A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

Abstract

BACKGROUNDUntreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy.OBJECTIVEThe aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden.METHODSPregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population.RESULTSA total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father.CONCLUSIONSAn increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders.

British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017

“…Methadone in pregnancy is associated with improved antenatal care, reduced maternal morbidity and improved neonatal outcomes (Burns et al, 2007) although a recent study found low birth weight in those on treatment compared to general population (Mactier et al, 2014). There are less data regarding buprenorphine in pregnancy, though evidence is increasing Minozzi et al, 2013b;Wurst et al, 2016). In a recent meta-analysis comparing pregnancy outcomes, buprenorphine was associated with around half the risk of preterm birth and with greater birth weight (around 10g) compared with methadone .…”

Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women

“…Infants exhibited NAS in 6.6% of women exposed to buprenorphine vs 55% of those exposed to methadone . Another population‐based study in Sweden found similar results when they evaluated 746,257 pregnancies and identified 176 women exposed to buprenorphine or buprenorphine and naloxone combination, and 52 exposed to methadone . This study calculated a PR compared to the general population and also found that women exposed to buprenorphine versus methadone had a lower likelihood of preterm birth (PR 1.31 [95% CI 0.79–2.16] vs 2.21 [95% CI 1.11–4.41]), any congenital malformation (PR 0.76 [95% CI 0.41–1.38] vs 2.05 [95% CI 1.08–3.87]), and a nonsignificant trend toward low birth weight (PR 1.42 [95% CI 0.80–2.51] vs 1.74 [95% CI 0.68–4.47]) .…”

“…Three prospective RCTs and eight prospective, observational, cohort, controlled studies comparing buprenorphine and methadone were included. In addition, four recent retrospective studies published in the past 2 years evaluating methadone versus buprenorphine or buprenorphine and naloxone combination in opioid‐addicted women were also included . There are very limited human data evaluating naltrexone use for treatment of opioid‐dependent pregnant women, with only two case studies identified and included in this article …”

“…This study calculated a PR compared to the general population and also found that women exposed to buprenorphine versus methadone had a lower likelihood of preterm birth (PR 1.31 [95% CI 0.79–2.16] vs 2.21 [95% CI 1.11–4.41]), any congenital malformation (PR 0.76 [95% CI 0.41–1.38] vs 2.05 [95% CI 1.08–3.87]), and a nonsignificant trend toward low birth weight (PR 1.42 [95% CI 0.80–2.51] vs 1.74 [95% CI 0.68–4.47]) . This study also found a lower rate of infant NAS with buprenorphine compared to methadone (PR 1358 [95% CI 987–1868] vs 2242 [95% CI 1525–3295]) . Last, a smaller retrospective study in North Carolina identified 31 women exposed to buprenorphine and naloxone combination and 31 exposed to methadone .…”

“…In addition, four recent retrospective studies published in the past 2 years evaluating methadone versus buprenorphine or buprenorphine and naloxone combination in opioid-addicted women were also included. [35][36][37][38] There are very limited human data evaluating naltrexone use for treatment of opioid-dependent pregnant women, with only two case studies identified and included in this article. 39,40 One study was a single-site, randomized, double-dummy, double-blind, flexible dosing comparison study evaluating 18 women who were assigned either methadone or buprenorphine during weeks 24-29 of gestation.…”