Prenatal Cannabis Exposure is Associated with Occipitotemporal Brain Surface Area in Neonates.

Dufford A.; Kim S.; Styner M.; Shen X.; Iisa E.; Huestis M.; Fried P.; Conageski C.; Phipers J.; Sempio C. et al. · NeuroImage · 2026

**Background & Methods** The Moms Helping Moms study is a prospective pre-birth cohort examining neonatal brain structural morphometry following chronic prenatal cannabis exposure. The analysis included 18 mother-neonate pairs with documented cannabis exposure (via maternal and infant biospecimens in third trimester and at birth) and 21 unexposed control pairs, with exclusion of alcohol, tobacco, and other substance use. T1-weighted structural MRI was obtained at median postnatal age of 24 days, focusing on prefrontal and occipitotemporal regions (fusiform and lingual gyri) to assess cortical thickness and surface area using NEOCIVET analysis with Destrieux parcellation and IPTW-adjusted generalized linear regression. **Key Findings** • Surface area was significantly reduced in exposed neonates bilaterally in the right fusiform gyrus and right lingual gyrus (occipitotemporal regions), detectable within the first month of life. • No statistically significant differences in cortical thickness were observed in the regions of interest between exposed and unexposed groups. • Prenatal cannabis exposure demonstrated measurable impact on neonatal brain structural morphometry despite prior uncertainty about whether early neurodevelopmental changes occur immediately after birth. **Dosage & Administration** Not reported. The study documented chronic prenatal cannabis exposure via detection of cannabis metabolites in maternal biospecimens during the third trimester and in infant biospecimens at birth, but specific quantities, frequency, or route of administration were not specified. **Safety & Adverse Effects** Not reported. The study focused on structural brain morphometry outcomes and did not discuss clinical safety endpoints, adverse effects, or neonatal health outcomes beyond brain surface area measurements. **Evidence Quality** This study represents limited evidence due to several constraints: small sample size (n=39 total dyads), cross-sectional neonatal imaging without longitudinal follow-up to determine clinical significance or trajectory of observed changes, and lack of functional outcome data. While the cohort controlled for confounding substances (alcohol, tobacco), unmeasured confounders related to maternal socioeconomic factors, nutrition, or genetic predisposition cannot be excluded. The findings are novel in demonstrating structural alterations detectable at birth, but the clinical significance of reduced occipitotemporal surface area in neonates remains unclear. Results require replication in larger prospective cohorts with longer follow-up to establish whether early morphometric changes predict subsequent neurodevelopmental consequences.

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