Maternal Illness Linked to Epigenetic Fetal Brain Changes

Maternal illness during pregnancy may influence fetal brain development through lasting epigenetic changes, according to new research from the Salk Institute. The study, published in Molecular Psychiatry on September 2, 2026, identifies thousands of epigenetic differences in the developing frontal cortex following maternal immune activation.

Key Points

• Maternal immune activation may alter fetal brain development through epigenetic programming.
• Deep-layer neurons in the developing frontal cortex showed particularly pronounced changes.
• Many altered regions occurred near genes associated with autism spectrum disorder (ASD).
• Increased DNA methylation appeared to interfere with Tbr1 activity, a key regulator of developing brain neurons.
• Prenatal immune challenges may change neurodevelopmental trajectories without determining an individual child’s outcome.
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Maternal Illness and Fetal Brain Development: What Does the Research Show?

Maternal illness has long been associated with an increased likelihood of neurodevelopmental and psychiatric conditions in offspring. Earlier epidemiological research linked influenza during pregnancy with a higher incidence of psychiatric disorders in children, prompting scientists to investigate whether the maternal immune response contributes to this association.

Salk Institute researchers used a mouse model of maternal immune activation (MIA) to examine how prenatal immune challenges affect the fetal epigenome. They used Poly(I), a viral mimic that models immune activation associated with viral infection.

Researchers analyzed frontal cortex cells from mid-gestation through two weeks after birth, assessing gene activity and DNA methylation. Offspring exposed to maternal immune activation demonstrated distinct transcriptomic and methylation patterns compared with offspring from healthy pregnancies.

Epigenetic Changes May Disrupt Developing Neurons

The most prominent differences occurred in deep-layer neurons, which play important roles in developing brain circuitry. Researchers identified increased methylation at regions associated with Tbr1, a transcription factor that regulates the development of these neurons.

Although Tbr1 levels increased, methylation appeared to limit its ability to regulate target genes. This disruption coincided with altered gene expression in regions important for deep-layer neuron development.

The researchers also compared their findings with the SFARI Gene Database, which catalogs genes associated with autism spectrum disorder. Approximately 25% of high-confidence autism-associated genes in the database showed dysregulation in the study dataset.

Electrophysiological recordings further indicated impaired development and function of deep-layer neurons following prenatal immune activation.

What Do These Findings Mean for Neurodevelopmental Disorders?

The findings provide new insight into how maternal immune activation and epigenetic changes may influence fetal brain development and potentially contribute to neurodevelopmental disorder risk.

Importantly, the researchers emphasize that maternal infection or illness does not determine whether a child will develop autism, ADHD, or another neurodevelopmental condition. Instead, prenatal immune challenges may alter the odds by influencing developmental pathways during sensitive periods of fetal brain development.

Further research will need to establish when these epigenetic changes emerge, which stages of pregnancy carry the greatest vulnerability, and whether maternal or fetal interventions could eventually reduce associated risks.

For More Updates in Neurology, register for the American Neurology Summit 2026

For clinicians and researchers across Maternal-Fetal Medicine, Neurology, Psychiatry, Pediatrics, and Neurodevelopmental Medicine, understanding the relationship between prenatal inflammation, epigenetic programming, and fetal brain development may help clarify the biological origins of some neurodevelopmental conditions.

Source:

Salk Institute