Associations of early life phthalate exposures with adolescent lipid levels and insulin resistance: The HOME Study.

BACKGROUND: Early-life phthalate exposures may disrupt metabolic processes; however few prospective studies have assessed whether these associations extend to cardiometabolic outcomes during adolescence. METHODS: Among 183 mother-adolescent pairs in a prospective cohort study that enrolled pregnant women in Cincinnati, OH (2003-2006), we quantified nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children. At age 12 years, we assessed triglycerides, high-density (HDL) and low-density (LDL) lipoprotein cholesterol, insulin, and glucose from fasting serum samples and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Using multiple informant models, we estimated covariate-adjusted associations between urinary phthalate concentrations at each time period and cardiometabolic biomarkers at age 12 years, including modification by child sex. RESULTS: Although most associations were weak or null, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and monobenzyl phthalate (MBzP) concentrations were generally associated with lower LDL at age 12 years. A 10-fold increase in 4- and 12-year MEP was associated with -15.3 mg/dL (95% CI: 27.5, -3.13 mg/dL) and -11.8 mg/dL (-22.0, -1.51 mg/dL) lower LDL, respectively. Discrepant associations were observed in females versus males: a 10-fold increase in 3-year MEP concentrations was associated with 12.0 mg/dL (95% CI: 7.11, 31.1 mg/dL) higher LDL levels in males and -30.4 mg/dL (95% CI: 50.9, -9.8 mg/dL) lower LDL levels in females. Some urinary phthalate concentrations were cross-sectionally associated with HOMA-IR. CONCLUSIONS: Early-life phthalate biomarker concentrations may be inversely associated with LDL during early adolescence in an exposure-period and sex-dependent manner.

Gestational and childhood phthalate exposures and adolescent body composition: The HOME study.

BACKGROUND: Early life phthalate exposures may disrupt metabolism but results from human studies are inconsistent and few have examined body composition during adolescence. We investigated associations of gestational and childhood urinary phthalate biomarker concentrations with body composition at age 12 years. METHODS: We used data from 206 mother-child pairs in a prospective pregnancy and birth cohort enrolled in Cincinnati, OH from 2003 to 2006. We measured nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children at 1, 2, 3, 4, 5, 8, and 12 years. At age 12 years, we assessed fat and lean mass of the whole body and android and gynoid subregions, and visceral fat area with dual x-ray absorptiometry, and calculated android to gynoid %fat ratio and age- and sex-standardized fat and lean mass index z-scores. Using a multiple informant model, we estimated covariate-adjusted associations between urinary phthalate biomarker concentrations at each time period and outcomes at age 12 years. We assessed effect measure modification by child sex using stratified models. RESULTS: Generally, urinary mono-benzyl phthalate (MBzP) concentrations were modestly associated with lower fat and lean mass. Each 10-fold increase in urinary MBzP concentrations during gestation and at ages 5 and 8 years was associated with a -0.34 (95%CI: -0.72, 0.05), -0.44 (95% CI: -0.83, -0.05), and -0.35 (95% CI: -0.71, 0.00) z-score difference in lean body mass index, respectively. Urinary monoethyl phthalate, mono-(3-carboxypropyl) phthalate, and summed di(2-ethylhexyl) phthalate metabolites were associated with greater lean mass at some exposure periods. Slightly weaker but similar patterns of association were found with other body composition measures; associations did not differ by child sex. CONCLUSION: While most associations were weak, exposure to certain phthalates during gestation and childhood may be associated with adolescent body composition, particularly lean mass.

Prenatal maternal organophosphorus pesticide exposures, paraoxonase 1, and childhood adiposity in the Mount Sinai Children's Environmental Health Study.

