Search

BACKGROUND: Prenatal exposures to certain poly- and perfluoroalkyl substances (PFAS) are associated with reduced humoral responses to some childhood immunizations. OBJECTIVE: We estimated associations between prenatal PFAS exposure and child antibody titers for measles, mumps, rubella (MMR), and varicella after immunization. METHODS: We measured serum antibody titers of 145 children (4–8 y old) enrolled in the Healthy Start cohort in Colorado, whose mothers had PFAS quantified mid-pregnancy (2009–2014). We used linear and logistic regression models to assess the relationship between five PFAS detected in > 65% of mothers and continuous or non–high-censored (“low”) antibody titers and quantile g-computation to evaluate the overall effect of the PFAS mixture. RESULTS: Median concentrations of individual PFAS were at or below the median reported among females in the United States. After receiving two vaccine doses, seropositive levels of antibodies were detected among most (93%–100%) children. Each log-unit increase in perfluorononanoate was associated with 2.09 [95% confidence interval (CI): 1.13, 3.87] times higher odds of a low measles titer, and each log-unit increase in perfluorooctanoate was associated with 2.46 (95% CI: 1.28, 4.75) times higher odds of a low mumps titer. Odds ratios for all other PFAS were elevated, but CIs included the null. Each quartile increase in the PFAS mixture was associated with 1.35 (95% CI: 0.80, 2.26) times higher odds of a low measles titer and 1.44 (95% CI: 0.78, 2.64) times higher odds of a low mumps titer. No significant associations were observed between PFAS and varicella or rubella antibodies. In stratified analyses, associations were negative among female children, except for perfluorohexane sulfonate and varicella, whereas they were positive among males. DISCUSSION: Some prenatal PFAS were associated with lower antibody titers among fully immunized children. The potential for immunotoxic effects of PFAS requires further investigation in a larger study, because exposure is ubiquitous globally. [ABSTRACT FROM AUTHOR]

BACKGROUND: Population studies support the adverse associations of air pollution exposures with child behavioral functioning and cognitive performance, but few studies have used spatiotemporally resolved pollutant assessments. OBJECTIVES: We investigated these associations using more refined exposure assessments in 1,967 mother–child dyads from three U.S. pregnancy cohorts in six cities in the ECHO-PATHWAYS Consortium. METHODS: Pre- and postnatal nitrogen dioxide (NO2) and particulate matter (PM) ≤2.5 µm in aerodynamic diameter (PM2.5) exposures were derived from an advanced spatiotemporal model. Child behavior was reported as Total Problems raw score using the Child Behavior Checklist at age 4–6 y. Child cognition was assessed using cohort-specific cognitive performance scales and quantified as the Full-Scale Intelligence Quotient (IQ). We fitted multivariate linear regression models that were adjusted for sociodemographic, behavioral, and psychological factors to estimate associations per 2- unit increase in pollutant in each exposure window and examined modification by child sex. Identified critical windows were further verified by distributed lag models (DLMs). RESULTS: Mean NO2 and PM2.5 ranged from 8.4 to 9.0 ppb and 8.4 to 9.1 µg/m³, respectively, across pre- and postnatal windows. Average child Total Problems score and IQ were 22.7 [standard deviation (SD): 18.5] and 102.6 (SD: 15.3), respectively. Children with higher prenatal NO2 exposures were likely to have more behavioral problems [b: 1.24; 95% confidence interval (CI): 0.39, 2.08; per 2 ppb NO2], particularly NO2 in the first and second trimester. Each 2-µg/m³ increase in PM2.5 at age 2–4 y was associated with a 3.59 unit (95% CI: 0.35, 6.84) higher Total Problems score and a 2.63 point (95% CI: -5.08, -0.17) lower IQ. The associations between PM2.5 and Total Problems score were generally stronger in girls. Most predefined windows identified were not confirmed by DLMs. DISCUSSION: Our study extends earlier findings that have raised concerns about impaired behavioral functioning and cognitive performance in children exposed to NO2 and PM2.5 in utero and in early life. [ABSTRACT FROM AUTHOR]

Background: Perfluoroalkyl substances (PFAS) may affect body mass index (BMI) and other components of cardiometabolic (CM) risk during childhood, but evidence is scarce and inconsistent. OBJECTIVES: We estimated associations between prenatal PFAS exposures and outcomes relevant to cardiometabolic risk, including a composite CM- risk score. METHODS: We measured perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluoro- nonanoic acid (PFNA) in maternal plasma (first trimester). We assessed weight gain from birth until 6 mo. At 4 and 7 y, we calculated the age- and sex-specific z-scores for BMI, waist circumference (WC), and blood pressure (BP) (n ≈ 1,000). At age 4, we calculated the age-, sex-, and region- specific z-scores for cholesterol, triglycerides (TGs), high-density (HDL-C), and low-density lipoprotein cholesterol (LDL-C) (n = 627). At age 4, we calculated a CM-risk score (n = 386) as the sum of the individual age-, sex-, and region-specific z-scores for WC, BP, HDL-C, and TGs. We used the average between the negative of HDL-C z-score and TGs z-score to give similar weight to lipids and the other components in the score. A higher score indicates a higher cardiometabolic risk at age 4. Results: PFOS and PFOA were the most abundant PFAS (geometric mean: 5.80 and 2.32ng/mL, respectively). In general, prenatal PFAS concentrations were not associated with individual outcomes or the combined CM-risk score. Exceptions were positive associations between prenatal PFHxS and TGs z-score [for a doubling of exposure, β = 0.11; 95% confidence interval (CI): 0.01, 0.21], and between PFNA and the CM-risk score (β = 0.60; 95% CI: 0.04, 1.16). There was not clear or consistent evidence of modification by sex. Conclusions: We observed little or no evidence of associations between low prenatal PFAS exposures and outcomes related to cardiometabolic risk in a cohort of Spanish children followed from birth until 7 y. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mercury is a global pollutant, and prenatal exposure is associated with adverse health effects. To date, no studies have evaluated the association between prenatal mercury exposure and DNA hydroxymethylation, an epigenetic modification important for tissue differentiation and embryonic development. OBJECTIVES: We sought to evaluate the association between prenatal mercury exposure and offspring global DNA methylation and hydroxymethylation at birth and test for persistence of the association in childhood. METHODS: Within Project Viva, a U.S. prebirth cohort, we examined associations of maternal second trimester red blood cell mercury (RBC-Hg) concentrations with global 5-hydroxymethylcytosine (%-5hmC) and 5-methylcytosine (%-5mC) DNA content in blood collected at birth (n = 306), early childhood (n = 68; 2.9 to 4.9 y), and midchildhood (n = 260; 6.7 to 10.5 y). RESULTS: Median prenatal RBC-Hg concentration was 3.23 lg/g [interquartile range (IQR) = 3.29]. At birth, median cord blood %-5mC, %-5hmC, and their ratio were 4.95%, 0.22%, and 24.37, respectively. The mean adjusted difference [95% confidence interval (CI)] of blood %-5hmC for a doubling in prenatal RBC-Hg concentration was -0.013% (-0.029, 0.002), -0.031% (-0.056, -0.006), and 0.005% (-0.007, 0.018) at birth, early, and midchildhood, respectively. The corresponding relative adjusted change in the genomic ratio of %-5mC to %-5hmC for a doubling in prenatal RBC- Hg concentration was 4.70% (0.04, 9.58), 22.42% (7.73, 39.11), and 0.73% (-4.18, 5.88) at birth, early, and midchildhood, respectively. No associations were present between prenatal maternal RBC-Hg and %-5mC at any time point. CONCLUSIONS: Prenatal mercury exposure was associated with lower %-5hmC genomic content and a corresponding increase in the ratio of %-5mC to %-5hmC in cord blood. This association was persistent in early but not midchildhood blood. Our results demonstrate the potential malleability of epigenetic modifications associated with mercury exposure in utero. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hair is a commonly used exposure biomarker for metals and other trace elements, but concern has been raised regarding its appropriateness for assessing the internal dose. OBJECTIVES: The aim of the present study was to evaluate children's hair as biomarker of internal dose for toxic (As, Mn, Cd, Pb) and essential elements (Mg, Ca, Fe, Co, Cu, Zn, Se, Mo). METHODS: In 207 children (9-10 years of age), originating from a population-based cohort in rural Bangladesh, we measured concentrations of the selected elements in hair (2 cm closest to the scalp) using ICP-MS. We compared these with previously measured concentrations in erythrocytes, urine, and water. For a subset of children (n=19), we analyzed four consecutive 2 cm pieces of hair. RESULTS: There were strong associations between hair As and the other biomarkers (erythrocytes: rs=0.73, p<0.001; urine: rS=0.66, p<0.001); and water (rs=0.60, p<0.001); and there were significant correlations between Se in hair and erythrocytes (overall rs=0.38, p<0.001), and urine (rs=0.29, p<0.001). Hair Co and Mo showed weak correlations with concentrations in erythrocytes. Hair Mn was not associated with Mn in erythrocytes, urine, or water, and the geometric mean concentration increased almost five times from the 2 cm closest to the head to the 7th-8th cm (p<0.001). Also Mg, Ca, Co, Cd, and Pb increased from the scalp outward (>50% higher in 7th-8th cm compared with 1st-2nd cm, p<0.001). CONCLUSIONS: Hair was found to be a useful exposure biomarker of absorbed As and Se only. Of all measured elements, hair Mn seemed the least reflective of internal dose. [ABSTRACT FROM AUTHOR]

