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BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7–9 y old, and reenrolled at 13–18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height–weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (푛 = 123) were 98% White and 54% female and had a mean age of 16 y (range: 13–18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diarrheal disease is a leading cause of childhood morbidity and mortality globally. Household water, sanitation, and handwashing (WASH) interventions can reduce exposure to diarrhea-causing pathogens, but meteorological factors may impact their effectiveness. Information about effect heterogeneity under different weather conditions is critical to refining these targeted interventions. OBJECTIVES: We aimed to determine whether temperature and precipitation modified the effect of low-cost, point-of-use WASH interventions on child diarrhea. METHODS: We analyzed data from a trial in rural Bangladesh that compared child diarrhea prevalence between clusters (푁 = 720) that were randomized to different WASH interventions between 2012 and 2016 (NCT01590095). We matched temperature and precipitation measurements to diarrhea outcomes (푁 = 12,440 measurements, 6,921 children) by geographic coordinates and date. We estimated prevalence ratios (PRs) using generative additive models and targeted maximum likelihood estimation to assess the effectiveness of each WASH intervention under different weather conditions. RESULTS: Generally, WASH interventions most effectively prevented diarrhea during monsoon season, particularly following weeks with heavy rain or high temperatures. The PR for diarrhea in the WASH interventions group compared with the control group was 0.49 (95% CI: 0.35, 0.68) after 1 d of heavy rainfall, with a less-protective effect [PR = 0:87 (95% CI: 0.60, 1.25)] when there were no days with heavy rainfall. Similarly, the PR for diarrhea in the WASH intervention group compared with the control group was 0.60 (95% CI: 0.48, 0.75) following above-median temperatures vs. 0.91 (95% CI: 0.61, 1.35) following below-median temperatures. The influence of precipitation and temperature varied by intervention type; for precipitation, the largest differences in effectiveness were for the sanitation and combined WASH interventions. DISCUSSION: WASH intervention effectiveness was strongly influenced by precipitation and temperature, and nearly all protective effects were observed during the rainy season. Future implementation of these interventions should consider local environmental conditions to maximize effectiveness, including targeted efforts to maintain latrines and promote community adoption ahead of monsoon seasons. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have been shown to protect against fine particulate matter <2.5 μm in aerodynamic diameter (PM2.5)-induced hazards. However, limited evidence is available for respiratory health, particularly in pregnant women and their offspring. OBJECTIVES: We aimed to investigate the association of prenatal exposure to PM2.5 and its chemical components with allergic rhinitis (AR) in children and explore effect modification by maternal erythrocyte PUFAs. METHODS: This prospective birth cohort study involved 657 mother–child pairs from Guangzhou, China. Prenatal exposure to residential PM2.5 mass and its components [black carbon (BC), organic matter (OM), sulfate (SO42- ), nitrate (NO3 - ), and ammonium (NH4 +)] were estimated by an established spatiotemporal model. Maternal erythrocyte PUFAs during pregnancy were measured using gas chromatography. The diagnosis of AR and report of AR symptoms in children were assessed up to 2 years of age. We used Cox regression with the quantile-based g-computation approach to assess the individual and joint effects of PM2.5 components and examine the modification effects of maternal PUFA levels. RESULTS: Approximately 5.33% and 8.07% of children had AR and related symptoms, respectively. The average concentration of prenatal PM2.5 was 35.50 ± 5.31 μg/m³. PM2.5 was positively associated with the risk of developing AR [hazard ratio (HR)= 1.85; 95% confidence interval (CI): 1.16, 2.96 per 5 μg/m³] and its symptoms (HR = 1.79; 95% CI: 1.22, 2.62 per 5 μg/m³) after adjustment for confounders. Similar associations were observed between individual PM2.5 components and AR outcomes. Each quintile change in a mixture of components was associated with an adjusted HR of 3.73 (95% CI: 1.80, 7.73) and 2.69 (95% CI: 1.55, 4.67) for AR and AR symptoms, with BC accounting for the largest contribution. Higher levels of n-3 docosapentaenoic acid and lower levels of n-6 linoleic acid showed alleviating effects on AR symptoms risk associated with exposure to PM2.5 and its components. CONCLUSION: Prenatal exposure to PM2.5 and its chemical components, particularly BC, was associated with AR/symptoms in early childhood. We highlight that PUFA biomarkers could modify the adverse effects of PM2.5 on respiratory allergy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Air pollution risk assessments do not generally quantify health impacts using multipollutant risk estimates, but instead use results from single-pollutant or copollutant models. Multipollutant epidemiological models account for pollutant interactions