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Fetal DNA Methylation Associates with Early Spontaneous Preterm Birth and Gestational Age

Sasha E Parets1, Karen N Conneely, Varun Kilaru

  • 1Genetics and Molecular Biology Program, Emory University, Atlanta, Georgia, United States of America.

Plos One
|July 5, 2013
PubMed

Insights

Fetal DNA methylation patterns differ significantly in babies born preterm compared to those born at term. These epigenetic changes may offer insights into the long-term health risks associated with preterm birth (PTB).

Area of Science:

  • Epigenetics
  • Genomics
  • Perinatal Medicine

Background:

  • Spontaneous preterm birth (PTB) is a leading cause of infant morbidity and mortality.
  • Fetal DNA methylation patterns are known to vary with gestational age (GA).
  • The association between fetal epigenetic modifications and PTB remains unclear.

Purpose of the Study:

  • To investigate genome-wide fetal DNA methylation patterns in African American infants.
  • To determine if specific CpG sites are associated with early PTB or overall GA.
  • To explore the relationship between fetal epigenetic changes and PTB.

Main Methods:

  • Genome-wide DNA methylation analysis using the HumanMethylation450 BeadChip on fetal leukocyte DNA.
  • Comparison of methylation profiles between infants born preterm (24-34 weeks) and at term (39-40 weeks).
  • Statistical analysis using linear models to assess associations between CpG sites, PTB, and GA, adjusting for covariates.

Main Results:

  • 29 CpG sites were significantly associated with PTB, independent of GA.
  • 9,637 CpG sites were associated with GA, with most showing decreased methylation at shorter GAs.
  • GA-associated CpG sites were enriched in genes involved in embryonic development and extracellular matrix functions.

Conclusions:

  • Significant differences in fetal DNA methylation exist between preterm and term births.
  • These distinct epigenetic patterns at birth may indicate long-term health consequences for preterm infants.
  • The study identifies specific epigenetic markers potentially linked to PTB and developmental trajectories.

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