BACKGROUND: Certain perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widespread, persistent environmental contaminants. Prenatal PFAS exposure has been associated with lower birth weight; however, impacts on body composition and factors responsible for this association are unknown. OBJECTIVES: We aimed to estimate associations between maternal PFAS concentrations and offspring weight and adiposity at birth, and secondarily to estimate associations between PFAS concentrations and maternal glucose and lipids, and to evaluate the potential for these nutrients to mediate associations between PFAS and neonatal outcomes. METHODS: Within the Healthy Start prospective cohort, concentrations of 11 PFAS, fasting glucose, and lipids were measured in maternal mid-pregnancy serum (n=628). Infant body composition was measured using air displacement plethysmography. Associations between PFAS and birth weight and adiposity, and between PFAS and maternal glucose and lipids, were estimated via linear regression. Associations were decomposed into direct and indirect effects. RESULTS: Five PFAS were detectable in >50% of participants. Maternal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) concentrations were inversely associated with birth weight. Adiposity at birth was approximately 10% lower in the highest categories of PFOA, PFNA, and perfluorohexane sulfonate (PFHxS) compared to the lowest categories. PFOA, PFNA, perfluorodecanoate (PFDeA), and PFHxS were inversely associated with maternal glucose. Up to 11.6% of the effect of PFAS on neonatal adiposity was mediated by maternal glucose concentrations. Perfluorooctane sulfonate (PFOS) was not significantly associated with any outcomes studied. CONCLUSIONS: Follow-up of offspring will determine the potential long-term consequences of lower weight and adiposity at birth associated with prenatal PFAS exposure. [ABSTRACT FROM AUTHOR]

BACKGROUND: When a biologic mechanism of interest is anticipated to operate differentially according to sex, as is often the case in endocrine disruptors research, investigators routinely estimate sex-specific associations. Less attention has been given to potential sexual heterogeneity of confounder associations with outcomes. When relationships of covariates with outcomes differ according to sex, commonly applied statistical approaches for estimating sex-specific endocrine disruptor effects may produce divergent estimates. OBJECTIVES: We discuss underlying assumptions and evaluate the performance of two traditional approaches for estimating sex-specific effects, stratification and product terms, and introduce a simple modeling alternative: an augmented product term approach. METHODS: We describe the impact of assumptions regarding sexual heterogeneity of confounder relationships on estimates of sex-specific effects of the exposure of interest for three approaches: stratification, traditional product terms, and augmented product terms. Using simulated and applied examples, we demonstrate properties of each approach under a range of scenarios. RESULTS: In simulations, sex-specific exposure effects estimated using the traditional product term approach were biased when confounders had sexdependent associations with the outcome. Sex-specific estimates from stratification and the augmented product term approach were unbiased but less precise. In the applied example, the three approaches yielded similar estimates, but resulted in some meaningful differences in conclusions based on statistical significance. CONCLUSIONS: Investigators should consider sexual heterogeneity of confounder associations when choosing an analytic approach to estimate sexspecific effects of endocrine disruptors on health. In the presence of sex-dependent confounding, our augmented product term approach may be advantageous over stratification when there is prior knowledge available to fit reduced models or when investigators seek an automated test for effect measure modification. [ABSTRACT FROM AUTHOR]

