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Association of Early Life Exposure to Phthalates With Obesity and Cardiometabolic Traits in Childhood: Sex Specific Associations.

ABSTRACT: Few studies have investigated longitudinal associations between early life phthalate exposure and subsequent obesity and cardiovascular risks in children with inconsistent results. We aimed to evaluate the associations between phthalate exposure during gestation and childhood with offspring obesity and cardiometabolic risk factors in 500 mother-child pairs from the Rhea pregnancy cohort in Crete, Greece. Seven phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were quantified in spot urine samples collected from mothers (1st trimester) and their children at 4 years of age. We calculated the molar sum of DEHP metabolites (MEHP, MEHHP, MEOHP). We measured child weight, height, waist circumference, skinfold thicknesses, blood pressure (BP), and lipids at 4 and 6 years and leptin, adiponectin, and C-reactive protein at 4 years. We used generalized estimating equations to examine associations at each age and tested for interaction by sex. Child exposure to phthalate metabolites was associated with lower BMI z-scores in boys and higher BMI z-scores in girls. Each 10-fold increase in ?DEHP was associated with a change in waist circumference of -2.6 cm (95% CI: -4.72, -0.48) in boys vs. 2.14 cm (95% CI: -0.14, 4.43) in girls (p-sex interaction = 0.003) and a change in waist-to-height ratio of -0.01 (95% CI: -0.03, 0.01) in boys vs. 0.02 (95% CI: 0.01, 0.04) in girls (p-sex interaction = 0.006). Phthalate metabolite concentrations at age 4 were negatively associated with systolic and diastolic blood pressure. MEP was associated with lower systolic BP z-scores (adj. ? = -0.22; 95% CI: -0.36, -0.08) at 4 years. MnBP and MBzP were associated with lower diastolic BP z-scores (adj. ? = -0.13; 95%CI: -0.23, -0.04, and adj. ? = -0.11; 95% CI: -0.21, -0.01, respectively). A 10-fold increase in MiBP was associated with 4.4% higher total cholesterol levels (95% CI: 0.2, 8.7). Prenatal phthalate exposure was not consistently associated with child adiposity and cardiometabolic measures. Our findings suggest that early life phthalate exposure may affect child growth and adiposity in a sex-specific manner and depends on the timing of exposure.

SUBMITTER: Vafeiadi M

PROVIDER: S-EPMC6277685 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association of Early Life Exposure to Phthalates With Obesity and Cardiometabolic Traits in Childhood: Sex Specific Associations.

Vafeiadi Marina M Myridakis Antonis A Roumeliotaki Theano T Margetaki Katerina K Chalkiadaki Georgia G Dermitzaki Eirini E Venihaki Maria M Sarri Katerina K Vassilaki Maria M Leventakou Vasiliki V Stephanou Euripides G EG Kogevinas Manolis M Chatzi Leda L

Frontiers in public health 20181127

Few studies have investigated longitudinal associations between early life phthalate exposure and subsequent obesity and cardiovascular risks in children with inconsistent results. We aimed to evaluate the associations between phthalate exposure during gestation and childhood with offspring obesity and cardiometabolic risk factors in 500 mother-child pairs from the Rhea pregnancy cohort in Crete, Greece. Seven phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono- ...[more]

PMID: 30538977

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Project description:BackgroundEmerging evidence suggests that phthalate exposure may be associated with behavior problems in children and that these associations may be sex specific.MethodsIn a follow up study of 411 inner-city minority mothers and their children, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monethyl phthalate (MEP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in maternal urine samples collected during the third trimester and in child urine samples at ages 3 and 5 years. The Conners' Parent Rating Scale-Revised: Long Form (CPRS) and Child Behavior Checklist (CBCL) were administered to the mothers to assess children's behavior problems at 7 years of age. The analysis included children with available measures of CBCL, CPRS and phthalates measured in maternal urine. We performed both Quasi-Poisson regression and a mixture analysis using Weighted Quantile Sum(WQS) regression to assess the risk for CPRS scores and for internalizing and externalizing behaviors (from the CBCL) following intra-uterine exposure to the phthalate metabolites for boys and girls separately.ResultsAmong boys, increases in in anxious-shy behaviors were associated with prenatal exposure to MBzP (Mean Ratio [MR] = 1.20, 95%CI 1.05-1.36) and MiBP (Mean Ratio (MR) = 1.22, 95%CI 1.02-1.47). Among girls, increases in perfectionism were associated with MBzP (MR = 1.15, 95%CI 1.01-1.30). In both boys and girls, increases in psychosomatic problems were associated with MiBP (MR = 1.28, 95%CI 1.02-1.60), and MnBP (MR = 1.28, 95%CI 1.02-1.59), respectively. Among girls, decreased hyperactivity was associated with two DEHP metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MR = 0.83, 95%CI 0.71-0.98) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MR = 0.85, 95%CI 0.72-0.99). Using weighted Quantile Sum logistic regression, no associations were found between the Weighted Quantile Sum (WQS) of phthalate metabolites and CPRS scores or externalizing and internalizing behaviors. Nonetheless, when the analysis was performed separately for DEHP and non-DEHP metabolites significant associations were found between the WQS of DEHP metabolites and social problems in boys (OR = 2.15, 95%CI 1.13-4.06, p-value = 0.02) anxious-shy problems in girls (OR = 2.19, 95%CI 1.15-4.16, p = 0.02), and emotional lability problems in all children (OR = 0.61, 95%CI 0.38-0.97, p = 0.04). MEHP and MEOHP were the most highly weighted DEHP metabolites in WQS mixture. The analysis performed with CBCL scale corroborated these associations.ConclusionConcentration of non-DEHP metabolites was associated with anxious-shy behaviors among boys. DEHP phthalate metabolites were associated with decreased hyperactivity and impulsivity among girls on CPRS scores. These findings lend further support to the adverse associations between prenatal phthalate exposure and childhood outcomes, and clearly suggest that such associations are sex and mixture specific.

