Dynamic changes in DNA methylation occur during the first Year of life in preterm infants

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 C_pG sites within the IGF₂ and FKBP₅ 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 IGF₂ (IGF₂DMR₂) and FKBP₅ was lower in preterm infants at birth- and term-corrected age compared to term infants at birth. IGF₂DMR₂ and FKBP₅ methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation at IGFlDMR₂ at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation at FKBP₅ 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 IGF₂/H1₉ and FKBP₅ 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.