BACKGROUND: Early-life arsenic exposure has been associated with reduced cell-mediated immunity, but little is known about its effects on humoral immunity. OBJECTIVE: We evaluated whether prenatal and childhood arsenic exposure was associated with humoral immune function in school-aged children. METHODS: Children born in a prospective mother–child cohort in rural Bangladesh were immunized with measles, mumps, and rubella (MMR) vaccines at 9 years of age (n=525). Arsenic exposure was assessed in urine (U-As), from mothers during pregnancy and their children at 4.5 and 9 years of age. Total IgG (tIgG), tIgE, tIgA, and MMR-specific IgG concentrations were measured in plasma using immunoassays. RESULTS: Arsenic exposure was positively associated with child tIgG and tIgE, but not tIgA. The association with tIgG was mainly apparent in boys (p for interaction=0.055), in whom each doubling of maternal U-As was related to an increase in tIgG by 28 mg/dL. The associations of U-As at 9 years with tIgG and tIgE were evident in underweight children (p for interaction <0.032). Childhood arsenic exposure tended to impair mumps-specific vaccine response, although the evaluation was complicated by high preimmunization titers. Postimmunization mumps–specific IgG titers tended to decrease with increasing U-As at 4.5 and 9 years of age [regression coefficient (β)=-0.16; 95% confidence interval (CI): -0.33, 0.01; p=0.064 and β=-0.12; 95% CI: -0.27, -0.029; p=0.113, respectively) in 25% children with the lowest preexisting mumps-specific IgG titers. CONCLUSIONS: Arsenic exposure increased tIgG and tIgE in plasma, and tended to decrease mumps-specific IgG in children at 9 years of age. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although 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 lm; PM2.5) and its joint effect with the mother's prepregnancy body mass index (MPBMI) on COWO remain unclear. OBJECTIVES: The present study was conducted to examine the individual and joint effects of ambient PM2.5 exposures and MPBMI on the risk of COWO. METHODS: We estimated exposures to ambient PM2.5 in 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. RESULTS: Comparing 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 μg=m³-10:89 μg=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]. CONCLUSIONS: In 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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Serum concentrations of polybrominated diphenyl ethers (PBDEs) in U.S. women are believed to be among the world's highest; however, little information exists on the partitioning of PBDEs between serum and breast milk and how this may affect infant exposure. OBJECTIVES: Paired milk and serum samples were measured for PBDE concentrations in 34 women who participated in the U.S. EPA MAMA Study. Computational models for predicting milk PBDE concentrations from serum were evaluated. METHODS: Samples were analyzed using gas chromatography isotope-dilution high-resolution mass spectrometry. Observed milk PBDE concentrations were compared with model predictions, and models were applied to NHANES serum data to predict milk PBDE concentrations and infant intakes for the U.S. population. RESULTS: Serum and milk samples had detectable concentrations of most PBDEs. BDE-47 was found in the highest concentrations (median serum: 18.6; milk: 31.5 ng/g lipid) and BDE-28 had the highest milk:serum partitioning ratio (2.1 ± 0.2). No evidence of depuration was found. Models demonstrated high reliability and, as of 2007-2008, predicted U.S. milk concentrations of BDE-47, BDE-99, and BDE-100 appear to be declining but BDE-153 may be rising. Predicted infant intakes (ng/kg/day) were below threshold reference doses (RfDs) for BDE-99 and BDE-153 but above the suggested RfD for BDE-47. CONCLUSIONS: Concentrations and partitioning ratios of PBDEs in milk and serum from women in the U.S. EPA MAMA Study are presented for the first time; modeled predictions of milk PBDE concentrations using serum concentrations appear to be a valid method for estimating PBDE exposure in U.S. infants. CITATION: Marchitti SA, Fenton SE, Mendola P, Kenneke JF, Hines EP. 2017. Polybrominated diphenyl ethers in human milk and serum from the U.S. EPA MAMA Study: modeled predictions of infant exposure and considerations for risk assessment. Environ Health Perspect 125:706-713; http://dx.doi.org/10.1289/EHP332 [ABSTRACT FROM AUTHOR]

BACKGROUND: Glycol ethers (GE) are widely used organic solvents. Despite the potential neurotoxicity of several families of organic solvents, little is known about the impact of GE on the neurodevelopment of infants and children. OBJECTIVES: We investigated the relation between urinary concentrations of GE metabolites in pregnant women and neurocognitive abilities in their 6-year-old children in the PELAGIE mother-child cohort. METHODS: Five GE metabolites were measured in first morning void urine samples of 204 French pregnant women in early pregnancy (< 19 weeks of gestation). Psychologists assessed the neurocognitive abilities of their 6-year-old children with the Wechsler Intelligence Scale for Children IV (WISC) and the Developmental Neuropsychological Assessment (NEPSY). We analyzed the results with linear (WISC) and Poisson regression models (NEPSY), adjusted for potential confounders, including child's stimulation at home. RESULTS: GE metabolites were detected in 90-100% of maternal urine samples. The WISC Verbal Comprehension score was significantly lower for children with the highest tertile of urinary phenoxyacetic acid (PhAA) [ss (third vs. first tertile) = -6.53; 95% CI: -11.44, -1.62]. Similarly, the NEPSY Design Copying subtest score was lower in those with the highest tertile of urinary ethoxyacetic acid (EAA) [ss (third vs. first tertile) = -0.11; 95% CI: -0.21, 0.00]. The other GE metabolites we studied were not significantly associated with WISC or NEPSY scores. CONCLUSIONS: Prenatal urine concentrations of two GE metabolites were associated with lower WISC Verbal Comprehension Index scores and NEPSY Design Copying subscale scores, respectively, at age 6 years. PhAA is the primary metabolite of 2-phenoxyethanol (EGPhE), which is commonly found in cosmetics, and precursors of EAA are frequently used in cleaning agents. Additional research is needed to confirm our findings and further explore potential effects of prenatal GE exposures on neurocognitive performance in children. CITATION: Béranger R, Garlantézec R, Le Maner-Idrissi G, Lacroix A, Rouget F, Trowbridge J, Warembourg C, Monfort C, Le Gléau F, Jourdin M, Multigner L, Cordier S, Chevrier C. 2017. Prenatal exposure to glycol ethers and neurocognitive abilities in 6-year-old children: the PELAGIE cohort study. Environ Health Perspect 125:684-690; http://dx.doi.org/10.1289/EHP39 [ABSTRACT FROM AUTHOR]

BACKGROUND: Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. METHODS: We studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. RESULTS: Children with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: - 17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. CONCLUSIONS: We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. CITATION: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487; http://dx.doi.org/10.1289/EHP303 [ABSTRACT FROM AUTHOR]

BACKGROUND: Many women of childbearing age are occupationally active, which leads to a large number of pregnancies potentially exposed to occupational exposures. Occupational noise has been identified as a risk factor for hearing impairment in adults. However, very few studies have assessed the effect of occupational noise on the fetus. OBJECTIVES: The aim of this study was to investigate whether occupational exposure to noise during pregnancy is associated with hearing dysfunction in children. METHODS: This population based cohort study included 1,422,333 single births in Sweden 1986-2008. Data on mothers' occupation, smoking habits, age, ethnicity, body mass index, leave of absence, and socioeconomic factors were obtained from interviews performed by prenatal care unit staff at approximately 10 weeks of gestation and from national registers. Occupational noise exposure was classified by a job-exposure-matrix as < 75, 75-84, or ≥ 85 dB[sub LAeq,8h.] Diagnosed cases of hearing dysfunction (ICD-10 codes H90.3-7, 91.0, 91.2-3, 91.8, 93.1-2) were identified from a register of specialized medical care. Cox proportional hazards models were used to estimate associations. RESULTS: In the full sample, containing a mixture of part-time and full-time workers during pregnancy, the adjusted HR for hearing dysfunction associated with maternal occupational noise exposure ≥ 85 vs. < 75 dB[sub LAeq,8h ]was 1.27 (95% CI: 0.99, 1.64; 60 exposed cases). When restricted to children whose mothers worked full-time and had < 20 days leave of absence during pregnancy, the corresponding HR was 1.82 (95% CI: 1.08, 3.08; 14 exposed cases). CONCLUSIONS: This study showed an association between occupational noise exposure during pregnancy and hearing dysfunction in children. In view of mechanistic evidence and earlier indicative epidemiological and experimental findings, the results support that pregnant women should not be exposed to high levels of noise at work. [ABSTRACT FROM AUTHOR]