and joint effects but can be computationally complex and data intensive. Risk estimates from multipollutant studies are therefore challenging to implement in the quantification of health impacts. OBJECTIVES: Our objective was to conduct a case study using a developmental multipollutant version of the Environmental Benefits Mapping and Analysis Program—Community Edition (BenMAP-CE) to estimate the health impact associated with changes in multiple air pollutants using both a single and multipollutant approach. METHODS: BenMAP-CE was used to estimate the change in the number of pediatric asthma emergency department (ED) visits attributable to simulated changes in air pollution between 2011 and 2025 in Atlanta, Georgia, applying risk estimates from an epidemiological study that examined shortterm single-pollutant and multipollutant (with and without first-order interactions) exposures. Analyses examined individual pollutants (i.e., ozone, fine particulate matter, carbon monoxide, nitrogen dioxide (NO2), sulfur dioxide, and particulate matter components) and combinations of these pollutants meant to represent shared properties or predefined sources (i.e., oxidant gases, secondary pollutants, traffic, power plant, and criteria pollutants). Comparisons were made between multipollutant health impact functions (HIF) and the sum of single-pollutant HIFs for the individual pollutants that constitute the respective pollutant groups. RESULTS: Photochemical modeling predicted large decreases in most of the examined pollutant concentrations between 2011 and 2025 based on sector specific (i.e., source-based) estimates of growth and anticipated controls. Estimated number of avoided asthma ED visits attributable to any given multipollutant group were generally higher when using results from models that included interaction terms in comparison with those that did not. We estimated the greatest number of avoided pediatric asthma ED visits for pollutant groups that include NO2 (i. e., criteria pollutants, oxidants, and traffic pollutants). In models that accounted for interaction, year-round estimates for pollutant groups that included NO2 ranged from 27.1 [95% confidence interval (CI): 1.6, 52.7; traffic pollutants] to 55.4 (95% CI: 41.8, 69.0; oxidants) avoided pediatric asthma ED visits. Year-round results using multipollutant risk estimates with interaction were comparable to the sum of the single-pollutant results corresponding to most multipollutant groups [e.g., 52.9 (95% CI: 43.6, 62.2) for oxidants] but were notably lower than the sum of the single-pollutant results for some pollutant groups [e.g., 77.5 (95% CI: 66.0, 89.0) for traffic pollutants]. DISCUSSION: Performing a multipollutant health impact assessment is technically feasible but computationally complex. It requires time, resources, and detailed input parameters not commonly reported in air pollution epidemiological studies. Results estimated using the sum of single-pollutant models are comparable to those quantified using a multipollutant model. Although limited to a single study and location, assessing the trade-offs between a multipollutant and single-pollutant approach is warranted. [ABSTRACT FROM AUTHOR]

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]

The article focuses on a study that measured lead levels in maternal and cord blood in a convenience sample of mothers delivering at a hospital that serves women from the informal settlements of Dandora and Kariobangi in Nairobi. It describes the methods used to investigate maternal lead exposures in the settlements as well as associations between potential lead sources and blood lead levels. It discusses the implications of the discovery of high BLL found in the study participants.

BACKGROUND: Ambient air pollution may be a developmental endocrine disruptor. In animal models, gestational and perinatal exposure to diesel exhaust and concentrated particulate matter alters anogenital distance (AGD), a marker of prenatal androgen activity, in both sexes. Little is known in humans. OBJECTIVES: We examined exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) in relation to human AGD at birth and at 1 year of age, focusing on exposures during critical windows of reproductive development: the male programming window (MPW; gestational weeks 8–14) and mini-puberty (postnatal months 1–3). METHODS: The Infant Development and Environment Study (TIDES) recruited first trimester pregnant women (β = 687) at four U.S. sites (Minneapolis, Minnesota; Rochester, New York; San Francisco, California; and Seattle, Washington) from 2010 to 2012. We measured anus to clitoris (AGD-AC) and anus to fourchette (AGD-AF) in female infants at birth; in males, we measured anus to penis (AGD-AP), anus to scrotum (AGDAS), and penile width at birth and at 1 year of age. Using advanced spatiotemporal models, we estimated maternal exposure to PM2.5 and NO2 in the MPW and mini-puberty. Covariate-adjusted, sex-stratified linear regression models examined associations between PM2.5 and NO2 and AGD. RESULTS: In males, a 1-μg/m³ increase in PM2.5 exposure during the MPW was associated with shorter AGD at birth, but a longer AGD at 1 year of age (e.g., birth AGD-AP: β = -0.35 mm; 95% CI: -0.62, -0.07; AGD-AS: β = 0.37 mm; 95% CI: 0.02, 0.73). Mini-pubertal PM2.5 exposure was also associated with shorter male AGD-AP (β = -0.50 mm; 95% CI: -0.89, -0.11) at 1 year of age. Although not associated with male AGD measures, 1-ppb increases in NO2 exposure during the MPW (β = -0.07 mm; 95% CI: -0.02, -0.12) and mini-puberty (β = -0.04 mm; 95% CI: -0.08, 0.01) were both associated with smaller penile width at 1 year of age. Results were similar in multipollutant models, where we also observed that in females AGD-AC was inversely associated with PM2.5 exposure, but positively associated with NO2 exposure. DISCUSSION: PM2.5 and NO2 exposures during critical pre- and postnatal windows may disrupt reproductive development. More work is needed to confirm these novel results and clarify mechanisms. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. OBJECTIVE: The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children’s body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. METHODS: Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (푛=1,911), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4′-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. RESULTS: In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%–32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE concentration=1.19 (95% CI: 1.05, 1.35); RRR for PFNA=1.32 (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the mixture=1.70; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. DISCUSSION: This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pesticide exposures are suspected of being a risk factor for several childhood cancers, particularly acute leukemia (AL). Most of the evidence is based on self-reported parental domestic use of pesticides, but some studies have also addressed associations with agricultural use of pesticides near the place of residence. OBJECTIVES: The objective of the study was to evaluate the risk of AL in children living close to vines, a crop subject to intensive pesticide use. METHODS: Data were drawn from the national registry-based GEOCAP study. We included all of the AL cases under the age of 15 years diagnosed in 2006–2013 (푛 = 3,711) and 40,196 contemporary controls representative of the childhood population in France. The proximity of the vines (probability of presence within 200, 500, and 1,000 m) and the viticulture density (area devoted to vines within 1,000 m) were evaluated around the geocoded addresses in a geographic information system combining three national land use maps. Logistic regression models were used to estimate odds ratios (ORs) for all AL and for the lymphoblastic (ALL) and myeloid (AML) subtypes. Heterogeneity between regions was studied by stratified analyses. Sensitivity analyses were carried out to take into account, in particular, geocoding uncertainty, density of other crops and potential demographic and environmental confounders. RESULTS: In all, about 10% of the controls lived within 1 km of vines. While no evidence of association between proximity to vines and AL was found, viticulture density was positively associated with ALL [OR=1.05 (1.00–1.09) for a 10% increase in density], with a statistically significant heterogeneity across regions. No association with AML was observed. The results remained stable in all the sensitivity analyses. CONCLUSION: We evidenced a slight increase in the risk of ALL in children living in areas with high viticulture density. This finding supports the hypothesis that environmental exposure to pesticides may be associated with childhood ALL. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gestational phthalate and phenol exposure disrupts adipogenesis, contributing to obesity in mice. Whether gestational phthalate or phenol exposure is associated with infant body composition has not been investigated in humans. OBJECTIVE: We examined associations between biomarkers of phthalate and phenol exposure in midpregnancy and infant size and body composition at birth and at 5 months of age. METHODS: Analyses were conducted among 438 infants from the Healthy Start prospective pregnancy cohort. Sixteen phthalate and phenol biomarkers were quantified in spot urine samples collected at 24–28 wk of gestation. Infant outcomes measured at birth and at 5 months of age included size [weight (in grams)] and body composition [fat and lean masses (in grams); percentage fat mass]. Single- (linear) and multipollutant (quantile g-computation) models were used to estimate associations of phthalate and phenol biomarkers with infant outcomes at birth and at 5 months of age. Models were adjusted for sociodemographics, sample collection timing, and lifestyle factors and used to examine for effect modification by infant sex. RESULTS: In single-pollutant models, mono-benzyl phthalate and di-n-butyl phthalate were inversely associated with percentage fat mass [ß: -0.49 (95% CI: -0:91, -0:08) and -0:51 (95% CI: -1.02, 0.01), respectively] in male but not female infants at birth. Similar, but less precise, associations were observed at 5 months of age. In multipollutant models, a 1-quartile increase in the phthalate and phenol biomarker mixture was inversely associated with percentage fat mass at birth [-1.06 (95% CI: -2.21, 0.1)] and at 5 months of age [-2.14 (95% CI: -3.88, -0.39)] among males, but associations were null among females [0.48 (95% CI: -0.78, 1.75) and -0.64 (95% CI: -2.68, 1.41), respectively]. Similar associations were observed with infant weight. CONCLUSION: In this U.S.-based prospective cohort, gestational phthalate and phenol biomarkers were inversely associated with infant weight and fat mass, particularly in males. [ABSTRACT FROM AUTHOR]

