claims data and vital statistics during 2008-16. Time-varying exposure was evaluated in early (0-20 weeks) and late (≥ 21 weeks) pregnancy. Marginal structural models with inverse probability of treatment weighting were applied.. Of 400 eligible pregnancies, 85 and 137 individuals received buprenorphine and methadone, respectively, during early pregnancy. Compared with 152 untreated pregnancies with opioid use disorders, methadone exposure in both periods was associated with an increased risk of preterm birth (adjusted odds ratio [aOR]: 2.52; 95% confidence interval [CI] 1.07-5.95), low birth weight (aOR: 2.99; 95% CI 1.34-6.66), neonatal intensive care unit admission (aOR, 5.04; 95% CI 2.49-10.21), neonatal abstinence syndrome (aOR: 11.36; 95% CI 5.65-22.82), respiratory symptoms (aOR, 2.71; 95% CI 1.17-6.24), and maternal hospital stay > 7 days (aOR, 14.51; 95% CI 7.23-29.12). Similar patterns emerged for buprenorphine regarding neonatal abstinence syndrome (aOR: 10.27; 95% CI 4.91-21.47) and extended maternal hospital stay (aOR: 3.84; 95% CI 1.83-8.07). However, differences were found favoring the use of buprenorphine for preterm birth versus untreated pregnancies (aOR: 0.17; 95% CI 0.04-0.77), and for several outcomes versus methadone.. Methadone and buprenorphine prescribed for the treatment of opioid use disorder during pregnancy are associated with varying perinatal risks. However, buprenorphine may be preferred in the setting of pregnancy opioid agonist treatment. Further research is necessary to confirm our findings and minimize residual confounding.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Premature Birth; Retrospective Studies

Buprenorphine (BUP) is the preferred treatment for opioid use disorder during pregnancy but can cause neonatal opioid withdrawal syndrome (NOWS). Norbuprenorphine (NorBUP), an active metabolite of BUP, is implicated in BUP-associated NOWS. We hypothesized that BUP, a low-efficacy agonist of mu opioid receptors, will not antagonize NorBUP, a high-efficacy agonist of mu opioid receptors, in producing NOWS. To test this hypothesis, we treated pregnant Long-Evans rats with BUP (0, 0.01, 0.1 or 1mg/kg/day) ± NorBUP (1mg/kg/day) from gestation day 9 until pup delivery, and tested pups for opioid dependence using our established NOWS model. We used LC-MS-MS to quantify brain concentrations of BUP, NorBUP, and their glucuronide conjugates. BUP had little effect on NorBUP-induced NOWS, with the exception of 1mg/kg/day BUP significantly increasing NorBUP-induced NOWS by 58% in females. BUP and NorBUP brain concentrations predicted NOWS in multiple linear regression models. Interestingly, NorBUP contributed more to NOWS in females (β

Topics: Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Infant, Newborn; Male; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Rats; Rats, Long-Evans; Receptors, Opioid, mu

Southern Appalachia is a region of the United States that is disproportionately affected by the opioid epidemic and by increasing rates of neonatal abstinence syndrome (NAS). NAS rates increased approximately 400% between 1999 and 2012. Buprenorphine prescriptions written to treat opioid use disorder also increased dramatically. The present study was undertaken to ascertain any relationship between the number of buprenorphine prescriptions compared with NAS rates in southern Appalachia.. A total of 250 southern Appalachian counties across seven states, including all of West Virginia and portions of Virginia, Kentucky, Maryland, North Carolina, Ohio, and Tennessee were identified. A retrospective cohort analysis of these counties was conducted for the years 2005-2018. All of the data were obtained from publicly accessible sources or direct communication with government offices. Measures from each county in southern Appalachia included annual NAS rates, buprenorphine prescription rates, drug-induced death rates, and opioid prescribing rates. Associations among these variables were examined using a generalized linear regression.. Significant linear associations exist between the rising rate of NAS diagnoses and the rising rate of buprenorphine prescriptions (. This is the first report that documents an association between rising NAS rates and increasing buprenorphine prescribing. Between the years 2010 and 2018, the NAS rate in southern Appalachia rose by 335%, and the number of buprenorphine prescriptions rose by 413%. Discussions regarding the current policies for buprenorphine management during pregnancy are warranted. We suggest a reevaluation of buprenorphine prescribing recommendations during pregnancy and further research on establishing the lowest effective buprenorphine dose for each pregnant patient.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Practice Patterns, Physicians'; Pregnancy; Pregnancy Complications; Prescriptions; Retrospective Studies; United States

The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications-methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS).. In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine.. Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant.. Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS.. Medications for opioid use disorder (MOUD), such as buprenorphine and methadone, are effective in reducing the significant harms associated with untreated opioid use disorder (OUD) in nonpregnant and pregnant adults. While previous research clearly documents that the risks of MOUD in pregnancy are less than the risks of untreated OUD in pregnancy, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of methadone and buprenorphine. In a clinical sample of infants born to women with OUD, we showed that buprenorphine-exposed infants were at significantly reduced risk for neonatal abstinence syndrome compared with methadone-exposed infants. Our study adds to the growing body of evidence supporting the use of buprenorphine over methadone for the treatment of OUD among pregnant women.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies

Topics: Analgesics, Opioid; Buprenorphine; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Racial Groups

Topics: Administration, Intravenous; Administration, Sublingual; Adult; Aged; Analgesics, Opioid; Biotransformation; Buprenorphine; Child; Child, Preschool; Cytochrome P-450 CYP3A; Drug Dosage Calculations; Female; Hepatobiliary Elimination; Humans; Infant, Newborn; Male; Middle Aged; Models, Biological; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Oral Mucosal Absorption; Treatment Outcome; Young Adult

America's opioid epidemic has spawned an epidemic of neonatal abstinence syndrome (NAS). Studies have not tested approaches to promoting contraceptive services for women with opioid use disorder (OUD) along with treatment for this disorder. This pilot study examined the promotion of medication for OUD (MOUD) treatment and contraception use, primarily long-acting reversible contraception (LARC), for women with OUD.. In Appalachia, a peer-delivered contraception and MOUD promotion intervention was delivered to a sample of 30 women with OUD. Primary outcomes were attendance of initial appointments to receive MOUD and counseling about contraceptive options. Peer recovery coaches also offered to help the women schedule appointments and attend the appointment with them or give them a ride if necessary and requested by the patients.. Two-thirds experienced all seven symptoms of opioid dependence. Within 30 days of a brief counseling session, over one-half of the women (56.7%) were referred to MOUD, with all of them initiating treatment within 30 days. Just under one-half of the women (46.7%) were referred to a contraception consultation, with 85.7% of those receiving a LARC implant.. Study findings indicate the potential efficacy of a single-session, peer-delivered counseling intervention for linking women with OUD and at high risk of unintended pregnancy to MOUD and to services that provide women with highly reliable contraceptives.. This study is unique in exploring the efficacy of linking high-risk opioid-using women to contraceptive options and treatment for MOUD to prevent NAS.

Topics: Analgesics, Opioid; Buprenorphine; Contraceptive Agents; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pilot Projects; Pregnancy

To examine the evidence for emerging treatment options, buprenorphine or clonidine, as monotherapy for the treatment of neonatal abstinence syndrome (NAS) against standards of care, morphine or methadone.. A PubMed literature search from 1946 to 2019 was performed using the terms NAS, neonatal withdrawal, buprenorphine and NAS, clonidine and NAS, morphine and NAS, methadone and NAS, opioids and pregnancy, opioids and NAS, prenatal exposure and opioids.. Study evaluation was limited to English-language studies conducted in humans. Articles were eliminated if subjects did not have a formal diagnosis of NAS. Additionally, studies were eliminated if neonates received diluted tincture of opium. Additional references were identified from a manual citation review.. Eight articles were evaluated. Five articles compared buprenorphine to either morphine or methadone. Buprenorphine was found to decrease length of NAS treatment an average of 9.2 days and decrease hospital length of stay (LOS) an average of 8.2 days. Three articles evaluated the use of clonidine for NAS, two as an adjunct to morphine and one as monotherapy. Adjunctive clonidine plus morphine versus phenobarbital plus morphine both significantly reduced the total morphine treatment duration; however, patients remained on adjunctive phenobarbital significantly longer than clonidine. As monotherapy, clonidine was found to decrease NAS treatment an average of 11 days and decrease overall LOS an average of six days compared to morphine treatment.. Treatment with buprenorphine or clonidine has shown favorable effects by reducing length of NAS treatment and LOS. These emerging therapies may be as effective as morphine or methadone for NAS, in combination with nonpharmacologic strategies. Long-term follow-up is needed.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy

To assess the cost effectiveness of buprenorphine versus methadone in the management of opioid use disorder (OUD) during pregnancy.. We designed a decision-analytic model to evaluate the costs and outcomes associated with buprenorphine compared to methadone for pregnant people with OUD. We used a theoretical cohort of 22,400 pregnant people, which is an estimation of pregnancies affected by OUD per year in the United States. Outcomes included maternal retention in maintenance treatment, neonatal opioid withdrawal syndrome, preterm birth, fetal growth restriction, cerebral palsy, and maternal overdose in addition to cost and quality-adjusted life-years (QALYs). We used a willingness-to-pay threshold of $100,000/QALY. All model inputs were derived from the literature and varied in sensitivity analyses to assess the robustness of our baseline inputs.. In our theoretical cohort, treatment of OUD with buprenorphine during pregnancy resulted in 2413 fewer cases of neonatal opioid withdrawal syndrome, 1089 fewer preterm births, 299 fewer cases of fetal growth restriction, 32 fewer stillbirths, and 13 fewer cases of cerebral palsy compared to methadone treatment. Despite lower rates of retention, buprenorphine treatment saved nearly 123 million healthcare dollars and resulted in 558 additional QALYs, making it the dominant strategy compared to methadone treatment. Our findings were robust over a wide range of assumptions.. Our data suggest that buprenorphine should be considered a cost effective treatment option for OUD in pregnancy, as it is associated with improved neonatal outcomes compared to methadone despite the risk of treatment discontinuation.

Topics: Analgesics, Opioid; Buprenorphine; Cerebral Palsy; Cost-Benefit Analysis; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Premature Birth

Topics: Behavior, Addictive; Buprenorphine; Child; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Postpartum Period; Pregnancy; Qualitative Research

Evidence on the perinatal health of mother-infant dyads affected by opioids is limited. Elevated risks of opioid-related harms for people with opioid use disorder (OUD) increase the urgency to identify protective factors for mothers and infants. Our objectives were to determine perinatal outcomes after an OUD diagnosis and associations between opioid agonist treatment and birth outcomes.. We conducted a population-based retrospective study among all women with diagnosed OUD before delivery and within the puerperium period in British Columbia, Canada, between 2000 and 2019 from provincial health administrative data. Controlling for demographic and clinical characteristics, we determined associations of opioid agonist treatment on birth weight, gestational age, infant disorders related to gestational age and birth weight, and neonatal abstinence syndrome via logistic regression.. The population included 4574 women and 6720 live births. Incidence of perinatal OUD increased from 166 in 2000 to 513 in 2019. Compared with discontinuing opioid agonist treatment during pregnancy, continuous opioid agonist treatment reduced odds of preterm birth (adjusted odds ratio: 0.6; 95% confidence interval: 0.4-0.8) and low birth weight (adjusted odds ratio: 0.4; 95% confidence interval: 0.2-0.7). Treatment with buprenorphine-naloxone (compared with methadone) reduced odds of each outcome including neonatal abstinence syndrome (adjusted odds ratio: 0.6; 95% confidence interval: 0.4-0.9).. Perinatal OUD in British Columbia tripled in incidence over a 20-year period. Sustained opioid agonist treatment during pregnancy reduced the risk of adverse birth outcomes, highlighting the need for expanded services, including opioid agonist treatment to support mothers and infants.

Topics: Adult; Analgesics, Opioid; British Columbia; Buprenorphine; Female; Humans; Incidence; Infant, Newborn; Logistic Models; Longitudinal Studies; Methadone; Naloxone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Retrospective Studies

The opioid epidemic resulted in vast increase in neonatal opioid withdrawal syndrome (NOWS). To mitigate NOWS and opioid dependency among women, staff established a gender specific, patient driven, autonomy based, outpatient therapeutic substitution program.. Prospective observational study of obstetric patients receiving prenatal care 7/1/2016-12/31/2019. Patients underwent universal urine drug screens to identify illicit drug use with dependency and offered addiction counseling with voluntary outpatient therapeutic substitution in an obstetrical-addictions combined clinic to achieve abstinence with oral Buprenorphine tapering protocol. Urine substance screening and cord blood testing were obtained at delivery. Birth outcomes compared among groups who achieved abstinence at birth, were successful at tapering, or continued opioid use.. Of 783 births, 165 (20.9%) demonstrated opioid use with 91 (55.2%) participating at some point in pregnancy in therapeutic substitution program. At birth, 14/94 (14.9%) patients completed the program and achieved opioid abstinence, 22/94 (23.4%) still enrolled and actively tapering. 57/94 (34.5%) patients were lost to follow-up, relapsed, or terminated due to non-compliance. Seventy-four of 67 (44.3%) opioid positive mothers chose not to enroll. Of 14 women who completed the program, 0 babies born with NOWS, compared to 11/22 (50%) still enrolled in program and actively tapering, 29/57 (50.9%) lost to follow-up, relapsed, or terminated due to non-compliance, and 28/74 (37.8%) never enrolled in program.. Outpatient therapeutic substitution with oral Buprenorphine with abstinence is possible in pregnant patients and results zero NOWS. More data are needed to confirm findings and explore methods for enhanced success in obtaining abstinence.. Appalachian Regional Commission and Prevention (ARC) 1

Topics: Analgesics, Opioid; Buprenorphine; Critical Pathways; Female; Humans; Infant; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Buprenorphine has been shown to be effective in treating infants with neonatal opioid withdrawal syndrome. However, an evidence-based buprenorphine dosing strategy has not been established in the treatment of neonatal opioid withdrawal syndrome because of a lack of exposure-response data. The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic model to predict buprenorphine treatment outcomes in newborns with neonatal opioid withdrawal syndrome.. Clinical data were obtained from 19 newborns with a median (range) gestational age of 37 (34-41) weeks enrolled in a pilot pharmacokinetic study of buprenorphine. Sparse blood sampling, comprising three specimens obtained around the second dose of buprenorphine, was performed using heel sticks with dried blood spot technology. Standardized neonatal opioid withdrawal syndrome severity scores (Finnegan scores) were collected every 3-4 h based on symptoms by bedside nursing staff. Mean Finnegan scores were used as a pharmacodynamic marker in the exposure-response modeling. The blood concentration-Finnegan score relationship was described using a physiologic indirect response model with inclusion of natural disease remission.. A total of 52 buprenorphine blood concentrations and 780 mean Finnegan scores were available for the pharmacokinetic/pharmacodynamic modeling and exposure-response analysis. A one-compartment model with first-order absorption adequately described the pharmacokinetic data. The buprenorphine blood concentration at 50% of maximum effect for the inhibition of disease progression was 0.77 ng/mL (95% confidence interval 0.32-1.2). The inclusion of natural disease remission described as a function of postnatal age significantly improved the model fit.. A buprenorphine pharmacokinetic/pharmacodynamic model was successfully developed. The model could facilitate model-informed optimization of the buprenorphine dosing regimen in the treatment of neonatal opioid withdrawal syndrome.

