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Developmental age, Aging, Epigenetic clock, DNA methylation, Preterm birth, Cord blood, Fetus, Blood spot, Biomarker, Medicaid, Socioeconomic status, Birthweight
Abstract:
Background: Gestational age is often used as a proxy for developmental
maturity by clinicians and researchers alike. DNA methylation has
previously been shown to be associated with age and has been used to
accurately estimate chronological age in children and adults. In the
current study, we examine whether DNA methylation in cord blood can be
used to estimate gestational age at birth.
Results: We find that gestational age can be accurately estimated from
DNA methylation of neonatal cord blood and blood spot samples. We
calculate a DNA methylation gestational age using 148 CpG sites selected
through elastic net regression in six training datasets. We evaluate
predictive accuracy in nine testing datasets and find that the accuracy
of the DNA methylation gestational age is consistent with that of
gestational age estimates based on established methods, such as
ultrasound. We also find that an increased DNA methylation gestational
age relative to clinical gestational age is associated with birthweight
independent of gestational age, sex, and ancestry.
Conclusions: DNA methylation can be used to accurately estimate
gestational age at or near birth and may provide additional information
relevant to developmental stage. Further studies of this predictor are
warranted to determine its utility in clinical settings and for research
purposes. When clinical estimates are available this measure may
increase accuracy in the testing of hypotheses related to developmental
age and other early life circumstances.
