Objective: To determine whether prenatal cannabis use alone increases the likelihood of fetal and neonatal morbidity and mortality. Study Design: We searched bibliographic databases, such as PubMed, Embase, Scopus, Cochrane reviews, PsycInfo, MEDLINE, Clinicaltrials.gov, and Google Scholar from inception through February 14, 2022. Cohort or case-control studies with prespecified fetal or neonatal outcomes in pregnancies with prenatal cannabis use. Primary outcomes were preterm birth (PTB; <37 weeks of gestation), small-for-gestational-age (SGA), birthweight (grams), and perinatal mortality. Two independent reviewers screened studies. Studies were extracted by one reviewer and confirmed by a second using a predefined template. Risk of bias assessment of studies, using the Newcastle-Ottawa Quality Assessment Scale, and Grading of Recommendations Assessment, Development, and Evaluation for evaluating the certainty of evidence for select outcomes were performed by two independent reviewers with disagreements resolved by a third. Random effects meta-analyses were conducted, using adjusted and unadjusted effect estimates, to compare groups according to prenatal exposure to cannabis use status. Results: Fifty-three studies were included. Except for birthweight, unadjusted and adjusted meta-analyses had similar results. We found very-low- to low-certainty evidence that cannabis use during pregnancy was significantly associated with greater odds of PTB (adjusted odds ratio [aOR], 1.42; 95% confidence interval [CI], 1.19 to 1.69; I2, 93%; p=0.0001), SGA (aOR, 1.76; 95% CI, 1.52 to 2.05; I2, 86%; p<0.0001), and perinatal mortality (aOR, 1.5; 95% CI, 1.39 to 1.62; I2, 0%; p<0.0001), but not significantly different for birthweight (mean difference, -40.69 g; 95% CI, -124.22 to 42.83; I2, 85%; p=0.29). Because of substantial heterogeneity, we also conducted a narrative synthesis and found comparable results to meta-analyses. Conclusion: Prenatal cannabis use was associated with greater odds of PTB, SGA, and perinatal mortality even after accounting for prenatal tobacco use. However, our confidence in these findings is limited. Limitations of most existing studies was the failure to not include timing or quantity of cannabis use. This review can help guide health care providers with counseling, management, and addressing the limited existing safety data. Protocol Registration: PROSPERO CRD42020172343.
Keywords: cannabis; marijuana; perinatal mortality; prenatal cannabis exposure; preterm birth; small for gestational age.