BACKGROUND-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.

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The aim of the present study was to estimate the prevalence of unintended pregnancy and its three subtypes (mistimed, unwanted, ambivalent) among opioid-abusing women. In the general population, 31–47% of pregnancies are unintended; data on unintended pregnancy in opioid- and other drug-abusing women are lacking. Pregnant opioid-abusing women (N=946) screened for possible enrollment in a multi-site randomized controlled trial comparing opioid maintenance medications completed a standardized interview assessing sociodemographic characteristics, current and past drug use, and pregnancy intention. Almost 9 of every 10 pregnancies were unintended (86%), with comparable percentages mistimed (34%), unwanted (27%), and ambivalent (26%). Irrespective of pregnancy intention, more than 90% of the total sample had a history of drug abuse treatment, averaging more than 3 treatment episodes. Interventions are sorely needed to address the extremely high rate of unintended pregnancy among opioid-abusing women. Drug treatment programs are likely to be an important setting for such interventions.

This article addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance, based on both research evidence and the collective clinical experience of the authors, which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, is provided to aid clinical decision making. The MOTHER project is a double-blind, double-dummy, flexible-dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the treatment of opioid dependence in pregnant women and their neonates. The article begins with a discussion of appropriate assessment during pregnancy and then addresses clinical management stages including maintenance medication selection, induction, and stabilization; opioid agonist medication management before, during, and after delivery; pain management; breast-feeding; and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed.

ObjeCtiveTo provide absolute and relative risk estimates of neonatal abstinence syndrome (NAS) based on duration and timing of prescription opioid use during pregnancy in the presence or absence of additional NAS risk factors of history of opioid misuse or dependence, misuse of other substances, non-opioid psychotropic drug use, and smoking.Design Observational cohort study.setting Medicaid data from 46 US states. PartiCiPantsPregnant women filling at least one prescription for an opioid analgesic at any time during pregnancy for whom opioid exposure characteristics including duration of therapy: short term (<30 days) or long term (≥30 days); timing of use: early use (only in the first two trimesters) or late use (extending into the third trimester); and cumulative dose (in morphine equivalent milligrams) were assessed.

Aims 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. Methods Within each outcome area, findings are summarized first for the 3 randomized controlled 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 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 physiologic 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. Conclusions Buprenorphine produces a less severe neonatal abstinence syndrome than methadone, but there is still a role for methadone in the treatment of opioid dependence during pregnancy.

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Objective-In utero exposure to drugs of abuse can lead to the Neonatal Abstinence Syndrome (NAS), 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. The primary objective of this study was to demonstrate the feasibility and to the extent possible in this sized study, the safety of sublingual buprenorphine in the treatment of NAS. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered.Methods-We conducted a randomized, open-label, active control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to sublingual buprenorphine 13.2-39 mcg/kg/day administered in three divided doses and thirteen to standard of care oral neonatal opium solution (NOS). Dose decisions were made using a modified Finnegan scoring system. Results-Sublingual buprenorphine was largely effective in controlling NAS. 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 receiving buprenorphine and one infant receiving standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for the NOS group was 32 compared to 22 days for the buprenorphine group. The mean length of stay for the NOS group was 38 days compared to 27 days for the buprenorphine group. Treatment with buprenorphine was well tolerated.Conclusions-Buprenorphine administered via the sublingual route is feasible and apparently safe, and may represent a novel treatment for NAS.