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Epigenetic age and neurodevelopmental outcomes in children born preterm

Rhandi Christensen1,2, Chaini Konwar3,4,5, Beryl C Zhuang3,4,5

  • 1Department of Pediatrics, University of Toronto and The Hospital for Sick Children, Toronto, ON, Canada.

Genetics in Medicine Open
|January 19, 2026
PubMed

Insights

Epigenetic age acceleration in preterm infants is linked to improved cognitive and motor skills at three years. This highlights epigenetic modifications as key factors influencing neurodevelopmental outcomes in this vulnerable population.

Area of Science:

  • Pediatric Neurodevelopment
  • Epigenetics
  • Perinatal Medicine

Background:

  • Preterm birth (<32 weeks gestation) is associated with significant neurodevelopmental challenges.
  • Epigenetic age, a biological marker, may offer insights into developmental trajectories.
  • Understanding predictors of epigenetic age is crucial for identifying at-risk preterm infants.

Purpose of the Study:

  • To identify predictors of epigenetic age in preterm infants.
  • To examine the association between epigenetic age difference (EAD) and neurodevelopmental outcomes at 3 years.
  • To explore the influence of clinical factors and sex on epigenetic age.

Main Methods:

  • Prospective cohort study of 102 infants born 24-32 weeks gestation.
  • Epigenetic age determined using the Pediatric Buccal Epigenetic Clock.
  • Neurodevelopmental assessments (Bayley-III) and multivariable regression analysis were performed at 3 years.

Main Results:

  • Neonatal morbidity was linked to epigenetic age deceleration (lower EAD).
  • Sex modified EAD associations with prematurity, retinopathy, and infection; males showed higher EAD (acceleration).
  • Higher EAD at 3 years correlated with better cognitive and motor scores.

Conclusions:

  • Epigenetic age acceleration is associated with enhanced cognitive and motor outcomes in preterm children.
  • Epigenetic modifications play a significant role in neurodevelopmental variability among preterm infants.
Abstract

Keywords:
Epigenetic AgeNeurodevelopmentPediatric buccal epigenetic agePrematurity

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