Maternal Opioid-related Diagnosis in Pregnancy and Risk of Adverse Perinatal Outcomes

Objectives: To examine the associations between opioid-related diagnoses in pregnancy and maternal and neonatal outcomes in a large, diverse population-based cohort. Methods: This is a retrospective cohort study of California linked hospital discharge-vital statistics data from 2008 to 2020. We included singleton pregnancies with gestational age of 23–42 weeks. Data analysis was completed on May 17, 2025. Opioid-related diagnosis, maternal morbidity, and neonatal outcomes were identified using ICD-9 and ICD-10 codes from hospital discharge data. χ 2 and multivariable Poisson regression models with robust variance estimator were utilized for statistical analyses. Results: A total of 5,546,744 pregnancies met the inclusion criteria, and 13,749 (0.25%) had an opioid-related diagnosis. The prevalence of an opioid-related diagnosis increased from 0.14% in 2008 to 0.33% in 2020 ( P < 0.001) in pregnant individuals. Individuals with opioid-related diagnoses were associated with a higher risk of hypertensive disease (aRR = 1.23; 95% CI: 1.18–1.29), severe maternal morbidity (SMM; aRR = 1.84, 95% CI: 1.68–2.01), nontransfusion SMM (aRR = 2.16; 95% 1.87–2.49) and blood transfusion (aRR = 1.77; 95% 1.60–1.96). Neonates of individuals with an opioid-related diagnosis had higher risk of infant death (aRR = 1.72, 95% CI: 1.44–2.05), preterm birth <37 weeks (aRR = 1.71; 95% CI: 1.64–1.77), NICU admission (aRR = 2.80, 95% CI: 2.74–2.86), respiratory distress syndrome (aRR = 2.40, 95% CI: 2.28–2.53), and neonatal abstinence syndrome (aRR = 70.18, 95% CI: 64.34–76.56). Conclusions: Over the past decade, rates of an opioid-related diagnosis in pregnant individuals have more than doubled. In this large, diverse, population-based cohort study, a prenatal opioid-related diagnosis was associated with a significantly increased risk of maternal and neonatal morbidity.