Female children may face greater emotional and immune challenges from prenatal stress, study finds

Maternal stress in late pregnancy may reprogram newborns’ stress and immune systems, researchers from the Hebrew University of Jerusalem find.

 Pregnant woman (illustrative) (photo credit: INGIMAGE)
Pregnant woman (illustrative)
(photo credit: INGIMAGE)

A study published in early April by Prof. Hermona Soreq and Shani Vaknine Treidel from the Edmond and Lily Safra Center for Brain Sciences at the Hebrew University of Jerusalem found a correlation between a pregnant mother’s stress and the molecular imprint on her female babies.

The research, published in the biology and psychiatry journal Molecular Psychiatry, examined RNA molecules in newborns’ blood and the brain’s stress-regulating enzymes.

The study describes how a stressful prenatal environment reprograms molecular pathways in a baby’s body, particularly those related to the cholinergic system, a branch of the autonomic nervous system responsible for regulating heartbeat, stress response, inflammation, and other vital functions.

When mothers reported high stress levels during their third trimester, researchers analyzed umbilical cord blood, focusing on tRNA fragments (tRFs) — small RNA molecules that regulate gene expression. The team discovered that stress did not alter a single tRF but instead affected entire families of tRFs, particularly those with mitochondrial DNA origins.

These developments were seen specifically in female newborns, who showed the most dramatic shift compared to the boys. The females were reported to have a decline in specific mitochondrial tRFs. These tRFs, termed “CholinotRFs,” target genes that control acetylcholine—a neurotransmitter essential for immune regulation and brain function.

 Infant holding their parent's hand (illustrative) (credit: PEXELS)
Infant holding their parent's hand (illustrative) (credit: PEXELS)

“We found that even before babies take their first breath, the stress their mothers experience can shape how their bodies manage stress themselves,” said Prof. Soreq.

The researchers additionally measured the levels of acetylcholinesterase (AChE), the enzyme that breaks down acetylcholine. The newborns of stressed mothers—particularly the boys—had significantly higher levels of AChE, indicating an imbalance in their stress-response systems even before birth.

Researchers were able to accurately classify female newborns as exposed or unexposed to maternal stress based on their CholinotRF profiles, achieving a classification success rate of 95%.

Children vulnerable to developing psychiatric challenges

The research demonstrates how some children may be more vulnerable to developing psychiatric challenges and opens opportunities for early diagnosis or preventive interventions for future mothers.

The study was conducted in collaboration with the Technical University of Munich and the University of Washington, as part of the international FELICITy project. Blood samples were collected from more than 120 mother-infant pairs and analyzed at the Hebrew University’s Center for Genomic Technologies.

“This study provides a powerful glimpse into how the maternal environment can leave a lasting biological imprint on the next generation,” said Vaknine Treidel. “It also underscores the importance of recognizing and supporting mental health during pregnancy—not just for the mother, but for the lifelong health of the child.”