Background: In some animal studies, perfluorinated alkyl substances are suggested to induce weight gain. Human epidemiological studies investigating these associations are sparse. Objective: We examined pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and the prevalence of offspring overweight (> 1 SD) and waist-toheight ratio (WHtR) > 0.5 at 5-9 years of age. Methods: Sera from 1,022 pregnant women enrolled in the INUENDO cohort (2002-2004) from Greenland and Kharkiv (Ukraine) were analyzed for PFOA and PFOS using liquid chromatography- tandem mass spectrometry. Relative risks (RR) of being overweight and having WHtR > 0.5 in relation to continuous and categorized (tertiles) PFOA and PFOS were calculated at follow-up (2010-2012) using generalized linear models. Results: Pooled PFOA median (range) was 1.3 (0.2-5.1) and PFOS median (range) was 10.8 (0.8- 73.0) ng/mL. For each natural logarithm-unit (ln-unit) increase of pregnancy PFOA, the adjusted RR of offspring overweight was 1.11 [95% confidence interval (CI): 0.82, 1.53] in Greenlandic children. In Ukrainian children, the adjusted RR of offspring overweight was 1.02 (95% CI: 0.72, 1.44) for each ln-unit increase of pregnancy PFOA. Prenatal exposure to PFOS was not associated with overweight in country-specific or pooled analysis. The adjusted RR of having WHtR > 0.5 for each ln-unit increase of prenatal exposure to PFOA was 1.30 (95% CI: 0.97, 1.74) in the pooled analysis. For 1-ln-unit increase of prenatal exposure to PFOS, the adjusted RR of having a WHtR > 0.5 was 1.38 (95% CI: 1.05, 1.82) in the pooled analysis. Conclusions: The results indicate that prenatal PFOA and PFOS exposures may be associated with child waist-to-height ratio > 0.5. Prenatal PFOA and PFOS exposures were not associated with overweight. [ABSTRACT FROM AUTHOR]

Background: Studies suggest that phthalate exposures may adversely affect child respiratory health. Objectives: We evaluated associations between asthma diagnosed in children between 5 and 11 years of age and prenatal exposures to butylbenzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), and diethyl phthalate (DEP). Methods: Phthalate metabolites were measured in spot urine collected from 300 pregnant inner-city women. Children were examined by an allergist or pulmonologist based on the first parental report of wheeze, other respiratory symptoms, and/or use of asthma rescue/controller medication in the preceding 12 months on repeat follow-up questionnaires. Standardized diagnostic criteria were used to classify these children as either having or not having current asthma at the time of the physician examination. Children without any report of wheeze or the other asthma-like symptoms were classified as nonasthmatics at the time of the last negative questionnaire. Modified Poisson regression analyses were used to estimate relative risks (RR) controlling for specific gravity and potential confounders. Results: Of 300 children, 154 (51%) were examined by a physician because of reports of wheeze, other asthma-like symptoms, and/or medication use; 94 were diagnosed with current asthma and 60 without current asthma. The remaining 146 children were classified as nonasthmatic. Compared with levels in nonasthmatics, prenatal metabolites of BBzP and DnBP were associated with a history of asthma-like symptoms (p < 0.05) and with the diagnosis of current asthma: RR = 1.17 (95% CI: 1.01, 1.35) and RR = 1.25 (95% CI: 1.04, 1.51) per natural log-unit increase, respectively. Risk of current asthma was > 70% higher among children with maternal prenatal BBzP and DnBP metabolite concentrations in the third versus the first tertile. Conclusion: Prenatal exposure to BBzP and DnBP may increase the risk of asthma among inner-city children. However, because this is the first such finding, results require replication. [ABSTRACT FROM AUTHOR]

BACKGROUND: Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma. OBJECTIVE: Our aim was to investigate the impact of gene variants associated with oxidative stress and inflammation on associations between air pollution and incident childhood asthma. METHODS: Traffic-related air pollution, asthma, wheeze, gene variant, and potential confounder data were pooled across six birth cohorts. Parents reported physician-diagnosed asthma and wheeze from birth to 7-8 years of age (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution [nitrogen dioxide (NO2), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, ozone] were assigned to each child's birth address using land use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala114Val and rs1695/IIe105Val) and TNF (rs1800629/G-308A) was investigated. RESULTS: Data on asthma, wheeze, potential confounders, at least one SNP of interest, and NO2 were available for 5,115 children. GSTP1 rs1138272 and TNF rs1800629 SNPs were associated with asthma and wheeze, respectively. In relation to air pollution exposure, children with one or more GSTP1 rs1138272 minor allele were at increased risk of current asthma [odds ratio (OR) = 2.59; 95% CI: 1.43, 4.68 per 10 μg/m3 NO2] and ever asthma (OR = 1.64; 95% CI: 1.06, 2.53) compared with homozygous major allele carriers (OR = 0.95; 95% CI: 0.68, 1.32 for current and OR = 1.20; 95% CI: 0.98, 1.48 for ever asthma; Bonferroni-corrected interaction p = 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO2 and current and ever asthma had ORs of 1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70), respectively, for minor allele carriers compared with ORs of 0.82 (95% CI: 0.52, 1.32) and 1.12 (95% CI: 0.84, 1.49) for homozygous major allele carriers (Bonferroni-corrected interaction p-values 0.48 and 0.09). There were no clear differences by TNF genotype. CONCLUSIONS: Children carrying GSTP1 rs1138272 or rs1695 minor alleles may constitute a susceptible population at increased risk of asthma associated with air pollution. [ABSTRACT FROM AUTHOR]

Background: Human milk is a potential source of lead exposure. Yet lactational transfer of lead from maternal blood into breast milk and its contribution to infant lead burden remains poorly understood. Objectives: We explored the dose-response relationships between maternal blood, plasma, and breast milk to better understand lactational transfer of lead from blood and plasma into milk and, ultimately, to the breastfeeding infant. Methods: We measured lead in 81 maternal blood, plasma, and breast milk samples at 1 month postpartum and in 60 infant blood samples at 3 months of age. Milk-to-plasma (M/P) lead ratios were calculated. Multivariate linear, piecewise, and generalized additive models were used to examine dose-response relationships between blood, plasma, and milk lead levels. Results: Maternal lead levels (mean ± SD) were as follows: blood: 7.7 ± 4.0 μg/dL; plasma: 0.1 ± 0.1 μg/L; milk: 0.8 ± 0.7 μg/L. The average M/P lead ratio was 7.7 (range, 0.6–39.8) with 97% of the ratios being > 1. The dose–response relationship between plasma lead and M/P ratio was nonlinear (empirical distribution function = 6.5, p = 0.0006) with the M/P ratio decreasing by 16.6 and 0.6 per 0.1 μg/L of plasma lead, respectively, below and above 0.1 μg/L plasma lead. Infant blood lead level (3.4 ± 2.2 μg/dL) increased by 1.8 μg/dL per 1 μg/L milk lead (p < 0.0001, R2 = 0.3). Conclusions: The M/P ratio for lead in humans is substantially higher than previously reported, and transfer of lead from plasma to milk may be higher at lower levels of plasma lead. Breast milk is an important determinant of lead burden among breastfeeding infants. [ABSTRACT FROM AUTHOR]

