Outcomes of Neonates Exposed to Buprenorphine versus Methadone in Utero: A Systematic Review and Meta-Analysis of Safety in the Fetus and Neonate

Abstract

We assessed the prevalence of neonatal abstinence syndrome (NAS) and fetal growth outcomes in neonates exposed to methadone compared to buprenorphine in utero. Three authors assessed the titles and abstracts of all potentially eligible studies. The selection criteria were randomized controlled trials and observational cohort studies from January 2000 to January 2020 which indexed and reported original data for occurrence of NAS and fetal growth outcomes in pregnant people who received methadone vs. buprenorphine treatment. The quality and possible bias of each study was assessed using the Cochrane-risk-of-bias tool. Data were pooled to compare the occurrence of NAS and fetal growth restriction among women who received methadone vs. buprenorphine treatment. Of the 106 articles screened, 1 randomized controlled trial and 5 observational cohort studies including 2041 pregnancies fulfilled the inclusion criteria. Buprenorphine is associated with less NAS and improved growth outcomes compared to methadone. (OR = 0.515; p-value < 0.001). Compared to methadone, buprenorphine is associated with less adverse neonatal outcomes in terms of gestational age at birth, birthweight, and head circumference. With the prevalence of NAS continuing to rise, this study adds to the expanding academic research aimed at creating safer treatment protocols.

Keywords

• buprenorphine
• methadone
• fetus
• neonatal abstinence syndrome
• opioid use disorder
• pregnancy