Abstract
BACKGROUND AND AIMS: Δ9-tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, has been implicated in affecting fetal neurodevelopment by readily crossing the placenta. However, little is known regarding the long-term effects of intrauterine cannabis exposure. This systematic review and meta-analysis synthesized prospective and cross-sectional human studies to measure the effects of intrauterine cannabis exposure on birth, behavioral, psychological and cognitive outcomes in infancy until early childhood. METHODS: Reporting according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, cross-sectional and prospective studies published from database inception until June 2023, investigating developmental outcomes of infants, toddlers and young children with intrauterine cannabis exposure were considered. All articles were obtained from PubMed or PsycINFO databases. RESULTS: The literature search resulted in 932 studies, in which 57 articles met eligibility criteria. The meta-analysis revealed that intrauterine cannabis exposure increases the risk of preterm delivery [odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.05-2.71, P = 0.03], low birth weight (OR = 2.60, CI = 1.71-3.94, P < 0.001) and requirement for neonatal intensive care unit (NICU) admission (OR = 2.51, CI = 1.46-4.31; P < 0.001). Our qualitative synthesis suggests that intrauterine cannabis exposure may be associated with poorer attention and externalizing problems in infancy and early childhood. We found no evidence for impairments in other cognitive domains or internalizing behaviors. CONCLUSIONS: Prenatal cannabis use appears to be associated with lower birth weight, preterm birth and neonatal intensive care unit admission in newborns, but there is little evidence that prenatal cannabis exposure adversely impacts behavioral or cognitive outcomes in early childhood, with the exception of attention and externalizing problems.