Analgesic opioids in pregnancy and placental malperfusion-related disorders: a population-based cohort study.

Background: Analgesic opioid use in pregnancy could increase the risk of disorders related to placental malperfusion, but this relationship is incompletely characterized. We aimed to study the causal association between analgesic opioids in pregnancy and placental abruption, pre-eclampsia, preterm birth, and fetal growth restriction (FGR).

Methods: We conducted a population-based cohort study of pregnancies resulting in birth at ≥20 weeks of gestation between July 2013 and December 2019 in New South Wales, Australia. Linked data on pregnancy, births, medication dispensation, and health services were used. Opioid exposure was defined as at least one opioid dispensation from the last menstrual period to birth. We stratified analyses by exposure in early (≤20 weeks) and/or late (>20 weeks) pregnancy and opioid type by using non-exposed pregnancies as a comparator. We estimated risks by using Cox proportional-hazards models and time-varying exposure, adjusting for demographics, comorbidities, and other medications.

Results: Among 509 971 births, 32 266 (6.3%) had an opioid dispensation. We observed modestly increased risks with any opioid exposure for placental abruption [adjusted hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.06-1.41] and preterm birth (adjusted HR 1.23, 95% CI 1.18-1.28), but not for pre-eclampsia (adjusted HR 1.06, 95% CI 0.99-1.13) or FGR (adjusted HR 0.95, 95% CI 0.88-1.02). Risks of abruption were the most elevated when exposure occurred in both early and late pregnancy (adjusted HR 1.76, 95% CI 1.30-2.40) and for preterm birth when exposure occurred in late-only pregnancy (adjusted HR 1.36, 95% CI 1.27-1.45). Monotherapy with both codeine and oxycodone was associated with elevated risks of abruption and preterm birth.

Conclusion: In this population-based cohort study, we observed modestly increased risks of preterm birth and placental abruption after analgesic opioid use in pregnancy, driven by codeine and oxycodone-the two most frequently used opioids.