Project description:BackgroundSex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different associations of adiposity with cardiometabolic risk in females and males. We examined whether adiposity is differently associated with cardiometabolic trait levels in females and males at 3 different life stages.Methods and findingsData were from 2 generations (offspring, Generation 1 [G1] born in 1991/1992 and their parents, Generation 0 [G0]) of a United Kingdom population-based birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). Follow-up continues on the cohort; data up to 25 y after recruitment to the study are included in this analysis. Body mass index (BMI) and total fat mass from dual-energy X-ray absorptiometry (DXA) were measured at mean age 9 y, 15 y, and 18 y in G1. Waist circumference was measured at 9 y and 15 y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15 y, 18 y, and 25 y in G1. In G0, all 3 adiposity measures and the same 148 traits were available at 50 y. Using linear regression models, sex-specific associations of adiposity measures at each time point (9 y, 15 y, and 18 y) with cardiometabolic traits 3 to 6 y later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross-sectionally at 50 y. A total of 3,081 G1 and 4,887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males compared with females at younger ages (15 y to 25 y), and associations were more similar between the sexes or stronger in females at 50 y, particularly for apolipoprotein B-containing lipoprotein particles and lipid concentrations. For example, a 1 standard deviation (SD) (3.8 kg/m2) higher BMI at 18 y was associated with 0.36 SD (95% confidence interval [CI] = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25 y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females, P value for sex difference = 0.02. By contrast, at 50 y, a 1 SD (4.8 kg/m2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females, respectively, P value for sex difference = 0.42. Sex-specific associations of DXA-measured fat mass and waist circumference with cardiometabolic traits were similar to findings for BMI and cardiometabolic traits at each age. The main limitation of this work is its observational nature, and replication in independent cohorts using methods that can infer causality is required.ConclusionsThe results of this study suggest that associations of adiposity with adverse cardiometabolic risk begin earlier in the life course among males compared with females and are stronger until midlife, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts.

Project description:BackgroundAlthough previous studies suggest that exposure to traffic-related pollution during childhood increases the risk of childhood overweight or obesity (COWO), the role of early life exposure to fine particulate matter (aerodynamic diameter <2.5 ?m; PM2.5) and its joint effect with the mother’s prepregnancy body mass index (MPBMI) on COWO remain unclear.ObjectivesThe present study was conducted to examine the individual and joint effects of ambient PM2.5 exposures and MPBMI on the risk of COWO.MethodsWe estimated exposures to ambient PM2.5in utero and during the first 2 y of life (F2YL), using data from the U.S. Environmental Protection Agency’s (EPA’s) Air Quality System matched to residential address, in 1,446 mother–infant pairs who were recruited at birth from 1998 and followed up prospectively through 2012 at the Boston Medical Center in Massachusetts. We quantified the individual and joint effects of PM2.5 exposure with MPBMI on COWO, defined as the child’s age- and sex-specific BMI z-score ?85th?percentile at the last well-child care visit between 2 and 9 y of age. Additivity was assessed by estimating the reduced excess risk due to interaction.ResultsComparing the highest and lowest quartiles of PM2.5, the adjusted relative risks (RRs) [95% confidence intervals (CIs)] of COWO were 1.3 (95% CI: 1.1, 1.5), 1.2 (95% CI: 1.0, 1.4), 1.2 (95% CI: 1.0, 1.4), 1.3 (95% CI: 1.1, 1.6), 1.3 (95% CI: 1.1, 1.5) and 1.3 (1.1, 1.5) during preconception; the first, second, and third trimesters; the entire period of pregnancy; and F2YL, respectively. Spline regression showed a dose–response relationship between PM2.5 levels and COWO after a threshold near the median exposure (10.46 ?g/m3–10.89 ?g/m3). Compared with their counterparts, children of obese mothers exposed to high levels of PM2.5 had the highest risk of COWO [RR?2.0, relative excess risk due to interaction (RERI) not significant].ConclusionsIn the present study, we observed that early life exposure to PM2.5 may play an important role in the early life origins of COWO and may increase the risk of COWO in children of mothers who were overweight or obese before pregnancy beyond the risk that can be attributed to MPBMI alone. Our findings emphasize the clinical and public health policy relevance of early life PM2.5 exposure. https://doi.org/10.1289/EHP261

Dataset Information

Association of Early Life Exposure to Phthalates With Obesity and Cardiometabolic Traits in Childhood: Sex Specific Associations.

Publications

Association of Early Life Exposure to Phthalates With Obesity and Cardiometabolic Traits in Childhood: Sex Specific Associations.

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