3 - Early pregnancy cannabis exposure and adverse pregnancy outcomes

The endocannabinoid system regulates placental implantation. Thus, exogenous cannabis may interfere with this process. Our objective was to evaluate the relationship between early pregnancy use and placentally-mediated adverse pregnancy outcomes.

Study Design:

Ancillary of the Monitoring Nulliparous Mothers-To-Be (nuMoM2b) study. Participants from 8 U.S. medical centers with frozen stored urine samples from the initial study visit (6-14 weeks’ gestation) and abstracted pregnancy outcome data were included. Exposure to cannabis was ascertained by urine immunoassay for 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH); positive results were confirmed with liquid chromatography tandem mass spectrometry (cutoff of 15 THC-COOH ng/mL). Our primary composite outcome included small for gestational age, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy. The primary endpoint analysis was performed using propensity score weighting, with weights computed to estimate the average effect of cannabis exposure among exposed participants.  Multiple imputation was used for missing data. In sensitivity analyses, we performed modeling without multiple imputation, and we considered both a minimal and extended list of covariates. All models adjusted for tobacco exposure ascertained by urine cotinine levels and other drugs.

Results:

9,257 of 10,038 nuMoM2b participants were included and 540 (5.8%) were exposed to cannabis. Baseline characteristics are in Table. The primary composite outcome occurred in 27.4% of the cannabis exposed group and 18.1% of the unexposed group (p < 0.001). In the propensity weight analyses, cannabis exposure was associated with the primary composite outcome (Figure). The association was robust to multiple sensitivity analyses with covariates including demographics, tobacco and other drug use, medical comorbidities, and psychosocial stress (Figure).

Conclusion:

In a large, diverse multicenter cohort with cannabis use ascertained by biological sampling, early pregnancy use was associated with adverse pregnancy outcomes that are mediated by the placenta.