Prenatal Adversities and Risk of Persistent Youth Psychopathology and Altered Cortical Thinning

Importance: Adverse prenatal exposures (APEs) often co-occur and independently associate with risk for childhood psychopathology. Whether exposure to multiple APEs is associated with persistent clinical effects through adolescence or underlying changes in brain maturation remains uncertain. Objective: To evaluate longitudinal associations among cumulative APE burden, risk for psychopathology, and age-related cortical thinning in adolescents. Design, Setting, and Participants: This cohort study analyzed 4-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study, which enrolled 11 868 youth aged 9 to 10 years beginning in 2016. Sibling-comparison analysis was performed on 414 nonadopted sibling pairs with discordant APEs. Statistical analysis occurred from March to September 2025. Exposures: Cumulative APE burden was calculated by summing 6 binary prenatal exposures that independently associated with psychopathology at baseline: unplanned pregnancy; early maternal prenatal alcohol, tobacco, or marijuana use; complicated pregnancy; and complicated birth. Main Outcomes and Measures: Outcomes included annual Child Behavior Checklist (CBCL) scores of dimensional psychopathology, using both continuous and thresholded outcomes and biennial cortical thickness measures from structural magnetic resonance imaging, analyzed using linear mixed-effects models. Results: Of 8515 singleton children (mean [SD] baseline age, 9.9 [0.6] years; 4460 male [52.4%]), 6644 (78%) were exposed to at least 1 APE. Multiple APEs persistently and dose-dependently associated with increased odds of clinically significant psychopathology (CBCL total problems: exposure to 1 APE [odds ratio (OR), 2.01; 95% CI, 1.28-3.16; corrected P = .006], 2 APEs [OR, 3.82; 95% CI, 2.39-6.11; corrected P