Topics: Analgesics, Opioid; Buprenorphine; Gestational Age; Humans; Infant; Infant, Newborn; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Treatment Outcome

The worsening opioid crisis has increased the number of infants exposed to maternal opioids. Standard treatment of newborns exposed to opioids prenatally often requires prolonged hospitalization and separation of the mother-infant dyad. These practices can potentially increase severity of withdrawal symptoms, interrupt breastfeeding, and disturb mother-infant bonding. Use of the Eat, Sleep, Console (ESC) model may ameliorate symptoms, decrease mother-infant separation, and decrease hospital length of stay.. To manage opioid exposed infants in a more holistic manner to decrease neonatal intensive care unit (NICU) admissions, reduce the need for pharmacotherapy, and evaluate response and total length of treatment after a unit protocol change from morphine to buprenorphine.. Implemented ESC model, optimized nonpharmacologic bundle, and prescribed buprenorphine therapy instead of morphine as needed for adjunctive therapy.. Admissions of opioid-exposed infants from the Mother-Baby Unit (MBU) to the NICU decreased by 22%, and the number of infants who required pharmacotherapy was reduced by 50%. The average length of pharmacotherapy fell from 14 to 6.5 days.. The successful implementation of the ESC model helped keep the mother-infant dyad together, reduced admissions to the NICU, and lessened the need for pharmacotherapy. The change to buprenorphine further reduced our average length of treatment.. Investigation of monotherapy with buprenorphine needs to be evaluated as a valid treatment option. The buprenorphine dosing and weaning chart will need to be revised and modified if indicated.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Length of Stay; Mothers; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Sleep; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Buprenorphine; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Neonatal Abstinence Syndrome

To assess if treating neonatal abstinence syndrome (NAS) with sublingual buprenorphine (SLB) would decrease the mean duration of therapy (DOT) and length of birth hospital stay (LOS).. Conducted at a tertiary hospital with >6000 annual deliveries and a 2% incidence of NAS, a quality improvement study using plan-do-study-act (PDSA) cycles were utilized. Outcomes were measured using statistical process control (SPC) charts.. All NAS patients were treated with SLB, no adverse reactions were reported and the need for an adjunctive agent was static. SPC charts demonstrated decreased variability and special cause variation indicating a reduction in both DOT (from 14.5 to 8.5 days) and LOS (from 18.5 to 13 days).

Topics: Buprenorphine; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Quality Improvement

Women with histories of opioid misuse face drug-related stigma, which can be amplified during pregnancy. While women are often blamed for their drug use and urged to change, the social contexts that create and reinforce stigma are largely unchallenged. Drawing on a multidimensional model of stigma, we examine how stigma manifested across women's pregnancy journeys to shape access and quality of care.. We triangulate in-depth interviews with 28 women with histories of opioid misuse who were pregnant or recently gave birth and 18 healthcare providers in Ohio. Thematic analysis examined how stigma operates across contexts of care.. Providers represented physicians, nurses, social workers, counselors, and healthcare administrators. Among 28 women, average age was 30 (range: 22-41) and 79 % were White. Most women used prenatal medication-assisted treatment (MAT), including Suboxone (n = 19) or methadone (n = 8), and 15 were pregnant. Evidence of stigma emerged across healthcare contexts. Structural stigma encoded barriers to care in insurance practices and punitive drug treatment, while enacted stigma manifested as mistreatment and judgment from providers. Unpredictability of an infant diagnosis of neonatal abstinence syndrome (NAS), even when women were "doing everything right" by using MAT, perpetuated anticipated stigma from fear of loss of custody and internalized stigma among women who felt guilty about the diagnosis. Providers recognized the harmful effects of these stigmas and many actively addressed it.. We recommend harm reduction approaches to address the multiplicity of stigmas that women navigate in opioid misuse and pregnancy to improve healthcare experiences.

Topics: Adult; Buprenorphine; Female; Health Personnel; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Ohio; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Opioid use by women during pregnancy has risen dramatically since 2004, accompanied by a striking increase in the prevalence of neonatal opioid withdrawal syndrome (NOWS) and other long-term neurological deficits. However, the mechanisms underlying the impact of prenatal opioid exposure on fetal neurodevelopment are largely unknown. To translate from the clinical presentation, we developed a novel mouse model to study the neurodevelopmental consequences of maternal opioid use and management. Female mice were treated with oxycodone (OXY) before mating to mimic opioid use disorder (OUD) in humans. Following pregnancy confirmation, dams were switched to buprenorphine (BUP) via oral administration, simulating medication management of OUD (MOUD) in pregnant women. Here, we document critical changes in fetal brain development including reduced cortical thickness, altered corticogenesis, and ventriculomegaly in embryos from dams that were treated with opioids before and throughout pregnancy. Maternal care giving behavior was slightly altered without affecting gross growth of offspring. However, adolescent offspring exposed to maternal opioid use during pregnancy exhibited hyperactivity in late adolescence. Remarkably, we also show increased generation of dopaminergic neurons within the ventral tegmental area (VTA) of mice exposed to prenatal opioids. These data provide critical evidence of teratogenic effects of opioid use during pregnancy and suggest a causal relationship between maternal opioid use and neurodevelopmental/behavioral anomalies in adolescence.

Topics: Adolescent; Analgesics, Opioid; Animals; Buprenorphine; Female; Humans; Infant, Newborn; Mice; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects

To test the effect of the duration of medication for opioid use disorder (MOUD) use during pregnancy on maternal, perinatal and neonatal outcomes.. Retrospective cohort analysis of claims, encounter and pharmacy data.. Pennsylvania, USA.. We analyzed 13 320 pregnancies among 10 741 women with opioid use disorder aged 15-44 years enrolled in Pennsylvania Medicaid between 2009 and 2017.. We examined five outcomes during pregnancy and for 12 weeks postpartum: (1) overdose, (2) postpartum MOUD continuation, (3) preterm birth (< 37 weeks gestation), (4) term low birth weight (< 2500 g at ≥ 37 weeks) and (5) neonatal abstinence syndrome (NAS). Our primary exposure was the duration (count of weeks) of any MOUD use, including methadone or buprenorphine, during pregnancy.. Among 13 320 pregnancies, 306 (2.3%) were complicated by an overdose, 1753 (13.2%) resulted in a preterm birth and 6787 (50.9%) continued MOUD postpartum. Among infants, 874 (7.6%) were low birth weight at term and 7706 (57.9%) were diagnosed with NAS. As the duration of MOUD use increased, we found a statistically significant decrease in the rate of overdose and preterm birth, a statistically significant increase in the rate of postpartum MOUD continuation and NAS and a decline in term low birth weight. Specifically, for each additional week of MOUD, the adjusted odds of overdose decreased by 2% [adjusted odds ratio (aOR) = 0.98; 95% confidence interval (CI) = 0.97, 0.99], preterm birth decreased by 1% (aOR = 0.99; 95% CI = 0.99, 1.00), postpartum MOUD continuation increased by 95% (aOR = 1.95; 95% CI = 1.87, 2.04) and NAS increased by 41% (aOR = 1.41; 95% CI = 1.35, 1.47). The odds of term low birth weight did not change (aOR = 1.00; 95% CI = 0.99, 1.00), although the rate declined with a longer duration of MOUD use during pregnancy.. Longer duration of medication for opioid use disorder use during pregnancy appears to be associated with improved maternal and perinatal outcomes.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Premature Birth; Retrospective Studies

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Medicaid; Neonatal Abstinence Syndrome; North Carolina; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Retrospective Studies; United States; Young Adult

Topics: Buprenorphine; Female; Humans; Infant; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Retrospective Studies

The purpose of this study was to describe an identified association between necrotizing enterocolitis (NEC) and prenatal opioid exposure with neonatal abstinence syndrome (NAS) in late preterm and full-term neonates.. In this single-center retrospective cohort study, we analyzed inborn neonates with the diagnosis of NEC discharged from 2012 through 2017. We compared infants with NEC > 35 weeks' gestation to those with NEC<35 weeks' gestation. We compared gestational age, birth weight, age of onset of symptoms, and incidence of prenatal drug exposure between groups. Significance was determined using Mann-Whitney and Fisher's exact tests.. Over the study period, 23 infants were identified with NEC, 9 (39%) were babies > 35 weeks at birth and 14 (61%) < 35 weeks. Those > 35 weeks had a higher birth weight, earlier onset of symptoms, and a higher percentage of prenatal exposure to opioids compared to those < 35 weeks' gestation. We further described seven infants with late gestational age onset NEC associated with prenatal opioid exposure.. In this cohort of infants with NEC discharged over a 6 year period we found a higher than expected percentage of infants born at a later gestational age. We speculate that prenatal opioid exposure might be a risk factor for NEC in neonates born at > 35 weeks.

Topics: Analgesics, Opioid; Buprenorphine; Cohort Studies; Enterocolitis, Necrotizing; Female; Fetal Blood; Gestational Age; Heroin; Humans; Infant, Newborn; Infant, Premature; Male; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies

Objectives To compare pregnancy outcomes with medication assisted treatment using. methadone or buprenorphine in term mothers with opioid use disorder. Methods A cohort of women receiving medication assisted treatment with either methadone or buprenorphine were identified from delivery records over a 10-year period. Women were excluded with delivery <37 weeks, multiple gestations, or a known anomalous fetus. Maternal demographics, medications, mode of delivery, birthweight, newborn length of stay, and neonatal abstinence syndrome were extracted. The study was IRB approved and a p-value of <0.05 was significant. Results There were 260 women, 140 (53.8%) with methadone use and 120 (46.2%) with buprenorphine use. Groups were similar for maternal age, race, parity, homeless rate, tobacco use, mode of delivery and incidence of neonatal abstinence syndrome. The methadone group had a lower mean newborn birthweight (2874±459 g) and a greater incidence of low birth weight (11.4%) than the buprenorphine group (3282±452 g; p<0.001 and 2.5%; p=0.006). The incidence of neonatal abstinence syndrome was similar between groups (97% methadone vs. 92.5% buprenorphine; p=0.08). The methadone group had a longer newborn length of stay (11.4+7.4 days) and more newborn treatment with morphine (44.6%) than the buprenorphine group (8.2+4.4 days; p<0.001 and 24.2%; p<0.001). Maternal methadone use was an independent predictor for a newborn length of hospital stay >7 days (OR 3.61; 95% confidence interval 1.32-9.86; p=0.01). Conclusions Medication assisted treatment favors buprenorphine use when compared to. methadone with an increased birthweight, reduced need for newborn treatment, and a shorter newborn length of stay in term infants.

Topics: Birth Weight; Buprenorphine; Delivery, Obstetric; Female; Humans; Infant, Newborn; Length of Stay; Male; Maternal Age; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; United States

Determine odds ratios for neonatal abstinence syndrome (NAS) and neonatal intensive care unit (NICU) admissions for babies born to women associated with severe mental illness (SMI) and gestational opioid use.. A retrospective pharmacoepidemiologic study using Medicaid data included 17,130 mothers with and 170,430 mothers without SMI, and their babies. Odds ratios for NAS and NICU admissions among babies born to mothers associated with SMI diagnoses and associated with varying degrees of gestational opioid use were determined using logistic regression.. The adjusted odds ratio for a baby in the methadone or buprenorphine group having NAS was 168.93 [95% confidence interval (CI) 148.78-191.71, P < 0.001] and was 9.64 (95% CI 8.74-10.65, P < 0.001) for NICU admissions compared to babies with no opioid exposure.. Chronicity of prescription maternal opioid use was the strongest factor associated with NAS and NICU admissions.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Mental Health; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies

Many addicted pregnant patients receiving buprenorphine medication-assisted therapy (MAT) wish to discontinue this medication while pregnant. This study was undertaken to determine whether outpatient detoxification from buprenorphine during pregnancy is safe and effective when confirmed with postdetoxification urine drug screens (UDSs).. This case series reports the maternal and neonatal outcomes for 21 patients who ended MAT with buprenorphine while pregnant. A retrospective chart review of both maternal and newborn electronic medical records was performed to obtain results. Newborn neonatal abstinence syndrome (NAS) diagnosis, need for morphine, maternal safety and fetal/newborn complications were assessed. Maternal sobriety was documented with UDSs at the time of admission for delivery. Umbilical cord blood also was assessed for substances of abuse. An additional 182 pregnant women who lowered their buprenorphine doses but did not decide to end MAT were assessed via routine quality assurance methods.. None of the women who stopped buprenorphine during their pregnancy as confirmed by UDSs and umbilical cord sampling delivered neonates who had NAS. Eleven patients ended MAT with medical assistance and 10 ended MAT without medical assistance. No overdoses were reported for the 182 additional pregnant patients who indicated an intention to taper buprenorphine dosage while pregnant but who did not decide to end MAT; the neonatal benefits were obtained without any identified maternal harm.. The neonates of pregnant women enrolled in an outpatient buprenorphine MAT tapering program who are able to completely stop taking buprenorphine (as documented by negative urinary drug screen) are very unlikely to have NAS. Further research will be important.

Topics: Adult; Ambulatory Care; Buprenorphine; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies; Young Adult

The incidence of opioid use during pregnancy is increasing, and drug overdoses are a leading cause of postpartum mortality. Most women who are pregnant do not receive medications for treatment of opioid use disorder, despite the mortality benefit that these agents confer. Furthermore, buprenorphine is associated with milder symptoms of neonatal abstinence syndrome (NAS) compared with methadone.. To describe the prevalence and geographic distribution across the US of obstetrician-gynecologists who can prescribe buprenorphine (henceforth described as X-waivered) in 2019.. A cross-sectional, nationwide study linking physician-specific data to county- and state-level data was conducted from September 1, 2019, to March 31, 2020. Data were obtained on 31 211 obstetrician-gynecologists who accept Medicaid insurance through the Centers for Medicare & Medicaid Services Physician Compare data set and linked to the Drug Addiction Treatment Act buprenorphine-waived clinician list.. State-level NAS incidence and county-level uninsured rates and rurality.. Prevalence and geographic distribution of obstetrician-gynecologists who are trained to prescribe buprenorphine.. Among the 31 211 identified obstetrician-gynecologists, 18 710 (59.9%) were women. Most had hospital privileges (23 236 [74.4%]) and worked in metropolitan counties (28 613 [91.7%]). Only 560 of the identified obstetrician-gynecologists (1.8%) were X-waivered. Obstetrician-gynecologists in counties with fewer than 5% uninsured residents had nearly twice the odds of being X-waivered (adjusted odds ratio [aOR], 1.59; 95% CI, 1.04-2.44; P = .04) compared with those in counties with greater than 15% uninsured residents. Compared with those located in metropolitan counties, obstetrician-gynecologists in suburban counties (eg, urban population of ≥20 000 and adjacent to a metropolitan area) were more likely to be X-waivered (aOR, 1.85; 95% CI, 1.26-2.71; P = .002). Compared with states with an NAS rate of 5 per 1000 births or less, obstetrician-gynecologists in states with an NAS rate of 15 per 1000 births or greater had nearly 5 times the odds of being X-waivered (aOR, 4.94; 95% CI, 3.60-6.77; P < .001). Obstetrician-gynecologists without hospital privileges were more likely to be X-waivered (aOR, 1.32; 95% CI, 1.08-1.61; P = .007).. Fewer than 2% of obstetrician-gynecologists who accept Medicaid are able to prescribe buprenorphine, and their geographic distribution appears to be skewed in favor of suburban counties. This finding suggests that there is an opportunity for health systems and professional societies to incentivize X-waiver trainings among obstetrician-gynecologists to increase patients' access to buprenorphine, especially during pregnancy.

