The Oxygen Load Supplied during Delivery Room Stabilization of Preterm Infants Modifies the DNA Methylation Profile

Autores de IIS La Fe

• Sheila Lorente Pozo

  Autor

• Anna Parra Llorca

  Autor

• Antonio Guillermo Núñez Ramiro

  Autor

• María Cernada Badía

  Autor

• David Hervás Marín

  Autor

• Nuria Boronat González

  Autor

• Juan Sandoval Del Amor

  Autor

• Máximo Vento Torres

  Autor

Grupos

• Perinatología

• Unidad de Biomarcadores y Medicina de Precisión (UBYMP)

Abstract

Objectives To determine whether the amount of oxygen provided during postnatal stabilization changes the DNA methylome in preterm infants. Study design This prospective, observational study included 32 preterm infants <= 32 weeks of gestation who received oxygen in the delivery room. Patients were monitored using a respiratory function monitor to determine the amount of oxygen received upon stabilization. Blood samples were processed for comparison of DNA methylation before and after resuscitation using a DNA methylation high-resolution microarray Infinium Human DNA methylation EPIC 850K BeadChip. Results The median amount oxygen provided to preterm infants during stabilization was 644 mLO(2)/kg. Male sex and vaginal delivery were associated with increased oxygen needs. There were 2626 differentially methylated CpGs representing 1567 genes that showed an association with oxygen load selected and, of these. 85% were hypomethylated. We found that oxygen loads of >500 mLO(2)/kg changed the methylation pattern of the selected CpGs. Genes associated with these CpGs were "enriched" in KEGG pathways involved in cell cycle progression, DNA repair, and oxidative stress. Conclusions The oxygen load provided upon resuscitation modified the DNA methylome. Differential methylation may lead to altered expression of genes related to cell cycle progression, oxidative stress, and DNA repair. The reversibility of these early epigenetic changes is unknown but merits further study.

Keywords

• delivery room, epigenetics, oxidative stress, prematurity, stabilization