Abstract
Confounding may account for the apparently improved infant outcomes after prenatal exposure to buprenorphine versus methadone. We used Massachusetts Medicaid Analytic eXtract (MAX) data to identify a cohort of opioid-dependent mother-infant pairs (2006-2011), supplemented with confounder data from an external Boston, Massachusetts, cohort (2015-2016). Associations between prenatal buprenorphine exposure versus methadone exposure and infant outcomes in the MAX cohort were adjusted for measured MAX confounders and were additionally adjusted for unmeasured confounders with bias analysis using external cohort data. A total of 477 women in MAX were treated with methadone and 543 with buprenorphine. More buprenorphine users than methadone users were white and used psychotropic medications. After adjustment for MAX confounders, risk ratios among infants exposed to buprenorphine versus those exposed to methadone were 0.45 (95% confidence interval (CI): 0.34, 0.61) for preterm birth (birth at <37 weeks) and 0.75 (95% CI: 0.51, 1.11) for low birth weight for gestational age. The mean difference in infant hospitalization was -7.35 days (95% CI: -9.16, -5.55). After further adjustment with bias analysis, the risk ratios were 0.53 (95% CI: 0.39, 0.71) for preterm birth and 1.14 (95% CI: 0.77, 1.69) for low birth weight for gestational age, and the mean difference in infant hospitalization was -3.66 days (95% CI: -5.46, -1.87). External confounder data can be used to adjust for unmeasured confounding in studies of prenatal outcomes among women on opioid agonist therapy based on administrative databases.