A "DNA Clock" in Children Born Very Early: What It Can and Cannot Tell Families About Development

A plain-language guide to Christensen et al. (JAMA Network Open, 2026), a Toronto study of biological age, brain injury, family background and development at age 3

Scientists can now estimate a child's "biological age" from tiny chemical tags on the DNA inside cheek cells. A Canadian study of 102 three-year-olds who were born very early found that children whose DNA clock read further ahead of their real age scored slightly higher on thinking and movement tests, but the differences were small, and this kind of test is not ready to guide any child's care.

If your baby was born many weeks early, you have probably asked the question every parent in the newborn intensive care unit (NICU) asks: how will my child grow and learn? Doctors can offer some guidance, but no one can predict an individual child's future with certainty. Researchers are looking for new clues, including clues hidden in the way a child's genes are switched on and off. This article explains what one new study found, why its results surprised even the researchers, and what it does and does not mean for your family.

Why some children born early do better than others

Being born very early, months before the due date, increases the chance of later difficulties with thinking, language and movement [1][2][3]. A large study across 19 US hospitals in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network found that, among assessed toddlers born before 27 weeks of pregnancy, about one in five had severe developmental difficulties around age 2, while nearly half had no or only mild difficulties [2]. A national study in France, called EPIPAGE-2, found that about half of children born at 24 to 26 weeks scored below the expected range on a developmental check-up questionnaire at age 2 [3].

For many years, families and doctors have relied on three kinds of clues to think about the future. The first is how sick the baby was in the NICU. A large international study, the Trial of Indomethacin Prophylaxis in Preterms (TIPP), which followed 910 very small babies in 32 NICUs in Canada, the United States, Australia, New Zealand and Hong Kong, found that problems were much more common in babies who had had serious lung disease, brain injury or eye disease of prematurity: 18% of babies with none of these had a poor outcome at 18 months, rising to 88% of those with all three [4]. The second clue is brain injury seen on scans, such as bleeding into the fluid spaces of the brain or damage to the brain's "wiring", called white matter [5]. The third is the home: children whose mothers had more education, and whose parents interacted with them in a closely tuned, responsive way, tended to do better on thinking tests [6][7]. In everyday terms, this has meant that many parents leave the NICU with a list of things that went well or badly, a follow-up appointment and a great deal of uncertainty, and then learn their child's path gradually, visit by visit, over the first years of life. Even so, these clues leave a lot unexplained, and the researchers behind the new study wanted to know whether biology could fill in some of the gaps [1].

What a "DNA clock" is

Our DNA is the instruction book in every cell. Without changing the words in that book, the body adds small chemical tags, called methyl groups, that act a bit like bookmarks or sticky notes, helping decide which instructions are used. This tagging is called DNA methylation, and it changes in a predictable way as we grow older, increasing through the first few years of life [8]. Scientists discovered that, by reading the tags at a few hundred chosen spots, they could estimate a person's age quite accurately; this estimate is called "epigenetic age" [9]. Researchers then built a version made specifically for children that works from a simple cheek swab, called the pediatric buccal epigenetic (PedBE) clock ("buccal" means from the cheek) [10].

Earlier research in babies born early pointed in different directions. In a large US study of babies born before 30 weeks, called the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, babies with more newborn health problems tended to have "older" DNA clocks [11]. In a small Toronto study of 35 very early babies who had infections, an "older" clock near the due date went with lower thinking and language scores at 18 months [12]. But when the Toronto team checked 102 children from the same group at age 3, very probably the same children who are in the new study, they found the reverse: an "older" clock went with better development [13].

How the new study was done

The new study, by Rhandi Christensen and colleagues, followed babies born between 24 and 32 weeks of pregnancy (roughly 2 to 4 months early) who were cared for in the NICUs of two Toronto hospitals, The Hospital for Sick Children and Mount Sinai Hospital, between 2015 and 2019 [1]. Of 195 babies who joined, 102 gave a cheek swab at age 3; these appear to be the same 102 children as in the earlier report, although neither paper says so directly. The typical child was born at 27 weeks. Every baby had two brain scans, one soon after birth and one around the original due date, and 16 children had a severe brain injury. Mothers' education was recorded as a measure of the family's social and economic circumstances. At age 3, trained specialists tested the children's thinking and movement skills with a standard developmental assessment called the Bayley Scales of Infant and Toddler Development (Bayley-III).

What the researchers found

The first surprise was that the DNA clock read older than the children really were. The typical child was about 159 weeks old (just over 3 years), but the clock read about 213 weeks, a gap of about 53 weeks, or roughly a year. At least three out of every four children had a clock reading older than their real age. So in this study, a "faster" clock simply means a bigger gap than other children in the group had, not that a child is ageing too quickly. The clock and real age agreed only moderately well, which may partly reflect that the clock was designed for children born at full term.

