buprenorphine and Premature-Birth

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

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

To assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder.. We searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid-dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random-effects models for each outcome with two or more studies.. Three RCTs (n = 223) and 15 cohort OBSs (n = 1923) met inclusion criteria. In meta-analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes.. Moderately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater harms.

Topics: Abnormalities, Drug-Induced; Analgesics, Opioid; Birth Weight; Buprenorphine; Female; Fetal Death; Fetal Development; Humans; Infant, Newborn; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Safety; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic; Sudden Infant Death

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

Opioid use disorder (OUD) has dramatically increased over the last few decades, with 11.5 million American misusing opioids in 2016. Untreated OUD in pregnancy is associated with unique adverse obstetric and perinatal outcomes including insufficient prenatal care, preterm birth (PTB), fetal growth restriction, fetal demise, and placental abruption . The mainstay treatment for OUD management in pregnancy is medication for opioid use disorder (MOUD) including methadone or buprenorphine. The association of PTB and opioid use in pregnancy has been described for over 50 years, and efforts to significantly eliminate this risk are challenged by the many confounding risks described above. When comparing rates of PTB in individuals with OUD on methadone vs buprenorphine. Buprenorphine has been associated with overall lower PTB than Methadone by almost 50 %.. Pregnancies complicated by opioid use disorder are at an increased risk for preterm birth, defined as delivery <37 weeks' gestation. Limited literature is available on the prevalence and risk factors for preterm birth in pregnancies complicated by opioid use disorder maintained on buprenorphine. Therefore, we sought to determine the rate of preterm birth and risk factors for preterm birth in this population.. We performed a retrospective cohort study of pregnant individuals with singleton gestations receiving buprenorphine for opioid use disorder, who delivered at a tertiary academic medical center between July 1, 2013 and June 30, 2018. Individuals who had at least 3 visits to our colocated clinic were included in the analysis. Patients were divided into 2 groups: the preterm group for patients who delivered at <37 weeks of gestation and the term group for those who delivered at ≥37 weeks of gestation. We defined "supplements to buprenorphine" to include any illicit drugs found on antepartum urine toxicology. Variables evaluated as potential risk factors for preterm birth included medical and infectious comorbidities and illicit polysubstance use.. The overall preterm birth rate in this cohort was 22.7% (115/507). There was a nonsignificant trend toward decrease in overall preterm birth and provider-initiated preterm birth rate over the study period. No differences were found between the groups in spontaneous preterm birth rate at <34 weeks of gestation. There were no differences between the groups in the use of tobacco or alcohol, number of prenatal visits, or gestational age when prenatal care started. Individuals with preterm birth in the index pregnancy were more likely to have a history of preterm birth than individuals with term delivery (73% vs 16%; P<.01). No medical or infectious comorbidity or any specific supplement increased the risk of preterm birth. Among individuals using 0, 1, 2, or 3 or more illicit supplements in addition to confirmed buprenorphine for opioid use disorder, the preterm birth rate was 27.4% (reference), 18.0% (P=.09), 18.1% (P=.44), and 15.8% (P=.77), respectively.. The preterm birth rate among individuals using buprenorphine for opioid use disorder (22.7%) is higher than the national average but lower than the reported preterm birth rate in individuals using methadone for the treatment of opioid use disorder. No medical or infectious comorbidity or use of additional illicit substances increased the risk of preterm birth.

Topics: Buprenorphine; Female; Humans; Infant, Newborn; Methadone; Opioid-Related Disorders; Placenta; Pregnancy; Premature Birth; Retrospective Studies; Risk Factors

Opioid agonist therapy is strongly recommended for pregnant persons with opioid use disorder. Buprenorphine may be associated with more favorable neonatal and maternal outcomes than methadone, but existing data are limited.. We conducted a cohort study involving pregnant persons who were enrolled in public insurance programs in the United States during the period from 2000 through 2018 in which we examined outcomes among those who received buprenorphine as compared with those who received methadone. Exposure to the two medications was assessed in early pregnancy (through gestational week 19), late pregnancy (gestational week 20 through the day before delivery), and the 30 days before delivery. Risk ratios for neonatal and maternal outcomes were adjusted for confounders with the use of propensity-score overlap weights.. The data source for the study consisted of 2,548,372 pregnancies that ended in live births. In early pregnancy, 10,704 pregnant persons were exposed to buprenorphine and 4387 to methadone. In late pregnancy, 11,272 were exposed to buprenorphine and 5056 to methadone (9976 and 4597, respectively, in the 30 days before delivery). Neonatal abstinence syndrome occurred in 52.0% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73; 95% confidence interval [CI], 0.71 to 0.75). Preterm birth occurred in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (adjusted relative risk, 0.58; 95% CI, 0.53 to 0.62); small size for gestational age in 12.1% and 15.3%, respectively (adjusted relative risk, 0.72; 95% CI, 0.66 to 0.80); and low birth weight in 8.3% and 14.9% (adjusted relative risk, 0.56; 95% CI, 0.50 to 0.63). Delivery by cesarean section occurred in 33.6% of pregnant persons exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (adjusted relative risk, 1.02; 95% CI, 0.97 to 1.08), and severe maternal complications developed in 3.3% and 3.5%, respectively (adjusted relative risk, 0.91; 95% CI, 0.74 to 1.13). Results of exposure in late pregnancy were consistent with results of exposure in early pregnancy.. The use of buprenorphine in pregnancy was associated with a lower risk of adverse neonatal outcomes than methadone use; however, the risk of adverse maternal outcomes was similar among persons who received buprenorphine and those who received methadone. (Funded by the National Institute on Drug Abuse.).

Topics: Buprenorphine; Cesarean Section; Cohort Studies; Female; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Live Birth; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; United States

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

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

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

Pregnant women with opioid use disorder (OUD) are at risk of overdose, infectious diseases, and inadequate prenatal care. Additional risks include adverse pregnancy and infant outcomes, such as preterm birth and neonatal abstinence syndrome. Management and treatment of OUD during pregnancy are associated with improved maternal and infant outcomes. Professional organizations, including the American College of Obstetricians and Gynecologists, recommend offering opioid agonist pharmacotherapy (

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Humans; Infant; Infant, Newborn; Opiate Substitution Treatment; Opioid-Related Disorders; Population Surveillance; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Treatment Outcome

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

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