Dataset Information

Phthalates and thyroid function in preschool age children: Sex specific associations.

ABSTRACT: BACKGROUND:Research relating either prenatal or concurrent measures of phthalate exposure to thyroid function in preschool children is inconclusive. METHODS:In a study of inner-city mothers and their children, metabolites of di-n-butyl phthalate, butylbenzyl phthalate, di-isobutyl phthalate, di(2-ethylhexyl) phthalate, and diethyl phthalate were measured in a spot urine sample collected from women in late pregnancy and from their children at age 3years. We measured children's serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) at age 3. Linear regression models were used to investigate the associations between phthalate metabolites, measured in maternal urine during late pregnancy and measured in child urine at age 3 and thyroid function measured at age 3. RESULTS:Mean concentrations (ranges) were 1.42ng/dL (1.02-2.24) for FT4, and 2.62uIU/mL (0.61-11.67) for TSH. In the children at age 3, among girls, FT4 decreased with increasing loge mono-n-butyl phthalate [estimated b=-0.06; 95% CI: (-0.09, -0.02)], loge mono-isobutyl phthalate [b=-0.05; 95% CI: (-0.09, -0.01)], loge monoethyl phthalate [b=-0.04; 95% CI: (-0.07, -0.01)], and loge mono(2-ethyl-5-hydroxyhexyl) phthalate [b=-0.04; 95% CI: (-0.07, -0.003)] and loge mono(2-ethyl-5-oxy-hexyl) phthalate [b=-0.04; 95% CI: (-0.07, -0.004)]. In contrast, among boys, we observed no associations between FT4 and child phthalate metabolites at age 3. On the other hand, in late gestation, FT4 increased with increasing loge mono-(2-ethylhexyl) phthalate [estimated b=0.04; 95% CI: (0.02, 0.06)] and no sex difference was observed. We found no associations between phthalate biomarkers measured in either the child or prenatal samples and TSH at age 3. CONCLUSIONS:The data show inverse and sex specific associations between specific phthalate metabolites measured in children at age 3 and thyroid function in preschool children. These results may provide evidence for the hypothesis that reductions in thyroid hormones mediate associations between early life phthalate exposure and child cognitive outcomes.

SUBMITTER: Morgenstern R

PROVIDER: S-EPMC5533628 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Phthalates and thyroid function in preschool age children: Sex specific associations.

Morgenstern Rachelle R Whyatt Robin M RM Insel Beverly J BJ Calafat Antonia M AM Liu Xinhua X Rauh Virginia A VA Herbstman Julie J Bradwin Gary G Factor-Litvak Pam P

Environment international 20170527

<h4>Background</h4>Research relating either prenatal or concurrent measures of phthalate exposure to thyroid function in preschool children is inconclusive.<h4>Methods</h4>In a study of inner-city mothers and their children, metabolites of di-n-butyl phthalate, butylbenzyl phthalate, di-isobutyl phthalate, di(2-ethylhexyl) phthalate, and diethyl phthalate were measured in a spot urine sample collected from women in late pregnancy and from their children at age 3years. We measured children's seru ...[more]