Background: In some previous studies, prenatal exposure to persistent organochlorines such as 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′−DDE), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) has been associated with higher body mass index (BMI) in children. Objective: Our goal was to evaluate the association of maternal serum levels of β-hexachlorocyclohexane (β HCH), p,p′−DDE, dichlorodiphenyltrichloroethane (p,p′−DDT), dieldrin, heptachlor epoxide, HCB, trans-nonachlor, oxychlordane, and PCBs with offspring obesity during childhood. Methods: The analysis was based on a subsample of 1,915 children followed until 7 years of age as part of the U.S. Collaborative Perinatal Project (CPP). The CPP enrolled pregnant women in 1959-1965; exposure levels were measured in third-trimester maternal serum that was collected before these organochlorines were banned in the United States. Childhood overweight and obesity were defined using age- and sex-specific cut points for BMI as recommended by the International Obesity Task Force. Results: Adjusted results did not show clear evidence for an association between organochlorine exposure and obesity; however, a suggestive finding emerged for dieldrin. Compared with those in the lowest quintile (dieldrin, < 0.57 µg/L), odds of obesity were 3.6 (95% CI: 1.3, 10.5) for the fourth and 2.3 (95% CI: 0.8, 7.1) for the highest quintile. Overweight and BMI were unrelated to organochlorine exposure. Conclusions: In this population with relatively high levels of exposure to organochlorines, no clear associations with obesity or BMI emerged. [ABSTRACT FROM AUTHOR]

Background: Ambient air pollution may have neurotoxic effects in children. Data examining associations between traffic-related air pollution and attention domains remain sparse. Objectives: We examined associations between black carbon (BC), a marker of traffic particles, and attention measures ascertained at 7-14 years of age among 174 children in a birth cohort based in the Boston, Massachusetts, area. Methods: We estimated BC levels using a validated spatial-temporal land-use regression model based on residence during children's lifetime. Children completed the Conner's Continuous Performance Test (CPT) measuring omission errors, commission errors, and hit reaction time (HRT), with higher scores indicating increased errors or slower reaction time. Multivariable-adjusted linear regression analyses were used to examine associations between BC and each attention outcome. Results: Children were primarily Hispanic (56%) and Caucasian (41%); 53% were boys. We found a positive association between higher BC levels with increased commission errors and slower HRT, adjusting for child IQ, age, sex, blood lead level, maternal education, pre- and postnatal tobacco smoke exposure, and community-level social stress. Notably, the association was weaker, though still positive, for the highest BC quartile relative to the middle two quartiles. Sex-stratified analysis demonstrated statistically significant associations between BC and both commission errors and HRT in boys, but BC was not significantly associated with any of the CPT outcomes in girls. Conclusions: In this population of urban children, we found associations between BC exposure and higher commission errors and slower reaction time. These associations were overall more apparent in boys than girls. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA), a widely used endocrine-disrupting chemical, has been associated with increased body weight and fat deposition in rodents. Objectives: We examined whether prenatal and postnatal urinary BPA concentrations were associated with body mass index (BMI), waist circumference, percent body fat, and obesity in 9-year-old children (n = 311) in the CHAMACOS longitudinal cohort study. Methods: BPA was measured in spot urine samples collected from mothers twice during pregnancy and from children at 5 and 9 years of age. Results: Prenatal urinary BPA concentrations were associated with decreased BMI at 9 years of age in girls but not boys. Among girls, being in the highest tertile of prenatal BPA concentrations was associated with decreased BMI z-score (β = -0.47, 95% CI: -0.87, -0.07) and percent body fat (β = -4.36, 95% CI: -8.37, -0.34) and decreased odds of overweight/obesity [odds ratio (OR) = 0.37, 95% CI: 0.16, 0.91] compared with girls in the lowest tertile. These findings were strongest in prepubertal girls. Urinary BPA concentrations at 5 years of age were not associated with any anthropometric parameters at 5 or 9 years, but BPA concentrations at 9 years were positively associated with BMI, waist circumference, fat mass, and overweight/obesity at 9 years in boys and girls. Conclusions: Consistent with other cross-sectional studies, higher urinary BPA concentrations at 9 years of age were associated with increased adiposity at 9 years. However, increasing BPA concentrations in mothers during pregnancy were associated with decreased BMI, body fat, and overweight/obesity among their daughters at 9 years of age. [ABSTRACT FROM AUTHOR]

Background: Perfluorinated compounds (PFCs) are ubiquitous pollutants. Experimental data suggest that they may be associated with adverse health outcomes, including asthma. However, there is little supporting epidemiological evidence. Methods: A total of 231 asthmatic children and 225 nonasthmatic controls, all from northern Taiwan, were recruited in the Genetic and Biomarkers study for Childhood Asthma. Structure questionnaires were administered by face-to-face interview. Serum concentrations of 11 PFCs and levels of immunological markers were also measured. Associations of PFC quartiles with concentrations of immunological markers and asthma outcomes were estimated using multivariable regression models. Results: Nine PFCs were detectable in most children (≥ 84.4%), of which perfluorooctane sulfonate (PFOS) was the most abundant (median serum concentrations of 33.9 ng/mL in asthmatics and 28.9 ng/mL in controls). Adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFC exposure ranged from 1.81 (95% CI: 1.02, 3.23) for the perfluorododecanoic acid (PFDoA) to 4.05 (95% CI: 2.21, 7.42) for perfluorooctanic acid (PFOA). PFOS, PFOA, and subsets of the other PFCs were positively associated with serum IgE concentrations, absolute eosinophil counts (AEC), eosinophilic cationic protein (ECP) concentrations, and asthma severity scores among asthmatics. Conclusions: This study suggests an association between PFC exposure and juvenile asthma. Because of widespread exposure to these chemicals, these findings may be of potential public health concern. [ABSTRACT FROM AUTHOR]

Background: Urban landscape elements, particularly trees, have the potential to affect airflow, air quality, and production of aeroallergens. Several large-scale urban tree planting projects have sought to promote respiratory health, yet evidence linking tree cover to human health is limited. Objectives: We sought to investigate the association of tree canopy cover with subsequent development of childhood asthma, wheeze, rhinitis, and allergic sensitization. Methods: Birth cohort study data were linked to detailed geographic information systems data characterizing 2001 tree canopy coverage based on LiDAR (light detection and ranging) and multispectral imagery within 0.25 km of the prenatal address. A total of 549 Dominican or African-American children born in 1998-2006 had outcome data assessed by validated questionnaire or based on IgE antibody response to specific allergens, including a tree pollen mix. Results: Tree canopy coverage did not significantly predict outcomes at 5 years of age, but was positively associated with asthma and allergic sensitization at 7 years. Adjusted risk ratios (RRs) per standard deviation of tree canopy coverage were 1.17 for asthma (95% CI: 1.02, 1.33), 1.20 for any specific allergic sensitization (95% CI: 1.05, 1.37), and 1.43 for tree pollen allergic sensitization (95% CI: 1.19, 1.72). Conclusions: Results did not support the hypothesized protective association of urban tree canopy coverage with asthma or allergy-related outcomes. Tree canopy cover near the prenatal address was associated with higher prevalence of allergic sensitization to tree pollen. Information was not available on sensitization to specific tree species or individual pollen exposures, and results may not be generalizable to other populations or geographic area [ABSTRACT FROM AUTHOR]

