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A systematic review investigating prenatal cannabis and tobacco co-exposure: Impacts on neonatal, behavioral, cognitive and physiological outcomes

Mathilde Argote,Leah Hilson,Maryam Sorkhou,Rachel A. Rabin

Published 2025 in Drug and Alcohol Dependence Reports

ABSTRACT

Background Despite the high and increasing rates of cannabis and nicotine/tobacco product (NTP) use during pregnancy, the impact of their combined use on health outcomes in offspring remains poorly understood. Given the growing body of research on prenatal cannabis and NTP co-exposure and its effects on neonatal, behavioral, cognitive, and physiological outcomes in offspring, we conducted a systematic review to synthesize the existing literature and evaluate whether prenatal co-exposure results in additive and/or synergistic adverse effects compared to prenatal cannabis-only exposure and prenatal NTP-only exposure. Methods We searched Medline, Embase, and PsycINFO databases via OVID for human and animal studies examining the association between prenatal co-exposure and single-substance exposure on neonatal, behavioral, cognitive, and physiological outcomes in offspring. Results Of 3217 records identified, 46 articles were included in the review (human, n = 43; preclinical n = 3). For select neonatal outcomes, co-exposed infants exhibited a higher risk of compromised physical development and birth defects relative to infants with single-substance exposure. Behavioral outcomes, particularly emotion regulation/reactivity, and physiological outcomes demonstrated a similar pattern. In contrast, other neonatal outcomes (e.g., preterm birth and respiratory distress), and cognition were similar between the prenatal co-exposure and single-substance exposure groups. Conclusions This review suggests additive and/or synergistic adverse consequences associated with co-exposure on several outcomes in offspring relative to single substance exposure. These findings highlight the urgent need for prevention and treatment strategies addressing cannabis and NTP use in pregnant women. We discuss the limitations of the included studies and highlight key areas for future research.

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