BACKGROUND: Animal studies suggest that organophosphorus pesticides (OPs) may be environmental obesogens. While prenatal OP exposures have been associated with altered infant glucose metabolism, associations with pediatric adiposity remain unknown. METHODS: We summed concentrations of three dimethylphosphate (∑DMP) and three diethylphosphate (∑DEP) metabolites of OPs measured in third trimester spot urine samples collected from pregnant women enrolled in New York City, 1998-2002. We measured percent fat mass using bio-electrical impedance analysis and calculated age- and sex-standardized body mass index (BMI) z-scores from anthropometric measurements collected at approximately 4, 6, and 7-9 years of age (166 children, 333 observations). We assessed covariate-adjusted associations of OPs with repeated adiposity measures using linear mixed models and evaluated effect measure modification (EMM) by sex and paroxonase (PON) 1 -108C/T and Q192R polymorphisms measured in maternal peripheral blood samples. RESULTS: The geometric mean urinary concentration of ∑DMP metabolites (29.9 nmol/L, IQR: 105.2 nmol/L) was higher than ∑DEP metabolites (8.8 nmol/L, IQR: 31.2 nmol/L). Adjusted associations were null, with differences in fat mass per 10-fold increase in prenatal ∑DMP and ∑DEP concentrations of 0.7% (95% CI: -0.6, 2.0) and 0.8% (95% CI: -0.4, 2.0), respectively. Maternal PON1-108C/T polymorphisms modified relationships of prenatal ∑DMP with percent fat mass (EMM p-value = 0.18) and ∑DEP with BMI z-scores (EMM p-value = 0.12). For example, ∑DMP was modestly associated with increased percent fat mass among children of mothers with the at-risk CT or TT genotype (ß = 1.2%, 95% CI: -0.6, 3.0) but not among those whose mothers had the CC genotype (ß = -0.4%, 95% CI: -2.4, 1.5). Associations were not modified by sex or maternal PON1 Q192R polymorphisms. CONCLUSIONS: We observed little evidence of a relationship between prenatal OP exposures and child adiposity, although there was some suggestion of increased risk among offspring of mothers who were slow OP metabolizers. Larger studies are warranted to further evaluate possible associations of prenatal OP exposures with child adiposity and differences by maternal PON1 genotype, which regulates OP metabolism and may increase susceptibility to exposure.

Associations of serum perfluoroalkyl substance and vitamin D biomarker concentrations in NHANES, 2003-2010.

Perfluoroalkyl substances (PFAS) are persistent endocrine disrupting chemicals found in industrial and commercial products. Previous research has shown that other endocrine disrupting chemicals such as phthalates and bisphenol A may alter circulating levels of vitamin D; however, no research has examined associations between PFAS and vitamin D biomarkers. We conducted a cross-sectional analysis of 7040 individuals aged 12 years and older participating in the 2003-2010 cycles of the United States National Health and Nutrition Examination Survey (NHANES). Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and total 25-hydroxyvitamin D [25(OH)D] were measured in serum samples. We used multivariable linear regression to estimate covariate-adjusted differences in total 25(OH)D or prevalence odds of vitamin D deficiency per log2 change in PFAS concentrations. We also assessed potential effect measure modification by gender, age, and race/ethnicity. PFAS were detected in over 98% of the samples. In adjusted models, each 2-fold increase in PFOS was associated with 0.9 nmol/L (95% CI: 0.2, 1.5) lower total 25(OH)D concentrations, with associations significantly stronger among whites (ß: -1.7; 95% CI: -2.6, -0.7) and individuals older than 60 years of age (ß: -1.7; 95% CI: -2.9, -0.5). Each 2-fold increase in PFHxS was associated with 0.8 nmol/L (95% CI: 0.3, 1.3) higher total 25(OH)D, and this association was not modified by age, gender, and race/ethnicity. PFOA and PFNA were not associated with total 25(OH)D. When assessing prevalence odds of vitamin D deficiency, we observed similar patterns of association with PFAS concentrations. Our results suggest that some PFAS may be associated with altered vitamin D levels in the United States population, and associations may vary by chemical, age, and race/ethnicity. Prospective epidemiological studies are needed to confirm our findings and determine their implications for vitamin D-associated health outcomes in children and adults.

Urinary triclosan concentrations during pregnancy and birth outcomes.

BACKGROUND: Triclosan is an antimicrobial chemical used in consumer products, and exposure is ubiquitous among pregnant women in the United States. Triclosan may reduce the levels of thyroid hormones that are important for fetal growth and development. OBJECTIVE: We investigated the relationship of prenatal triclosan exposure with birth anthropometry and gestational duration. METHODS: We used data from 378 mother-child pairs participating in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort from Cincinnati, OH. We measured triclosan concentrations in maternal urine samples collected at 16 and 26 weeks of pregnancy. We abstracted information on neonatal anthropometry and gestational duration from medical records. We used multivariable linear regression to estimate the covariate-adjusted association between the average of the two urinary triclosan concentrations and gestational age standardized weight z-score, length, head circumference, and gestational age at birth. RESULTS: Median urinary triclosan concentrations were 16ng/mL (range: <2.4 to 1501ng/mL). Each 10-fold increase in triclosan was associated with a predicted 0.15 standard deviation decrease (95% CI: -0.30, 0.00) in birth weight z-score, 0.4-cm decrease (95% CI: -0.8, 0.1) in birth length, 0.3-cm decrease (95% CI: -0.5, 0.0) in head circumference, and 0.3-week decrease (95% CI: -0.6, -0.1) in gestational age. Child sex did not modify the associations between triclosan and birth outcomes. CONCLUSIONS: In this cohort, maternal urinary triclosan concentrations during pregnancy were inversely associated with infants' birth weight, length, head circumference, and gestational age.