Topics: Adult; Buprenorphine; Cross-Sectional Studies; Female; Humans; Infant, Newborn; Male; Medicaid; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Obstetrics; Opioid-Related Disorders; Physicians; Pregnancy; Pregnancy Complications; Prevalence; Rural Health; Staff Development; United States

Topics: Adult; Analgesics, Opioid; Buprenorphine; Case-Control Studies; Female; Humans; Infant, Newborn; Mothers; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pilot Projects; Postnatal Care; Pregnancy; Pregnancy Complications; Prenatal Care; Retrospective Studies; Rooming-in Care

The mainstay of the management of opioid use disorder in pregnancy is with methadone or buprenorphine medication-assisted treatment. Methadone and buprenorphine are opioid agonist drugs. Naltrexone, an opioid antagonist, is also a medication-assisted treatment option; however, to date, only a few retrospective studies have reported its use in pregnancy.. Our study objective was to evaluate prospectively obstetric and newborn outcomes and the maternal/fetal effects of the use of naltrexone as a medication-assisted treatment in pregnant patients with opioid use disorder.. We performed a prospective cohort study collecting data on all pregnant women who were treated with naltrexone medication-assisted treatment compared with pregnant women who were treated with methadone or buprenorphine medication-assisted treatment. Based on a sample size calculation, it was determined that for a power of 90, a minimum of 160 study participants (80 in each group) was needed with an alpha of .01 and an expected 60% rate of newborn infants who were treated for neonatal abstinence syndrome in the methadone or buprenorphine medication-assisted treatment group compared with a 30% rate in the naltrexone medication-assisted treatment group. In a random subset of 20 maternal/newborn dyads, blood levels for naltrexone and 6-beta-naltrexol (an active metabolite) were analyzed at delivery.. A total of 230 patients were studied: 121 patients with naltrexone medication-assisted treatment compared with 109 patients with methadone or buprenorphine medication-assisted treatment. No differences between groups were seen regarding demographics, the use of comedications/drugs, or obstetric outcomes. For newborn outcomes, the rate of neonatal abstinence syndrome in neonates >34 weeks gestation was significantly lower in the naltrexone medication-assisted treatment group (10/119 [8.4%] vs 79/105 [75.2%]; P<.0001). Multivariate analysis demonstrated that the only significant factor for the rate of neonatal abstinence syndrome was the form of medication-assisted treatment. Of 87 patients who received naltrexone up to delivery, no neonates experienced symptoms of neonatal abstinence syndrome. No maternal relapses occurred in the 7-day no-treatment window before the initiation of naltrexone therapy. No cases of spontaneous abortion or stillbirth occurred in either group. In 64 patients who started naltrexone therapy at ≥24 weeks gestation, no changes were seen in the fetal heart monitor tracing with drug initiation. The incidence of birth anomalies was no different between the groups. Umbilical cord blood and maternal levels for naltrexone and 6-beta-naltrexol matched; no levels were elevated, and values were undetected if naltrexone was discontinued >60 hours before delivery.. These study data demonstrate that, in pregnant women who choose to completely detoxify off opioid drugs during gestation, naltrexone, as a continued form of medication-assisted treatment, is a viable option for some pregnant patients who experience opioid use disorder. Naltrexone crosses the placenta, and maternal and fetal levels are concordant. Because naltrexone clears quickly from the maternal circulation, this rapid clearance needs to be addressed with patients. This is important because maternal relapse could occur in a short time-period if the oral drug is discontinued without the knowledge of their healthcare providers. Nonetheless, the drug is well-tolerated by both mother and fetus, and newborn infants do not experience symptoms of neonatal abstinence syndrome if naltrexone medication-assisted treatment is maintained to delivery.

Topics: Abortion, Spontaneous; Adult; Analgesics, Opioid; Buprenorphine; Case-Control Studies; Female; Humans; Infant, Newborn; Methadone; Naltrexone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prospective Studies; Stillbirth; Young Adult

There is lack of knowledge about the safety of treatment with methadone and buprenorphine as part of opioid maintenance treatment (OMT) during pregnancy. The purpose of this study was to examine neonatal outcomes concerning the use of OMT during pregnancy. We used nationwide registry linkages from the Czech Republic (2000-2014) and Norway (2004-2013). We compared prenatally OMT-exposed newborns with (a) newborns of women hospitalized with opioid use disorder during pregnancy in the Czech sample and (b) newborns with neonatal abstinence syndrome (NAS) in Norway. We performed multivariate linear and binary logistic regression exploring the associations between OMT and neonatal outcomes (growth parameters, gestational age, fetal death, small for gestational age, Apgar score, and NAS). Regression coefficients (

Topics: Adult; Buprenorphine; Child Development; Czech Republic; Female; Humans; Infant, Newborn; Logistic Models; Methadone; Neonatal Abstinence Syndrome; Norway; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Registries; Young Adult

Adult opioid use and neonatal abstinence syndrome (NAS) are growing public health problems in the United States (U.S.). Our objective was to determine how opioid use disorder treatment access impacts the relationship between adult opioid use and NAS.. We conducted a cross-sectional state-level ecologic study using 36 states with available Healthcare Cost and Utilization Project State Inpatient Databases in 2014. Opioid use disorder treatment access was determined by the: 1) proportion of people needing but not receiving substance use treatment, 2) density of buprenorphine-waivered physicians, and 3) proportion of individuals in outpatient treatment programs (OTPs). The incidence of NAS was defined as ICD-9 code 779.5 (drug withdrawal syndrome in newborn) from any discharge diagnosis field per 1000 live births in that state.. Unmet need for substance use disorder treatment correlated with NAS (r = 0.54, 95% CI: 0.26-0.73). The correlation between adult illicit drug use/dependence and NAS was higher in states with a lower density of buprenorphine-waivered physicians and individuals in OTPs.. Measures of opioid use disorder treatment access dampened the correlation between illicit drug use/dependence and NAS. Future studies using community- or individual-level data may be better poised to answer the question of whether or not opioid use disorder treatment access improves NAS relative to adult opioid use.

Topics: Buprenorphine; Correlation of Data; Cross-Sectional Studies; Female; Health Services Accessibility; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; United States

The opioid crisis has led to an increased number of pregnant opioid-dependent women receiving opioid-maintenance therapy (e.g. buprenorphine, BUP), but little is known about the consequences of gestational BUP exposure on pregnancy outcomes, maternal care, or offspring development.. Our translational rodent model began BUP exposure to adult female rats (N = 30) at least 7 days before conception and continued throughout the postpartum period. Both therapeutic low-dose (BUP-LD, 0.3 mg/kg, s.c.) and overexposure high-dose (BUP-HD, 1.0 mg/kg) doses of BUP were compared to saline control. Female rats were bred in house with drug-naïve adult male rats. The day after parturition, litters were culled to 5 males/5 females and assigned randomly to various behavioral tests and assessed either neonates or adolescents. Litter characteristics, maternal caregiving, Neonatal Opioid Withdrawal Syndrome (NOWS), offspring development and adolescent behaviors were evaluated.. BUP-LD decreased maternal care, delayed offspring development, decreased offspring body weight, length, temperature, and pain sensitivity (p's < .05). BUP-HD drastically reduced maternal care and offspring survival, altered litter characteristics, and increased NOWS (p's < .05).. These results demonstrate that the therapeutic BUP-LD in rats was relatively safe with subtle effects on maternal care and rodent offspring. However, overexposure BUP-HD in rats produced NOWS and compromised maternal caregiving as well as rodent offspring survival. More research is critical to validate the translational implication of these findings for human opioid-dependent mothers maintained on BUP-maintenance therapy.

Topics: Age Factors; Analgesics, Opioid; Animals; Animals, Newborn; Behavior, Animal; Buprenorphine; Dose-Response Relationship, Drug; Female; Male; Maternal Behavior; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Substance Withdrawal Syndrome

BACKGROUND With the increasing prevalence of substance use in pregnancy, the rates of neonatal abstinence syndrome (NAS) are dramatically increasing. There is little information on the use of multiple substances in adults, even less so of polysubstance abuse during pregnancy and the consequences for the fetus as well as the mother. CASE REPORT A newborn male born at 35 weeks presented post-delivery with hips bilaterally dislocated and hyperflexed. The patient's legs fully extended and their shoulders were bilaterally mid-flexed with arms fully extended. This neonate was also reported to have bilateral hearing and vision loss as well as NAS symptoms of high-pitched crying and respiratory distress. During pregnancy the mother in this case study admitted to using buprenorphine, benzodiazepines, gabapentin, and heroin. The consequences of using this combination has not been well studied in pregnancy. CONCLUSIONS The presented case had severe complications, likely due to maternal polysubstance use and poor prenatal care in pregnancy. Clonidine was used to control the NAS symptoms, ranitidine was used to treat the gastroesophageal reflux, and glycopyrronium bromide was used for the neonate's excessive secretions. After delivery, the patient was placed on a nasal noninvasive cannula for respiratory distress and was transferred to a different hospital for treatment of the more serious comorbid conditions.

Topics: Benzodiazepines; Buprenorphine; Female; Gabapentin; Heroin; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Male; Neonatal Abstinence Syndrome; Pregnancy; Prenatal Exposure Delayed Effects

The growing opioid epidemic in the United States has led to increasingly high rates of neonatal abstinence syndrome (NAS). Preliminary studies have shown that buprenorphine maintenance treatment (BMT) may lead to better outcomes for infants than methadone maintenance treatment (MMT).. The authors gathered recent evidence to answer the following PICO (population, intervention, comparison, and outcome) question: In opioid-dependent pregnant women, how does buprenorphine compared with methadone administration affect NAS?. A literature search was completed in PubMed, Scopus, Embase, and Web of Science databases and limited to the past 5 years. The following parameters were analyzed in the articles: NAS occurrence, length of hospital stay in days, NAS treatment length, and amount of pharmacotherapy administered to treat NAS.. In comparison to methadone, buprenorphine exposure in utero is associated with significantly shorter hospital stays for the infant after delivery, shorter length of NAS treatment, and decreased frequency/duration of pharmacotherapy for NAS symptoms in the infant.. Based on the findings, a weak recommendation can be made for the use of BMT over MMT in opioid-dependent pregnant women. However, further research is necessary to definitively recommend buprenorphine over methadone use in this population, especially regarding the effect of maternal severity of addiction on adherence to BMT, and long-term effects of in utero buprenorphine exposure.

Topics: Adult; Buprenorphine; Female; Humans; Infant; Infant, Newborn; Length of Stay; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnant Women

In general populations, prenatal food insecurity negatively affects maternal and infant health. Our aim was to estimate and test the association between prenatal food insecurity and neonatal abstinence syndrome (NAS) severity.. Single-site prospective cohort design. Women receiving opioid agonist treatment with methadone or buprenorphine were interviewed (including demographics and food insecurity) during the third trimester at the combined obstetric/opioid use disorder treatment clinic at Boston Medical Center (BMC) in Boston, MA, USA, a large urban safety-net hospital. During postnatal hospitalization, infants were assessed and treated per hospital NAS protocol. Maternal clinic and infant hospitalization data were abstracted from medical records.. Women (n = 75; aged ≥ 18 years; fluent English; singleton pregnancy; intending to deliver at BMC and maintain parental custody) receiving care in the specialized clinic were study eligible (2013-15). Women who delivered infants < 36 weeks gestational age or required prolonged newborn intensive care unit stay were excluded from analyses.. Predictors: validated two-question Hunger Vital Sign™ food insecurity screener; outcomes: extent of NAS pharmacological treatment and length of hospital stay (LOS) for NAS.. Of the mother-infant dyads, 61 (81%) infants were treated pharmacologically for NAS. Mean hospital LOS was 19.9 (standard deviation = 9.4) days. Maternal food insecurity (n = 43, 57.3%) was associated with infant NAS pharmacological treatment in logistic regression analyses individually adjusted for prenatal: maternal depression [adjusted odds ratios (aOR) = 3.69 (95% confidence intervals (CI) = 1.02-13.43, P = 0.05)] and methadone agonist treatment [aOR = 4.17 (95% CI = 1.05-16.50, P = 0.04)]. Associations of food insecurity and LOS were inconclusive regardless of covariate control (P > 0.05).. Among women receiving opioid agonist treatment, prenatal food insecurity appears to be associated with increased risk for neonatal abstinence syndrome pharmacological treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Food Supply; Humans; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Care; Prenatal Exposure Delayed Effects; Prospective Studies

Topics: Buprenorphine; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Network Meta-Analysis; Opiate Substitution Treatment

Buprenorphine, used for opioid use disorder (OUD) treatment during pregnancy, provides unknown effects on maternal physiological activity. The primary aim of this report is to document acute effects of buprenorphine administration on indicators of maternal autonomic functioning. Effects of maternal buprenorphine dose and other substance exposures on maternal measures were examined, as were neonatal abstinence syndrome (NAS) outcomes.. Forty-nine pregnant, buprenorphine-maintained women yielded maternal physiologic information (heart rate and variability, electrodermal activity, and respiratory rate) at 24, 28, 32 and 36 weeks gestation. Monitoring at trough and peak maternal medication levels was implemented to ascertain acute physiologic effects of buprenorphine administration.. Buprenorphine administration accelerated maternal heart rate and reduced variability at two gestational ages (24 and 36 weeks) and suppressed sympathetic (electrodermal) activation at 24, 28 and 32 weeks at times of peak maternal medication levels. Maternal autonomic parameters were unrelated to polysubstance exposure with the exception of cigarette smoking. Heavier smoking dampened maternal heart rate variability across gestation and potentiated reactivity to buprenorphine at 24 and 36 weeks. Heavier smoking was also associated with reduced electrodermal activity at 36 weeks. Buprenorphine dose was unrelated to observed effects. Larger degree of maternal heart rate reactivity to buprenorphine administration was related to more severe NAS expression.. These findings detail the maternal autonomic response to buprenorphine administration but also illustrate the significant effect of concurrent cigarette use on maternal autonomic regulation. This suggests the importance of smoking-reduction strategies in the comprehensive, medication-assisted treatment of women with OUD.

Topics: Adult; Autonomic Nervous System; Buprenorphine; Female; Gestational Age; Heart Rate; Humans; Infant, Newborn; Maternal Exposure; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Severity of Illness Index; Young Adult

The growing incidence of neonatal abstinence syndrome (NAS) among newborns is a public health crisis that is a sequela of the national opioid crisis. When fetuses are exposed to opioids in utero, whether through prescription pain medication, illicit substances, or supervised medication-assisted opioid treatment, neonates can experience withdrawal symptoms shortly after birth. Opioid withdrawal manifests with symptoms of central nervous system and autonomic nervous system dysfunction. Treatment of NAS begins with nonpharmacologic interventions, and if a neonate requires more intensive treatment, care will escalate to include pharmacologic treatments, including morphine, methadone, and buprenorphine. When pharmacologic therapy begins, nonpharmacologic intervention is not ceased; rather, the two are used in conjunction in an attempt to reduce the amount of medication required for successful treatment. Herein we review nonpharmacologic nursing interventions, discuss the most common pharmacologic treatments for NAS, and present practice implications for nurses who work with childbearing families.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pregnancy; Pregnancy Complications; Treatment Outcome

To generate effect sizes of preliminary program outcomes and identify areas for program improvement related to a nurse-led, community-based screening, referral, and advocacy program for women with perinatal opioid use disorder (OUD): the Engaging Mothers for Positive Outcomes with Early Referrals (EMPOWER) program.. We extracted outcomes retrospectively from medical records for the first 19 mother-newborn dyads who participated in the program (postintervention group). We compared these outcomes with those of 19 randomly selected mother-newborn dyads in which mothers had perinatal OUD and received care before the program launch (preintervention group).. A maternity care practice and community hospital in a rural Massachusetts county with high rates of perinatal OUD.. Women with perinatal OUD and their neonates.. As part of the EMPOWER program, women with perinatal OUD developed individualized pregnancy plans; were referred to community resources in the prenatal period; and received education about neonatal abstinence syndrome, nonpharmacologic newborn care, and breastfeeding. We compared the pre- and postintervention groups for maternal and neonatal outcomes and prenatal community referrals and generated effect sizes using Cohen's d and Cramer's phi (Φ).. Rates of breastfeeding initiation (Φ = 0.289) and continuation (Φ = 0.318), mean neonatal birth weight (d = 0.675), and length of hospital stay (d = 0.541) were greater in the postintervention group with medium effect sizes. Diagnosis of neonatal abstinence syndrome and admission to the NICU were also greater in the postintervention group, with small effect sizes (Φ = 0.246 and Φ = -0.144, respectively.) Significantly more women in the postintervention group received prenatal referrals for peer/family support services. We identified areas for program improvement as prenatal education on smoking and postpartum contraceptive use.. Preliminary findings suggest that the EMPOWER program may contribute to improved outcomes for mothers and newborns affected by OUD; however, further data collection after instituting program improvements is needed.