PMID: 28554096

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Project description:BackgroundEvolving animal studies and limited epidemiological data show that prenatal air pollution exposure is associated with childhood obesity. Timing of exposure and child sex may play an important role in these associations. We applied an innovative method to examine sex-specific sensitive prenatal windows of exposure to PM2.5 on anthropometric measures in preschool-aged children.MethodsAnalyses included 239 children born ≥ 37 weeks gestation in an ethnically-mixed lower-income urban birth cohort. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatio-temporal model. Body mass index z-score (BMI-z), fat mass, % body fat, subscapular and triceps skinfold thickness, waist and hip circumferences and waist-to-hip ratio (WHR) were assessed at age 4.0 ± 0.7 years. Using Bayesian distributed lag interaction models (BDLIMs), we examined sex differences in sensitive windows of weekly averaged PM2.5 levels on these measures, adjusting for child age, maternal age, education, race/ethnicity, and pre-pregnancy BMI.ResultsMothers were primarily Hispanic (55%) or Black (26%), had ≤ 12 years of education (66%) and never smoked (80%). Increased PM2.5 exposure 8-17 and 15-22 weeks gestation was significantly associated with increased BMI z-scores and fat mass in boys, but not in girls. Higher PM2.5 exposure 10-29 weeks gestation was significantly associated with increased WHR in girls, but not in boys. Prenatal PM2.5 was not significantly associated with other measures of body composition. Estimated cumulative effects across pregnancy, accounting for sensitive windows and within-window effects, were 0.21 (95%CI = 0.01-0.37) for BMI-z and 0.36 (95%CI = 0.12-0.68) for fat mass (kg) in boys, and 0.02 (95%CI = 0.01-0.03) for WHR in girls, all per µg/m3 increase in PM2.5.ConclusionsIncreased prenatal PM2.5 exposure was more strongly associated with indices of increased whole body size in boys and with an indicator of body shape in girls. Methods to better characterize vulnerable windows may provide insight into underlying mechanisms contributing to sex-specific associations.

Project description: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.

Project description:BackgroundEnvironmental health research has reported mixed findings on the associations between prenatal exposure to phthalates and parent-ratings of child behavioral problems.ObjectiveWe examined the consistency of the associations between prenatal urinary phthalate concentrations and child behavior scores across two standardized instruments - the Behavior Assessment System for Children-Second Edition (BASC-2) and the Child Behavior Checklist (CBCL) - using two analytical approaches used to correct for urine dilution.MethodA sample of 351 mother-child pairs were selected from a prospective birth cohort of pregnant women enrolled between 2009 and 2012. Women provided spot urine samples during the second trimester of pregnancy, which were analyzed for levels of nine urinary phthalate metabolites. When their typically developing children were 3-4 years of age, mothers completed the BASC-2 and CBCL on the same day. Adjusted regression analyses examined the associations between maternal prenatal phthalate concentrations and child behavior scores on the BASC-2 and CBCL. To correct for urine dilution, primary regression analyses included urinary creatinine concentration as a separate independent variable (i.e., covariate). In the secondary regression analyses, creatinine-adjusted phthalate concentrations were used.ResultsPrimary logistic regression analyses that included urinary creatinine as a covariate showed that higher prenatal phthalate concentrations were related to increased odds of scores falling into the borderline or clinical range on the Hyperactivity, Aggression, Anxiety, Depression, Withdrawal, Externalizing Problems, Internalizing Problems, and Behavioral Symptoms Index scales on the BASC-2 (ORs from 1.39 to 2.07), but only the Anxious/Depressed and Externalizing Problems scales on the CBCL (ORs from 1.80 to 3.28). Primary linear regression analyses showed that higher prenatal phthalate concentrations were related to higher scores on the Externalizing Problems (β's = 0.16), Internalizing Problems (β's from 0.16 to 0.20), and Behavioral Symptoms Index (β's from 0.18 to 0.21) scales on the BASC-2, but not related to any CBCL scales. Sex-stratified analyses found that many associations were only significant for male children. Secondary analyses using creatinine-adjusted phthalate concentrations revealed that some of the associations from the primary analyses remained significant; however, a number of unique associations were observed.ConclusionPrenatal phthalate exposure was associated with preschool behavioral development; however, findings were not consistent for the BASC-2 and CBCL, especially related to the clinical/syndrome scales and Internalizing Problems scale. Further, many findings differed based on the analytical approach used to correct for urine dilution. Future work is needed to delineate the similarities and differences between similarly named child behavior constructs assessed by different neurodevelopmental assessments. Also, research is needed to better understand why and how different analytical approaches influence the reported associations between maternal prenatal phthalate concentrations and children's behavior problems.

