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.

Background:Some evidence suggests that fluoride may be neurotoxic to children. Few of the epidemiologic studies have been longitudinal, had individual measures of fluoride exposure, addressed the impact of prenatal exposures or involved more than 100 participants.Objective:Our aim was to estimate the association of prenatal exposure to fluoride with offspring neurocognitive development.Methods:We studied participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project. An ion-selective electrode technique was used to measure fluoride in archived urine samples taken from mothers during pregnancy and from their children when 6–12 y old, adjusted for urinary creatinine and specific gravity, respectively. Child intelligence was measured by the General Cognitive Index (GCI) of the McCarthy Scales of Children’s Abilities at age 4 and full scale intelligence quotient (IQ) from the Wechsler Abbreviated Scale of Intelligence (WASI) at age 6–12.Results:We had complete data on 299 mother–child pairs, of whom 287 and 211 had data for the GCI and IQ analyses, respectively. Mean (SD) values for urinary fluoride in all of the mothers (n=299) and children with available urine samples (n=211) were 0.90 (0.35) mg/L and 0.82 (0.38) mg/L, respectively. In multivariate models we found that an increase in maternal urine fluoride of 0.5mg/L (approximately the IQR) predicted 3.15 (95% CI: −5.42, −0.87) and 2.50 (95% CI −4.12, −0.59) lower offspring GCI and IQ scores, respectively.Conclusions:In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6–12 y. https://doi.org/10.1289/EHP655

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Objective To compare self-report and physician assessments of sexual maturation against serum hormone markers to evaluate the hypothesis that the validity of self-assessed sexual maturation is underestimated in traditional validation studies. Study design We adapted a self-assessment instrument that 248 Mexican children and adolescents, age 8–13 years, completed. Participants were examined by a trained pediatrician and provided fasting blood samples for measurement of reproductive (testosterone, estradiol, sex hormone-binding globulin (SHBG), Inhibin B) and other hormones (C-peptide, insulin-like growth factor 1 (IGF-1), leptin, dehydroepiandrosterone sulfate (DHEA-S)) known to change during adolescence. Spearman correlations (r) were calculated among the average rank of all hormones, self-, and physician-assessed Tanner stage. The method of triads was used to assess validity of self-reports by estimating correlations between self-assessments and true, but unobservable, sexual maturation based on all available data. 95% confidence intervals (CI) were constructed using bootstrap sampling. Results Validity of self-reported genitalia staging for boys was modest (r[95%CI]=0.50[0.31–0.65]) and inferior to physician assessment (0.75[0.56–0.93]). Breast stage was well reported (0.89[0.79–0.97]) and superior to physician assessment (0.80[0.70–0.89]). Pubic hair stage reported by boys (0.91[0.79–0.99]) and girls (0.99[0.96–1.00]) were superior to physician assessment (0.79[0.57–0.97] and 0.91[0.83–0.97], respectively). Conclusion Self-assessment can be validly used in epidemiologic studies for evaluation of sexual maturation in children. Physician assessment may be necessary for accurate assessment of genitalia development in boys.

Background Consumption of sugar-sweetened beverages (SSB) has been associated with risk of obesity, but little evidence exists to evaluate if age of introduction and cumulative SSB consumption increases risk in children. Objectives To estimate the relationship between age of introduction and cumulative SSB consumption with the risk of obesity in a cohort of 227 Mexican children. Methods SSB intake was measured every six months; age of introduction and cumulative consumption during the pre-school period were calculated. Height, weight, waist circumference, SSB intake and other relevant variables were measured at age 8–14 years and obesity defined using standard criteria. Results All participants were introduced to SSB before age 24 months and most (73%) before 12 months. Early SSB introduction (≤12 months) was not significantly associated with increased odds of obesity (OR=2.00, 95% CI: 0.87, 4.59). However, children in the highest tertile of cumulative SSB consumption, compared to the lowest, had almost three times the odds of general (OR=2.99, 95% CI: 1.27, 7.00) and abdominal (OR=2.70, 95% CI: 1.03, 7.03) obesity at age 8–14 years. Conclusions High SSB consumption increased the likelihood of obesity in 8–14 year-old children. Our results suggest that SSB intake should be delayed and excessive SSB consumption in pre-school period should be avoided.