BACKGROUND: The developing fetal brain is sensitive to many environmental exposures. However, the independent and joint effects of prenatal exposure to metals and micronutrients on child cognition are not well understood. OBJECTIVES: Our aim was to evaluate associations of first-trimester (~10 wk) maternal erythrocyte concentrations of mixtures of nonessential and essential metals and micronutrients with early (~3 y) and mid-childhood (~8 y) cognitive test scores in Project Viva, a prebirth cohort in Boston, Massachusetts, USA. METHODS: We measured concentrations of five essential metals (Cu, Mg, Mn, Se, Zn) and two micronutrients (vitamin B12 and folate), together termed the “nutrient mixture,” as well as six nonessential metals (As, Ba, Cd, Cs, Hg, Pb), together termed the “neurotoxic mixture,” in first-trimester (~10 wk) maternal erythrocytes (metals) or plasma (micronutrients). We assessed visual-motor function and receptive vocabulary in early childhood (~3 y), and visual-motor function, visual memory, and fluid and crystallized intelligence in mid-childhood (~8 y). We employed adjusted quantile g-computation and linear regression to estimate mixture and individual component associations, respectively. RESULTS: Analyses included 900 mother–child pairs (74% college graduates; 52% male children). In mixture analyses, a quartile increase in the nutrient mixture was associated with a mean difference in early childhood receptive vocabulary score of 1.58 points [95% confidence interval (CI): 0.06, 3.10], driven by Zn and Se. A quartile increase in the neurotoxic mixture was associated with a mean difference in mid-childhood visual-motor score of -3.01 points (95% CI: -5.55, -0.47), driven by Ba and Cs. Linear regressions supported quantile g-computation findings for mixture component contributions. DISCUSSION: Maternal circulating concentrations of several essential (Zn and Se) and nonessential (Ba and Cs) metals were associated with some domains of child cognition. In this folate-replete cohort, first-trimester circulating concentrations of known neurotoxic metals, such as Pb, were not associated with child cognition. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ambient air pollution exposure has been associated with childhood asthma, but previous studies have primarily focused on prevalence of asthma and asthma-related outcomes and urban traffic-related exposures. OBJECTIVE: We examined nationwide associations between pre- and postnatal exposure to ambient air pollution components and asthma incidence in children age 0–19 y. METHODS: Asthma incidence was identified from hospital admission, emergency room, and outpatient contacts among all live-born singletons born in Denmark between 1998 and 2016. We linked registry data with monthly mean concentrations of particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM2.5) and PM with aerodynamic diameter ≤10 μm (PM10), nitrogen dioxide (NO2), nitrogen oxides, elemental carbon, and organic carbon (OC), sulfur dioxide, ozone, sulfate, nitrate, ammonium, secondary organic aerosols, and sea salt. Associations were estimated with Cox proportional hazard models using fixed prenatal exposure means and time-varying postnatal exposures. RESULTS: Of the 1,060,154 children included, 6.1% had asthma during the mean follow-up period of 8.8 y. The risk of asthma increased with increasing prenatal exposure to all pollutants except for O3 and sea salt. We also observed increased risk after restriction to asthma after age 4 y, after additional adjustment for area-specific socioeconomic status, and for postnatal exposure to most pollutants. The hazard ratio (HR) associated with an interquartile range increase of 2.4 and 8.7 µg/m³ in prenatal exposure was 1.06 [95% confidence interval (CI): 1.04, 1.08] for PM2.5 and 1.04 (95% CI: 1.02, 1.05) for NO2, respectively. This association with PM2.5 was stable after adjustment for NO2, whereas it attenuated for NO2 to 1.01 (95% CI: 0.99, 1.03) after adjustment for PM2.5. For a 0.5-µg/m³ increase in prenatal OC exposure, for which biomass is an important source, the HR was 1.08 (95% CI: 1.06, 1.10), irrespective of adjustment for PM2.5. DISCUSSION: These findings suggest that early-life exposure to ambient air pollution from multiple sources contributes to asthma development. [ABSTRACT FROM AUTHOR]

