Prenatal Exposure to Buprenorphine or Methadone Is Not Clearly Associated with Children’s Cognitive Outcomes

Buprenorphine and methadone are associated with improved substance use, pregnancy, and infant outcomes and are the standard of care for pregnant persons with opioid use disorder (OUD). Mixed results from retrospective cohort studies have suggested a potential negative association between prenatal exposure to buprenorphine or methadone and longer-term cognitive outcomes. This meta-analysis pooled data from 16 retrospective studies to examine this association while considering important potential confounding variables, including maternal education and employment and other substance exposure.

• Maternal characteristics associated with cognitive outcomes in children were highly imbalanced between groups that were exposed to and not exposed to buprenorphine and methadone:
  • 67% of exposed versus 34% not exposed had less than high school education.
  • 19% of exposed versus 67% not exposed were employed.
  • 89% of exposed versus 40% not exposed had tobacco use.
• Pooled results suggest that if children were selected at random from exposed and unexposed groups, 66% of the time the child exposed to buprenorphine or methadone would have lower cognitive development scores.
• Cognitive development score differences did not persist when restricting the sample to studies balanced on tobacco exposure.

Comments: Prenatal exposure to buprenorphine or methadone is not clearly associated with cognitive outcomes when accounting for potential confounding. Furthermore, the comparison group in these cohort studies was not restricted to mothers with OUD, questioning the clinical relevance of these studies. A more appropriate comparison group in future studies would be children of mothers with OUD during pregnancy who had not been treated with methadone or buprenorphine. Buprenorphine and methadone should be offered to all pregnant persons with OUD.

Marc R. Larochelle, MD, MPH

Reference: Nelson LF, Yocum VK, Patel KD, et al. Cognitive outcomes of young children after prenatal exposure to medications for opioid use disorder: a systematic review and meta-analysis. JAMA Netw Open. 2020;3(3):e201195.