Preprint
Association of Adverse Prenatal Exposure Burden with Persistent Psychopathology and Accelerated Cortical Thinning in Youth
medRxiv : the preprint server for health sciences
Cold Spring Harbor Laboratory
07/23/2025
DOI: 10.1101/2025.07.23.25331227
PMCID: PMC12330414
PMID: 40778183
Abstract
Adverse prenatal exposures (APEs) often co-occur and independently associate with risk for childhood psychopathology. Whether exposure to multiple APEs associates with persistent clinical effects through adolescence or underlying changes in brain maturation remains uncertain.
To evaluate longitudinal associations among cumulative APE burden, risk for psychopathology, and age-related cortical thinning in adolescents.
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 non-adopted sibling pairs with discordant APEs. Statistical analysis occurred from March to June 2025.
Cumulative APE burden was calculated by summing six 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.
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.
Of 8,515 singleton children (4,055 females [47.6%]), 78% were exposed to at least one APE. Multiple APEs persistently and dose-dependently associated with increased odds of clinically significant psychopathology (CBCL total problems: odds ratio=2.01-6.75; corrected P=.0065-1.31×10
). Associations of APEs with attention-deficit/hyperactivity disorder symptoms attenuated over time (interaction: F=13.51; corrected P=7.13×10
), while those with depressive symptoms potentiated (interaction: F=5.82; corrected P=.0019). Greater APE burden associated with accelerated age-related cortical thinning in 36 of 68 cortical regions (interactions: F=3.26-8.89; corrected P's=0.039-4.86×10
). Siblings with more exposures demonstrated persistently higher CBCL total problems (T=2.25; P=0.025) and accelerated cortical thinning (interactions: T=-3.00--2.10; P's<.05) in 5 of the 36 regions implicated in the larger sample.
Multiple prenatal adversities associated with altered developmental trajectories of psychopathology and cortical maturation into mid-adolescence. These findings highlight the importance of fetal programming to mental health across life course, and the need for additional study of risk and resiliency-conferring factors in utero.
Details
- Title: Subtitle
- Association of Adverse Prenatal Exposure Burden with Persistent Psychopathology and Accelerated Cortical Thinning in Youth
- Creators
- Dongmei Zhi - Harvard Medical SchoolSofia A Perdomo - Athinoula A. Martinos Center for Biomedical ImagingLiam R Arteaga - Harvard Medical SchoolDylan E Hughes - University of California, Los AngelesErin C Dunn - Purdue University West LafayettePhil H Lee - Massachusetts General HospitalA Eden Evins - Harvard Medical SchoolHarrison T Reeder - Harvard Medical SchoolScott E Hadland - Harvard Medical SchoolAlysa E Doyle - Massachusetts General HospitalJacqueline A Clauss - Athinoula A. Martinos Center for Biomedical ImagingJing Sui - Beijing Normal UniversityJoshua L Roffman - Athinoula A. Martinos Center for Biomedical ImagingJodi M Gilman - Harvard Medical School
- Resource Type
- Preprint
- Publication Details
- medRxiv : the preprint server for health sciences
- DOI
- 10.1101/2025.07.23.25331227
- PMID
- 40778183
- PMCID
- PMC12330414
- Publisher
- Cold Spring Harbor Laboratory; United States
- Grant note
- U01 DA041134 / NIDA NIH HHS R01 DA057566 / NIDA NIH HHS U01 DA041028 / NIDA NIH HHS U01 DA051016 / NIDA NIH HHS U24 DA041123 / NIDA NIH HHS K02 DA052684 / NIDA NIH HHS U01 DA051039 / NIDA NIH HHS U01 DA041048 / NIDA NIH HHS U24 DA041147 / NIDA NIH HHS U01 DA050989 / NIDA NIH HHS
- Language
- English
- Date posted
- 07/23/2025
- Academic Unit
- Psychiatry
- Record Identifier
- 9985222820402771
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