Project description:BackgroundThe gut microbiota is recognized as a regulator of brain development and behavioral outcomes during childhood. Nonetheless, associations between the gut microbiota and behavior are often inconsistent among studies in humans, perhaps because many host-microbe relationships vary widely between individuals. This study aims to stratify children based on their gut microbiota composition (i.e., clusters) and to identify novel gut microbiome cluster-specific associations between the stool metabolomic pathways and child behavioral outcomes.MethodsStool samples were collected from a community sample of 248 typically developing children (3-5 years). The gut microbiota was analyzed using 16S sequencing while LC-MS/MS was used for untargeted metabolomics. Parent-reported behavioral outcomes (i.e., Adaptive Skills, Internalizing, Externalizing, Behavioral Symptoms, Developmental Social Disorders) were assessed using the Behavior Assessment System for Children (BASC-2). Children were grouped based on their gut microbiota composition using the Dirichlet multinomial method, after which differences in the metabolome and behavioral outcomes were investigated.ResultsFour different gut microbiota clusters were identified, where the cluster enriched in both Bacteroides and Bifidobacterium (Ba2) had the most distinct stool metabolome. The cluster characterized by high Bifidobacterium abundance (Bif), as well as cluster Ba2, were associated with lower Adaptive Skill scores and its subcomponent Social Skills. Cluster Ba2 also had significantly lower stool histidine to urocanate turnover, which in turn was associated with lower Social Skill scores in a cluster-dependent manner. Finally, cluster Ba2 had increased levels of compounds involved in Galactose metabolism (i.e., stachyose, raffinose, alpha-D-glucose), where alpha-D-glucose was associated with the Adaptive Skill subcomponent Daily Living scores (i.e., ability to perform basic everyday tasks) in a cluster-dependent manner.ConclusionsThese data show novel associations between the gut microbiota, its metabolites, and behavioral outcomes in typically developing preschool-aged children. Our results support the concept that cluster-based groupings could be used to develop more personalized interventions to support child behavioral outcomes. Video Abstract.

Project description:BackgroundThyroid hormones are essential for early neurocognitive development and growth and development in childhood and adolescence. However, the reference intervals (RIs) for thyroid hormones in Chinese pediatric individuals remain unclear. This study aimed to establish thyroid hormone RIs for a Chinese pediatric population according to appropriate age- and sex-specific partitioning.MethodsIn this prospective observational study, a total of 1,279 healthy children (singletons, aged from 1 day to 12 years) were recruited, and serum samples were analyzed on a Mindray automated chemiluminescence immunoassay analyzer CL-6000i for thyroid hormone detection, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (T3), and total thyroxine (T4). Age and sex-specific RIs were established, and the corresponding 95% confidence intervals (CIs) were calculated in accordance with the Clinical Laboratory Standards Institute (CLSI) document C28-A3 guidelines.ResultsQuantile testing revealed that the median (P50) and RIs [2.5th percentile (P2.5)-97.5th percentile (P97.5)] for TSH, FT3, T3, and T4 of males differed significantly from those of females (P<0.05), except for FT4 (P=0.483). For FT3 and T3, the RIs of males were higher than that of females, and the RI of T4 for males was narrower and higher than that of females [P2.5-P97.5: 72.33-171.60 vs. 72.31-176.27 nmol/L; P50: 116.75 vs. 113.47 nmol/L, P=0.011]. RIs for TSH, FT3, FT4, T3, and T4 showed sex- and age-specific properties and displayed a wide variation during the first month of life but gradually narrowed and concentrated with increasing age. In addition, RIs of TSH, FT3, FT4, and T3 in males differed significantly from females in the first month of life (TSH: 1.46-10.87 vs. 1.08-11.35 mIU/L; FT3: 2.96-7.08 vs. 2.35-7.27 pmol/L, FT4: 13.34-28.65 vs. 13.82-31.83 pmol/L; T3: 0.83-2.33 vs. 0.72-2.46 nmol/L). The RI of T4 also exhibited a difference between males and females in the 9- to 12-year age group (59.31-150.72 vs. 63.29-146.94 pmol/L for males and females, respectively).ConclusionsPediatric RIs of thyroid hormones display age- and sex-specific trends. The RIs established in this study will improve the accuracy of TSH assay result interpretations and clinical decision-making in clinical laboratories that utilize the Mindray analytical platform.

Dataset Information

Phthalates and thyroid function in preschool age children: Sex specific associations.

Publications

Phthalates and thyroid function in preschool age children: Sex specific associations.

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