The second surprise was the direction. Children whose clock gap was bigger tended to score slightly higher, not lower, on both thinking and movement tests. The differences were tiny for each week of gap: for every extra week, scores were a fraction of a point higher, so even a 10-week difference meant less than one point on the thinking test and less than two on the movement test, by our own calculation.

Familiar clues showed much bigger differences. Children whose mothers had a graduate degree scored on average almost 12 points higher on thinking tests than children whose mothers had the least education (the comparison group in the analysis). Children with severe brain injury, and those born extremely early, scored lower on movement tests. Neither brain injury nor mother's education was linked to the DNA clock itself.

Finally, among the 16 children with severe brain injury, the link between a bigger clock gap and better movement scores appeared stronger. With so few children, this is a hint for future research, not a firm finding.

What this means for your family

The most important message is reassuring: nothing in this study suggests your child needs a DNA clock test, or that such a test could help plan your child's care. The study measured the clock and development at the same time (age 3), so it cannot tell whether the clock predicts anything about the future, and it cannot show cause and effect. The researchers themselves describe the relationship as depending on each child's circumstances [1].

What the study does underline is something families can act on. The strong link between a mother's education and her child's thinking skills likely reflects many everyday things, such as time, resources and support, that shape a child's learning, and earlier work has linked warm, responsive interaction with parents to better development [7]. Follow-up clinics, early-intervention services and parent support programmes exist to help every family give their child that support, whatever their background. If your child had a severe brain injury, regular follow-up with your care team, including attention to movement skills, remains the right place to raise questions about development.

What researchers are working on next

The research team suggests that DNA-based ageing should be considered alongside other risk factors, and calls for studies testing whether it can help predict development [1]. To get there, scientists need to take repeated cheek swabs from the newborn period into school age, build clocks designed for children born early, and check whether the findings hold up in other, larger groups of children. They also want to look at language and behaviour, not just thinking and movement.

The bottom line

In 102 Toronto children born very early, a DNA clock reading further ahead of their real age went along with slightly better thinking and movement scores at age 3. A mother's education and severe brain injury were linked to much larger differences in scores, and the extra finding in children with severe brain injury is based on only 16 children. For now, the DNA clock is a fascinating research tool, not a test for your child, and the familiar ways to support development (follow-up care, early support when needed and engaged, responsive parenting) remain the ones that matter.

References

  1. Christensen R, Konwar C, Zhuang BC, et al. Preterm Risk Factors, Epigenetic Age, and Neurodevelopmental Outcomes. JAMA Netw Open. 2026;9(10):e2639409. doi:10.1001/jamanetworkopen.2026.39409 ↩
  2. Bell EF, Hintz SR, Hansen NI, et al. Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA. 2022;327(3):248-263. doi:10.1001/jama.2021.23580 ↩
  3. Pierrat V, Marchand-Martin L, Arnaud C, et al. Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks' gestation in France in 2011: EPIPAGE-2 cohort study. BMJ. 2017;358:j3448. doi:10.1136/bmj.j3448 ↩
  4. Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003;289(9):1124-1129. doi:10.1001/jama.289.9.1124 ↩
  5. Rees P, Callan C, Chadda KR, et al. Preterm Brain Injury and Neurodevelopmental Outcomes: A Meta-analysis. Pediatrics. 2022;150(6):e2022057442. doi:10.1542/peds.2022-057442 ↩
  6. Benavente-Fernández I, Synnes A, Grunau RE, et al. Association of Socioeconomic Status and Brain Injury With Neurodevelopmental Outcomes of Very Preterm Children. JAMA Netw Open. 2019;2(5):e192914. doi:10.1001/jamanetworkopen.2019.2914 ↩
  7. Treyvaud K, Anderson VA, Howard K, et al. Parenting behavior is associated with the early neurobehavioral development of very preterm children. Pediatrics. 2009;123(2):555-561. doi:10.1542/peds.2008-0477 ↩
  8. Jones MJ, Goodman SJ, Kobor MS. DNA methylation and healthy human aging. Aging Cell. 2015;14(6):924-932. doi:10.1111/acel.12349 ↩
  9. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):R115. doi:10.1186/gb-2013-14-10-r115 ↩
  10. McEwen LM, O'Donnell KJ, McGill MG, et al. The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells. Proc Natl Acad Sci U S A. 2020;117(38):23329-23335. doi:10.1073/pnas.1820843116 ↩
  11. Paniagua U, Lester BM, Marsit CJ, et al. Epigenetic age acceleration, neonatal morbidities, and neurobehavioral profiles in infants born very preterm. Epigenetics. 2023;18(1):2280738. doi:10.1080/15592294.2023.2280738 ↩
  12. Gomaa N, Konwar C, Gladish N, et al. Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection. JAMA Netw Open. 2022;5(11):e2239796. doi:10.1001/jamanetworkopen.2022.39796 ↩
  13. Christensen R, Konwar C, Zhuang BC, et al. Epigenetic age and neurodevelopmental outcomes in children born preterm. Genet Med Open. 2026;4:103479. doi:10.1016/j.gimo.2025.103479 ↩