The Impact of Opioid, Opioid Agonist Therapy, and Cannabis Exposure on Fetal Growth: A Population-Based Cohort Study

Objectives. The primary objective is to determine the extent to which fetal growth profiles in opioid and opioid agonist (OAT) exposed pregnancies are influenced by cannabis exposure. Secondary objectives are to examine differences in fetal and neonatal morbidity and mortality. Design. Population-based cohort study. Setting. Ontario, Canada, in a public healthcare system. Participants. All live/stillborn births between April 1st, 2013, and March 31st, 2021. Exposures. Substance exposure in pregnancy, including opioids, opioid agonist therapy, cannabis, and nicotine. Main Outcome Measures. Primary outcome measures included incidence of small for gestational age (<3rd and <10th percentile for sex) and intrauterine growth restriction. Secondary outcome measures included incidence of stillbirth, severe neonatal morbidity (SNM), neonatal mortality, and neonatal abstinence syndrome (NAS). Results. 959,731 births are included with exposures classified as 864,508 (88.0%) no substance, 73,815 (7.7%) nicotine, 23,003 (2.4%) cannabis, 7,694 (0.8%) opioid, and 5,353 (0.6%) OAT. Cannabis co-exposure was reported in 1 out of every 6 opioid and/or OAT exposed births. The observed proportions of SGA and IUGR were approximately doubled across substance-exposed groups compared with the no substance exposure group. In adjusted analyses, cannabis exposure alone was associated with an 84% increased risk of IUGR, compared with 14% for opioid exposure alone and 60% for OAT exposure alone. SNM was observed in 7.2% of no substance exposure neonates, compared to 13.9% and 14.2% of opioid and OAT exposed neonates, respectively. NAS was diagnosed in 70.6% of all OAT exposed neonates, compared to 34.3% of all opioid exposed neonates. Risks for all outcomes across all cannabis co-exposure groups were significantly elevated relative to the no substance exposure group, with estimates ranging from 43% to 107% increased risk. Conclusions. Prenatal co-exposure to opioid and/or OAT along with cannabis appears to place infants at the highest risk. Isolated cannabis use has similar, if not more significant, impacts on fetal growth as opioid and/or OAT use. This information may serve as an important starting point in the design of effective harm reduction strategies in this patient population.