Topics: Adult; Buprenorphine; Databases, Factual; Female; Hospitals, Community; Humans; Infant Health; Massachusetts; Maternal Health; Maternal Health Services; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Practice Patterns, Nurses'; Pregnancy; Program Evaluation; Retrospective Studies; Rural Population; Treatment Outcome; Young Adult

Opioid use disorder during pregnancy is a growing health concern. Methadone maintenance is the treatment of choice but emerging data indicate buprenorphine is a viable alternative. Due to costs and limited accessibility of methadone, pregnant women may require transition from methadone to buprenorphine for maintenance treatment.. To assess safety and effectiveness of transitioning from methadone to buprenorphine when necessary during pregnancy.. A standardized protocol using low buprenorphine doses to minimize emergent withdrawal symptoms under careful obstetric and psychiatric monitoring was implemented in 20 pregnant women. Outpatient maternal and neonatal outcomes were assessed.. Women maintained on an average methadone dose of 44 ± 4.77 (20-100) mg/day (mean±standard error mean (SEM); range) were successfully transitioned to 12.60 ± 0.8 (8-16) mg/day (mean±SEM; range) of buprenorphine. Within 4 weeks of transition, 15% had illicit drugs detected in urine drug screens. Ninety percent of women maintained outpatient follow-up until delivery. At delivery, 38.9% of mothers were exclusively adherent to buprenorphine (without use of illicit substances and/or other psychotropic medications); this resulted in significantly lower rates of neonatal abstinence syndrome (NAS) and shorter hospital stays.. Pregnant women transitioned from methadone to buprenorphine maintenance showed maternal and neonatal outcomes comparable to studies of women on buprenorphine throughout pregnancy. Infants born to buprenorphine-maintained women who abstained from illicit substances and other prescribed psychotropic medications experienced less severe NAS and shorter hospitalizations compared with women with illicit substance use and other psychotropic medications. These findings suggest women can safely be transitioned from methadone to buprenorphine during pregnancy.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Drug Substitution; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Treatment Outcome

Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS.. This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded.. Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001).. Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.

Topics: Adult; Buprenorphine; Female; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Male; Maternal Age; Methadone; Multivariate Analysis; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Propensity Score; Proportional Hazards Models; Retrospective Studies; United States; Young Adult

Our objective was to estimate the association between methadone and neonatal abstinence syndrome compared with buprenorphine using a probabilistic bias analysis to account for unmeasured confounding by severity of addiction.. We used a cohort of live-born infants exposed in utero to methadone or buprenorphine for maternal opioid maintenance therapy at Magee-Womens Hospital in Pittsburgh, PA, from 2013 to 2015 (n = 716). We determined exposure and outcome status using pharmacy billing claims. We used log-binomial regression models to assess association of treatment with neonatal abstinence syndrome after adjusting for parity, maternal race, age, delivery year, employment, hepatitis c, smoking, marital, and insurance status. We implemented probabilistic bias analysis, informed by an internal validation study, to assess the impact of unmeasured confounding by severity of addiction.. Infants exposed to methadone in utero were more likely to experience neonatal abstinence syndrome compared with those exposed to buprenorphine (RR, 1.3; 95% CI, 1.2, 1.5). After adjustment, infants exposed to methadone were more likely (adjusted RR, 1.3; 95% CI, 1.1, 1.5) than infants exposed to buprenorphine to have the syndrome. In the validation cohort (n = 200), severe addiction was more common in methadone- versus buprenorphine-exposed deliveries (77% vs. 32%). However, adjustment for severe addiction in the bias analysis only slightly attenuated the association (RR, 1.2; 95% CI, 1.0, 1.4), supporting conventional analysis.. Methadone is associated with increased risk of neonatal abstinence syndrome compared with buprenorphine in infants exposed in utero. This association is subject to minimal bias due to unmeasured confounding by severity of addiction.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pennsylvania; Pregnancy

 The objective of this study was to compare duration of opioid treatment and length of stay outcomes for neonatal abstinence syndrome (NAS) using sublingual buprenorphine versus traditional weaning with methadone or morphine..  This retrospective cohort analysis evaluated infants treated for NAS at a single community hospital from July 2013 through June 2017. A standardized weaning protocol was introduced in June 2015, allowing for treatment with sublingual buprenorphine regardless of type of intrauterine opioid exposure. General linear models were used to calculate adjusted mean duration of opioid treatment and length of hospitalization with 95% confidence intervals for infants treated with buprenorphine compared with traditional weaning with either methadone or morphine..  A total of 360 infants were treated with either buprenorphine (.  Our study provides an independent confirmation that among infants experiencing NAS following a wide array of intrauterine opioid exposures, buprenorphine weaning supports a shortened treatment duration compared with conventional weaning agents.

Topics: Analgesics, Opioid; Buprenorphine; Drug Administration Schedule; Female; Humans; Infant, Newborn; Length of Stay; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Retrospective Studies; Time Factors

Assessments of effects of prenatal opioid exposure on the neonate have consisted principally of evaluations of neonatal abstinence syndrome (NAS) to determine the need for pharmacotherapy. The purpose of this study was to comprehensively evaluate the effects of gestational maternal buprenorphine maintenance on newborn neurobehavioral functioning.. Maternal substance use history and psychosocial demographics that can contribute to the neurobehavioral functioning of the infant were explored. Infants were assessed using the NICU Network Neurobehavioral Scale (NNNS) to measure their neurologic and behavioral functioning and signs of stress/abstinence on days 3, 14 and 30 of life.. Participants were 41 pregnant buprenorphine-maintained women and their infants.. Maternal buprenorphine dose at delivery was negatively correlated with infant quality of movement and self-regulation, and positively correlated with the central nervous system parameters of stress/abstinence at day 3 of life. As maternal buprenorphine dose increased, the mean morphine dose that the infant required for NAS treatment significantly increased. No differences were found when comparing the NNNS domain scores between infants who required pharmacotherapy for NAS versus those who did not at day 3 of life.. Buprenorphine exposure during pregnancy can alter neonatal neurobehavioral and physiological responses to stimuli. A systematic evaluation of the newborn's functional domains above NAS assessment alone is crucial to address the challenges created by neurobehavioral dysregulation associated with substance exposure, improve caregiver/infant interaction and developmental trajectory. Comprehensive pre/postnatal treatment of buprenorphine-maintained mothers can lead to healthier outcomes for the dyad.

Topics: Adult; Buprenorphine; Child Development; Female; Humans; Infant Behavior; Infant, Newborn; Male; Movement; Narcotic Antagonists; Neonatal Abstinence Syndrome; Pregnancy; Prenatal Exposure Delayed Effects

Pregnant women treated with methadone as opioid maintenance therapy are more likely than women treated with buprenorphine to deliver preterm. Preterm birth is associated with less risk of neonatal abstinence syndrome (NAS). We sought to assess the role of preterm birth as a mediator of the relationship between in utero exposure to methadone and NAS compared with buprenorphine.. We studied 716 women receiving methadone or buprenorphine and delivering liveborn infants at Magee-Womens Hospital, Pittsburgh, Pennsylvania (2013-15). We implemented inverse probability weighted marginal structural models to isolate the role of preterm birth (<37 weeks' gestation). Weights accounted for confounding by maternal age, race, insurance, parity, delivery year, marital, employment, hepatitis C, and smoking status.. Approximately 57% of the cohort were treated with methadone. Preterm birth was more common in methadone-exposed pregnancies (25% versus 14%). The incidence of NAS treatment was higher in methadone compared with buprenorphine-exposed infants (65% vs 49%), and term compared with preterm births (64% vs 36%). For every 100 infants liveborn to mothers treated for opioid dependence, there were 13 excess cases of NAS among infants exposed to methadone compared with buprenorphine (adjusted risk difference [RD] 13.3, 95% confidence interval [CI] 5.7, 20.9). Among term births, this increased to 17 excess cases of NAS in methadone- compared with buprenorphine-exposed (RD 16.7, 95% CI 9.3, 24.0).. The further increased risk of NAS associated with methadone use vs buprenorphine in term deliveries emphasises the utility of buprenorphine in clinical settings aimed at decreasing NAS.

Topics: Adult; Buprenorphine; Female; Humans; Infant, Newborn; Maternal Age; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pennsylvania; Pregnancy; Premature Birth; Risk Factors

Opioid maintenance treatment (OMT) is recommended to opioid-dependent females during pregnancy. However, it is not clear which medication should be preferred. We aimed to compare neonatal outcomes after prenatal exposure to methadone (M) and buprenorphine (B) in two European countries.. Nation-wide register-based cohort study using personalized IDs assigned to all citizens for data linkage.. The Czech Republic (2000-14) and Norway (2004-13). [Correction added after online publication on 26 April 2018: The Czech Republic (2000-04) corrected to (2000-14).] PARTICIPANTS: Opioid-dependent pregnant Czech (n = 333) and Norwegian (n = 235) women in OMT who received either B or M during pregnancy and their newborns.. We linked data from health registries to identify the neonatal outcomes: gestational age, preterm birth, birth weight, length and head circumference, small for gestational age, miscarriages and stillbirth, neonatal abstinence syndrome (NAS) and Apgar score. We performed multivariate linear regression and binary logistic regression to explore the associations between M and B exposure and outcomes. Regression coefficient (β) and odds ratio (OR) were computed.. Most neonatal outcomes were more favourable after exposure to B compared with M, but none of the differences was statistically significant. For instance, in the multivariate analysis, birth weight was β = 111.6 g [95% confidence interval (CI) = -10.5 to 233.6 and β = 83.1 g, 95% CI = -100.8 to 267.0] higher after B exposure in the Czech Republic and Norway, respectively. Adjusted OR of NAS for B compared with M was 0.94 (95% CI = 0.46-1.92) in the Norwegian cohort.. Two national cohorts of women receiving opioid maintenance treatment during pregnancy showed small but not statistically significant differences in neonatal outcomes in favour of buprenorphine compared with methadone.

Topics: Abortion, Spontaneous; Adult; Analgesics, Opioid; Apgar Score; Buprenorphine; Czech Republic; Female; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Linear Models; Logistic Models; Male; Methadone; Neonatal Abstinence Syndrome; Norway; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Registries; Stillbirth; Young Adult

Among opioid-exposed infants, psychiatric medication co-exposure is common. Our objective was to compare Neonatal Abstinence Syndrome (NAS) outcomes based on individual psychiatric medication co-exposures.. A retrospective study of 744 opioid-exposed mother-infant dyads from a single institution was performed. Mothers on pharmacotherapy with methadone or buprenorphine at delivery were included. Data were collected on maternal demographics, psychiatric medication use, and NAS outcomes, including any medication treatment, adjunctive medication treatment, length of hospital stay (LOS), and opioid treatment days. The extent to which individual psychiatric medication and polypharmacy exposure were associated with NAS outcomes was assessed using multivariable regression.. Fifty-four percent of the mothers were on ≥1 psychiatric medication, with 32% on ≥2 or psychiatric medications (polypharmacy group). In adjusted models, polypharmacy exposure was associated with longer LOS (β = 4.31 days, 95% CI 2.55-6.06) and opioid treatment days (β = 3.98 days, 95% CI 2.24-5.72) and more treatment with adjunctive medication for NAS (aOR = 2.49, 95% CI 1.57-3.95). Benzodiazepines were associated with longer LOS (β = 4.94, 95% CI 2.86-7.03) and opioid treatment days (β = 4.86, 95% CI 2.61-6.75), and more adjunctive medication treatment (aOR = 2.57, 95% CI 1.49-4.42). Gabapentin was associated with longer LOS (β = 2.79, 95% CI 0.54-5.03), more NAS medication treatment (aOR = 2.96, 95% CI 1.18-7.42) including more adjunctive medications (aOR = 1.92, 95% CI 1.05-3.53).. For infants of mothers with OUD who are also on concurrent psychiatric medications, polypharmacy was associated with worse NAS severity. When medically indicated, limiting use of multiple psychiatric medications, particularly benzodiazepines and gabapentin, during pregnancy should be considered to improve NAS outcomes.

Topics: Adult; Analgesics, Opioid; Benzodiazepines; Buprenorphine; Female; Gabapentin; Humans; Infant; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Retrospective Studies; Severity of Illness Index

There is a paucity of data characterizing mother-infant pairs with prenatal opioid dependence in Canada. We therefore conducted a study of relevant births in Ontario from 2002 to 2014.. We used data from the Institute for Clinical Evaluative Sciences, the linked databases of coded population-based Ontario health services records. Differences in characteristics of opioid-dependent mother-neonate pairs and infant hospital costs by year were assessed using linear regression, and we calculated rates of preterm birth, low birth weight, birth defects, mortality, and neonatal abstinence syndrome.. The number of infants born to opioid-dependent women in Ontario rose from 46 in 2002 to almost 800 in 2014. Methadone was most frequently used for prenatal opioid dependence; there was little buprenorphine or buprenorphine + naloxone use. Rates of preterm birth and low birth weight were high. The proportion of neonates with neonatal abstinence syndrome (58%) was stable over the study period. The mean length of neonatal hospital stay was 13.96 days. Infant hospital costs increased from $724 774 in 2003 to $10 539 988 in 2013, and the mean cost per infant grew from $9928 to $12 917. Birth defect prevalence was 75.84/1000 live births (95% CI 68.12/1000 to 84.10/1000). The stillbirth rate was 11.39/1000 births (95% CI 8.47/1000 to 14.99/1000), and the infant mortality rate was 12.21/1000 live births (95% CI 9.16/1000 to 15.95/1000).. We observed a 16-fold increase in the number of mother-infant pairs affected by opioid dependence in Ontario over the past decade. Adverse birth outcome rates were high. Expanded services for opioid-dependent women and their children are needed.

Topics: Adult; Buprenorphine; Congenital Abnormalities; Databases, Factual; Female; Health Care Costs; Humans; Infant; Infant Mortality; Infant, Newborn; Length of Stay; Male; Methadone; Naloxone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Ontario; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Stillbirth; Young Adult

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy

Naltrexone may provide a suitable alternative to methadone and buprenorphine in the treatment of pregnant opioid-dependent women; however, little is known about its effects on neonatal morbidity and mortality.. The aim was to evaluate the health of neonates exposed to naltrexone in utero, and compare it with outcomes in neonates exposed to methadone or buprenorphine and a non-exposed control group.. Sequential cohorts of Western Australian (WA) opioid-dependent women treated with implant naltrexone, oral methadone or sublingual buprenorphine were identified via records from a drug and alcohol clinic (Subiaco, WA) for naltrexone and state prescribing records for methadone and buprenorphine. A control cohort of non-opioid-dependent women was obtained from the WA electoral roll. Identifying information and treatment records for these women were linked against the Midwife Notification System records to identify exposed offspring born between 2001 and 2011. Birth characteristics, congenital anomalies and perinatal mortality for all neonates were extracted from state records.. The birth characteristics of naltrexone-exposed neonates (n = 68) were superior to methadone-exposed neonates (n = 199) in terms of birth size (birth weight, head circumference and length), hospital length of stay (5.5 vs. 11.3 days), and rates of neonatal abstinence syndrome (NAS) (7.5 vs. 51.5%). Naltrexone-exposed neonates were generally not significantly different to buprenorphine-exposed neonates (n = 124), with the exception of significantly lower rates of NAS (7.5 vs. 41.8%) and shorter hospital length of stay (5.5 vs. 8.0 days) in naltrexone-exposed neonates. Compared with the control group of neonates (n = 569), naltrexone-exposed neonates were not significantly different in terms of overall rates of congenital anomalies, stillbirths and neonatal mortality; however, they were significantly smaller (3137.1 vs. 3378.0 g), spent more time in hospital following birth (5.5 vs. 4.3 days) and had higher rates of NAS (7.5 vs. 0.2%). Exposure of neonates to prenatal methadone was associated with a high incidence of neonatal mortality (2.0 vs. 0.2 per 100 live births) and congenital anomalies (10.6 vs. 4.4 per 100 births) compared with the control group. Rates of neonatal mortality and congenital abnormalities in buprenorphine-exposed neonates were not significantly different to the control group.. The use of implant naltrexone during pregnancy was not associated with higher rates of negative birth outcomes compared with methadone- and buprenorphine-exposed neonates. Significantly, naltrexone and buprenorphine were not associated with the high rates of neonatal mortality or congenital anomalies seen in methadone-exposed neonates.

