The Impact of Opioid, Opioid Agonist Therapy, and Cannabis Exposure on Fetal Growth: A Population-Based Cohort Study
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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 1 st , 2013, and March 31 st , 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 (<3 rd and <10 th 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.
Tweetable abstract
Prenatal co-exposure to cannabis and opioid and/or opioid agonist therapy (OAT) use places infants at increased risk for impaired fetal growth and severe neonatal morbidity. Isolated cannabis use in pregnancy has similar, if not greater, impacts on fetal growth than opioid and/or OAT use.
Summary Boxes
Section 1: What is already known on this topic
Across North America, rates of opioid exposure during pregnancy range from 1.1-42%. Multi-substance use is common, with concurrent cannabis exposure estimated at 36-75% among opioid users. Opioid use in pregnancy is associated with altered fetal growth, including low birthweight and small for gestational age (SGA) infants. Cannabis use in pregnancy is likewise associated with compromised fetal and neonatal growth, along with neurocognitive developmental deficits in offspring. Despite these known risks in isolation, little is known about the impact of co-use, which is concerning given the high rates of concurrent substance exposure.
Section 2: What this study adds
This study demonstrates that babies exposed to cannabis, opioids and/or OAT in pregnancy are more likely to experience complications, including failure to reach ideal growth potential, stillbirth, difficulties adapting to life after birth, readmission to hospital within 42 days of delivery, and neonatal death. Prenatal cannabis co-exposure with opioid and/or OAT places infants at the highest risk. Isolated cannabis use has similar, if not greater, impacts on fetal growth than isolated opioid or OAT use, significantly increasing the risks of impaired fetal growth (including fetal growth restriction (FGR) and SGA) and severe neonatal morbidity (SNM).