Background: The results of previous studies suggest that prenatal exposure to bis[p-chlorophenyl]-1,1,1-trichloroethane (DDT) and to its main metabolite, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), impairs psychomotor development during the first year of life. However, information about the persistence of this association at later ages is limited. Objectives: We assessed the association of prenatal DDE exposure with child neurodevelopment at 42-60 months of age. Methods: Since 2001 we have been monitoring the neurodevelopment in children who were recruited at birth into a perinatal cohort exposed to DDT, in the state of Morelos, Mexico. We report McCarthy Scales of Children's Abilities for 203 children at 42, 48, 54, and 60 months of age. Maternal DDE serum levels were available for at least one trimester of pregnancy. The Home Observation for Measurement of the Environment scale and other covariables of interest were also available. Results: After adjustment, a doubling of DDE during the third trimester of pregnancy was associated with statistically significant reductions of -1.37, -0.88, -0.84, and -0.80 points in the general cognitive index, quantitative, verbal, and memory components respectively. The association between prenatal DDE and the quantitative component was weaker at 42 months than at older ages. No significant statistical interactions with sex or breastfeeding were observed. Conclusions: These findings support the hypothesis that prenatal DDE impairs early child neurodevelopment; the potential for adverse effects on development should be considered when using DDT for malaria control. [ABSTRACT FROM AUTHOR]

Background: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. Objectives: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. Methods: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations. Results: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-α (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations. Conclusions: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-α genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Cadmium is a commonly occurring toxic food contaminant, but health consequences of early-life exposure are poorly understood. Objectives: We evaluated the associations between cadmium exposure and neurobehavioral development in preschool children. Methods: In our population-based mother-child cohort study in rural Bangladesh, we assessed cadmium exposure in 1,305 women in early pregnancy and their children at 5 years of age by measuring concentrations in urine (U-Cd), using inductively coupled plasma mass spectrometry. Children's IQ at 5 years of age, including Verbal (VIQ), Performance (PIQ), and Full-Scale IQ (FSIQ), were measured by Wechsler Preschool and Primary Scale of Intelligence. Behavior was assessed by the Strengths and Difficulties Questionnaire (SDQ). Results: In multiple linear regression models, adjusted for sex, home stimulation, socioeconomic status (SES), and maternal and child characteristics, a doubling of maternal U-Cd was inversely associated with VIQ (-0.84 points; 95% confidence interval: -1.3, -0.40), PIQ (-0.64 points; -1.1, -0.18), and FSIQ (-0.80 points; -1.2, -0.39). Concurrent child U-Cd showed somewhat weaker association with VIQ and FSIQ, but not PIQ. Stratification by sex and SES indicated slightly stronger associations with PIQ and FSIQ in girls than in boys and in higher-income compared with lower-income families. Concurrent U-Cd was inversely associated with SDQ-prosocial behavior and positively associated with SDQ-difficult behavior, but associations were close to the null after adjustment. Quantile regression analysis showed similar associations across the whole range of each developmental outcome. Conclusion: Early-life low-level cadmium exposure was associated with lower child intelligence scores in our study cohort. Further research in this area is warranted. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA), an endocrine-disrupting chemical that is routinely detected in > 90% of Americans, promotes experimental asthma in mice. The association of prenatal BPA expo­sure and wheeze has not been evaluated in humans. Objective: We examined the relationship between prenatal BPA exposure and wheeze in early childhood. Methods: We measured BPA concentrations in serial maternal urine samples from a prospective birth cohort of 398 mother-infant pairs and assessed parent-reported child wheeze every 6 months for 3 years. We used generalized estimating equations with a logit link to evaluate the association of prenatal urinary BPA concentration with the dichotomous outcome wheeze (wheeze over the previous 6 months). Results: Data were available for 365 children; BPA was detected in 99% of maternal urine samples during pregnancy. In multivariable analysis, a one-unit increase in log-transformed creatinine-standardized mean prenatal urinary BPA concentration was not significantly associated with child wheeze from birth to 3 years of age, but there was an interaction of BPA concentration with time (p = 0.003). Mean prenatal BPA above versus below the median was positively associated with wheeze at 6 months of age [adjusted odds ratio (AOR) = 2.3; 95% confidence interval (CI): 1.3, 4.1] but not at 3 years (AOR = 0.6; 95% CI: 0.3, 1.1). In secondary analyses evaluating associations of each prenatal BPA concentration separately, urinary BPA concentrations measured at 16 weeks gestation were associated with wheeze (AOR = 1.2; 95% CI: 1.0, 1.5), but BPA concentrations at 26 weeks of gestation or at birth were not. Conclusions: Mean prenatal BPA was associated with increased odds of wheeze in early life, and the effect diminished over time. Evaluating exposure at each prenatal time point demonstrated an association between wheeze from 6 months to 3 years and log-transformed BPA concentration at 16 weeks gestation only [ABSTRACT FROM AUTHOR]

Background: There are limited data on the associations between maternal or newborn and child exposure to perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS). This study provides an opportunity to assess the association between PFAA concentrations in mother-child pairs in a population exposed to PFOA via drinking water. Objectives: We aimed to determine the relationship between mother-child PFAA serum concentrations and to examine how the child:mother ratio varies with child's age, child's sex, drinking-water PFOA concentration, reported bottled water use, and mother's breast-feeding intention. Methods: We studied 4,943 mother-child pairs (children, 1.19 years of age). The child:mother PFAA ratio was stratified by possible determinants. Results are summarized as geometric mean ratios and correlation coefficients between mother-child pairs, overall and within strata. Results: Child and mother PFOA and PFOS concentrations were correlated (r = 0.82 and 0.26, respectively). Up to about 12 years of age, children had higher serum PFOA concentrations than did their mothers. The highest child:mother PFOA ratio was found among children ≤ 5 years (44% higher than their mothers), which we attribute to in utero exposure and to exposure via breast milk and drinking water. Higher PFOS concentrations in children persisted until at least 19 years of age (42% higher than their mothers). Boys > 5 years of age had significantly higher PFOA and PFOS child:mother ratios than did girls. Conclusion: Concentrations of both PFOA and PFOS tended to be higher in children than in their mothers. This difference persisted until they were about 12 years of age for PFOA and at least 19 years of age for PFOS. [ABSTRACT FROM AUTHOR]

Background: Perfluoroalkyl acids are persistent compounds used in various industrial applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring. Objective: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans. Methods: A prospective cohort of 665 Danish pregnant women was recruited in 1988.1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified in a subset (n = 422) of participants. Results: After adjusting for covariates, including maternal prepregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years. Conclusions: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age. [ABSTRACT FROM AUTHOR]

