Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Calafat Antonia M[original query] |
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Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study.
Starling AP , Liu C , Shen G , Yang IV , Kechris K , Borengasser SJ , Boyle KE , Zhang W , Smith HA , Calafat AM , Hamman RF , Adgate JL , Dabelea D . Environ Health Perspect 2020 128 (12) 127014 BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. OBJECTIVES: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. METHODS: Among 583 mother-infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate (FDR) < 0.05 and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted p < 0.05). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin. RESULTS: Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations (ρ = 0.28 - 0.76). Methylation at one DMP (cg18587484), annotated to the gene TJAP1, was associated with perfluorooctanoate (PFOA) at FDR < 0.05. Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (RPTOR), lipid homeostasis (PON1, PON3, CIDEB, NR1H2), inflammation and immune activity (RASL11B, RNF39), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively (FDR < 0.1). DISCUSSION: DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888. |
Temporal trends and determinants of serum concentrations of per- and polyfluoroalkyl substances among Northern California mothers with a young child, 2009-2016.
Kim K , Bennett DH , Calafat AM , Hertz-Picciotto I , Shin HM . Environ Res 2020 186 109491 BACKGROUND/OBJECTIVE: Human exposure to per- and polyfluoroalkyl substances (PFAS) has changed since the early 2000s, in part, because of the phase-out and replacement of some long-chain PFAS. Studies of PFAS exposure and its temporal changes have been limited to date mostly to adults and pregnant women. We examined temporal trends and determinants of PFAS serum concentrations among mothers with a young child who participated in the CHARGE (CHildhood Autism Risk from Genetics and Environment) case-control study. METHODS: We quantified nine PFAS in serum samples collected from 2009 to 2016 in 450 Northern California mothers when their child was 2-5 years old. With five compounds that were detected in more than 50% of the samples, we performed multiple regression to estimate least square geometric means (LSGMs) of PFAS concentrations with adjustment for sampling year and other characteristics that may affect maternal concentrations (e.g., breastfeeding duration). We also used time-related regression coefficients to calculate percent changes over the study period. RESULTS: LSGM concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) decreased over the study period [percent change (95% confidence interval): -10.7% (-12.7%, -8.7%); -10.8% (-12.9%, -8.5%); -8.0% (-10.5%, -5.5%), respectively]. On the other hand, perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) showed mixed time trends. Among the selected covariates, longer breastfeeding duration was associated with decreased maternal serum concentrations of PFOA, PFOS, PFHxS, PFNA and PFDA. CONCLUSIONS: Our study demonstrated that body burden of some common long-chain PFAS among California mothers with a young child decreased over the study period and that breastfeeding appears to contribute to the elimination of PFAS in lactating mothers. |
Prenatal exposure to nonpersistent endocrine disruptors and behavior in boys at 3 and 5 years
Philippat C , Nakiwala D , Calafat Antonia M , Botton J , De Agostini M , Heude B , Slama R . Environ Health Perspect 2017 125 (9) 1-9 BACKGROUND: Sex-specific associations have been reported between phthalates, bisphenol A (BPA), and child behavior. No data on large study populations are available for other phenols with possible endocrine-disrupting properties. OBJECTIVES: We aimed to study associations between prenatal exposure to phthalates and several phenols on behavior among male infants. METHODS: We quantified 11 phthalate metabolites and nine phenols (four parabens, benzophenone-3, BPA, two dichlorophenols, triclosan) in spot urine samples collected during pregnancy among EDEN cohort mothers who delivered a boy. Mothers completed the Strength and Difficulties Questionnaire (SDQ) when their children were 3.1 (n=529) and 5.6 (n=464) y old. RESULTS: BPA was positively associated with the relationship problems subscale at 3 y [incidence rate ratio (IRR): 1.11; 95% confidence interval (CI): 1.03, 1.20] and the hyperactivity-inattention subscale scores at 5 y (IRR: 1.08; 95% CI: 1.01, 1.14). Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problem, and emotional symptom scores at 3 y. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 y. After dichotomizing SDQ scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 y. CONCLUSIONS: The observed associations between BPA, MnBP, and behavior in boys are consistent with previous findings. Further health impact assessment studies based on dose-response functions corrected for exposure misclassification are required to quantify the public health burden possibly entailed by such associations. |
Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children.
Huen K , Calafat AM , Bradman A , Yousefi P , Eskenazi B , Holland N . Environ Res 2016 148 55-62 Phthalates are frequently used in personal care products and plasticizers and phthalate exposure is ubiquitous in the US population. Exposure to phthalates during critical periods in utero has been associated with a variety of adverse health outcomes but the biological mechanisms linking these exposures with disease are not well characterized. In this study, we examined the relationship of in utero phthalate exposure with repetitive element DNA methylation, an epigenetic marker of genome instability, in children from the longitudinal birth cohort CHAMACOS. Methylation of Alu and long interspersed nucleotide elements (LINE-1) was determined using pyrosequencing of bisulfite-treated DNA isolated from whole blood samples collected from newborns and 9 year old children (n=355). Concentrations of eleven phthalate metabolites were measured in urine collected from pregnant mothers at 13 and 26 weeks gestation. We found a consistent inverse association between prenatal concentrations of monoethyl phthalate, the most frequently detected urinary metabolite, with cord blood methylation of Alu repeats (beta(95%CI): -0.14 (-0.28,0.00) and -0.16 (-0.31, -0.02)) for early and late pregnancy, respectively, and a similar but weaker association with LINE-1 methylation. Additionally, increases in urinary concentrations of di-(2-ethylhexyl) phthalate metabolites during late pregnancy were associated with lower levels of methylation of Alu repeats in 9 year old blood (significant p-values ranged from 0.003 to 0.03). Our findings suggest that prenatal exposure to some phthalates may influence differences in repetitive element methylation, highlighting epigenetics as a plausible biological mechanism through which phthalates may affect health. |
Urinary bisphenol A concentrations and cytochrome P450 19 A1 (Cyp19) gene expression in ovarian granulosa cells: an in vivo human study.
Ehrlich S , Williams PL , Hauser R , Missmer SA , Peretz J , Calafat AM , Flaws JA . Reprod Toxicol 2013 42C 18-23 BACKGROUND: Exposure to bisphenol A (BPA), a chemical widely used in consumer products, has been associated with in vitro Cyp19 gene expression. OBJECTIVE: To evaluate an in vivo human model of Cyp19 gene expression in granulosa cells. STUDY DESIGN: A subset of an ongoing prospective cohort study of women undergoing in vitro fertilization (IVF) at Massachusetts General Hospital. METHODS: Mixed effect models were used to evaluate the association of urinary BPA concentrations with granulosa cell Cyp19 mRNA expression. RESULTS: In 61 women undergoing 76 IVF cycles, adjusted changes in mean Cyp19 expression (beta estimate (95% CI)) for quartiles 2, 3 and 4 as compared to the lowest quartile were: -0.97 (-2.22, 0.28); -0.97 (-2.18, 0.24) and -0.38 (-1.58, 0.82). CONCLUSIONS: An in vivo model for evaluation of Cyp19 gene expression was developed for use in epidemiologic studies. In this pilot study, we found no statistically significant linear association between urinary BPA concentrations and Cyp19 expression. |
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