Prenatal Tobacco and Alcohol Exposure and Cortical Change Among Youths

The associations of prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) with adolescent neuroanatomical development are typically evaluated cross-sectionally. It is unclear whether observed effects persist throughout life or reflect different developmental trajectories.

To examine whether PAE and PTE are associated with early-adolescent cortical structure and development.

This cohort study included children aged 9 to 12 years who participated in the Adolescent Brain Cognitive Development (ABCD) Study's first 2 neuroimaging time points (data collected 2016-2021) at 21 US study sites. Data analysis was conducted from March 2024 to March 2025.

PAE and PTE, based on caregiver reports of alcohol and tobacco use during pregnancy, both before and after pregnancy recognition.

Cortical thickness (in millimeters) and cortical surface area (in millimeters squared) measured approximately 2 years apart, across 68 bilateral cortical regions. Summary scores from the Behavioral Inhibition and Behavioral Activation Scale, the Child Behavior Checklist, the Sleep Disturbances Scale for Children, and the Urgency, Perseverance, Premeditation, and Sensation Seeking Scale were collected.

At baseline data collection, the 5417 youth participants (2912 [53.8%] assigned male at birth; 724 [13.4%] Black, 1048 [19.3%] Hispanic, and 3640 [67.2%] White) had a mean (SD) age of 9.9 (0.6) years; the mean (SD) age at the second appointment was 11.9 (0.6) years. Cortical thickness decreased with age. Cortical surface area either expanded or contracted with age, depending on region. PAE was not associated with cortical structure (main correlation) or development (PAE × age interaction). PTE had false discovery rate-corrected main correlations with cortical thickness in the bilateral parahippocampal and left lateral orbitofrontal cortices (eg, right parahippocampal: |rp| = 0.04; P < .001) and was associated with faster rates of cortical thinning (PTE × age interactions) in medial and anterior frontal lobe regions (eg, right rostral middle frontal: |rp| = 0.04; P < .001). Post hoc analyses on PTE's associations with cortical structure and development among children whose mother continued tobacco use after pregnancy recognition and among those whose mother did not also use alcohol had weaker effect sizes. Exploratory developmental-outcome analyses suggested that faster cortical thinning was associated with more externalizing behavior and sleep problems (eg, right pars orbitalis and externalizing behavior: |rp| = 0.04, P = .003), primarily in those with PTE.

In this study, PTE was correlated with cortical thickness development. Analyzing developmental trajectories informs not only how PTE and PAE affect cortical structure (and related behavioral outcomes) but also how the cortex develops long after prenatal exposures occurred. Future analyses involving cotinine biomarkers of PTE would enhance the temporal resolution of the ABCD's PTE-related queries of tobacco use before and after learning of the pregnancy.