Determining gestational age using genome methylation profile

Background: Gestational age determination by traditional tools (last menstrual period, ultrasonography measurements and Ballard Maturational Assessment in newborns) have major limitations and therefore there is a need to find molecular marker approaches that can be used to determine the accurate gestational age of the newborn. Methods: We performed RRBS (Reduced Representation Bisulfite Sequencing) on 41 cord blood and matching placenta samples. Results: We identified a set of 316 Differentially Methylated Regions (DMRs) that undergo demethylation in late gestational age in cord blood cells and can predict the gestational age (r = -0.7, p value<0.0001). 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=0.77, p value=1.87E-05). Conclusion: Taken together, this study demonstrates that DNA methylation can accurately predict gestational age. The clinical use of this predictor should be further investigated. Cord blood and placenta samples were collected from 48 pregnancies that met the enrolment criteria. Samples with low quality DNA were removed. The methylation profile was determined for 40 whole blood samples and 41 placenta samples.