Invited Commentary: A Novel Strategy for Addressing Unmeasured Confounding When Comparing Opioid Agonist Therapies in Pregnancy.

Opioid addiction in pregnancy is a growing concern that has recently received a great deal of attention. When comparing recommended opioid agonist therapies, many currently published studies guiding practice may have been affected by unmeasured confounding by indication. Populations of women who receive methadone are generally different from those treated with buprenorphine. Women treated with methadone frequently have more severe and uncontrolled addiction than buprenorphine-treated patients; however, these factors are typically unmeasured or unavailable in large observational data sets. Consequently, findings of superior perinatal outcomes with buprenorphine may in truth be a result of an overall healthier profile of women taking this medication. In this issue of the Journal, Brogly et al. (Am J Epidemiol. 2018;187(6):1153-1161) describe an approach utilizing detailed data from an external cohort (n = 113) to account for confounding by indication in a larger Medicaid population (n = 1,020) in order to more accurately compare opioid agonist therapies in pregnancy. They found that the decreases in risk of preterm birth and length of infant hospitalization associated with buprenorphine as compared with methadone were attenuated after accounting for the additional confounding. Brogly et al. should be commended for providing a novel method with which to address this bias in future studies.