CHILDREN born preterm with epigenetic age acceleration demonstrated higher cognitive and motor scores at 3 years, although the association between epigenetic ageing and neurodevelopment varied according to clinical risk factors, according to new research. The findings highlight the complex relationship between biological ageing, prematurity, and childhood development.
The prospective cohort study included 102 children born between 24 and 32 weeks of gestation, recruited from two neonatal intensive care units between 2015 and 2019. Participants were followed until January 2026, with clinical information, brain MRI findings, and neurodevelopmental assessments collected.
Researchers investigated whether preterm brain injury and socioeconomic factors modified the association between epigenetic ageing and neurodevelopmental outcomes. Epigenetic age was measured at 3 years using DNA from buccal epithelial cells and a paediatric epigenetic clock. Assessments included cognitive and motor domains from the Bayley Scales of Infant and Toddler Development, Third Edition.
The cohort had a median gestational age of 27.0 weeks, and 53% of participants were female.
Epigenetic age acceleration was associated with higher cognitive scores (β=0.07; 95% CI: 0.01–0.14; p=0.04) and motor scores (β=0.16; 95% CI: 0.06–0.27; p=0.003).
Higher maternal educational level was also associated with improved cognitive scores (β=11.65; 95% CI: 3.55–19.76; p=0.005). Conversely, extreme prematurity and severe brain injury were associated with lower motor scores, with β values of −5.66 and −10.99, respectively.
Importantly, severe brain injury modified the association between epigenetic ageing and motor outcomes (β=0.41; 95% CI: 0.08–0.74; p=0.02). Children with both severe brain injury and epigenetic age acceleration demonstrated higher motor scores.
The findings suggest that epigenetic ageing in preterm children should be considered alongside clinical and environmental risk factors when examining neurodevelopmental outcomes.
Although epigenetic age acceleration was associated with better cognitive and motor performance, the relationship was not consistent across all children. The interaction with severe brain injury highlights the importance of considering individual clinical circumstances when interpreting biological markers of development.
The researchers concluded that epigenetic ageing, severe brain injury, and socioeconomic status were associated with neurodevelopmental outcomes. Further investigation may help clarify how biological ageing interacts with preterm risk factors and influences developmental trajectories.
Reference
Christensen R et al. Preterm risk factors, epigenetic age, and neurodevelopmental outcomes. JAMA Netw Open. 2026;9;(10):e2639409.
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