DNA methylation and telomere length in 2-5 year olds with intrauterine preeclampsia exposure: a P4 sub-study.

Preeclampsia is a hypertensive disorder of pregnancy characterised by new onset hypertension at ≥ 20 weeks' gestation accompanied by maternal organ dysfunction and/ or fetal compromise. This hypertensive exposure in pregnancy has known long-term consequences for both the mother and child. Presently, the mechanisms for these cardiometabolic, immunological and neurodevelopmental consequences in the child aren't well characterised, but epigenetic changes in development and premature biological aging may play a role in the development of these long-term morbidities. To investigate, we assessed genome-wide DNA methylation and biological aging in the blood of 2-5 year-old children with (n = 20) or without (n = 20) previous intrauterine exposure to preeclampsia. Exposure to preeclampsia was associated with 103 differentially methylated regions (DMRs) proximal to both known and novel candidate genes. Biological aging, as determined by two telomere length quantification methods and an epigenetic clock, was found to not be statistically different between the preeclampsia exposure and normotensive pregnancy groups. From the 103 DMRs, gene ontology analysis highlighted that 17 regions are proximal to genes involved in cell-cell adhesion (p = 7.49 × 10-12), and more specifically homophilic cell adhesion (p = 7.49 × 10-12). This is the first study to consider genome-wide epigenetic changes in the blood of young children exposed to preeclampsia in utero, with previous studies concentrating on cord blood or placental biopsy material collected at birth.