Topics: Adult; Australia; Buprenorphine; Drug Administration Routes; Female; Humans; Incidence; Infant, Newborn; Male; Methadone; Naltrexone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Retrospective Studies

Maternal buprenorphine maintenance predisposes the infant to exhibit neonatal abstinence syndrome (NAS), but there is insufficient published information regarding the nature of NAS and factors that contribute to its severity in buprenorphine-exposed infants.. The present study evaluated forty-one infants of buprenorphine-maintained women in comprehensive substance use disorder treatment who participated in an open-label study examining the effects of maternal buprenorphine maintenance on infant outcomes. Modifiers of the infant outcomes, including maternal treatment and substance use disorder parameters, were also evaluated.. Fifty-nine percent of offspring exhibited NAS that required pharmacologic management. Both maternal buprenorphine dose as well as prenatal polysubstance exposure to illicit substance use/licit substance misuse were independently associated with NAS expression. Polysubstance exposure was associated with more severe NAS expression after controlling for the effects of buprenorphine dose. Other exposures, including cigarette smoking and SRI use, were not related to outcomes. Maternal buprenorphine dose was positively associated with lower birth weight and length.. Polysubstance exposure was the most potent predictor of NAS severity in this sample of buprenorphine-exposed neonates. This finding suggests the need for interventions that reduce maternal polysubstance use during medication assisted treatment for opioid use disorder, and highlights the necessity of a comprehensive approach, beyond buprenorphine treatment alone, for the optimal care for pregnant women with opioid use disorders.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Topics: Buprenorphine; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy Complications

Topics: Buprenorphine; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy Complications

Topics: Buprenorphine; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy Complications

Topics: Buprenorphine; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy Complications

To determine whether maternal and infant outcomes are associated with exposure to marijuana during the third trimester in a population of opioid dependent pregnant women maintained on buprenorphine.. This retrospective cohort study of 191 maternal-infant dyads exposed to buprenorphine during pregnancy examines a variety of variables including gestational age, birthweight, method of delivery, Apgar scores at one and five minutes, duration of infant hospital stay, peak neonatal abstinence syndrome (NAS) score, duration of NAS and incidence of pharmacologic treatment of NAS in infants exposed to marijuana during the third trimester as compared to infants not exposed to marijuana during the third trimester.. Analyses failed to support any significant relationship between marijuana use in the third trimester and a variety of maternal and infant outcomes. Two important variables - the likelihood of requiring pharmacologic treatment for NAS (27.6% in marijuana exposed infants vs. 15.7% in non-marijuana exposed infants, p=0.066) and the duration of infant hospital stay (7.7days in marijuana exposed infants vs. 6.6days in non-exposed infants, p=0.053) trended toward significance.. Preliminary results indicate that marijuana exposure in the third trimester does not complicate the pregnancy or the delivery process. However, the severity of the infant withdrawal syndrome in the immediate postnatal period may be impacted by marijuana exposure. Because previous study of prenatal marijuana exposure has yielded mixed results, further analysis is needed to determine whether these findings are indeed significant.

Topics: Analgesics, Opioid; Birth Weight; Buprenorphine; Cannabis; Female; Gestational Age; Humans; Infant; Infant, Newborn; Length of Stay; Marijuana Smoking; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Retrospective Studies; Substance Withdrawal Syndrome

Topics: Buprenorphine; Diseases in Twins; Female; Hospitalization; Humans; Infant, Newborn; Male; Methadone; Morphine; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Phenobarbital; Pregnancy; Referral and Consultation; Retrospective Studies; Substance Abuse Treatment Centers; Treatment Outcome

Topics: Buprenorphine; Gestational Age; Humans; Infant, Newborn; Methadone; Morphine; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy Complications

To determine whether concurrent in utero exposure to buprenorphine and antidepressants impacts the course of neonatal abstinence syndrome (NAS) in infants.. A retrospective cohort study of 148 infants who were exposed to buprenorphine during pregnancy. Univariate and bivariate analyses were used to examine associations between concurrent maternal use of buprenorphine and antidepressants as compared to maternal use of buprenorphine alone.. The time to onset of NAS resolution was significantly longer in infants exposed to both buprenorphine and antidepressants during pregnancy when compared to those exposed to buprenorphine alone (129.8 h versus 70.2 h, p = 0.042).. Women who are prescribed both antidepressants and buprenorphine during pregnancy should be counseled about the possibility of a prolonged course of neonatal abstinence syndrome.

Topics: Adult; Antidepressive Agents; Buprenorphine; Drug Interactions; Female; Humans; Infant, Newborn; Male; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pregnancy; Retrospective Studies

To determine whether there is a dose-response relationship between maternal dose of buprenorphine at delivery and neonatal outcomes.. This retrospective cohort study of 155 maternal-infant dyads exposed to buprenorphine during pregnancy examines the relationship between maternal dose of buprenorphine at delivery and gestational age, birthweight, method of delivery, Apgar scores at 1 and 5 min, duration of infant hospital stay, peak neonatal abstinence syndrome (NAS) score, duration of NAS and incidence of pharmacologic treatment of NAS.. Analyses failed to support any relationship between maternal dose of buprenorphine at delivery and any of the 9 clinical outcomes (all p values >0.093).. This study failed to provide any evidence to support limiting or reducing maternal dose of buprenorphine during pregnancy in order to reduce possible adverse outcomes to the infant. Findings suggest that healthcare providers can focus medication decisions on maternal opioid cravings to reduce the risk of relapse to illicit opioid use rather than out of concern for adverse infant outcomes.

Topics: Adult; Apgar Score; Birth Weight; Buprenorphine; Delivery, Obstetric; Dose-Response Relationship, Drug; Female; Gestational Age; Humans; Infant, Newborn; Length of Stay; Maine; Male; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pregnancy; Prenatal Exposure Delayed Effects; Retrospective Studies; Young Adult

Breastfeeding is recommended for women with opioid use disorder who are treated with methadone or buprenorphine. Infants with neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure have unique challenges related to breastfeeding but also have significant benefits including improved NAS symptoms with a decreased need for pharmacotherapy. Poor understanding of substance use disorder and treatment, lack of evidence-based recommendations, and vague guidelines from national academies create controversy about breastfeeding eligibility for these women. Defining breastfeeding guidelines is often difficult, particularly in large institutions with multiple providers caring for the mother-infant dyad. Based on the available evidence and review of our institutional data, we revised our breastfeeding guidelines for mothers with opioid use disorder. The aims of our new guidelines are (a) to safely promote breastfeeding in all mothers with opioid use disorder who are in recovery, (b) to improve NAS outcomes through use of breastfeeding as a key nonpharmacologic treatment modality, and (c) to improve staff communication and consistency on the subject of breastfeeding in this patient population.

Topics: Analgesics, Opioid; Boston; Breast Feeding; Buprenorphine; Female; Health Promotion; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Postnatal Care; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications

To compare the duration of opioid treatment and length of stay among infants treated for neonatal abstinence syndrome (NAS) by using a pilot buprenorphine vs conventional methadone treatment protocol.. This retrospective cohort analysis evaluated infants who received pharmacotherapy for NAS at 6 hospitals in Southwest Ohio from January 2012 through August 2014. A single neonatology provider group used a standardized methadone protocol across all 6 hospitals. However, at one of the sites, infants were managed with a buprenorphine protocol unless they had experienced chronic in utero exposure to methadone. Linear mixed models were used to calculate adjusted mean duration of opioid treatment and length of inpatient hospitalization with 95% CIs in infants treated with oral methadone compared with sublingual buprenorphine. The use of adjunct therapy was examined as a secondary outcome.. A total of 201 infants with NAS were treated with either buprenorphine (n = 38) or methadone (n = 163) after intrauterine exposure to short-acting opioids or buprenorphine. Buprenorphine therapy was associated with a shorter course of opioid treatment of 9.4 (CI 7.1-11.7) vs 14.0 (12.6-15.4) days (P < .001) and decreased hospital stay of 16.3 (13.7-18.9) vs 20.7 (19.1-22.2) days (P < .001) compared with methadone therapy. No difference was detected in the use of adjunct therapy (23.7% vs 25.8%, P = .79) between treatment groups.. The choice of pharmacotherapeutic agent is an important determinant of hospital outcomes in infants with NAS. Sublingual buprenorphine may be superior to methadone for management of NAS in infants with select intrauterine opioid exposures.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Clinical Protocols; Cohort Studies; Female; Humans; Infant, Newborn; Length of Stay; Linear Models; Male; Methadone; Neonatal Abstinence Syndrome; Ohio; Opioid-Related Disorders; Retrospective Studies

The current recommendation regarding the management of a pregnant patient with opioid dependence is not to perform detoxification during pregnancy because of a potential risk for preterm labor, fetal distress, or fetal demise.. The objective of the study was to evaluate the safety of full opiate detoxification during pregnancy in a large number of patients through 4 different methods and analyze the rate of newborn treatment of neonatal abstinence syndrome for each method.. This was a retrospective analysis of data collected prospectively during ongoing prenatal care of opiate-addicted pregnant women. Data were analyzed for pregnancy complications including fetal demise and preterm labor of opiate-addicted pregnant women who underwent detoxification during pregnancy through 4 different methods: acute detoxification of incarcerated patients; inpatient detoxification with intense outpatient follow-up management; inpatient detoxification without intense outpatient follow-up management; and slow outpatient buprenorphine detoxification. The rates of newborns treated for neonatal abstinence syndrome were also assessed for each group.. Over 5.5 years, 301 opiate-addicted pregnant patients were fully detoxified during pregnancy with no adverse fetal outcomes related to detoxification identified. There were 94 patients who delivered newborns treated for neonatal abstinence syndrome (31%). There was an 18.5% rate of neonatal abstinence syndrome in the 108 acutely detoxified while incarcerated, a 17.4% rate of neonatal abstinence syndrome in the 23 who had inpatient detoxification with intense outpatient follow-up management, a 17.2% rate of neonatal abstinence syndrome in the 93 who went through slow outpatient buprenorphine detoxification, but a 70.1% rate of neonatal abstinence syndrome in the 77 who had inpatient detoxification without intense outpatient follow-up management.. With these data and other published studies, more than 600 patients have been reported to detoxify from opiates during pregnancy with no report of fetal harm related to the process. These data highly suggest that detoxification of opiate-addicted pregnant patients is not harmful. The rate of neonatal abstinence syndrome is high but primarily when no continued long-term follow-up occurs. Once a patient is drug free, intense behavioral health follow-up is needed for continued success.

Topics: Adolescent; Adult; Ambulatory Care; Buprenorphine; Female; Hospitalization; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Mental Health Services; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prisoners; Retrospective Studies; Tennessee; Young Adult

To describe the effect of in utero exposure to the buprenorphine+naloxone combination product in a rural and remote population.. A district hospital that services rural and remote, fly-in communities in Northwestern Ontario, Canada.. A retrospective cohort study was conducted of 855 mother infant dyads between 1 July 2013 and 30 June 2015. Cases included all women who had exposure to buprenorphine+naloxone during pregnancy (n=62). 2 control groups were identified; the first included women with no opioid exposure in pregnancy (n=618) and the second included women with opioid exposure other than buprenorphine+naloxone (n=159). Women were excluded if they had multiple pregnancy or if they were part of a methadone programme (n=16). The majority of women came from Indigenous communities.. The primary outcomes were birth weight, preterm delivery, congenital anomalies and stillbirth. Secondary neonatal outcomes included gestational age at delivery, Apgar scores at 1 and 5 min, NAS Score >7 and treatment for neonatal abstinence syndrome (NAS). Secondary maternal outcomes included the number of caesarean sections, postpartum haemorrhages, out of hospital deliveries and transfer of care to tertiary centres.. No difference was found in the primary outcomes or in the Apgar score and caesarean section rate between in utero buprenorphine+naloxone exposure versus no opioid exposure in pregnancy. Compared to women taking other opioids, women taking buprenorphine+naloxone had higher birthweight babies (p=0.001) and less exposure to marijuana (p<0.001) during pregnancy.. Retrospective data suggest that there likely is no harm from taking buprenorphine+naloxone opioid agonist treatment in pregnancy. Larger, prospective studies are needed to further assess safety.

Topics: Adult; Apgar Score; Birth Weight; Buprenorphine; Female; Humans; Infant, Newborn; Naloxone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Ontario; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnant Women; Retrospective Studies; Rural Population; Treatment Outcome

Development of a healthy gut microbiome is essential in newborns to establish immunity and protection from pathogens. Recent studies suggest that infants who develop dysbiosis may be at risk for lifelong adverse health consequences. Exposure to opioid drugs during pregnancy is a factor of potential importance for microbiome health that has not yet been investigated. Since these infants are born after an entire gestation exposed to mu opioid receptor agonists and have severe gastrointestinal and neurological symptoms, we hypothesize that these infants are at risk for dysbiosis. We speculate that opioid exposure during gestation and development of NAS at birth may lead to a dysbiotic gut microbiome, which may impair normal microbiome succession and development, and impact future health of these children.

Topics: Analgesics, Opioid; Buprenorphine; Child; Child, Preschool; Dysbiosis; Female; Gastrointestinal Tract; Humans; Infant; Infant, Newborn; Maternal Exposure; Methadone; Microbiota; Models, Theoretical; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk; Substance Withdrawal Syndrome

Topics: Buprenorphine; Female; Humans; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Opioid exposure during pregnancy is a potential risk factor for the developing central nervous system of the fetus. We studied evoked responses in buprenorphine-exposed newborns who displayed neonatal abstinence syndrome (NAS) to elucidate the possible alterations in functioning of the somatosensory and auditory systems.. We compared somatosensory (SEFs) and auditory evoked magnetic fields (AEFs), recorded with magnetoencephalography (MEG), of 11 prenatally buprenorphine-exposed newborns with those of 12 healthy newborns. Peak latencies, source strength and location of SEFs or AEFs were recorded.. AEFs were present in all buprenorphine-exposed newborns without significant differences from those of healthy newborns. In contrast, though no group level differences in SEFs existed, at individual level the response deviated from the typical neonatal morphology in four buprenorphine-exposed newborns.. Although buprenorphine exposure during pregnancy does not seem to cause constant deficiencies in somatosensory or auditory processing, in some newborns the typical development of somatosensory networks may be - at least transiently - disrupted.

Topics: Analgesics, Opioid; Auditory Pathways; Buprenorphine; Evoked Potentials, Auditory; Evoked Potentials, Somatosensory; Female; Gestational Age; Humans; Infant, Newborn; Magnetoencephalography; Male; Maternal-Fetal Exchange; Neonatal Abstinence Syndrome; Pregnancy; Somatosensory Disorders

To compare neonatal abstinence syndrome prevalence and characteristics among neonates born to women prescribed buprenorphine and naloxone compared with methadone during pregnancy.. Retrospective cohort analysis of mother-neonate dyads treated with either buprenorphine and naloxone or methadone during pregnancy. Primary neonatal outcomes included diagnosis of neonatal abstinence syndrome, neonatal abstinence syndrome peak scores, total amount of morphine used to treat neonatal abstinence syndrome (mg), and duration of treatment for neonatal abstinence syndrome (days). Secondary outcomes included head circumference, birth weight, length, preterm birth, neonatal intensive care unit admission, Apgar scores, and overall length of hospitalization.. From January 1, 2011, to November 30, 2013, we identified 62 mother-neonate dyads, 31 treated with methadone and 31 treated with buprenorphine and naloxone. Sixteen neonates (51.6%) in the methadone group were diagnosed with neonatal abstinence syndrome compared with eight (25.1%) in the buprenorphine and naloxone group (adjusted odds ratio 2.55, 95% confidence interval [CI] 1.31-4.98, P = .01). The buprenorphine and naloxone-exposed neonates had lower peak neonatal abstinence syndrome scores (9.0 ± 4.4 compared with 10.7 ± 3.7, multivariate-adjusted mean difference = -2.77, 95% CI -4.99 to -0.56, P = .02) and shorter overall hospitalization (5.6 ± 5.0 compared with 9.8 ± 7.4 days, multivariate-adjusted mean difference = -3.90, 95% CI, -7.13 to -0.67, P = .02). We found no other differences in primary or secondary outcomes.. In a cohort of pregnant patients treated with either methadone or buprenorphine and naloxone in pregnancy, newborns exposed to maternal buprenorphine and naloxone had less frequent neonatal abstinence syndrome. Additionally, neonates exposed to buprenorphine and naloxone had shorter overall hospitalization lengths.

