Meta-analysis linked prenatal cannabis to small increased risk of birth defects

Pooling data from 18 cohort and 18 case-control studies (>19 million subjects), prenatal cannabis exposure was associated with any birth defect (pooled ORs 1.25-1.33). ORs were also elevated for cardiovascular, gastrointestinal, nervous system, genitourinary, and musculoskeletal defects but not orofacial defects. Effects were smaller and less often significant in adjusted analyses.

Review and critical appraisal of two meta-analyses pooling cohort and case-control studies of prenatal cannabis exposure and birth defects. Discusses both unadjusted and adjusted estimates, cumulative meta-analyses, and methodological strengths and shortcomings.

5-10% of US pregnancies are exposed to cannabis, with highest use in the first trimester when organs are forming. Even a small increase in birth defect risk could affect a meaningful number of pregnancies at the population level.

This analysis also serves as a methodological teaching tool, highlighting how pooling different study designs and repeated representation of samples in forest plots can affect meta-analysis results. The cumulative meta-analysis showed when findings became consistently significant over time.

The meta-analysis pooled cohort and case-control ORs together, which is methodologically problematic. Some forest plots included the same sample multiple times. Adjusted analyses showed weaker associations. First-trimester exposure was not always distinguishable from overall pregnancy exposure.