naloxone and Neonatal-Abstinence-Syndrome

Topics: Female; GABA Modulators; Humans; Infant, Newborn; Naloxone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opium; Parasympatholytics; Phenobarbital; Pregnancy

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

Neonatal abstinence syndrome (NAS) is a significant problem. Opioid withdrawal induces oxidative stress and disrupts glutamate and glutathione homeostasis. We hypothesized that N-acetylcysteine (NAC) administered during acute opioid withdrawal in neonatal rats would decrease withdrawal behaviors and normalize CNS glutathione and glutamate.. Osmotic minipumps with methadone (opioid dependent, OD) and saline (Sham) were implanted into Sprague Dawley dams 7 days prior to delivery. Pups were randomized to receive either naloxone plus saline or NAC (50-100 mg/kg), administered on postnatal day (PND) 7. We performed MR spectroscopy on PND6-7 before, 30 min, and 120 min after withdrawal. On PND7, we assessed withdrawal behaviors for 90 min after naloxone administration and summed scores during peak withdrawal period.. In antenatal OD, NAC maintains CNS glutathione and mitigates acute opioid withdrawal in neonatal rats. This is the first study to demonstrate acute opioid withdrawal neurochemical changes in vivo in neonatal OD. NAC is a potential novel treatment for NAS.

Topics: Acetylcysteine; Analgesics, Opioid; Animals; Animals, Newborn; Behavior, Animal; Central Nervous System; Female; Glutamic Acid; Glutathione; Magnetic Resonance Spectroscopy; Maternal Exposure; Naloxone; Neonatal Abstinence Syndrome; Osmosis; Oxidative Stress; Pregnancy; Pregnancy, Animal; Rats; Rats, Sprague-Dawley

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

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

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

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

Treatment of developing rat pups with morphine (MOR) causes the development of physical dependence, but the relationship of the withdrawal syndrome to the duration/intensity of treatment has not been described.. The purpose of the present study was to characterize the emergence of various behavioral components of withdrawal in neonatal rats, and to develop a useful measure of overall intensity of withdrawal (OIW).. Rat pups were treated with morphine (MOR) (20 mg/kg, SC, b.i.d.) for 0-5 days. On postnatal day 10 (P10), animals received saline (SAL) or a challenge dose of MOR (25 mg/kg). Withdrawal was precipitated with naloxone HCl (NAL) (0.1, 0.5 or 2.5 mg/kg) 2 h after the MOR injection, and behaviors were quantitated for 10 min. To investigate the ability of clonidine HCl (CLON) to suppress withdrawal, pups were treated for 0 or 5 days with MOR, given a MOR challenge and either SAL or CLON (0.2 mg/kg), followed by SAL or NAL (2.5 mg/kg, SC). To evaluate endocrine components of withdrawal, growth hormone responses to withdrawal were examined.. The OIW and NAL-induced GH suppression increased with increasing NAL dose and duration of morphine treatment. However, individual behaviors showed differing patterns of expression. Clonidine decreased the severity of tremor and reduced the OIW.. These results demonstrate that the intensity of neonatal opiate withdrawal is related to the duration and intensity of treatment. The profile of observed withdrawal behaviors may reflect the involvement of the noradrenergic system.

Topics: Animals; Animals, Newborn; Female; Growth Hormone; Humans; Infant, Newborn; Male; Motor Activity; Naloxone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Rats; Rats, Sprague-Dawley; Reaction Time; Time Factors; Vocalization, Animal

The cases of two children with congenital heart disease and severe opioid dependency who underwent ultrarapid opioid detoxification are presented. This technique entails rapid opioid reversal with the opioid antagonist naloxone while under general anesthesia. The procedures were not technically difficult to perform and both children were successfully detoxified at the end of the procedure. In the weeks following the procedure, the first child exhibited accelerated neurodevelopment. Ultrarapid opioid detoxification is possible in children and may have a neurodevelopmental advantage over a prolonged wean.

Topics: Analgesics, Opioid; Down Syndrome; Heart Defects, Congenital; Humans; Inactivation, Metabolic; Infant; Infant, Newborn; Male; Naloxone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

Maternal drug use during pregnancy may result in neonatal withdrawal. This statement presents current information about the clinical presentation, differential diagnosis, therapeutic options, and outcome for the offspring associated with intrauterine drug exposure.

Topics: Diagnosis, Differential; Humans; Infant, Newborn; Naloxone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Prognosis

Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the alpha 2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.

Topics: Adrenergic alpha-Agonists; Animals; Animals, Newborn; Brain; Clonidine; Humans; Infant, Newborn; Methoxyhydroxyphenylglycol; Naloxone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Neurologic Examination; Norepinephrine; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley

Topics: Female; Humans; Infant, Newborn; Naloxone; Neonatal Abstinence Syndrome; Opium; Pregnancy; Seizures; Time Factors