Topics: Adult; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Naloxone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies; Young Adult

To compare early growth and developmental outcome of infants with in-utero exposure to low-dose methadone (<100 mg per  day), high-dose methadone (⩾100 mg  per day) and buprenorphine.. A retrospective review of infants with in-utero methadone and buprenorphine exposure who were evaluated at the Southcoast Developmental Pediatric clinic in New Bedford, MA, USA was completed. Growth data and developmental testing results during infancy were compared among the groups.. Infants in the high-dose methadone group had lower head circumference z scores and a lower mean score on the Alberta Infant Motor Scale (AIMS). Regression results confirmed an association between methadone dose and head circumference z score and AIMS score.. Exposure to maternal methadone dose in excess of 100 mg is associated with a reduction in infant head circumference when compared with buprenorphine or lower dose methadone, and may have a negative impact on motor skill development during early infancy.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Massachusetts; Methadone; Mother-Child Relations; Neonatal Abstinence Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Retrospective Studies; Young Adult

Neonatal abstinence syndrome (NAS)--a clinical entity of infants from in utero exposure to psychoactive xenobiotic and buprenorphine--has been successfully used to treat NAS. However, nothing is known about the pharmacokinetics (PK) of buprenorphine in neonates with NAS. To our knowledge, this is the first study to investigate the population pharmacokinetic of sublingual buprenorphine in neonates with NAS.. A retrospective population PK analysis of: (1) neonates with NAS treated with sublingual buprenorphine in randomized, double blinded clinical study and (2) data from healthy adults from a previously published pharmacokinetic study.. Neonatal intensive care unit and general clinical research unit.. Twenty-four neonates with NAS and five healthy adults.. All participants received sublingual buprenorphine per study protocol.. A total of 303 PK data from 29 neonates and adults were used for model development. A population pharmacokinetic analysis was conducted using a first order conditional estimation with interaction in the NONMEM software program. A two-compartment linear PK model with first-order absorption process best described the pharmacokinetics of sublingual buprenorphine in neonates. The apparent clearance (CL) of buprenorphine was linearly related to body weight and matured with increasing age via two distinct saturated pathways. A typical neonate with NAS (body weight, 2.9 kg; postnatal age; 5.4 days) had a CL of 3.5 L/kg/hour and elimination half-life of 11 hours. Phenobarbital did not affect the clearance of buprenorphine compared to neonates of similar age and weight.. This is the first study to investigate the population PK of sublingual buprenorphine in neonatal NAS. To our knowledge, this is also the first report to describe the age-dependent changes of buprenorphine PK in this patient population. No buprenorphine dose adjustment is needed for neonates with NAS treated with buprenorphine and concurrent phenobarbital.

Topics: Administration, Sublingual; Adult; Buprenorphine; Clinical Trials, Phase I as Topic; Female; Humans; Infant, Newborn; Male; Models, Biological; Neonatal Abstinence Syndrome; Randomized Controlled Trials as Topic; Receptors, Opioid, kappa; Receptors, Opioid, mu

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Methadone; Morphine; Neonatal Abstinence Syndrome

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Male; Methadone; Morphine; Neonatal Abstinence Syndrome

Perinatal opioid use disorders negatively impact maternal and neonatal outcomes and are a public health problem of increasing severity. More than half of women with a substance use disorder have a history of posttraumatic stress disorder that, if not adequately addressed, can impede substance use disorder treatment. This case report describes complexities in the treatment of a pregnant woman with opioid use disorder and posttraumatic stress disorder and reviews the psychotherapeutic and pharmacologic approaches available to treat these co-occurring disorders in pregnancy. This case demonstrates the importance of early screening and intervention for co-occurring posttraumatic stress disorder in pregnant women who use substances in a closely coordinated, multidisciplinary approach to improve outcomes for women and their infants.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Counseling; Female; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Smoking; Smoking Cessation; Stress Disorders, Post-Traumatic; Treatment Outcome; Young Adult

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Naloxone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Weight Gain; Young Adult

Although opioid maintenance treatment (OMT) is the treatment of choice for pregnant opioid-dependent patients, some professionals argue that tapering the medication dose will reduce the severity of neonatal abstinence syndrome (NAS). This case description is based on the patient's detailed blog, and medical records from her general practitioner and the hospital. The patient is an employed, 32-year-old drug-abstinent woman in OMT. Her taper from 24 mg of buprenorphine started at 14 weeks' gestation and is slow, with withdrawal symptoms increasing gradually. In pregnancy week 31, she is off buprenorphine but she has severe withdrawal symptoms. She chose to go back on 4 mg of buprenorphine. The patient's son was born in pregnancy week 38+3, weighs 2950 g and does not require pharmacological treatment for NAS. The fetus most probably did experience fetal stress during the patient's tapering. It was the right decision by the patient to go back on buprenorphine.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Fetus; Gestational Age; Humans; Infant, Newborn; Male; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Parturition; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome

To determine whether infant gender influences the course of neonatal abstinence syndrome (NAS) following exposure to buprenorphine during pregnancy.. A retrospective cohort study was performed in which maternal and infant data were collected for 46 male and 44 female infants. All infants were born to women enrolled in a buprenorphine treatment program from December 2007 until October 2012. Maternal and infant characteristics and outcomes were compared by infant gender.. Male infants had a significantly higher mean peak NAS score (10.04 vs. 7.98, P=0.028) and were more likely to require pharmacologic treatment for NAS (39.1% vs. 11.4%, P=0.005).. These data indicate that, following exposure to buprenorphine during pregnancy, male infants experience a more severe withdrawal syndrome and are more likely to require pharmacologic treatment for NAS.

Topics: Adult; Buprenorphine; Cohort Studies; Female; Humans; Infant, Newborn; Male; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies; Severity of Illness Index; Sex Characteristics

To determine the short-term outcomes of Australian buprenorphine-exposed mother/infant dyads.. Retrospective record review of drug-exposed mothers and infants in Australia. Groups were based on drug exposure: buprenorphine (55, 3.8%), non-buprenorphine opiates (O, 686, 48.6%) and non-opiates (NO, 671, 47.5%).. More than 30% of buprenorphine mothers continued to use heroin (21, 38%) and benzodiazepines (16, 29%). They were more likely to have child at risk concerns (29, 52.7%, P = 0.019) and have previous children placed in out-of-home care (9, 16.3%, P = 049). Buprenorphine babies were less likely to be preterm (16% vs. 25% (O), P = 0.001 and 23% (NO), P = 0.004) and had higher birthweights (median: 3165 g vs. 2842.5 g (O), P < 0.001 and 2900 g (NO), P = 0.004). Buprenorphine and non-buprenorphine opioid babies had similar maximum Finnegan scores (median 10 vs. 11(O), P = 0.144). The number of babies needing abstinence treatment (45% vs. 51% (O), P = 0.411) and length of hospital stay (median days 9 vs. 11(O), P = 0.067) were similar, but buprenorphine infants required lower maximum morphine doses (mg/kg/day) (median 0.4 mg vs. 0.5 mg (O), P = 0.009).. Short-term medical outcomes of infants of buprenorphine-using mothers are similar to those of non-buprenorphine opiate-using mothers, but interpretation of these results is confounded by the high rates of polydrug exposure in the buprenorphine group. This and other social concerns noted in buprenorphine mothers and infants warrant further study.

Topics: Adult; Analgesics, Opioid; Australian Capital Territory; Buprenorphine; Female; Humans; Infant, Newborn; Medical Audit; Morphine; Neonatal Abstinence Syndrome; New South Wales; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies; Severity of Illness Index; Treatment Outcome

The recommended standard of care calls for treating opioid-dependent pregnant women with methadone and observing neonates exposed in utero for five to seven postnatal days to see if treatment for neonatal abstinence syndrome (NAS) is needed. Data from a large multi-site randomized clinical trial comparing buprenorphine vs. methadone for the treatment of opioid dependence during pregnancy suggest buprenorphine-exposed neonates had less severe NAS, but may require pharmacologic treatment for NAS later than methadone-exposed neonates. The present study examined whether time to pharmacologic treatment initiation differed in a relatively large non-blinded clinical sample of buprenorphine- vs. methadone-exposed neonates treated for NAS.. Medical records for 75 neonates exposed to buprenorphine (n=47) or methadone (n=28) in utero who required treatment for NAS were examined. Time elapsed between birth and initiation of pharmacologic treatment was calculated for each neonate and time to treatment initiation compared between groups.. Median time to treatment initiation (hours:minutes, IQR) was significantly later in buprenorphine- vs. methadone-exposed neonates (71:02, 44:21-96:27 vs. 34:12, 21:00-55:41, respectively, p<.001). Estimates of mean time to treatment initiation from parametric analyses that adjusted for maternal and neonatal characteristics were very similar (73:10 (95% CI: 61:00-87:18) vs. 42:36 (95% CI: 33:06-53:30), respectively, p=.0005). This difference was not dependent on maternal age or neonatal sex, gestational age, or birth weight.. These findings confirm results from randomized clinical trials, adding generality to the observation that buprenorphine-exposed neonates require treatment significantly later than methadone-exposed neonates.

Topics: Birth Weight; Buprenorphine; Case-Control Studies; Female; Gestational Age; Humans; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Retrospective Studies; Time Factors

To examine the rate and duration of breastfeeding in a cohort of women in opioid maintenance treatment (OMT) in Norway, as well as the effect of breastfeeding on the incidence and duration of neonatal abstinence syndrome (NAS).. A national cohort of 124 women treated with either methadone or buprenorphine during pregnancy, and their neonates born between 1999 and 2009, was evaluated in three study parts. A standardized questionnaire was administered, and medical information from the hospitals and municipalities were collected to confirm self-reported data.. There were high initiation rates of breastfeeding (77%) for women in OMT, but also high rates of early cessation of breastfeeding. Breastfed neonates exposed to methadone prenatally had significantly lower incidence of NAS requiring pharmacotherapy (53% vs. 80%), and both the whole group of infants and the methadone-exposed neonates needed shorter pharmacological treatment of NAS (p < 0.05) than neonates who were not breastfed.. Breastfed neonates exposed to OMT medication prenatally, and methadone-exposed newborns in particular, have lower incidence of NAS and require shorter pharmacotherapy for NAS than infants who are not breastfed. The results add to the evidence regarding the benefits of breastfeeding for neonates prenatally exposed to OMT medications.

Topics: Adult; Breast Feeding; Buprenorphine; Cohort Studies; Female; Humans; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Norway; Opioid-Related Disorders

In Norway, most opioid-dependent women are in opioid maintenance treatment (OMT) with either methadone or buprenorphine throughout pregnancy. The inclusion criteria for both medications are the same and both medications are provided by the same health professionals in any part of the country. International studies comparing methadone and buprenorphine in pregnancy have shown differing neonatal outcomes for the two medications.. This study compared the neonatal outcomes following prenatal exposure to either methadone or buprenorphine in a national clinical cohort of 139 women/neonates from 1996 to 2009.. After adjusting for relevant covariates, buprenorphine-exposed newborns had larger head circumferences and tended to be heavier and longer than methadone-exposed newborns. The incidence of neonatal abstinence syndrome (NAS) and length of treatment of NAS did not differ between methadone- and buprenorphine-exposed newborns. There was little use of illegal drugs and benzodiazepines during the pregnancies. However, the use of any drugs or benzodiazepines during pregnancy was associated with longer lasting NAS-treatment of the neonates.. The clinical relevance of these findings is that both methadone and buprenorphine are acceptable medications for the use in pregnancy, in line with previous studies. If starting OMT in pregnancy, buprenorphine should be considered as the drug of choice, due to more favorable neonatal growth parameters. Early confirmation of the pregnancy and systematic follow-up throughout the pregnancy are of importance to encourage the women in OMT to abstain from the use of tobacco, alcohol, illegal drugs or misuse of prescribed drugs.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cohort Studies; Female; Follow-Up Studies; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Norway; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Retrospective Studies; Treatment Outcome

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Risk Assessment; Treatment Outcome

To examine opioid replacement therapy in pregnancy and effect on neonatal outcomes, including length of hospital stay for neonatal abstinence syndrome.. Retrospective descriptive study.. Labor and delivery unit and neonatal intensive care unit (NICU), Eastern Maine Medical Center, Bangor, Maine.. One hundred fifty-two opioid-dependent pregnant women on methadone maintenance therapy (MMT) (n = 136) or buprenorphine maintenance therapy (BMT) (n = 16) during pregnancy and their neonates. The neonates were born between January 1, 2005 and December 31, 2007.. A review of the electronic medical record (EMR) was conducted of all opioid-dependent women who were maintained on MMT or BMT at the time of admission for labor and delivery and their neonates.. Maternal methadone dose and concomitant in-utero exposure to benzodiazepines prolonged the length of hospital stay for neonates. Length of stay was shorter in breastfed neonates than formula-fed neonates or neonates who received formula and breast milk. Neonates with prenatal exposure to MMT spent more days in the hospital (21 vs. 14 days) for treatment of neonatal abstinence syndrome (NAS) than infants with prenatal exposure to BMT.. These findings are consistent with previous research on the simultaneous use of methadone and benzodiazepines during pregnancy and provide further direction for the treatment of opioid dependency during pregnancy. Harm reduction strategies for opioid-dependent pregnant women in substance abuse treatment with MMT may one day include guidance on daily treatment doses and recommendations to avoid the concomitant use of benzodiazepines to lessen NAS. Breastfeeding should be recommended to shorten length of stay. Understanding perinatal and neonatal outcomes of pregnant women on methadone or buprenorphine will help to identify optimal treatment for opioid dependency in pregnancy.

Topics: Adult; Buprenorphine; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Length of Stay; Linear Models; Male; Methadone; Multivariate Analysis; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Retrospective Studies; Risk Assessment; Time Factors; Treatment Outcome

Opioid use in pregnancy is not uncommon, and the use of illicit opioids during pregnancy is associated with an increased risk of adverse outcomes. The current standard of care for pregnant women with opioid dependence is referral for opioid-assisted therapy with methadone, but emerging evidence suggests that buprenorphine also should be considered. Medically supervised tapered doses of opioids during pregnancy often result in relapse to former use. Abrupt discontinuation of opioids in an opioid-dependent pregnant woman can result in preterm labor, fetal distress, or fetal demise. During the intrapartum and postpartum period, special considerations are needed for women who are opioid dependent to ensure appropriate pain management, to prevent postpartum relapse and a risk of overdose, and to ensure adequate contraception to prevent unintended pregnancies. Patient stabilization with opioid-assisted therapy is compatible with breastfeeding. Neonatal abstinence syndrome is an expected and treatable condition that follows prenatal exposure to opioid agonists.

Topics: Analgesics, Opioid; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Opioid dependence in the setting of pregnancy provides a distinct set of challenges for providers. Treatment plans must take into consideration psychiatric and medical comorbidities while balancing risks and benefits for the maternal-fetal dyad. Treatment is best offered through a comprehensive treatment program designed to effectively deliver opioid agonist maintenance treatment along with psychosocial and obstetric care. As misuse of prescription analgesics increases in the United States, identification of the problem in pregnancy will become more important because this misuse is expected to lead to an increased prevalence of opioid dependence in pregnancy. Buprenorphine as maintenance treatment of opioid dependence during pregnancy has promise and may offer some benefits, but more research is needed, especially regarding induction of actively addicted women during pregnancy. For the present, methadone maintenance remains the standard of care for agonist treatment of opioid dependence in pregnancy against which other treatments must be compared.

