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Blood and adipose tissue DNA methylation in adults born preterm with a very low birth weight - a sibling comparison

Helena H Hauta-Alus1,2,3, Justiina Ronkainen4, Juho Kuula2,3,5

  • 1Clinical Medicine Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.

Epigenomics
|November 17, 2025
PubMed

Insights

Adults born very low birth weight (VLBW) show lasting epigenetic changes in adipose tissue, specifically in genes related to lipid metabolism and neurodevelopment. These DNA methylation differences highlight potential long-term health implications for VLBW individuals.

Area of Science:

  • Epigenetics
  • Human Development
  • Metabolic Health

Background:

  • Preterm birth and very low birth weight (VLBW) are associated with increased risks for adverse health outcomes.
  • Epigenetic modifications, such as DNA methylation (DNAm), are hypothesized to mediate these risks.
  • Understanding tissue-specific DNAm patterns in VLBW adults is crucial for identifying long-term health consequences.

Purpose of the Study:

  • To investigate differences in DNA methylation (DNAm) between adults born very low birth weight (VLBW) and their siblings.
  • To compare DNAm patterns in blood and adipose tissue to identify tissue-specific epigenetic modifications.
  • To explore the biological pathways affected by these potential DNAm differences.

Main Methods:

  • Study included 75 adults born preterm with VLBW and 73 sibling controls.
  • DNA methylation at CpG sites in blood and adipose tissue was assessed using Illumina EPIC 850K array.
  • Pathway analysis was performed using QIAGEN ingenuity pathway analysis (IPA).

Main Results:

  • No significant differences in DNA methylation were observed in blood samples.
  • In adipose tissue, 458 CpG sites showed differential methylation between VLBW adults and siblings (FDR p < 0.05).
  • Differentially methylated sites were associated with genes involved in lipid metabolism (e.g., FADS2) and neural development (e.g., KIF26A), and enriched in 81 biological pathways.

Conclusions:

  • VLBW adults exhibit distinct, tissue-specific DNA methylation patterns compared to their siblings.
  • These epigenetic alterations are concentrated in pathways critical for lipid metabolism, neurodevelopment, and cardiometabolic regulation.
  • The findings suggest persistent, tissue-specific epigenetic modifications in individuals born with VLBW, potentially impacting long-term health.
Abstract

Keywords:
DNA methylationEpigenome-wide association studies (EWAS)adipose tissuepreterm birthvery low birth weight (VLBW)

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