Self-reported pregnancy exposures and placental DNA methylation in the MARBLES prospective autism sibling study.

Human placenta is a fetal-derived tissue that offers a unique sample of epigenetic and environmental exposures present in utero. In the MARBLES prospective pregnancy study of high-risk younger siblings of children with autism spectrum disorder (ASD), pregnancy and environmental factors collected by maternal interviews were examined as predictors of placental DNA methylation, including partially methylated domains (PMDs), an embryonic feature of the placental methylome. DNA methylation data from MethylC-seq analysis of 47 placentas of children clinically diagnosed at 3 years with ASD or typical development using standardized assessments were examined in relation to: child's gestational age, birth-weight, and diagnosis; maternal pre-pregnancy body mass index, smoking, education, parity, height, prenatal vitamin and folate intake; home ownership; pesticides professionally applied to lawns or gardens or inside homes, pet flea/tick pouches, collars, or soaps/shampoos used in the 3 months prior to or during pregnancy. Sequencing run, order, and coverage, and child race and sex were considered as potential confounders. Akaike information criterion was used to select the most parsimonious among candidate models. Final prediction models used sandwich estimators to produce homoscadisticity-robust estimates of the 95% confidence interval (CI) and P-values controlled the false discovery rate at 5%. The strongest, most robust associations were between pesticides professionally applied outside the home and higher average methylation over PMDs [0.45 (95% CI 0.17, 0.72), P = 0.03] and a reduced proportion of the genome in PMDs [-0.42 (95% CI - 0.67 to -0.17), P = 0.03]. Pesticide exposures could alter placental DNA methylation more than other factors

Variability of urinary pesticide metabolite concentrations during pregnancy in the MARBLES Study.

BackgroundVariability of short-lived urinary pesticide metabolites during pregnancy raises challenges for exposure assessment.ObjectivesFor urinary metabolite concentrations 3-phenoxybenzoic acid (3-PBA) and 3,5,6-trichloro-2-pyridinol (TCPy), we assessed: (1) temporal variability; (2) variation of two urine specimens within a trimester; (3) reliability for pesticide concentrations from a single urine specimen to classify participants into exposure tertiles; and (4) seasonal or year variations.MethodsPregnant mothers (N = 166) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) Study provided urine specimens (n = 528). First morning void (FMV), pooled, and 24-h specimens were analyzed for 3-PBA and TCPy. For 9 mothers (n = 88 specimens), each urine specimen was analyzed separately (not pooled) to estimate within- and between-person variance components expressed as intraclass correlation coefficients (ICC). Pesticide concentrations from two specimens within a trimester were also assessed using ICC's. Agreement for exposure classifications was assessed with weighted Cohen's kappa statistics. Longitudinal mixed effect models were used to assess seasonal or year variations.ResultsUrinary pesticide metabolites were detected in ≥ 93% of specimens analyzed. The highest ICC from repeated individual specimens was from specific gravity-corrected FMV specimens for 3-PBA (ICC=0.13). Despite high within-person variability, the median concentrations did not differ across trimesters. Concentrations from pooled specimens had substantial agreement predicting exposure categories for TCPy (K = 0.67, 95% CI (0.59, 0.76)) and moderate agreement for 3-PBA (K = 0.59, 95% CI (0.49, 0.69)). TCPy concentrations significantly decreased from 2007 to 2014.ConclusionsPooled specimens may improve exposure classification and reduce laboratory costs for compounds with short biological half-lives in epidemiological studies