Association of Maternal Opioid Use in Pregnancy With Adverse Perinatal Outcomes in Ontario, Canada, From 2012 to 2018.

Importance: A recent epidemic of opioid abuse has been described in many communities, although population-based data on trends in use in pregnancy and perinatal outcomes after in utero exposure remain limited. Objective: To assess trends in prenatal opioid use and the potential association between prenatal opioid use and preterm birth and adverse perinatal outcomes. Design, Setting, and Participants: This population-based retrospective cohort study covered live births and stillbirths among adolescents and women 15 years and older from April 1, 2012, to March 31, 2018, in Ontario, Canada. Data were analyzed from July 29 to October 15, 2019. Exposures: Any opioid use in pregnancy, ascertained through self-reporting and routine prenatal care. Main Outcome and Measures: The primary outcome was preterm birth before a gestational age of 37 weeks. Separate indicators for birth occurring at gestational ages of 34 to 36 weeks (plus 6 to 7 days; late preterm), 32 to 33 weeks (plus 6 to 7 days), 28 to 31 weeks (plus 6 to 7 days), and less than 28 weeks (very preterm birth). Secondary outcomes included small for gestational age, stillbirth, transfer to neonatal intensive care, and 5-minute Apgar score. Coarsened exact matching techniques and Poisson regression models were used to estimate the risk difference and relative risk (RR) of outcomes associated with cannabis exposure to control for confounding. Results: Among 710 911 women included in the analytic sample (mean [SD] age, 30.4 [5.3] years), 8059 used opioids (1.1%), with prevalence decreasing from 1.31% (95% CI, 1.25%-1.38%) in fiscal year 2012-2013 to 1.05% (95% CI, 0.99%-1.11%) in fiscal year 2017-2018 (P < .001 for trend). Use was highest among women in the lowest quintile of area-level income (2.36% vs 0.56% in the highest quintile; RR, 3.86; 95% CI, 3.58-4.15) and did not decrease over time in this group (from 2.63% [95% CI, 2.41%-2.87%] in 2012-2013 to 2.35% [95% CI, 2.14%-2.58%] in 2017-2018; P = .23 for trend). The crude rate of preterm birth at a gestational age of less than 37 weeks was 14.0% (n = 1127) among women with reported use in pregnancy and 6.0% (n = 42 226) among women who did not use opioids in the unmatched cohort. The adjusted RR for preterm birth before a gestational age of 37 weeks was 1.63 (95% CI, 1.52-1.75) among opioid users compared with nonusers and 1.77 (95% CI, 1.35-2.31) for preterm birth before 32 weeks. Among newborns, risk for neonatal intensive care was 40.5% with perinatal exposure to opioids compared with 13.9% in unexposed infants (RR, 2.91; 95% CI, 2.80-3.03). Conclusions and Relevance: Rates of opioid use in pregnancy have declined in recent years, although use remains significantly higher among lower-income women. In this large population-based cohort, opioid use in pregnancy was associated with an increased risk of preterm birth and admission to a neonatal intensive care unit.