BACKGROUND: Because fine particulate matter [PM, with aerodynamic diameter ≤2.5 μm (PM2.5)] is a ubiquitous environmental exposure, small changes in cognition associated with PM2.5 exposure could have great societal costs. Prior studies have demonstrated a relationship between in utero PM2.5 exposure and cognitive development in urban populations, but it is not known whether these effects are similar in rural populations and whether they persist into late childhood. OBJECTIVES: In this study, we tested for associations between prenatal PM2.5 exposure and both full-scale and subscale measures of IQ among a longitudinal cohort at age 10.5 y. METHODS: This analysis used data from 568 children enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort study in California’s agricultural Salinas Valley. Exposures were estimated at residential addresses during pregnancy using state of the art, modeled PM2.5 surfaces. IQ testing was performed by bilingual psychometricians in the dominant language of the child. RESULTS: A 3-μg/m³ higher average PM2.5 over pregnancy was associated with -1.79 full-scale IQ points [95% confidence interval (CI): -2.98, -0.58], with decrements specifically in Working Memory IQ (WMIQ) and Processing Speed IQ (PSIQ) subscales [WMIQ -1.72 (95% CI: -2.98, -0.45) and PSIQ -1.19 (95% CI: -2.54, 0.16)]. Flexible modeling over the course of pregnancy illustrated mid-to-late pregnancy (months 5-7) as particularly susceptible times, with sex differences in the timing of susceptible windows and in which subscales were most affected [Verbal Comprehension IQ (VCIQ) and WMIQ in males; and PSIQ in females]. DISCUSSION: We found that small increases in outdoor PM2.5 exposure in utero were associated with slightly lower IQ in late childhood, robust to many sensitivity analyses. In this cohort there was a larger effect of PM2.5 on childhood IQ than has previously been observed, perhaps due to differences in PM composition or because developmental disruption could alter the cognitive trajectory and thus appear more pronounced as children get older. [ABSTRACT FROM AUTHOR]

BACKGROUND: The prevalence of liver disorders and metabolic syndrome has increased among youth. Glyphosate, the most widely used herbicide worldwide, could contribute to the development of these conditions. OBJECTIVE: We aimed to assess whether lifetime exposure to glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), is associated with elevated liver transaminases and metabolic syndrome among young adults. METHODS: We conducted a prospective cohort study (푛=480 mother-child dyads) and a nested case-control study (푛=60 cases with elevated liver transaminases and 91 controls) using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We measured glyphosate and AMPA concentrations in urine samples collected during pregnancy and at child ages 5, 14, and 18 y from cases and controls. We calculated glyphosate residue concentrations: [glyphosate + (1.5 × AMPA)]. We estimated the amount of agricultural-use glyphosate applied within a 1-km radius of every residence from pregnancy to age 5 y for the full cohort using California Pesticide Use Reporting data. We assessed liver transaminases and metabolic syndrome at 18 y of age. RESULTS: Urinary AMPA at age 5 y was associated with elevated transaminases [relative risk (RR) per 2-fold increase=1.27, 95% confidence interval (CI): 1.06, 1.53] and metabolic syndrome (RR=2.07, 95% CI: 1.38, 3.11). Urinary AMPA and glyphosate residues at age 14 y were associated with metabolic syndrome [RR=1:80 (95% CI: 1.10, 2.93) and RR=1.88 (95% CI: 1.03, 3.42), respectively]. Overall, a 2-fold increase in urinary AMPA during childhood was associated with a 14% and a 55% increased risk of elevated liver transaminases and metabolic syndrome, respectively. Living near agricultural glyphosate applications during early childhood (birth to 5 y of age) was also associated with metabolic syndrome at age 18 y in the case-control group (RR=1.53, 95% CI: 1.16, 2.02). DISCUSSION: Childhood exposure to glyphosate and AMPA may increase risk of liver and cardiometabolic disorders in early adulthood, which could lead to more serious diseases later in life. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nationwide household transitions to the use of clean-burning cooking fuels are a promising pathway to reducing under-5 lower respiratory infection (LRI) mortality, the leading cause of child mortality globally, but such transitions are rare and evidence supporting an association between increased clean fuel use and improved health is limited. OBJECTIVES: This study aimed to investigate the association between increased primary clean cooking fuel use and under-5 LRI mortality in Ecuador between 1990 and 2019. METHODS: We documented cooking fuel use and cause-coded child mortalities at the canton (county) level in Ecuador from 1990 to 2019 (in four periods, 1988–1992, 1999–2003, 2008–2012, and 2015–2019). We characterized the association between clean fuel use and the rate of under-5 LRI mortalities at the canton level using quasi-Poisson generalized linear and generalized additive models, accounting for potential confounding variables that characterize wealth, urbanization, and child health care and vaccination rates, as well as canton and period fixed effects. We estimated averted under-5 LRI mortalities accrued over 30 y by predicting a counterfactual count of canton-period under-5 LRI mortalities were clean fuel use to not have increased and comparing with predicted canton-period under-5 LRI mortalities from our model and observed data. RESULTS: From 1990 to 2019, the proportion of households primarily using a clean cooking fuel increased from 59% to 95%, and under-5 LRI mortality fell from 28 to 7 per 100,000 under-5 population. Canton-level clean fuel use was negatively associated with under-5 LRI mortalities in linear and nonlinear models. The nonlinear association suggested a threshold at approximately 60% clean fuel use, above which there was a negative association. Increases in clean fuel use between 1990 and 2019 were associated with an estimated 7,300 averted under-5 LRI mortalities (95% confidence interval: 2,600, 12,100), accounting for nearly 20% of the declines in under-5 LRI mortality observed in Ecuador over the study period. DISCUSSION: Our findings suggest that the widespread household transition from using biomass to clean-burning fuels for cooking reduced under-5 LRI mortalities in Ecuador over the last 30 y. [ABSTRACT FROM AUTHOR]