Topics: Adolescent; Alcohol-Related Disorders; Analgesics, Opioid; Buprenorphine; Child; Comorbidity; Delivery, Obstetric; Female; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pain Management; Pregnancy; Pregnancy Complications; Prenatal Care; Prenatal Exposure Delayed Effects; Prescription Drugs; Self Medication; Substance Withdrawal Syndrome; United States

Substance use in pregnancy is potentially harmful to both the fetus and pregnant woman. At the Royal Women's Hospital, the Women's Alcohol and Drug Service (WADS) provides pregnancy care and counseling for women who have complex drug and/or alcohol issues and psychosocial needs. Women who are stable on pharmacotherapy attend the general pregnancy clinics.. What are the maternal characteristics, pregnancy and neonatal outcomes for a group of women attending for pregnancy care who were on pharmacotherapy substitution treatment, being prescribed buprenorphine or methadone?. All women prescribed buprenorphine or methadone from September 2005 to December 2006 were identified by the hospital pharmacy department where prescribing permits are retained during the woman's pregnancy and postnatal period. Data were collected from medical records and a specific Drug and Alcohol Service database and analysed using descriptive statistics.. Ninety-eight women were identified; 78 were prescribed methadone and 20 buprenorphine. Of these, 76 women also used other substances: tobacco (63%); cannabis (39%); and heroin (37%). Women who received no antenatal care had poorer outcomes overall. Twenty-four percent of live-born infants ≥33 weeks gestation (22/91) required medication for withdrawal. There was no difference in medication requirement where mothers were polysubstance users (18/70; 26%) compared with those who were not (2/21; 19%) (p=0.78), although these small numbers should be viewed with caution. The mean time until medication was required was 3.47 days.. A significant proportion of infants whose mothers used buprenorphine or methadone in pregnancy displayed enough symptoms of withdrawal to require medication. This is therefore an important clinical issue of which care providers need to be aware.. Further prospective research is required to explore whether factors such as specific substances are more likely to be associated with infant withdrawal.

Topics: Adult; Buprenorphine; Female; Humans; Infant, Newborn; Maternal Health Services; Maternal Welfare; Medical Audit; Medical Records; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care; Retrospective Studies; Substance-Related Disorders; Treatment Outcome; Young Adult

We report the case of a hypotrophic twin who presented neonatal abstinence syndrome to buprenorphine and developed neonatal seizures when the substitutive treatment by morphine was stopped. The other eutrophic twin did not develop withdrawal symptoms. This case demonstrates the unpredictable nature of transplacental transfer of buprenorphine. It also shows that neonatal abstinence syndrome can be potentially severe and that morphine treatment is not without risk.

Topics: Buprenorphine; Humans; Infant, Newborn; Morphine; Narcotics; Neonatal Abstinence Syndrome; Seizures; Twins

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Morphine; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Randomized Controlled Trials as Topic

To examine the relationship between maternal opioid agonists, methadone, or buprenorphine (BPH), and concurrent psychiatric medication use on length of hospitalization (LOS) among infants with neonatal abstinence syndrome (NAS).. We reviewed the charts of infants born at Boston Medical Center between 2003 and 2009 with a diagnosis of NAS whose mothers were prescribed methadone or BPH for opiate addiction. Univariate and multivariate linear regression analyses were used to examine associations between maternal opioid substitution concurrent with psychiatric medication use and infant LOS. We also tested whether exposure to BPH was associated with a shorter hospitalization.. A total of 273 mother-infant pairs were identified. The average LOS for all infants was 22.9 days (SD: 10.9). In bivariate analyses, maternal use of any psychiatric medication was associated with a longer infant LOS (P < 0.005). Compared with those prescribed methadone alone (n = 158), those also taking benzodiazepines (n = 56) had a 5.88-day longer LOS (95% confidence interval [CI]: 2.15-9.60, P = 0.002). Infants of mothers taking methadone plus an selective serotonin re-uptake inhibitor (n = 51) had a longer LOS (β = 4.47, 95% CI: 1.15-7.79) compared to methadone alone; results remained significant in an initial multivariate model, however the effect was attenuated when additional psychiatric medication use was added to the model. Compared with those exposed to methadone, those exposed to BPH (n = 22) had a significantly shorter LOS (ß = -7.35, CI: -0.18 to -14.52, P = 0.04).. Maternal use of prescribed methadone and benzodiazepines, compared to methadone alone, increased LOS for infants with NAS by 6 days. Maternal use of BPH was associated with a shorter LOS.

Topics: Boston; Buprenorphine; Cross-Sectional Studies; Drug Interactions; Drug Therapy, Combination; Female; Gestational Age; Humans; Infant, Newborn; Length of Stay; Male; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pregnancy; Prenatal Exposure Delayed Effects; Psychotropic Drugs; Risk Factors

Topics: Analgesics, Opioid; Biomedical Research; Buprenorphine; Female; Humans; Infant, Newborn; Internationality; Maternal Exposure; Methadone; Mothers; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Stereoisomerism

Gender, a biological determinant of mental health and illness, plays a critical role in determining patients' susceptibility, exposure to mental health risks, and related outcomes. Regarding sex differences in the epidemiology of opioid dependence, one third of the patients are women of childbearing age. Women have an earlier age of initiation of substance use and a more rapid progression to drug involvement and dependence than men. Generally few studies exist which focus on the special needs of women in opioid maintenance therapy. The aim of this paper is to provide an overview of treatment options for opioid-dependent women, with a special focus on buprenorphine, and to look at recent findings related to other factors that should be taken into consideration in optimizing the treatment of opioid-dependent women. Issues addressed include the role of gender in the choice of medication assisted treatment, sex differences in pharmacodynamics and pharmacokinetics of buprenorphine drug interactions, cardiac interactions, induction of buprenorphine in pregnant patients, the neonatal abstinence syndrome and breastfeeding. This paper aims to heighten the awareness for the need to take gender into consideration when making treatment decisions in an effort to optimize services and enhance the quality of life of women suffering from substance abuse.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Randomized Controlled Trials as Topic; Sex Factors; Treatment Outcome; Women

Woman who struggle with drug addiction during pregnancy are perhaps the most vulnerable of new mothers. The opioid substitution medications methadone and buprenorphine are both compatible with breastfeeding. The objective of this study is to determine breastfeeding rates among opioid-dependent women giving birth in a Baby-Friendly Hospital.. We performed a retrospective chart review of all infants born at Boston Medical Center (Boston, MA) between July 2003 and January 2009 with a diagnosis of neonatal abstinence syndrome. Feeding information was obtained, as well as baseline medical information about the mother-infant pairs. Breastfeeding eligibility was determined by a negative urine toxicology screen on admission, no illicit drug use in the third trimester, and a negative human immunodeficiency virus status.. Two hundred seventy-six mother-infant pairs were identified. Forty percent of the mothers carried one or more psychiatric diagnoses; 24% were taking two or more psychiatric medications. Sixty-eight percent of the mothers were eligible to breastfeed; of those, 24% breastfed to some extent during their infant's hospitalization. Sixty-percent of those who initiated stopped breastfeeding after an average of 5.88 days (SD 6.51).. Breastfeeding rates among opioid-dependent women were low, with three-quarters of those eligible electing not to breastfeed. Of the minority of women who did choose to breastfeed, more than half stopped within 1 week.

Topics: Adult; Breast Feeding; Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Mothers; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Retrospective Studies; Time Factors; Young Adult

This study was first conducted to compare the consequences of the use of methadone and high-dose buprenorphine in pregnancy in France and secondly to describe the heterogeneity of women under high-dose buprenorphine. This paper focuses on the second point only.. From October 1998 to September 1999, data on pregnancy, delivery outcomes and neonatal parameters were collected for 251 addicted women on methadone or high-dose buprenorphine (HDB) substitution followed in 35 hospitals and clinics in continental France. Then the data of 159 women who had been taking HDB during pregnancy and had delivered 160 live infants were analyzed.. Most of these women were treated as outpatients by general practitioners. 43% of them belong to what we considered a "hidden population" of drug users: most of them were native French citizens, who lived with the future fathers in their own homes, had at least some secondary education, and were usually not followed in specialized centers for drug addicts. Almost all the women smoked every day during their pregnancies; 20% used heroin during the last 4 weeks preceding delivery; 16% admitted having injected HDB at least once. Notably, neither the severity nor the duration of the neonatal abstinence syndrome (NAS) seemed to be related to the daily doses of the substitution agent. Half of the newborns were treated for NAS, mainly with morphine hydrochloride.. Although two different populations of women were clearly identified, 64 with no social disadvantage and 95 socially disadvantaged, there was no difference between the groups as for the severity of NAS which was only related to the mothers' compliance with a programme of treatment against addiction.

Topics: Adult; Buprenorphine; Female; France; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Prenatal Care; Prenatal Exposure Delayed Effects; Reproductive History; Socioeconomic Factors; Young Adult

Substitution treatment of opioid-dependent addicts was introduced in Norway in 1998. During the last 10 years, approximately 150 infants have been born to mothers taking part in this programme.. 10 mothers, who took part in the substitution treatment programme, gave birth to 15 infants at Haukeland University Hospital in the period 1999-2005. The infants were observed and monitored at the Department of Pediatrics, Haukeland University Hospital.. During pregnancy, six of the infants were only exposed to opiates, i.e methadone or buprenorphine. Eight infants were also exposed to heroine, benzodiazepines or cannabis. As a group, these infants had lower birth weight than the national average. 14 of the 15 children developed neonatal abstinence syndrome (NAS), 10 needed treatment and two children died from sudden infant death syndrome (SIDS). Long-term follow-up showed that six of 13 children had normal psychomotor development, five had various degrees of delayed psychomotor development and two children had symptoms indicating a hyperkinetic disorder. Five children were in foster care.. Infants of women included in substitution treatment programmes for drug addicts are at high risk compared to infants of women without such addiction. For the newborn, NAS was a frequent complication. The study also showed that symptoms of hyperkinetic disorder and delayed psychomotor development were common. Children who had been exposed to opiates in combination with additional drugs seemed to have a high risk of delayed development and behaviour disorders. As they get older many were placed in foster care, despite well-coordinated, multidisciplinary treatment for the mother.

Topics: Buprenorphine; Developmental Disabilities; Female; Humans; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Psychomotor Disorders; Risk Factors

Opioid maintenance treatment (OMT) is widely used to treat pregnant women with a history of opioid dependence. This study investigated whether maternal methadone/buprenorphine dose and nicotine use in pregnancy affects the occurrence and duration of neonatal abstinence syndrome (NAS) in the infant.. Forty-one pregnant women from OMT programmes in Norway who gave birth between January 2005 and January 2007 were enrolled in a national prospective study. Thirty-eight women (81% of the population) were interviewed in the last trimester of pregnancy and 3 months after delivery. Data from the European Addiction Severity Index and a questionnaire measuring enrolled birth information were compared with medical records and urine analyses.. Treatment requiring NAS occurred in 58% of the methadone-exposed and in 67% of the buprenorphine-exposed infants. There was no significant relationship between a maternal dose of methadone or buprenorphine in pregnancy and NAS treatment duration for the infant. The mean number of cigarettes consumed correlated significantly with NAS treatment duration for the methadone group. Birth weight for the methadone group was approximately 200 g above international findings despite high doses during pregnancy.. Maternal methadone/buprenorphine dose predicted neither the occurrence nor the need for NAS treatment for the infant.

Topics: Adult; Buprenorphine; Cohort Studies; Female; Humans; Infant, Newborn; Male; Methadone; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prospective Studies; Severity of Illness Index; Young Adult

Topics: Buprenorphine; Congenital Abnormalities; Female; France; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Obstetric Labor, Premature; Opioid-Related Disorders; Pregnancy; Pregnancy Outcome; Premature Birth; Prospective Studies

Infants exposed to opioides in-utero frequently demonstrate withdrawal symptoms in the neonatal period and have difficulties with state regulation.. This study examines sleep-wakefulness-distress patterns as indicators of regulatory mechanisms at 3 months of age.. A national infant cohort (N=35) born to women in high-dose maintenance treatment during pregnancy and a comparison group (N=36) of low-risk infants born in the same period.. Distributions and frequencies of sleep, wakefulness and distress measured in hours and episodes on sleep charts recorded by the mothers in the two groups.. Women in maintenance treatment were monitored closely during pregnancy to avoid illicit drug use and to be prepared for motherhood. They were also offered residential treatment before pregnancy and after the child was born. There were no statistical differences between the two groups in any of the 10 measures reflecting diurnal and nocturnal rhythmicity at 3 months despite of neonatal abstinence syndrome in 47% of the exposed infants and significant differences in infant characteristics with respect to birth weight, gestational age and maternal characteristics.. Follow-up procedures combining drug monitoring and counseling during pregnancy and in the first months after birth enhance the development of state regulation in terms of sleep-wakefulness patterns.

Topics: Adult; Buprenorphine; Chronobiology Disorders; Female; Humans; Infant; Infant Behavior; Infant, Newborn; Infant, Premature, Diseases; Longitudinal Studies; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Sleep; Stress, Psychological; Wakefulness

This study was undertaken to evaluate the adequacy of a hospital formulated oral morphine preparation for management of neonatal abstinence syndrome (NAS) and to compare clinical features in infants exposed to methadone or buprenorphine in utero.. Between October 1998 and October 2004 all infants born to mothers treated with buprenorphine or methadone during pregnancy were enrolled into this prospective study. Morphine hydrochloride solution (0.2 mg/ml) was prepared without preservatives under a flow laminar air box (class 100).. Morphine solution: quantitative and qualitative HPLC analysis and microbiological study at regular intervals during storage at 4 degrees C for 6 months. Maternal characteristics: age, opiate dose during pregnancy. Neonatal characteristics: gestational age at delivery, birth weight, Lipsitz scores. Morphine dose: daily morphine dose, maximum morphine dose, duration of NAS, and duration of treatment required to achieve stable Lipsitz scores below 4.. Kruskal-Wallis test for comparison of median values.. Microbiological and HPLC analysis showed that the morphine preparation remained stable for 6 months at 4 degrees C. Nine methadone-exposed infants and 13 buprenorphine-exposed infants were included in the study. All infants presented NAS requiring treatment with the morphine solution. Lipsitz scores at birth were significantly different in the methadone and buprenorphine groups (P < 0.05). The methadone group required significantly higher doses of morphine preparation than the buprenorphine group during the first 38 days of treatment (P < 0.05): 0.435 +/- 0.150 mg/kg/day vs. 0.257 +/- 0.083 mg/kg/day.. This hospital morphine solution is adequate for management of NAS. Preparations showed good stability and doses could be adjusted with a margin of 0.02 mg. The onset of NAS occurred within 24 h after birth in methadone-exposed infants (range 6-24 h) and within 48 h after birth in buprenorphine-exposed infants (range 24-168 h). Due to the possibility of delayed onset of NAS up to 7 days, infants born to mothers treated with buprenorphine should be kept in the hospital for an appropriate surveillance period. Treatment time was significantly longer (45 vs. 28 days) and the mean morphine doses were higher (1.7 fold) in methadone-exposed than buprenorphine-exposed infants.

