Dynamic Changes in DNA Methylation Occur during the First Year of Life in Preterm Infants.

BACKGROUND

Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity.

METHODS

Fifty preterm infants were seen and assessed at birth, term equivalent age, 3 months and 1-year corrected ages; 40 term infants were seen at birth, 3 months and 1 year. Saliva was collected for DNA extraction at birth, term, and 1 year. Pyrosequencing of bisulfite-converted DNA was performed to measure DNA methylation at specific CpG sites within the and loci.

RESULTS

Weight and head circumference was reduced in preterm infants at all time points. Preterm infants had a higher percentage body fat at term-corrected age, but this difference was not persistent. DNA methylation at the differentially methylated region (DMR) of () and was lower in preterm infants at birth- and term-corrected age compared to term infants at birth. and methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation at at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation at at birth. There were no persistent differences in DNA methylation at 1 year of age.

CONCLUSION

Changes in DNA methylation were identified at key regions of and in preterm infants in early life. Potential contributing factors include maternal smoking and social deprivation. However, these changes did not persist at 1 year of age and further longitudinal studies are required to determine any associations between altered DNA methylation in the perinatal period of individuals born preterm and their long-term health.