In an NIH-funded study led by researchers from Mass General Brigham , children with more adverse prenatal exposures (APEs) showed higher rates of behavior problems that persisted into mid-adolescence, faster cortical thinning across multiple brain regions, and more depressive symptoms than children with fewer APEs. The researchers' results are published in JAMA Psychiatry .
"We sought to understand how multiple adverse experiences during pregnancy affect children's mental health and brain development as they grow into adolescence," said lead author Jodi Gilman, PhD , principal investigator and director of neuroscience at the Center for Addiction Medicine in the Mass General Brigham Department of Psychiatry. "Early intervention is the key, which is why knowledge is so valuable. Knowing what could be risk factors is important in routine care—not only prenatal care but also pediatric screening and intervention when necessary."
APEs often occur together and are linked to the risk of childhood mental health issues, but it remained unclear whether exposure to multiple APEs causes lasting clinical effects during adolescence or impacts brain development. To investigate this, researchers examined six APEs, including unplanned pregnancy, maternal use of alcohol, tobacco, and marijuana before pregnancy was recognized, and medical complications of pregnancy and childbirth.
This study analyzed data from 8,515 youth aged 9 to 10 years at enrollment in the Adolescent Brain Cognitive Development (ABCD) Study. The children were followed over the next four years. Magnetic resonance imaging (MRI) was used to measure cortical thickness, a marker of brain maturation, and the Child Behavior Checklist (CBCL) was used to evaluate mental health symptoms.
Within these children, 78% were exposed to at least one APE, and 18% were exposed to 3 or more. Exposure to multiple APEs demonstrated a persistent association with higher odds of clinically significant pathology. Being exposed to several negative experiences during pregnancy was linked to a lasting increase in the chances of having mental health problems as kids grew older.
Researchers found that symptoms changed over time, noticing that younger children who had more APEs were more likely to have attention-deficit/hyperactivity disorder (ADHD) symptoms and older children were more likely to have emergent depression.
Additionally, participants with a greater number of APEs showed faster-than-normal thinning of the cerebral cortex during adolescence. This accelerated thinning occurred primarily in brain regions that control attention, memory processing, and visual perception – all of which are critical to adolescent brain maturation, and have previously been associated with risk for mental illness.
Researchers acknowledge that this study can't predict which specific children will develop mental health problems. Many factors during childhood—not just during pregnancy—can affect teen brain development. But the findings were strong, such that children with three or more APEs exhibited a nearly seven-fold increase in risk for clinically significant symptoms in adolescence. Further, in a subset of 414 sibling pairs who differed in the number of APEs, the sibling with more exposures had worse symptoms and faster cortical thinning, echoing the main findings while also controlling for family-level differences.
"This new evidence links two critical periods of brain development–prenatal life and adolescence– to trace risk for youth mental illness back to its earliest roots. 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 senior author Joshua Roffman, MD , principal investigator and director of the Mass General Early Brain Development Initiative , a collaborative effort across the Mass General Brigham departments of Psychiatry, Obstetrics & Gynecology, Pediatrics, and Medicine.
Authorship: Mass General Brigham authors of the study include Gilman and Roffman, who co-led the study, as well as Dongmei Zhi, Sofia A. Perdomo, Liam R. Arteaga, Phil H. Lee, A. Eden Evins, Harrison T. Reeder, Scott E. Hadland, Alysa E. Doyle, and Jacqueline A. Clauss. Additional authors include Dylan E. Hughes, Erin C. Dunn, and Jing Sui.
Disclosures: All authors have no interests to declare.
Funding: Roffman reports support by R01MH124694. Gilman is supported by K02DA052684 and R01DA051540. Hadland is supported by R01DA057566 and K18DA059913. The ABCD study is supported by the National Institutes of Health (NIH) and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, U24DA041147. Additional support for this work was made possible from NIEHS R01-ES032295 and R01-ES031074.
Paper cited: Gilman, J et al. "Association of Adverse Prenatal Exposure Burden with Persistent Psychopathology and Accelerated Cortical Thinning in Youth" JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2025.4080