BACKGROUND: Unconventional oil and gas development (UOGD) releases chemicals that have been linked to cancer and childhood leukemia. Studies of UOGD exposure and childhood leukemia are extremely limited. OBJECTIVE: The objective of this study was to evaluate potential associations between residential proximity to UOGD and risk of acute lymphoblastic leukemia (ALL), the most common form of childhood leukemia, in a large regional sample using UOGD-specific metrics, including a novel metric to represent the water pathway. METHODS: We conducted a registry-based case–control study of 405 children ages 2–7 y diagnosed with ALL in Pennsylvania between 2009–2017, and 2,080 controls matched on birth year. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between residential proximity to UOGD (including a new water pathway-specific proximity metric) and ALL in two exposure windows: a primary window (3 months preconception to 1 y prior to diagnosis/reference date) and a perinatal window (preconception to birth). RESULTS: Children with at least one UOG well within 2 km of their birth residence during the primary window had 1.98 times the odds of developing ALL in comparison with those with no UOG wells [95% confidence interval (CI): 1.06, 3.69]. Children with at least one vs. no UOG wells within 2 km during the perinatal window had 2.80 times the odds of developing ALL (95% CI: 1.11, 7.05). These relationships were slightly attenuated after adjusting for maternal race and socio-economic status [odds ratio (OR) = 1:74 (95% CI: 0.93, 3.27) and OR = 2:35 (95% CI: 0.93, 5.95)], respectively). The ORs produced by models using the water pathway-specific metric were similar in magnitude to the aggregate metric. DISCUSSION: Our study including a novel UOGD metric found UOGD to be a risk factor for childhood ALL. This work adds to mounting evidence of UOGD’s impacts on children’s health, providing additional support for limiting UOGD near residences [ABSTRACT FROM AUTHOR]

BACKGROUND: No safe level of lead in blood has been identified. Blood lead testing is required for children on Medicaid, but it is at the discretion of providers and parents for others. Elevated blood lead levels (EBLLs) cannot be identified in children who are not tested. OBJECTIVES: The aims of this research were to identify determinants of lead testing and EBLLs among North Carolina children and estimate the number of additional children with EBLLs among those not tested. METHODS: We linked geocoded North Carolina birth certificates from 2011–2016 to 2010 U.S. Census data and North Carolina blood lead test results from 2011–2018. We estimated the probability of being screened for lead and created inverse probability (IP) of testing weights. We evaluated the risk of an EBLL of =3 µg/dL at <30 months of age, conditional on characteristics at birth, using generalized linear models and then applied IP weights to account for missing blood lead results among unscreened children. We estimated the number of additional children with EBLLs of all North Carolina children using the IP-weighted population and bootstrapping to produce 95% credible intervals (CrI). RESULTS: Mothers of the 63.5% of children (402,002 of 633,159) linked to a blood lead test result were disproportionately young, Hispanic, Black, American Indian, or on Medicaid. In full models, maternal age =20 y [risk ratio (RR)=1.10; 95% confidence interval (CI): 1.13, 1.20] or smoking (RR=1.14; 95% CI: 1.12, 1.17); proximity to a major roadway (RR=1.10; 95% CI: 1.05, 1.15); proximity to a lead-releasing Toxics Release Inventory site (RR=1.08; 95% CI: 1.03, 1.14) or a National Emissions Inventory site (RR=1.11; 95% CI: 1.07, 1.14); and living in neighborhoods with more housing built before 1950 (RR=1.10; 95% CI: 1.05, 1.14) or before 1940 (RR=1.18; 95% CI: 1.11, 1.25) or more vacant housing (RR=1.14; 95% CI: 1.11, 1.17) were associated with an increased risk of EBLL, whereas overlap with a public water service system was associated with a decreased risk of EBLL (RR=0.85; 95% CI: 0.83, 0.87). Children of Black mothers were no more likely than children of White mothers to have EBLLs (RR=0.98; 95% CI: 0.96, 1.01). Complete blood lead screening in 2011–2018 may have identified an additional 17,543 (95% CrI: 17,462, 17,650) children with EBLLs =3 µg/dL. DISCUSSION: Our results indicate that current North Carolina lead screening strategies fail to identify over 30% (17,543 of 57,398) of children with subclinical lead poisoning and that accounting for characteristics at birth alters the conclusions about racial disparities in children’s EBLLs. [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: Prenatal phthalate exposure has been associated with lower birth weight but also higher weight in childhood. Few studies have examined weight or adiposity from birth to childhood