DNAMethylation
Source: Christoph Bock, Max Planck Institute for Informatics

A new meta-analysis shows that the length of a human pregnancy correlates with DNA changes, including DNA methylation changes. A study among 6,000 newborns shows that for each additional week of gestation, DNA methylation differences were observed in thousands of genes tested in umbilical cord blood. The study appears in Genome Medical.

Epigenetic reactions, such as DNA methylation, are known to have an important role in development. Because of this, researchers studied the associations between gestational age and blood DNA methylation in children.

Researchers from the International Pregnancy and Childhood Epigenetics (PACE) consortium found that most of the observed DNA methylations at birth tended not to persist into childhood, but in 17 percent the levels were completely stable from birth to adolescence.

“Knowledge about DNA methylation and gene expression profiles associated with length of gestation may help to better understand both the molecular basis of abnormal processes related to prematurity as well as normal human development,” the researchers wrote in their paper.

A total of 6,885 newborns from 26 different studies and among 20 different patient cohorts were first included in the meta-analysis. After excluding newborns with maternal complications, a subset of 3,648 newborns were further analyzed via cord blood.

To assess DNA methylation patters at later ages, the researchers looked at whole blood DNA methylation patterns observed at gestational followed out to early childhood (453 subjects), at school age (899 individuals), and adolescence (1,129 subjects).They also tested fetal brain and lung tissues in relation to gestational age.

The PACE researchers identified 8899 sites, known as CpGs, across the genome where gestational age at birth was associated with cord blood DNA methylation. They also found several differentially methylated regions (DMRs) associated with gestational age.

They also found clear overlap of differentially methylated CpGs in cord blood, fetal brain and fetal lung tissues in relation to gestational age. For the majority, changes were most prominent during early life with DNA methylation patterns stabilizing by school age. In about 17 percent of cases DNA methylation patterns seen at gestation persisted into childhood and into adolescence.

Further analysis showed that many DNA methylation changes were linked to several functional pathways involved in human disease, and were enriched for several known to be critical to fetal development.

“Our results provide a comprehensive catalogue of differential methylation in relation to gestational age at birth, which may serve as utility to the growing community of researchers studying the developmental origins of adult disease,” the authors write.

The group plans on investigating deeper into that link to see whether, and how, DNA changes are associated with health issues in premature babies and children.

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