Given the deep biological ties between a mother and her unborn child, it’s no surprise that an expecting woman’s lifestyle can leave lasting imprints on her child’s development. Now, at the A*STAR Institute for Human Development and Potential (A*STAR IHDP), Principal Scientist Ai Peng Tan and Senior Scientist Shi Yu Chan are among a multi-institutional team of researchers looking even further back in time, tracing the effects of maternal stress before pregnancy itself.
“Most people think stress during pregnancy is what matters most for a baby’s brain, but we showed that stress even before conception can shape how a child’s brain develops,” said Tan and Chan.
The study included researchers from A*STAR IHDP; the National University Health System, Singapore; the National University of Singapore; KK Women’s and Children’s Hospital, Duke-National University of Singapore; McGill University, Canada; and the University of Auckland, New Zealand.
Drawing on cohort data from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), the team examined how maternal mental health—both in the lead-up to and during pregnancy—might influence a child’s later behaviour. Using self-reported data and hair cortisol levels, the team tracked the stress levels of 351 ethnically-diverse women in Singapore who had planned to conceive within 1 year of study recruitment, following them through each trimester of pregnancy. The women were then grouped into low- or high-stress trajectories.
After delivery, the team observed the newborns’ nucleus accumbens (NAcc)—a tiny brain region key to motivation and reward—using magnetic resonance imaging (MRI) scans and an advanced diffusion MRI model called Neurite Orientation Dispersion and Density Imaging (NODDI).
“Think of the brain as a forest: traditional scans let us see its outline, but NODDI zooms in on individual ‘trees’ and ‘branches’, or the brain cells and dendrites respectively,” said Tan and Chan. “NODDI reveals how dense the trees are and how far their branches spread and connect, giving a far more detailed picture of brain wiring even in newborns.”
When paired with mothers’ reports of their children’s behaviour at ages three to four, a pattern emerged: children of mothers on high-stress trajectories, particularly before conception, had more rapidly-maturing and complex neuronal structures in the right NAcc. These children were also more likely to display externalising behaviours such as hyperactivity, impulsivity or aggression in their early years.
“This discovery reframes how we think about early-life stress,” said Tan. “Recognising the preconception period as a critical window opens new possibilities for prevention and support—helping mothers-to-be manage stress earlier, and giving children a healthier start in life.”
The researchers plan to further investigate the biological pathways linking early maternal stress to fetal brain development; whether they impact other brain areas; and whether they might help predict the risk of psychiatric conditions in adulthood.
The A*STAR-affiliated researchers contributing to this research are from A*STAR Institute for Human Development and Potential (A*STAR IHDP) previously known as the A*STAR Singapore Institute for Clinical Sciences (A*STAR SICS).
