Opioid Analgesic Exposure and Mental Health Disorders During Pregnancy: Exploring Their Independent and Joint Association With Adverse Birth Outcomes

Background Opioid use, depression and anxiety during pregnancy are independently associated with adverse perinatal outcomes, but their joint associations are less understood. Objective To examine the independent and joint associations, including interaction, of prenatal opioid analgesic exposure and maternal anxiety and depression with gestational age, preterm birth and birthweight‐for‐gestational‐age percentile. Methods We conducted a retrospective cohort study of 230,810 Wisconsin Medicaid singleton live births (2011–2019), linking Medicaid with birth record data. Multivariable regression models adjusted for maternal sociodemographics, comorbidities and year of delivery. Interaction was assessed using cross‐product terms and the relative excess risk due to interaction (RERI). Exposure duration was evaluated for dose–response effects. Results Prenatal anxiety, depression and opioid analgesic exposure were independently associated with modest reductions in gestational age and birthweight‐for‐gestational‐age percentile, and increased risk for preterm birth. There was no evidence of interaction between opioid analgesic exposure and anxiety or depression. Individuals with ≥ 90 days of opioid exposure and anxiety or depression had the largest deficits in gestational age (anxiety: −0.29 weeks, 95% confidence interval [CI] −0.49, −0.10; depression: −0.34 weeks, 95% CI −0.53, −0.15) and birthweight‐for‐gestational‐age percentile (anxiety: −4.14, 95% CI −6.63, −1.64; depression: −3.27, 95% CI −5.90, −0.64). For preterm birth, ≥ 90 days of opioid exposure was associated with increased risk among individuals with depression (RR 1.35, 95% CI 1.12, 1.63), whereas among those with anxiety, the association was strongest at 30–89 days of opioid exposure (RR 1.17, 95% CI 1.05, 1.30) and was not associated at ≥ 90 days (RR 1.18, 95% CI 0.97, 1.44). Conclusions Maternal anxiety or depression and prenatal opioid analgesic exposure were each associated with modest but consistent reductions in gestational age and birthweight‐for‐gestational‐age. Individuals with co‐occurring mental health conditions and prolonged opioid exposure experienced the greatest reductions, although there was no evidence of statistical interaction.