Background: In May 2010, a team of national and international organizations was assembled to investigate children's deaths due to lead poisoning in villages in northwestern Nigeria. Objectives: Our goal was to determine the cause of the childhood lead poisoning outbreak, investigate risk factors for child mortality, and identify children < 5 years of age in need of emergency chelation therapy for lead poisoning. Methods: We administered a cross-sectional, door-to-door questionnaire in two affected villages, collected blood from children 2-59 months of age, and obtained soil samples from family compounds. Descriptive and bivariate analyses were performed with survey, blood lead, and environmental data. Multivariate logistic regression techniques were used to determine risk factors for childhood mortality. Results: We surveyed 119 family compounds. Of 463 children < 5 years of age, 118 (25%) had died in the previous year. We tested 59% (204/345) of children < 5 years of age, and all were lead poisoned (≥ 10 &mgr;g/dL); 97% (198/204) of children had blood lead levels (BLLs) ≥ 45 &mgr;g/dL, the threshold for initiating chelation therapy. Gold ore was processed inside two-thirds of the family compounds surveyed. In multivariate modeling, significant risk factors for death in the previous year from suspected lead poisoning included the age of the child, the mother's work at ore-processing activities, community well as primary water source, and the soil lead concentration in the compound. Conclusion: The high levels of environmental contamination, percentage of children < 5 years of age with elevated BLLs (97%, > 45 &mgr;g/dL), and incidence of convulsions among children before death (82%) suggest that most of the recent childhood deaths in the two surveyed villages were caused by acute lead poisoning from gold ore-processing activities. Control measures included environmental remediation, chelation therapy, public health education, and control of mining activities. [ABSTRACT FROM AUTHOR]

Background: Previously, we reported an association between higher maternal polychlorinated biphenyl (PCB) concentrations and smaller thymus volume in newborns in a birth cohort residing in eastern Slovakia. Objective: In the present report we address whether thymus volume at later ages is influenced by prenatal and early postnatal PCB exposure. Methods: At the time of delivery, 1,134 mother-infant pairs were enrolled. Maternal and 6- and 16-month infant blood samples were collected and analyzed for 15 PCB congeners. Thymus volume was measured in infants shortly after birth and at ages 6 and 16 months using ultrasonography. Results: Higher maternal PCB concentration was associated with reduced thymus volume at birth [a 0.21 SD reduction in thymus volume for an increase in total maternal PCB concentration from the 10th to the 90th percentile; 95% confidence interval (CI): -0.37, -0.05], whereas maternal PCB concentration was not predictive of 6- and 16-month thymus volume. Six-month infant PCB concentration was associated with a 0.40 SD decrease in 6-month thymus volume (95% CI: -0.76, -0.04). There was also some suggestion that thymus volume at 16 months was positively associated with concurrent infant PCB concentration. Conclusions: The potential adverse effects of in utero PCB exposure on thymic development may extend beyond the neonatal period. Results from this highly exposed cohort provide suggestive evidence that postnatal PCB concentrations may be influential, but a smaller set of 6-month PCB measurements limited statistical power at that time point. Implications regarding impaired immunologic maturation or long-term clinical implications remain to be determined. [ABSTRACT FROM AUTHOR]

Background: Recent experimental evidence suggests that prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase postnatal obesity risk and that these effects may be sex or diet dependent. Objectives: We explored whether prenatal organochlorine compound (OC) concentrations [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT)] were associated with overweight at 6.5 years of age and whether child sex or fat intakes modified these associations. Methods: We studied 344 children from a Spanish birth cohort established in 1997-1998. Overweight at 6.5 years was defined as a body mass index (BMI) z-score = 85th percentile of the World Health Organization reference. Cord blood OC concentrations were measured and treated as categorical variables (tertiles). Children's diet was assessed by food frequency questionnaire. Relative risks (RRs) were estimated using generalized linear models. Results: After multivariable adjustment, we found an increased RR of overweight in the third tertile of PCB exposure [RR = 1.70; 95% confidence interval (CI): 1.09, 2.64] and the second tertile of DDE exposure (RR = 1.67; 95% CI: 1.10, 2.55), but no association with DDT exposure in the population overall. Associations between overweight and PCB and DDE concentrations were strongest in girls (p-interaction between 0.01 and 0.28); DDT was associated with overweight only in boys. For DDT we observed stronger associations in children with fat intakes at or above compared with below the median, but this interaction was not significant (p-interaction > 0.05). Conclusions: This study suggests that prenatal OC exposures may be associated with overweight in children and that sex and high-fat intake may influence susceptibility. [ABSTRACT FROM AUTHOR]

Background: Environmental factors influencing the developmental origins of health and disease need to be identified and investigated. In utero exposure to tobacco smoke has been associated with obesity and a small increase in blood pressure in children; however, whether there is a corresponding increased risk of conditions such as diabetes and hypertension during adulthood remains unclear. Objective: Our goal was to assess the association of self-reported in utero exposure to tobacco smoke with the prevalence of obesity, hypertension, type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM) in women 14-47 years of age. Methods: We conducted a cross-sectional analysis of the Norwegian Mother and Child Cohort Study, which enrolled pregnant women in Norway from 1999 thorough 2008. Exposure to tobacco smoke in utero (yes vs. no) was ascertained on the baseline questionnaire (obtained at ~ 17 weeks' gestation); the outcomes were ascertained from the Medical Birth Registry of Norway and the questionnaire. Our analysis included 74,023 women. Results: Women exposed to tobacco smoke in utero had 1.53 times the odds of obesity [95% confidence interval (CI): 1.45, 1.61] relative to those unexposed, after adjusting for age, education, and personal smoking. After further adjustment for body mass index, the odds ratio for hypertension was 1.68 (95% CI: 1.19, 2.39); for T2DM 1.14 (95% CI: 0.79, 1.65); and for GDM 1.32 (95% CI: 1.10, 1.58) among exposed compared with unexposed. Conclusions: Exposure to tobacco smoke in utero was associated with obesity, hypertension, and GDM in adult women. The possibility that the associations were attributable to unmeasured confounding cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: Air pollution effects on children's neurodevelopment have recently been suggested to occur most likely through the oxidative stress pathway. Objective: We aimed to assess whether prenatal exposure to residential air pollution is associated with impaired infant mental development, and whether antioxidant/detoxification factors modulate this association. Methods: In the Spanish INfancia y Medio Ambiente (INMA; Environment and Childhood) Project, 2,644 pregnant women were recruited during their first trimester. Nitrogen dioxide (NO2) and benzene were measured with passive samplers covering the study areas. Land use regression models were developed for each pollutant to predict average outdoor air pollution levels for the entire pregnancy at each residential address. Maternal diet was obtained at first trimester through a validated food frequency questionnaire. Around 14 months, infant mental development was assessed using Bayley Scales of Infant Development. Results: Among the 1,889 children included in the analysis, mean exposure during pregnancy was 29.0 µg/m3 for NO2 and 1.5 µg/m3 for benzene. Exposure to NO2 and benzene showed an inverse association with mental development, although not statistically significant, after adjusting for potential confounders [β (95% confidence interval) = -0.95 (-3.90, 1.89) and -1.57 (-3.69, 0.56), respectively, for a doubling of each compound]. Stronger inverse associations were estimated for both pollutants among infants whose mothers reported low intakes of fruits/vegetables during pregnancy [-4.13 (-7.06, -1.21) and -4.37 (-6.89, -1.86) for NO2 and benzene, respectively], with little evidence of associations in the high-intake group (interaction p-values of 0.073 and 0.047). Inverse associations were also stronger in non-breast-fed infants and infants with low maternal vitamin D, but effect estimates and interactions were not significant. Conclusions: Our findings suggest that prenatal exposure to residential air pollutants may adversely affect infant mental development, but potential effects may be limited to infants whose mothers report low antioxidant intakes. [ABSTRACT FROM AUTHOR]

