BackgroundGestational 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.ResultsWe 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.ConclusionsDNA 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1068-z) contains supplementary material, which is available to authorized users.

Epidemiologic studies revealed low mortality in hormone-dependent cancer in Japanese women and men consuming a traditional diet. We previously found that certain diphenolic food components, lignans and isoflavonoids, which are converted to biologically active hormone-like substances by intestinal microflora, may be cancer-protective agents. Therefore, we studied urinary excretion of these compounds (enterolactone, enterodiol, daidzein, equol, and O-desmethylangolensin) in 10 women and 9 men in a rural village south of Kyoto, Japan. The subjects consumed a typical low-fat diet with much rice and soy products, fish, and vegetables. An isotope-dilution gas chromatographic-mass spectrometric method was used for the assays. The urinary excretion of lignans was low but that of the isoflavonoids was very high. The excretion of isoflavonoids correlated with soybean-product intake. The low mortality in breast and prostate cancer of Japanese women and men, respectively, may be due to the high intake of soybean products.

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Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni < 1.06 x 10 −7 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

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