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Children born preterm are at increased risk for delays in thinking, language, and movement skills. Clinical and home factors, such as brain injury and socioeconomic status, are known to play a role, while biological factors have been studied less. A prospective cohort study from Canada followed 102 children born between 24 and 32 weeks of pregnancy until the age of 3. It examined how a biological marker called epigenetic age, brain injury, and socioeconomic status, measured by mothers’ education, related to the children’s development. Children whose epigenetic age was further ahead of their actual age tended to score higher on thinking and movement skills. Among children with severe brain injury, this link with movement skills was stronger.
Development in children born preterm can differ greatly from one child to the next. Established risk factors, such as gestational age, sex, newborn illness, socioeconomic status, and brain imaging, do not fully explain these differences. One biological factor is epigenetics, the way environmental influences can switch genes on or off without changing the DNA itself. Preterm birth brings stressors such as procedural pain, medical interventions, and separation from parents, which may be linked to epigenetic differences.
The study followed children who had been cared for in two neonatal intensive care units in Toronto. At age 3, an epigenetic clock developed for children estimated each child’s epigenetic age from chemical marks on the DNA in cheek cells. An estimate above actual age is called epigenetic age acceleration. Higher is not automatically better: in adults, epigenetic age acceleration has mostly been linked to poorer health, while in children earlier studies have linked it to both favorable and adverse outcomes.
Children were assessed at age 3 with a developmental test of thinking (cognitive) and movement (motor) skills. The further a child’s epigenetic age was ahead of actual age, the higher both scores tended to be. Children of mothers with a graduate degree had higher cognitive scores than those of mothers with primary or secondary education. Children with severe brain injury, meaning moderate or severe white matter damage or serious bleeding in the brain, had lower motor scores than those without. Children born extremely preterm also had lower motor scores than the other children. Epigenetic age was linked to both skill areas, maternal education only to cognitive scores, and severe brain injury only to motor scores.
In an additional, exploratory analysis, the researchers tested whether brain injury or maternal education changed the role of epigenetic age. Among children with severe brain injury, the link between epigenetic age acceleration and higher motor scores was stronger than among children without severe brain injury. The authors suggest this may reflect biological responses or adaptations to stressors such as severe brain injury, although severe brain injury itself was still linked to lower motor scores. The group with severe brain injury was also small, with only 16 children.
The authors conclude that epigenetic age is linked to development in children born preterm and may help explain why outcomes differ so much between children. They suggest considering it alongside established risk factors such as brain injury and socioeconomic status. Whether epigenetic age could help predict a child’s development in clinical care has not yet been studied.
Because epigenetic age and development were measured only once and at the same time, the study cannot show which came first. The authors call for studies that follow epigenetic age over time to understand how it relates to later development.
Paper available at: Preterm Risk Factors, Epigenetic Age, and Neurodevelopmental Outcomes | JAMA Network Open
Full list of authors: Christensen, R.; Konwar, C.; Zhuang, B.C.; MacIsaac, J.; Chau, V.; Cizmeci, M.N.; Ly, L.G.; Guo, T.; Branson, H.; Kobor, M.S.; Grunau, R.E.; Miller, S.P.
DOI: 10.1001/jamanetworkopen.2026.39409
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