Safety of prenatal opioid analgesics: Do results differ between public health insurance beneficiary and population-based cohorts?

Background — Pregnant patients with particular types of health insurance may have distinct demographic and medical characteristics that have a biologic effect on associations between opioid analgesics and congenital anomalies (CA).

Methods — We followed 199,884 pregnant prescription beneficiaries in Ontario, Canada (1996–2018). Opioid analgesics dispensed in the first trimester and CA were identified from universal-access administrative health records. We estimated propensity score adjusted risk ratios (RR) between first trimester exposure and CA (any, major, minor, specific). RRs were compared to those published from an Ontario population-based cohort (N = 599,579, 2013–2018).

Results — 15,724 (7.9%) were exposed to first trimester opioid analgesics, mainly codeine (58.1%) or oxycodone (21.3%); CA prevalence in exposed was 3.1%. RRs in the beneficiary cohort appeared higher than the population-based cohort for any CA with hydromorphone (RR = 2.34, 95% CI: 1.65, 3.30) and oxycodone (RR = 1.73, 95% CI: 1.46, 2.05) and major CA with hydromorphone (RR = 2.74, 95% CI: 1.91, 3.94) and oxycodone (RR = 1.72, 95% CI: 1.42, 2.08). Other RRs that appeared higher in the beneficiary cohort included cardiovascular (codeine, oxycodone), gastrointestinal (oxycodone), musculoskeletal (any, hydromorphone, oxycodone), CNS (oxycodone), chromosomal (codeine), and neoplasm and tumor (oxycodone) anomalies. The beneficiary cohort had higher opioid doses, was younger, had lower socioeconomic status, and greater comorbidities.

Conclusions — Increased risks of CA after first trimester opioid analgesics were observed in low-income prescription beneficiaries, and some estimates were higher than a population-based cohort from the same setting. Biological differences associated with younger age, lower socioeconomic status and greater comorbidity may affect generalizability of results from pregnant low-income beneficiaries.