Epigenetic age and neurodevelopmental outcomes in children born preterm

The objective of this study was to identify predictors of epigenetic age and its association with neurodevelopmental outcomes in children born preterm.

A prospective cohort of children born 24-to-32-weeks gestation, well characterized with clinical data, brain imaging, and neurodevelopmental assessments at 3 years (Bayley-III cognitive and motor composite), were included. Epigenetic age (in weeks) was determined using the Pediatric Buccal Epigenetic Clock and corrected for chronological age to give epigenetic age difference (EAD). The associations between EAD, clinical risk factors and neurodevelopmental outcomes were examined using multivariable linear regression.

A total of 102 study participants (47% males) were included. Epigenetic age showed a positive association with chronological age at term-equivalent age and 3 years. Neonatal morbidity was associated with a lower EAD (epigenetic age deceleration) at 3 years (β = -10.1, P = .03). Sex modified the association between EAD and extreme prematurity (P = .08), retinopathy of prematurity (P = .04), and infection (P = .06), with males having a higher EAD (epigenetic age acceleration). EAD at 3 years was associated with cognitive (β = 0.1, P = .004) and motor (β = 0.2, P = .001) scores at 3 years, with a higher EAD (epigenetic age acceleration) being associated with better outcomes.

Epigenetic age acceleration was associated with better cognitive and motor outcomes in children born preterm. Epigenetic modification is an important biological mechanism that contributes to the variability in neurodevelopmental outcomes in the preterm population.