Adverse Prenatal Exposures Are Linked to Higher Rates of Mental Health Issues and Brain Changes in Adolescents

Research continues to show that the prenatal environment plays a critical role in shaping long-term health, and a new large-scale study adds strong evidence that experiences during pregnancy can influence mental health outcomes and brain development well into adolescence. A study led by researchers from Mass General Brigham has found that children exposed to multiple adverse prenatal exposures (APEs) are more likely to experience persistent behavioral and emotional difficulties, along with measurable changes in brain structure as they grow older.

The findings, published in JAMA Psychiatry, highlight how risks that begin before birth may echo across key developmental stages, reinforcing the importance of early identification, screening, and intervention.

What Researchers Mean by Adverse Prenatal Exposures

Adverse prenatal exposures refer to negative or stressful factors experienced during pregnancy that may affect fetal development. In this study, researchers focused on six specific APEs that are relatively common and often occur together:

Unplanned pregnancy
Maternal alcohol use before pregnancy was recognized
Maternal tobacco use before pregnancy was recognized
Maternal marijuana use before pregnancy was recognized
Medical complications during pregnancy
Medical complications during childbirth

Rather than examining each exposure in isolation, the research team emphasized the cumulative impact of multiple exposures, reflecting real-world conditions where risks often overlap.

A Large, Long-Term Study of Brain and Behavior

The study analyzed data from 8,515 children who were part of the Adolescent Brain Cognitive Development (ABCD) Study, one of the largest long-term studies of brain development and child health in the United States. Participants were 9 to 10 years old at enrollment and were followed for four years, allowing researchers to observe changes as children moved into mid-adolescence.

To assess mental health, researchers used the Child Behavior Checklist (CBCL), a well-established tool for evaluating emotional and behavioral problems. Brain development was measured using magnetic resonance imaging (MRI), with a focus on cortical thickness, an important indicator of brain maturation.

How Common Were Prenatal Exposures?

The data revealed that APEs were widespread among the participants:

78% of children were exposed to at least one adverse prenatal factor
18% were exposed to three or more APEs

This distribution allowed researchers to examine how increasing exposure levels were associated with mental health and brain development outcomes over time.

Clear Links to Mental Health Problems

One of the strongest findings of the study was the dose-response relationship between APEs and mental health issues. In simple terms, the more prenatal exposures a child experienced, the higher their risk of developing clinically significant psychological symptoms during adolescence.

Children exposed to three or more APEs showed a nearly seven-fold increase in the likelihood of developing clinically significant mental health problems compared to children with no prenatal exposures. These effects were not temporary. The elevated risk persisted throughout adolescence, suggesting long-lasting consequences rather than short-term developmental delays.

Symptoms Change as Children Grow Older

The study also found that the type of mental health symptoms evolved with age:

In younger children, higher APE exposure was more strongly associated with attention-deficit and hyperactivity symptoms
As children entered mid-adolescence, these associations shifted toward depressive symptoms

This pattern suggests that prenatal adversity may influence developmental trajectories, affecting how and when mental health challenges emerge rather than producing a single fixed outcome.

Accelerated Brain Changes During Adolescence

Beyond behavior and emotional health, the researchers observed significant differences in brain development. Adolescents with higher numbers of APEs showed faster-than-normal thinning of the cerebral cortex.

Cortical thinning is a normal part of brain maturation during adolescence, reflecting processes such as synaptic pruning. However, accelerated thinning may indicate atypical development. In this study, accelerated thinning occurred across multiple brain regions, particularly those involved in:

Attention regulation
Memory processing
Visual perception

These regions are essential for cognitive and emotional functioning and have previously been linked to vulnerability for mental illness.

Strengthening the Evidence With Sibling Comparisons

To further strengthen their findings, the researchers examined a subset of 414 sibling pairs who differed in their levels of prenatal exposure. This approach helped control for shared genetic and family-level factors.

Within these sibling pairs, the sibling with more prenatal exposures consistently showed:

Worse mental health symptoms
Faster cortical thinning

These results closely mirrored the main findings and added confidence that the observed effects were specifically linked to prenatal exposures rather than broader family circumstances.

What the Study Can and Cannot Predict

The researchers were careful to emphasize that the study does not predict individual outcomes. Not every child exposed to prenatal adversity will develop mental health problems, and many factors during childhood and adolescence—such as environment, education, and social support—also shape brain development.

Still, the strength and consistency of the findings suggest that prenatal life and adolescence are deeply connected periods of brain development, with early risks influencing later vulnerability.

Why Early Identification Matters

The findings underscore the importance of early intervention. Recognizing prenatal risk factors can help guide:

Prenatal care strategies
Pediatric screening for behavioral and emotional issues
Early support services for at-risk children

By identifying children who may be more vulnerable, healthcare providers can intervene earlier, potentially reducing the severity or persistence of mental health challenges later in life.

Broader Context: Prenatal Health and Brain Development

Decades of research have shown that the prenatal period is a critical window for brain development. Factors such as maternal stress, substance exposure, and medical complications can influence how neural circuits form and mature. This study adds to a growing body of evidence supporting the concept of developmental programming, where early biological conditions shape long-term health trajectories.

Importantly, the study also highlights that many APEs are modifiable. Improving access to prenatal care, supporting maternal mental health, and reducing substance use during pregnancy could have meaningful long-term benefits for children’s mental and neurological health.

Looking Ahead

The researchers note that future work should focus on building resilience, especially for children who may already be predisposed to these risks. Understanding how supportive environments, early interventions, and targeted healthcare strategies can offset prenatal adversity will be an important next step.

By linking prenatal experiences to measurable brain changes and persistent mental health symptoms in adolescence, this study provides one of the clearest pictures yet of how early life conditions can shape mental health across the lifespan.

Research paper:
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/jamapsychiatry.2025.4080