Determining gestational age using genome methylation profile: A novel approach for fetal medicine

Gestational age determination by traditional tools (last menstrual period, ultrasonography measurements and Ballard Maturational Assessment in newborns) has major limitations and therefore there is a need to find different approaches. In this study, we looked for a molecular marker that can be used to determine the accurate gestational age of the newborn. To this end, we performed reduced representation bisulfite sequencing (RRBS) on 41 cord blood and matching placenta samples from women between 25 and 40 weeks of gestation and generated an epigenetic clock based on the methylation level at different loci in the genome. We identified a set of 332 differentially methylated regions (DMRs) that undergo demethylation in late gestational age in cord blood cells and can predict the gestational age (r = -.7, P = 2E-05). Once the set of 411 DMRs that undergo de novo methylation in late gestational age was used in combination with the first set, it generated a more accurate clock (R = .77, P = 1.87E-05). We have compared gestational age determined by Ballard score assessment with our epigenetic clock and found high concordance. Taken together, this study demonstrates that DNA methylation can accurately predict gestational age and thus may serve as a good clinical predictor.