Birth outcomes following intrauterine exposure to electronic nicotine delivery systems: A systematic review and meta-analysis

Abstract Introduction Despite Electronic Nicotine Delivery Systems (ENDS) being used for smoking cessation during pregnancy, the relative consequences are still unclear. Here, we systematically reviewed and meta-analyzed birth outcomes associated with ENDS use. Methods This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. OVID (MEDLINE, EMBASE, PsycINFO) and PubMed databases were searched from inception until August 2025, for studies comparing outcomes from in utero exclusive ENDS exposure to non-exposed, exclusive nicotine replacement therapy exposed, or exclusive combustible cigarette (CC) exposed neonates. Results We included k=22 studies with k=10 independent samples. In ENDS-exposed vs non-exposed births there were significantly greater odds of preterm birth (k=3; moderate confidence) but not small-for-gestational age (SGA; k=3; low confidence); these findings were less robust to sensitivity analysis. Additionally, there was no significant difference in SGA (k=3; moderate confidence) or preterm birth (k=3; high confidence) between CC-exposed and ENDS-exposed neonates; these findings were robust to sensitivity analysis. Analysis of continuous outcomes found lower birthweight in ENDS- vs non-exposed neonates (k=4; moderate confidence) and lower birthweight in CC- vs ENDS-exposed neonates (k=4; low confidence), and no difference in gestational age in either comparison (low confidence). Narrative synthesis suggests quitting ENDS improved birth outcomes, and associations between ENDS and infant motor maturity and reflexes. Conclusion ENDS exposure may confer comparable risk as cigarette smoking to preterm birth. Further research is needed given low to moderate confidence in findings and risk of bias conferred by limited classification of exclusive ENDS use.