Association Between Self-reported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes
Daniel J. Corsi, PhD; LauraWalsh, MSc; DeborahWeiss, PhD; Helen Hsu, MD; Darine El-Chaar, MD;
Steven Hawken, PhD; Deshayne B. Fell, PhD; MarkWalker,MD
JAMA, Published online June 18, 2019.
Question Is there an association between prenatal cannabis exposure and maternal, perinatal, and neonatal outcomes?
Findings In this retrospective cohort study that included 661 617 pregnancies and 9427 reported cannabis users, the rate of preterm birth among reported cannabis users was 12% vs 6% in nonusers, a statistically significant difference.
Meaning Reported cannabis use in pregnancy was associated with significant increases in the rate of preterm birth following adjustment for confounding.
IMPORTANCE : Recent evidence suggests that cannabis use during pregnancy is increasing, although population-based data about perinatal outcomes following in utero exposure remain limited.
OBJECTIVE : To assess whether there are associations between self-reported prenatal cannabis use and adverse maternal and perinatal outcomes.
DESIGN, SETTING, AND PARTICIPANTS : Population-based retrospective cohort study covering live births and stillbirths among women aged 15 years and older in Ontario, Canada, between April 2012 and December 2017.
EXPOSURES : Self-reported cannabis exposure in pregnancy was ascertained through routine
MAIN OUTCOMES AND MEASURES : The primary outcomewas preterm birth before 37weeks’ gestation. Indicators were defined for birth occurring at 34 to 36 6/7 weeks’ gestation (late preterm), 32 to 33 6/7 weeks’ gestation, 28 to 31 6/7 weeks’ gestation, and less than 28 weeks’ gestation (very preterm birth). Ten secondary outcomes were examined including small for gestational age, placental abruption, 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 (RD) and relative risk (RR) of outcomes associated with cannabis exposure and control for confounding.
RESULTS : In a cohort of 661 617 women, the mean gestational age was 39.3 weeks and 51%of infants were male. Mothers had a mean age of 30.4 years and 9427 (1.4%) reported cannabis use during pregnancy. Imbalance in measured maternal obstetrical and sociodemographic characteristics between reported cannabis users and nonusers was attenuated using matching, yielding a sample of 5639 reported users and 92 873 nonusers. The crude rate of preterm birth less than 37 weeks’ gestation was 6.1%among women who did not report cannabis use and 12.0% among those reporting use in the unmatched cohort (RD, 5.88% [95%CI, 5.22%-6.54%]). In the matched cohort, reported cannabis exposure was significantly associated with an RD of 2.98%(95%CI, 2.63%-3.34%) and an RR of 1.41 (95% CI, 1.36-1.47) for preterm birth. Compared with no reported use, cannabis exposure was significantly associated with greater frequency of small for gestational age (third percentile, 6.1% vs 4.0%; RR, 1.53 [95%CI, 1.45-1.61]), placental abruption (1.6%vs 0.9%; RR, 1.72 [95% CI, 1.54-1.92]), transfer to neonatal intensive care (19.3%vs 13.8%; RR, 1.40 [95%CI, 1.36-1.44]), and 5-minute Apgar score less than 4 (1.1% vs 0.9%; RR, 1.28 [95%CI, 1.13-1.45]).
CONCLUSIONS AND RELEVANCE : Among pregnantwomen in Ontario, Canada, reported
cannabis use was significantly associated with an increased risk of preterm birth. Findings may be limited by residual confounding.
Cannabis is commonly used during pregnancy, and in the United States, the prevalence was 7% in 2016 based on self-reports and toxicology.1 InCanada,data suggest that the prevalence of cannabis use has increasedamongyoungmen and women aged 15 to 24 years from 21.6% to 26.9% between 2011 and 2017,2 and among pregnant women aged 15 to 24 years from 4.9% to 6.5%between 2012 and 2017.3 Overall, cannabis use during pregnancy was reported by about2%among mothers in Ontario, Canada, in 2017.3 With recent legalization in Canada and the United States, coupled with evidence of the potential medical benefits of the cannabinoids cannabidiol and tetrahydrocannabinol ( THC), it is anticipated that cannabis use may further increase including among pregnant women.4,5
Cannabinoids can readily cross the placenta and enter the fetal bloodstream.6 Animal studies suggest that THC exposure during pregnancy can disrupt the complex fetal endogenous cannabinoid signaling system and may be associated with adverse pregnancy outcomes.7 Clinical studies have shown associations between prenatal cannabis consumption and incidence of stillbirth, lower birth weight, small for gestational age (SGA), and increased admission to neonatal intensive care compared with infants whose mothers did not use cannabis.8-10 Previous studies have varied in methodology and treatment of confounding factors, limiting the ability to identify an independent association of cannabis on pregnancy outcomes.11 A systematic review did not find maternal cannabis use to be independently associated with low birth weight or preterm delivery after adjusting for tobacco use.12
Using a comprehensive perinatal registry in the province of Ontario, the aim was to assess whether there are associations between reported prenatal cannabis use and maternal, perinatal, and neonatal outcomes.