Topics: Buprenorphine; Chromatography, High Pressure Liquid; Drug Contamination; Drug Stability; Female; Humans; Infant, Newborn; Methadone; Morphine; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Pharmaceutical Solutions; Pregnancy; Prospective Studies

To compare the effects of fetal buprenorphine and methadone exposure during maintenance treatment of pregnant heroin dependent subjects.. A population based comparison of consecutive, prospectively followed buprenorphine-exposed pregnancies in Stockholm County, Sweden, to retrospectively analyzed consecutive methadone-exposed pregnancies.. All 47 pregnancies in 39 women with opiate dependence and buprenorphine maintenance treatment 2001-2006, and all 35 methadone-exposed pregnancies (26 women) 1982-2006 in Stockholm County.. Intrauterine growth, birth outcome, malformations, neonatal adaptation, withdrawal syndrome and infant mortality.. Buprenorphine-exposed pregnancies resulted in 47 uneventful live births (2 twin pairs), 1 stillbirth (for which no explanation was found) and 1 miscarriage. The birth weight of the infants was normal. Neonatal abstinence syndrome (NAS) occurred in 19 cases (40.4%), the majority mild in nature and only 7 (14.9%) needing withdrawal treatment. Compared to 35 infants born after intrauterine methadone exposure at the same hospital since 1982 (77.8% of them exhibiting NAS and 52.8% needing withdrawal treatment), there were significant advantages with buprenorphine treatment: birth weight was higher, due to longer gestation. Incidence of NAS of any intensity, as well as incidence of NAS that required pharmacological treatment was lower, while length of hospital stay was shorter. When buprenorphine treatment started pre-conception, NAS at any level was significantly less frequent than in subjects with post-conception initiated treatment (7/27, 26%; 12/20, 60%, respectively).. Data from this non-randomized comparison suggest that buprenorphine may offer advantages for treatment of opiate dependence during pregnancy.

Topics: Birth Weight; Buprenorphine; Female; Fetal Growth Retardation; Heroin Dependence; Humans; Infant Mortality; Infant, Newborn; Methadone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Sweden

To evaluate the brains of newborns exposed to buprenorphine prenatally.. Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5 T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy.. Neither structural abnormalities nor abnormalities in signal intensity were recorded.. Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process.

Topics: Brain; Buprenorphine; Female; Humans; Infant, Newborn; Magnetic Resonance Imaging; Male; Narcotics; Neonatal Abstinence Syndrome; Pregnancy; Prenatal Exposure Delayed Effects

Exposure to illicit drugs in utero is associated with low birth weight and premature birth. Therefore, maintenance therapy for opioid dependence during pregnancy has been recommended to help withdrawal from street drugs, in order to improve maternal health and decrease risks to the fetus.. In 2002-2005, 67 pregnancies of 66 buprenorphine users were followed prospectively in an outpatient multidisciplinary antenatal setting by an obstetrician, a midwife, a psychiatric nurse and a social worker. Decreasing doses or even abstinence from buprenorphine was encouraged. Outcome measures were daily buprenorphine dose, fetal growth, gestational age at birth, mode of delivery, birth weight, Apgar scores, umbilical pH values, and occurrence of neonatal abstinence syndrome [NAS]. National statistics were used as reference values.. The daily dose of buprenorphine decreased by 2.3 mg (median, range increase of 8 mg to decrease of 24 mg). There were no more incidences of premature birth, cesarean section, low Apgar scores (< or = 6) or umbilical artery pH <7.05 at birth than in the national register, despite the lower birth weight. A total of 91% of the infants needed treatment in a neonatal care unit, 76% had NAS, and 57% needed morphine replacement therapy. Seven infants were taken into care directly from the maternity hospital. Two sudden infant deaths occurred later.. The pregnancies and deliveries of buprenorphine-using women were uneventful, but severe NAS and need for morphine replacement therapy was seen in 57% of the buprenorphine-exposed newborns. A high number of sudden infant deaths occurred.

Topics: Birth Weight; Buprenorphine; Female; Hepatitis C Antibodies; Humans; Infant, Newborn; Morphine; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Smoking; Sudden Infant Death

Evaluation of the effect of substitution therapy on the birth weight of the newborn, its postpartum adaptation and course of the neonatal abstinence syndrome.. A three-year prospective study.. The Department of Gynecology and Obstetrics of the Teaching Hospital and the 2nd Medical Faculty of the Charles University, Prague.. This prospective study was carried out in the period of 2005-2007. Included in the study were heroin-addicted pregnant women and pregnant women who undergoing methadone and buprenorphine substitution therapy. During the 3 years we followed-up 47 heroin-addicted women and 60 women under substitution therapy for prenatal screening. Of this number, 36 pregnant women were methadone-substituted and 24 buprenorphine-substituted. Individual groups were compared using the Kruskal-Wallis ANOVA test. Correlation of dichotomic variables was evaluated by means of longlinear models. Calculations were done by means of NCSS 2002 statistical software (Number Cruncher Statistical Systems, Kaysville, UT, USA).. Statistically birth weight of newborns was significantly lowest in the group of heroin-addicted women as compared to the group receiving substitution with buprenorphine p<0.01 and as compared to the group of methadone-substituted patients p<0.05. Having monitores changes in the placenta the statistically highest number of changes was exhibited by heroin users, both when compared to methadone users (p<0.01) and buprenorphine users (p<0.001). The highest statistically significant number of newborns with IUGR symptoms were born to heroin-addicted women. The lowest Apgar score was recorded in all three evaluations in the group of buprenorphine users and the highest in methadone-substituted women.. Substitution therapy provides pregnant women with the possibility of social stabilization, adaptation, and adequate prenatal care. With regard to the fact that methadone substitution protracts the newborn's abstinence syndrome, attention has been recently focused on substitution with buprenorphine that seems to be a more considerate option, from this point of view.

Topics: Apgar Score; Birth Weight; Buprenorphine; Female; Fetal Growth Retardation; Heroin Dependence; Humans; Infant, Newborn; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Narcotic Antagonists; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

An increase in illicit drug use in Northern Ireland may well have links to the resolution of political conflict, which started in the mid 1990s. Social issues, heretofore hidden, have emerged into the limelight and may be worsened by paramilitary involvement. Registered addicts in the four Health Board areas have shown an increase from 1997 with the greatest number resident within the Northern Board Area. As the prevalence of heroin use in Northern Ireland increased, the Department of Health and Social Services and Public Safety (DHSSPS) commissioned a report, to recommend the development of substitute prescribing services. A case series of pregnancies was reviewed, within the Northern Board Area, where the mother was taking opioid substitution therapy. This resulted in baseline data of outcome for both mother and baby specific to a Northern Ireland population. The different medications for opioid substitution are also assessed. This information will guide a co-ordinated approach that involves obstetrician, anaesthetist, psychiatrist, midwife and social worker to the care of these high-risk pregnancies. Eighteen pregnancies were identified in the study period. Sixteen of these had viable outcomes. One was a twin pregnancy. Outcome data was therefore available for 17 infants. Information was obtained regarding patients' social and demographic background, drug taking behaviour and substitution regimen. Antenatal and intrapartum care was assessed and infants were followed up to the time of hospital discharge.

Topics: Adult; Buprenorphine; Codeine; Female; Heroin Dependence; Humans; Infant, Newborn; Maternal-Fetal Exchange; Methadone; Neonatal Abstinence Syndrome; Northern Ireland; Obstetrics and Gynecology Department, Hospital; Perinatal Care; Pregnancy; Pregnancy Complications; Risk Assessment; Substance Abuse Detection

To report results on the prospective follow-up of 34 pregnant women exposed to buprenorphine maintenance for opiate dependence.. Prospective multicentre study: all pregnant women receiving buprenorphine as maintenance therapy were included as early as possible during their pregnancy.. The pregnant women were recruited from opiate maintenance therapy centres, general practitioner-networks involved in addiction, maternity hospitals and centres for drug information during pregnancy.. Women: drugs and medications consumed, medical and obstetrical events; offspring: withdrawal syndrome, malformation, neonatal disease.. The buprenorphine-exposed pregnancies resulted in 31 live births, one stillbirth, one spontaneous abortion and one voluntary termination. A neonatal withdrawal syndrome was observed in 13 cases (41.9%) and eight of these babies required opiate treatment. Two neonates had a malformation: a premature ductus arteriosus stricture and a tragus appendix.. Taken together with other prospective studies, no alarming results were observed concerning pregnancy outcomes. However, further data from the comparative prospective study are required to determine whether buprenorphine can be considered as a good alternative to methadone treatment in pregnant women.

Topics: Adult; Buprenorphine; Female; Follow-Up Studies; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Substance-Related Disorders

Topics: Adult; Apgar Score; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gestational Age; Heroin Dependence; Humans; Infant, Newborn; Labor, Induced; Narcotic Antagonists; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Victoria

In most European countries, methadone treatment is provided to only 20-30% of opiate abusers who need treatment due to regulations and concerns about safety. To address this need in France, all registered medical doctors since 1995 have been allowed to prescribe buprenorphine (BUP) without any special education or licensing. This led to treating approximately 65,000 patients per year with BUP, about ten times more than with more restrictive methadone policies. French physician compensation mechanisms, pharmacy services, and medical insurance funding all minimized barriers to BUP treatment. About 20% of all physicians in France are using BUP to treat about half of the estimated 150,000 problem heroin users. Daily supervised dosing by a pharmacist for the first six months resulted in significantly better treatment retention (80% vs 46%) and lower heroin use. Intravenous diversion of BUP may occur in up to 20% of BUP patients and has led to various infections and relatively rare overdoses in combination with sedatives. Opiate overdose deaths have declined substantially (by 79%) since BUP was introduced in 1995. Newborn opiate withdrawal in mothers treated with buprenorphine compared to methadone was reported to be less frequent, less severe, and of shorter duration. Although some of the public health benefits seen during the time of buprenorphine expansion in France might be contingent upon characteristics of the French health and social services system, the French model raises questions about the value of tight regulations on prescribing BUP imposed by many countries throughout the world.

Topics: Adult; Buprenorphine; Cause of Death; Cross-Cultural Comparison; Drug Approval; Drug Overdose; Drug Utilization; Female; Forecasting; France; Health Services Accessibility; Heroin Dependence; Humans; Infant, Newborn; Male; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy

To assess the effects of maternal buprenorphine treatment at conception and during pregnancy on neonates in terms of birth outcomes and neonatal abstinence syndrome (NAS).. Prospective, open-label, out-patient maintenance, case report study, conducted at the drug addiction out-patient clinic at the University Hospital Vienna.. Two buprenorphine-maintained pregnant women who had conceived during buprenorphine treatment. Both patients had previously given birth to healthy neonates following induction on to buprenorphine maintenance therapy in the second trimester.. Mothers: urinalysis. Neonates: gestational age at delivery, Apgar scores, birth weight, length and NAS (Finnegan Scale).. Urinalyses were negative for both women for 25 and 38 months, respectively, during the pregnancy period. There were no complications during the course of the pregnancy. The newborns delivered by both women were healthy, birth outcomes were within normal ranges and there were no NAS symptoms requiring treatment.. To our knowledge this is the first report detailing the pregnancies of women treated with buprenorphine at the time of conception and investigated in a prospective study. The NAS noted in neonates born to buprenorphine-maintained mothers appears to be less severe than the NAS observed in neonates born to methadone-maintained mothers. These preliminary data indicate that, in our patient cohort, buprenorphine maintenance at the time of conception and during pregnancy did not seem to affect birth outcome measurements such as pregnancy complications, week of delivery, birth weight, length, umbilical pH or neurodevelopmental progress. Future prospective studies with larger study populations are warranted.

Topics: Adult; Buprenorphine; Female; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Preconception Care; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care; Prospective Studies; Treatment Outcome

Topics: Buprenorphine; Congenital Abnormalities; Female; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Outcome

Topics: Adult; Buprenorphine; Child Development; Female; Heroin Dependence; Humans; Infant, Newborn; Male; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

To assess neonatal abstinence syndrome (NAS) and neurodevelopmental outcome in infants born to addicted mothers under buprenorphine substitution therapy.. District general hospital, Angoulême, France.. Retrospective case records study of infants admitted to the neonatal intensive care unit (NICU) and/or special care baby unit (SCBU) from January 1994 to December 2000 for surveillance and/or treatment of buprenorphine NAS.. Thirteen infants were born to addicted mothers under buprenorphine maintenance therapy during the study period. Eight were male and five were female; mean birth term and weight were 39 weeks gestation and 3000 g, respectively. Apgar scores were within normal limits; four infants were small for gestational age, none was dysmorphologic and none was extracted for fetal distress. NAS occurred in 11 cases (85%) and required treatment in 10 cases. Morphine chlorhydrate 0.5 mg/kg/day was administered in divided doses to seven children and gave better results than paregoric alone or in combination with diazepam. Upon follow-up, seven children presented transient lower limbs hypertonia, jerky movements and jitteriness that lasted 3-9 months. The overall milestones acquisitions were within normal limits.. Buprenorphine substitution seems to be safe during pregnancy, and has had no teratogenic effects reported to date. It induces NAS of variable intensity that is less prolonged in comparison to methadone; the neurodevelopmental outcome of exposed children is normal in the majority of cases, although some presented with transient motor abnormalities that resolved completely in 85% of those recruited to our study.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Male; Morphine; Narcotics; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Prenatal Care; Retrospective Studies; Treatment Outcome

The treatment of opioid dependence during pregnancy is a major challenge for doctors, social workers and gynaecologists. Continuous drug abuse during pregnancy can lead to a variety of complications in the mother, fetus and neonate. lt is recommended practice to maintain pregnant opioid-dependent women with synthetic opioids and according to international guidelines, methadone is the recommended substance so far. However, a neonatal abstinence syndrome (NAS) of varying severity is observed in 60 - 80 % of the neonates with even a longer course of duration in comparison to the NAS after heroin consumption during pregnancy. NAS is characterised by tremor, irritability, hypertonicity, vomiting, sneezing, fever, poor suckling, and sometimes convulsions. Recent studies have investigated the safety and efficacy of other synthetic opioids like sublingual buprenorphine for the treatment of pregnant patients. We present a 22 year old opioid-dependent woman, who has been maintained continuously on buprenorphine for 3 years. During the treatment episode she delivered two healthy newborns and both did not show any symptoms of NAS. The maintenance therapy with buprenorphine proved safety and efficacy during pregnancy, the mother was free of continuous heroin abuse, verified through supervised urine-toxicology. The quantitative and qualitative difference in NAS may be explained by the partial mu-receptor agonist and kappa-antagonist receptor profile of buprenorphine compared to pure mu-agonist action of methadone or heroin.

Topics: Adult; Buprenorphine; Female; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Topics: Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Risk Factors; Treatment Outcome

Topics: Buprenorphine; Drug Approval; Female; Heroin Dependence; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; United States; United States Food and Drug Administration

Opioid maintenance agents such as methadone and slow-release morphine have provided beneficial effects in pregnant opioid-dependent women in both themselves and their child. However, one of the major drawbacks involved with these agents is that they cause an increase in the severity of neonatal abstinence syndrome (NAS) when compared to mothers using heroin. Consequently, a trial was performed to investigate the effects of buprenorphine use during pregnancy. A total of nine pregnant opioid-dependent women were transferred from either a mean daily dose of 39.7 mg methadone or 400 mg slow-release morphine to a mean daily dose of 8.1 mg buprenorphine. The buprenorphine-maintained patients were integrated into an already established outpatient maintenance treatment programme covering all aspects of prenatal and perinatal care. Results demonstrated that buprenorphine administration in opioid-dependent pregnant patients is efficacious and well tolerated. Babies born to buprenorphine-maintained patients had birthweight and Apgar scores within the normal range (2,500-4,500 g and 9-10, respectively) and no evidence of opioid-related NAS was observed. The results from this preliminary study indicate the potential for buprenorphine maintenance therapy in pregnant addicts, although further research is required to confirm this hypothesis.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

A pregnant woman who was addicted to heroin rapidly withdrew from illicit drugs after the onset of a 4 mg/day buprenorphine treatment. In the newborn's blood, urine, and meconium 20 hours after birth, high concentrations of buprenorphine and its metabolite norbuprenorphine were detected, with a higher buprenorphine/norbuprenorphine ratio than in adults, possibly as a consequence of immature hepatic function; no illicit drugs were found. The child had a weak withdrawal syndrome on the second day of life and recovered rapidly. The measured buprenorphine daily dose ingested by the newborn through mother's milk was very low (3.28 micrograms) and probably had little pharmacologic effect because no withdrawal signs could be noted when maternal feeding was later abruptly interrupted. Further investigations are required to determine whether buprenorphine can be considered to be a good alternative to methadone in the treatment of pregnant heroin addicts to prevent marked withdrawal syndromes in newborns.

Topics: Adult; Breast Feeding; Buprenorphine; Female; Heroin Dependence; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications