In preterm toddlers, a faster 'epigenetic clock' tracked with better motor scores

How a baby born months early will develop is one of the hardest questions in neonatology, and clinicians still lean mostly on gestational age and brain imaging to answer it. A study published October 16 in JAMA Network Open adds a less familiar variable to that picture: the pace of a child's biological ageing, read from their DNA, and how it relates to how they think and move at age three [s1].

Measuring a child's biological age

The researchers followed a prospective cohort of children born at 24 to 32 weeks' gestation — the very preterm range — recruited from two neonatal intensive care units between 2015 and 2019 and followed to January 2026 [s1]. At age three, children provided buccal (inner-cheek) epithelial cells, from which DNA was analysed using the paediatric buccal epigenetic clock [s1]. That clock estimates a child's biological age in weeks; comparing it with the child's actual chronological age yields an "epigenetic age difference" — a measure of whether a child is ageing biologically faster or slower than the calendar says [s1].

Alongside the DNA, the cohort was characterised with clinical data, brain magnetic resonance imaging, and neurodevelopmental assessments using the Bayley-III scales for cognition and motor skills [s1]. In all, 102 children were included, with a median gestational age of 27.0 weeks (IQR, 25.6–28.9 weeks); 54 (53%) were female [s1].

Faster ageing, higher scores

The central finding runs against intuition. Epigenetic age acceleration — ageing faster than chronological age — was associated with better outcomes, not worse. Children with accelerated epigenetic ageing had higher cognitive scores (β = 0.07; 95% CI, 0.01–0.14; P = .04) and higher motor scores (β = 0.16; 95% CI, 0.06–0.27; P = .003) at three years [s1]. Higher maternal educational level was the other factor tied to better cognition (β = 11.65; 95% CI, 3.55–19.76; P = .005) [s1], a reminder that the social environment weighs heavily even in a biologically focused study.

The more conventional risk factors behaved as expected on the motor side. Extreme prematurity (β = −5.66; 95% CI, −10.85 to −0.46; P = .03) and severe brain injury (β = −10.99; 95% CI, −21.32 to −0.66; P = .04) were both associated with lower motor scores [s1].

The twist: context changes the signal

Where the study gets genuinely interesting is in how these factors interact. Severe brain injury modified the relationship between epigenetic ageing and motor outcomes (β = 0.41; 95% CI, 0.08–0.74; P = .02) [s1]. In plain terms: among children who had suffered severe brain injury, those whose epigenetic clocks were running fast had higher motor scores than those whose clocks were not [s1].

That suggests accelerated biological ageing is not a simple good or bad signal. The authors frame it as context dependent — its meaning shifts depending on whether a child also carries other preterm risk factors such as brain injury or socioeconomic disadvantage [s1]. The finding also fits with the researchers' note that earlier work had already linked epigenetic age acceleration to better neurodevelopment in preterm children; the new question was whether clinical and environmental factors change that link, and the answer is that they do [s1].

How to read it

Several cautions are built into a study of this size. With 102 children, the analyses are modest in power and the confidence intervals are wide — several brush right up against zero [s1]. This is an association in one well-characterised cohort, not a causal account of why a faster clock might accompany better function, and not a tool ready for the clinic. Epigenetic age is measured here at age three, the same time as the outcomes, so it describes a correlation rather than a prediction made at birth.

Still, the direction of the result is worth sitting with. One reading is that accelerated epigenetic ageing in these children reflects a kind of adaptive maturation — the biological system catching up after an early, disrupted start — rather than wear and tear. In adults, a fast epigenetic clock is generally a warning sign; in very preterm toddlers, at least in this cohort, it travelled with resilience [s1].

For now, the practical value is scientific rather than bedside: the study flags epigenetic ageing as a biomarker worth studying in larger preterm cohorts, and cautions against assuming that what "biological age" means in a 70-year-old carries over unchanged to a three-year-old who began life in intensive care [s1].

It also hints at why prognosis after very preterm birth is so stubbornly hard to call. Two children with the same gestational age and the same brain scan can follow very different paths, and clinicians currently have little to explain the divergence. A molecular marker that captures something about how fast a child's biology is maturing — and that behaves differently depending on whether brain injury is present — is at least a candidate explanation, and a measurable one [s1]. Whether it holds up in larger, more diverse cohorts, and whether it can be read earlier than age three, will decide if it ever becomes more than a research curiosity.