![]() ![]() The effects of gestational age at birth on health outcomes may be linked to epigenetic patterns established in utero or early in the postnatal period. ![]() Although gestational age at birth exhibits some normal variation, both preterm and post-term births are associated with an increased risk of adverse perinatal outcomes and health outcomes later in life. This is necessary for investigating the impact of prenatal factors on pregnancy outcomes and any deviation from normal fetal development. As more datasets are being generated on the EPIC platform, this clock will be valuable in studies using gestational age to assess neonatal development.Īccurate determination of gestational age is important for assessing fetal development and maturity. We present the first EPIC-based predictor of gestational age and demonstrate its robustness and precision in ART and non-ART newborns. Furthermore, validating the clock on ART newborns with known embryo transfer date confirmed that DNA methylation is an accurate predictor of gestational age ( R 2 = 0.767, MAD = 3.7 days). Restricting the analysis to CpGs shared between 450 K and EPIC did not reduce the precision of the clock. ![]() Our new epigenetic gestational age clock showed higher precision and accuracy in predicting gestational age than previous gestational age clocks ( R 2 = 0.724, median absolute deviation (MAD) = 3.14 days). The performance of the clock was compared to previously published gestational age clocks in an independent replication sample of 148 newborns from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restrictions (PREDO) study-a prospective pregnancy cohort of Finnish women. The predicted gestational age was compared to clinically estimated gestational age in 200 non-ART and 838 ART newborns using MM-type robust regression. For the ART-conceived newborns, the START dataset had detailed information on the embryo transfer date and the specific ART procedure used for conception. We built an epigenetic gestational age clock using Lasso regression trained on 755 randomly selected non-ART newborns from the Norwegian Study of Assisted Reproductive Technologies (START)-a substudy of the Norwegian Mother, Father, and Child Cohort Study (MoBa). Our aims here were to build an epigenetic gestational age clock specific for the EPIC array and to evaluate its precision and accuracy using the embryo transfer date of newborns from the largest EPIC-derived dataset to date on assisted reproductive technologies (ART). Previous predictors of epigenetic gestational age were based on DNA methylation data from the Illumina HumanMethylation 27 K or 450 K array, which have subsequently been replaced by the Illumina MethylationEPIC 850 K array (EPIC). DNA methylation at birth has proven to be an accurate predictor of gestational age. Gestational age is a useful proxy for assessing developmental maturity, but correct estimation of gestational age is difficult using clinical measures. ![]()
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