Key takeaways:
- Adverse prenatal exposures (APEs) are associated with higher rates of behavioral and mental health problems that persist into mid-adolescence.
- Risk increases in a dose-dependent manner, with substantially higher odds of psychopathology among children exposed to multiple APEs.
- Depressive symptoms intensified over time in children with greater prenatal adversity, while ADHD-related associations attenuated.
- Greater APE burden was linked to accelerated cortical thinning in multiple brain regions, suggesting altered brain maturation.
- Findings underscore the importance of early prenatal and pediatric screening to support prevention and targeted intervention.
Researchers from Mass General Brigham have identified increased rates of behavior problems persisting into mid-adolescence among children with more adverse prenatal exposures (APEs), publishing their findings in JAMA Psychiatry.1
The odds of clinically significant pathology were significantly increased by exposure to multiple APEs. Additionally, mental health problems were more likely upon growing older in children with exposure to several adverse experiences during pregnancy.1
“Early intervention is the key, which is why knowledge is so valuable,” said Jodi Gilman, PhD, principal investigator and director of neuroscience at Mass General Brigham’s Center for Addiction Medicine. “Knowing what could be risk factors is important in routine care—not only prenatal care but also pediatric screening and intervention when necessary.”1
Neuroimaging and behavioral assessments
The cohort study was conducted to assess longitudinal associations between cumulative APE burden, psychopathology risk, and age-related cortical thinning among adolescents.2 Data was obtained from the Adolescent Brain Cognitive Development study, which performed sibling-comparison analyses on 414 nonadopted sibling pairs.
These patients had discordant APEs and were aged 9 to 16 years during recruitment, which began in 2016. Investigators evaluated 4-year follow-up data to determine outcomes, including annual Child Behavior Checklist (CBCL) scores of dimensional psychopathology. Both continuous and threshold outcomes were assessed.2
Investigators also used magnetic resonance imaging to measure cortical thickness, which is often used as a marker of brain maturation.1 These findings were reported alongside CBCL outcomes, which were used to evaluate mental health symptoms.
Associations between APEs and psychopathology risk
Cumulative APE burden was the primary exposure.2 This was determined by summing 6 binary exposures independently linked to psychopathology at baseline:
- Unplanned pregnancy
- Early maternal prenatal alcohol use,
- Tobacco use
- Marijuana use
- Complicated pregnancy
- Complicated birth
There were 8515 singleton children aged a mean of 9.9 years at baseline included in the analysis, 78% of whom were exposed to at least 1 APE. Significant associations were reported between APEs and clinically significant psychopathology, including an odds ratio (OR) of 2.01 for exposure to 1 APE.2
Increased risks were identified from exposure to multiple APEs, with ORs of 3.82 and 6.75 for 2 and 3 or more, respectively. While attenuation over time was found for associations of APEs with attention-deficit/hyperactivity disorder symptoms, associations with depressive symptoms potentiated.2
Links to cortical thinning and sibling comparisons
Accelerated age-related cortical thinning was linked to APE burden in 36 of 68 cortical regions. Additionally, greater CBCL total problems were found in siblings with more exposures, alongside accelerated cortical thinning in 5 of the 36 regions implicated in the larger sample.2
Overall, these results indicated significant variations in developmental trajectories of psychopathology and cortical maturation among children with APEs into midadolescence. Investigators concluded there is a need for fetal programming to mental health across the life course.2
“The next step is to find ways to address the prenatal and early life environment to build resiliency, especially for children who are predisposed to some of these risks,” said Joshua Roffman, MD, senior author and director of the Mass General Early Brain Development Initiative.1
References
- Adverse prenatal exposures linked to higher rates of mental health issues, brain changes in adolescents. Mass General Brigham. January 7, 2026. Accessed January 12, 2026. https://www.eurekalert.org/news-releases/1111343
- Zhi D, Perdomo SA, Arteaga LR, et al. Prenatal adversities and risk of persistent youth psychopathology and altered cortical thinning. JAMA Psychiatry. 2026. doi:10.1001/jamapsychiatry.2025.4080
