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Updated: Jun 17, 2025
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Epigenetic associations with neonatal age in infants born very preterm, particularly among genes involved in
Kenyaita M Hodge1, Amber A Burt1, Marie Camerota2,3
1Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Atlanta, GA, 30322, USA.
Insights
Epigenetic changes in DNA methylation are linked to gestational and post-menstrual age in very preterm infants. These findings highlight critical developmental pathways, especially neurodevelopment, affected in these vulnerable infants.
Area of Science:
- Epigenetics
- Developmental Biology
- Neonatal Medicine
Background:
- The first year of life is crucial for human development, especially for infants born very preterm (VPT).
- VPT infants face disrupted developmental trajectories and increased risk of impairments.
- Epigenetic variations may illuminate developmental disruptions and aging in VPT infants.
Purpose of the Study:
- To investigate the relationship between gestational age (GA) and post-menstrual age (PMA) and DNA methylation in VPT infants.
- To identify specific epigenetic changes associated with early development in VPT neonates.
Main Methods:
- DNA methylation analysis in buccal cells from 538 VPT infants at NICU discharge.
- Statistical analysis adjusting for confounders and applying Bonferroni correction.
- Pathway enrichment analysis to identify biological processes affected by methylation changes.
Main Results:
- Identified 2,366 CpGs associated with GA and 14,979 CpGs associated with PMA.
- Detected multiple differentially methylated regions.
- Pathway analysis revealed significant associations with axonogenesis and neuron projection development.
Conclusions:
- Gestational and post-menstrual age significantly influence DNA methylation patterns in VPT infants.
- Epigenetic modifications are substantial in genes crucial for growth and neurodevelopment in this population.
- Findings provide insights into the epigenome's role in early development and potential long-term outcomes for VPT infants.
Abstract:
The time from conception through the first year of life is the most dynamic period in human development. This time period is particularly important for infants born very preterm (< 30 weeks gestation; VPT), as they experience a significant disruption in the normal developmental trajectories and are at heightened risk of experiencing developmental impairments and delays. Variations in the epigenetic landscape during this period may reflect this disruption and shed light on the interrelationships between aging, maturation, and the epigenome. We evaluated how gestational age (GA) and age since conception in neonates [post-menstrual age (PMA)], were related to DNA methylation in buccal cells collected at NICU discharge from VPT infants (n = 538). After adjusting for confounders and applying Bonferroni correction, we identified 2,366 individual CpGs associated with GA and 14,979 individual CpGs associated with PMA, as well as multiple differentially methylated regions. Pathway enrichment analysis identified pathways involved in axonogenesis and regulation of neuron projection development, among many other growth and developmental pathways (FDR q < 0.001). Our findings align with prior work, and also identify numerous novel associations, suggesting that genes important in growth and development, particularly neurodevelopment, are subject to substantial epigenetic changes during early development among children born VPT.
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