Most toxicologic studies focus on a single agent, although this does not reflect real-world scenarios in which humans are exposed to multiple chemicals. Objectives: We prospectively studied manganese-lead interactions in early childhood to examine whether manganese-lead coexposure is associated with neurodevelopmental deficiencies that are more severe than expected based on effects of exposure to each metal alone. Methods: Four hundred fifty-five children were enrolled at birth in an longitudinal cohort study in Mexico City, provided blood samples, and were followed until 36 months of age. We measured lead and manganese at 12 and 24 months and assessed neurodevelopment at 6-month intervals from 12 to 36 months of age using Bayley Scales of Infant Development-II. Results: Mean (± SD) blood concentrations at 12 and 24 months were, respectively, 24.7 ± 5.9 µg/L and 21.5 ± 7.4 µg/L for manganese and 5.1 ± 2.6 µg/dL and 5.0 ± 2.9 µg/dL for lead. Mixed-effects models, including Bayley scores at five time points, showed a significant interaction over time: highest manganese quintile x continuous lead; mental development score, â = -1.27 [95% confidence interval (CI): -2.18, -0.37]; psychomotor development score, β = -0.92 (95% CI: -1.76, -0.09). Slopes for the estimated 12-month lead effect on 18-month mental development and 24- through 36-month psychomotor development scores were steeper for children with high manganese than for children with midrange manganese levels. Conclusions: We observed evidence of synergism between lead and manganese, whereby lead toxicity was increased among children with high manganese coexposure. Findings highlight the importance of understanding health effects of mixed exposures, particularly during potentially sensitive developmental stages such as early childhood. [ABSTRACT FROM AUTHOR]

Background: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children's intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function. Methods: We investigated the associations of WAs and WMn with motor function in 304 children in Bangladesh, 8-11 years of age. We measured As and Mn concentrations in drinking water, blood,urine, and toenails. We assessed motor function with the Bruininks-Oseretsky test, version 2, in four subscales-fine manual control (FMC), manual coordination (MC), body coordination (BC), and strength and agility-which can be summarized with a total motor composite score (TMC). Results: Log-transformed blood As was associated with decreases in TMC [β = -3.63; 95% confidence interval (CI): -6.72, -0.54; p < 0.01], FMC (β = -1.68; 95% CI: -3.19, -0.18; p < 0.05), and BC (β = -1.61; 95% CI: -2.72, -0.51; p < 0.01), with adjustment for sex, school attendance, head circumference, mother's intelligence, plasma ferritin, and blood Mn, lead, and selenium. Other measures of As exposure (WAs, urinary As, and toenail As) also were inversely associated with motor function scores, particularly TMC and BC. Square-transformed blood selenium was positively associated with TMC (β = 3.54; 95% CI: 1.10, 6.0; p < 0.01), FMC (β = 1.55; 95% CI: 0.40, 2.70; p < 0.005), and MC (β= 1.57; 95% CI: 0.60, 2.75; p < 0.005) in the unadjusted models. Mn exposure was not significantly associated with motor function. Conclusion: Our research demonstrates an adverse association of As exposure and a protective association of Se on motor function in children. [ABSTRACT FROM AUTHOR]

Background: Certain chemical pollutants can exacerbate lower respiratory tract infections (LRIs), a common childhood ailment. Although formaldehyde (FA) is one of the most common air pollutants found in indoor environments, its impact on infant health is uncertain. Objective: Our aim was to determine the impact of FA exposure on the LRI incidence during the first year of life of infants from the Pollution and Asthma Risk: an Infant Study (PARIS) birth cohort. Methods: FA was measured in a random sample of 196 infants' dwellings, and exposure to this pollutant was estimated for 2,940 infants using predictive models based on measurements and data about potential determinants of FA levels. Health data were collected from parents by regular self-administered questionnaires. We used multivariate logistic regressions to estimate associations between FA exposure and the occurrence of LRI and wheezy LRI (wLRI), adjusting for potential confounders/risk factors. Results: During the first year of life, 45.8% of infants had at least one LRI, and LRI occurred simultaneously with wheezing in 48.7% of cases. The FA predictive models correctly classified 70% of dwellings as having high or low exposure, and we estimated that 43.3% of infants were exposed throughout the first year to levels of FA > 19.5 μg/m3. FA exposure was significantly associated with LRI and wLRI before and after adjustment for known LRI risk factors/confounders. For an interquartile increase in FA levels (12.4 μg/m3), we estimated a 32% [95% confidence interval (CI): 11, 55] and 41% (95% CI: 14, 74) increase in the incidence of LRI and wLRI, respectively. Conclusion: The findings of this study suggest that infants exposed to FA at an early age have an increased incidence of LRI. [ABSTRACT FROM AUTHOR]

Background: Cumulative prenatal lead exposure, as measured by maternal bone lead burden, has been associated with smaller weight of offspring at birth and 1 month of age, but no study has examined whether this effect persists into early childhood. Objective: We investigated the association of perinatal maternal bone lead, a biomarker of cumulative prenatal lead exposure, with children's attained weight over time from birth to 5 years of age. Methods: Children were weighed at birth and at several intervals up until 60 months. Maternal tibia and patella lead were measured at 1 month postpartum using in vivo K-shell X-ray fluorescence. We used varying coefficient models with random effects to assess the association of maternal bone lead with weight trajectories of 522 boys and 477 girls born between 1994 and 2005 in Mexico City. Results: After controlling for breast-feeding duration, maternal anthropometry, and socio- demographic characteristics, a 1-SD increase in maternal patella lead (micrograms per gram) was associated with a 130.9--g decrease in weight [95% confidence interval (CI), -227.4 to -34.4 g] among females and a 13.0--g nonsignificant increase in weight among males (95% CI, -73.7 to 99.9 g) at 5 years of age. These associations were similar after controlling for concurrent blood lead levels between birth and 5 years. Conclusions: Maternal bone lead was associated with lower weight over time among female but not male children up to 5 years of age. Given that the association was evident for patellar but not tibial lead levels, and was limited to females, results need to be confirmed in other studies. [ABSTRACT FROM AUTHOR]