and thus cannot assess growth trajectories associated with exposure. OBJECTIVE: We assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3–6 years of age). METHODS: Within The Infant Development and the Environment Study (TIDES), a prospective pregnancy cohort, we analyzed a panel of phthalate metabolites in urine collected at two visits from early and late gestation (푁 = 780). We estimated average phthalate metabolite associations with child weight 푧-scores from ~20 wk gestation (estimated by ultrasound), birth, and 1, 3, 4, and 6 years of age using linear mixed-effects (LME) models. We also modeled associations with adiposity 푧-scores from birth (weight for length) and 1, 3, 4, and 6 years of age [body mass index (BMI)] using LME models. RESULTS: For weight, we observed inverse associations between several phthalate metabolites and birth weight 푧-scores, but no associations were observed with postnatal weight 푧-scores in LME models. Regarding adiposity, we observed inverse associations between phthalate metabolites and weight-for-length 푧-scores at birth, but positive associations were observed with BMI 푧-scores at 3–4 years of age in LME models. For example, mono-ethyl phthalate was associated with a 0.17-unit decrease in birth weight-for-length 푧-score [95% confidence interval (CI): –0:29, –0:05] and a 0.18-unit increase in 4-years-of-age BMI 푧-score (95% CI: 0.04, 0.32). DISCUSSION: We observed associations between prenatal exposure to phthalates and lower weight at birth but not at childhood follow-up visits. However, for adiposity, we observed an interesting pattern of association with low adiposity at delivery as well as high adiposity at 3–4 years of age. Although it is not clear from our results whether these associations occur within the same children, such a pattern of adiposity in early life has been linked to cardiometabolic disease in adulthood and deserves special attention as an outcome in the study of prenatal exposures in the developmental origins of health and disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lead exposures from legacy sources threaten children’s health. Soil in Omaha, Nebraska, was contaminated by emissions from a lead smelter and refinery. The U.S. Environmental Protection Agency excavated and replaced contaminated soil at the Omaha Lead Superfund Site between 1999 and 2016. OBJECTIVES: The goal of this study was to assess the association of soil lead level (SLL) and soil remediation status with blood lead levels (BLLs) in children living near or on the site. METHODS: We linked information on SLL at residential properties with children’s BLLs and assigned remediation status to children’s BLL measurements based on whether their measurements occurred during residence at remediated or unremediated properties. We examined the association of SLL and remediation status with elevated BLL (EBLL). We distinguished the roles of temporal trend and the intervention with time-by-interventionstatus interaction contrasts. All analyses estimated odds ratios (ORs) with a generalized estimating equations approach to ensure robustness under the complex correlations among BLL measurements. All analyses controlled for relevant covariates including children’s characteristics. RESULTS: EBLL (>5 lg=dL) was associated with both residential SLL [e.g., OR = 2:00; 95% confidence interval (CI): 1.83, 2.19; >400–800 vs. =200 ppm] and neighborhood SLL [e.g., OR = 1:85 (95% CI: 1.62, 2.11; >400–800 vs. =200 ppm)] before remediation but only with neighborhood SLL after remediation. The odds of EBLL were higher before remediation [OR 1.52 (95% CI: 1.34, 1.72)]. Similarly, EBLL was positively associated with preremediation status in our interaction analysis [interaction OR = 1:18 (95%CI: 1.02, 1.37)]. DISCUSSION: Residential and neighborhood SLLs were important predictors of EBLLs in children residing near or on this Superfund site. Neighborhood SLL remained a strong predictor following remediation. Our data analyses showed the benefit of soil remediation. Results from the interaction analyses should be interpreted cautiously due to imperfect correspondence of remediation times between remediation and comparison groups. https://doi.org/10.1289/EHP8657 [ABSTRACT FROM AUTHOR]

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread persistent pollutants. Evidence regarding neurodevelopmental effects of PFAS have been mixed. The relation between PFAS exposure and anatomical markers that have been suggested to correlate with fetal brain development have not been studied. OBJECTIVES: We investigated the association between prenatal PFAS exposures and three craniofacial features in children measured at 5 years of age. METHODS: Measures of palpebral fissure length (PFL), philtrum groove, and upper-lip thickness were generated from standardized digital facial photographs from 656 children in the Danish National Birth Cohort. PFL was classified into two groups (shorter; normal), and the philtrum (grooved; smooth; normal) and upper-lip (thick; thin; normal) measures into three groups each. Six PFAS were measured in maternal plasma (median = 8 gestational wk). Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for each facial feature using the normal group as the reference according to log2-PFAS concentration (in nanograms per milliliter) or PFAS tertiles, adjusting for potential confounders, including maternal alcohol intake and smoking. Stratified analyses by maternal alcohol intake or child’s sex were performed. RESULTS: Prenatal exposure to each PFAS was associated with elevated odds for a shorter PFL, with the strongest association observed for perfluorodecanoic acid (PFDA; per doubling OR = 2.02; 95% CI: 1.11, 3.70). Some nonlinear associations were found for philtrum measures: the second tertile of PFDA and perfluorononanoic acid were associated with grooved philtrum, whereas the second tertile of perfluoroheptane sulfonate with smooth philtrum. The associations between PFAS exposure and a shorter PFL were stronger among mothers who consumed alcohol in the first trimester, some sex-specific associations were noted for philtrum and upper-lip measures. DISCUSSION: Prenatal PFAS exposures might influence fetal craniofacial development. A larger study is needed to replicate the potential modifying effects observed for alcohol exposure and to clarify whether associations of craniofacial markers observed reflect specific neurologic deficits. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hundreds of thousands of biodigesters have been constructed in Nepal. These household-level systems use human and animal waste to produce clean-burning biogas used for cooking, which can reduce household air pollution from woodburning cookstoves and prevent respiratory illnesses. The biodigesters, typically operated by female caregivers, require the handling of animal waste, which may increase domestic fecal contamination, exposure to diarrheal pathogens, and the risk of enteric infections, especially among young children. OBJECTIVE: We estimated the effect of daily reported biogas cookstove use on incident diarrhea among children <5 y old in the Kavrepalanchok District of Nepal. Secondarily, we assessed effect measure modification and statistical interaction of individual- and household-level covariates (child sex, child age, birth order, exclusive breastfeeding, proof of vaccination, roof type, sanitation, drinking water treatment, food insecurity) as well as recent 14-d acute lower respiratory infection (ALRI) and season. METHODS: We analyzed 300,133 person-days for 539 children in an observational prospective cohort study to estimate the average effect of biogas stove use on incident diarrhea using cross-validated targeted maximum likelihood estimation (CV-TMLE). RESULTS: Households reported using biogas cookstoves in the past 3 d for 23% of observed person-days. The adjusted relative risk of diarrhea for children exposed to biogas cookstove use was 1.31 (95% confidence interval (CI): 1.00, 1.71) compared to unexposed children. The estimated effect of biogas stove use on diarrhea was stronger among breastfed children (2.09; 95% CI: 1.35, 3.25) than for nonbreastfed children and stronger during the dry season (2.03; 95% CI: 1.17, 3.53) than in the wet season. Among children exposed to biogas cookstove use, those with a recent ALRI had the highest mean risk of diarrhea, estimated at 4.53 events (95% CI: 1.03, 8.04) per 1,000 person-days. DISCUSSION: This analysis provides new evidence that child diarrhea may be an unintended health risk of biogas cookstove use. Additional studies are needed to identify exposure pathways of fecal pathogen contamination associated with biodigesters to improve the safety of these widely distributed public health interventions. [ABSTRACT FROM AUTHOR]

The article discusses research on the impact of inn-line drinking water chlorination on fecal carriage of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) among Bangladeshi children in low-income communities. The study compared the prevalence and concentration of ESBL-E. coli and ESBL-Klebsiella, Enrerobacter, Shigella and Citrobacter groups in fecal samples collected. It determined the occurrence and relative abundance of beta-lactamase genes in fecal samples.

BACKGROUND: Evidence concerning the effects of greenness on childhood visual impairment is scarce. OBJECTIVES: We aimed to assess whether greenness surrounding schools was associated with visual impairment prevalence and visual acuity levels in Chinese schoolchildren and whether the associations might be explained by reduced air pollution. METHODS: In September 2013, we recruited 61,995 children and adolescents 6–18 years of age from 94 schools in seven provinces/municipalities in China. Greenness exposure was assessed using the normalized difference vegetation index (NDVI) and the soil-adjusted vegetation index (SAVI) from July to August 2013. Visual impairment was defined as at least one visual acuity level (dimensionless) lower than 4.9 (Snellen 5/6 equivalent). Three-year annual averages of particulate matter (PM) with an aerodynamic diameter of =1 lm (PM1) and nitrogen dioxide (NO2) at each school were assessed using machine learning methods. We used generalized linear mixed models to estimate the associations between greenness and prevalent visual impairment and visual acuity levels and used mediation analyses to explore the potential mediating role of air pollution. RESULTS: In the adjusted model, an interquartile range increase in NDVI500m was associated with lower odds of prevalent visual impairment [odds ratio (OR)=0.95; 95% confidence interval (CI): 0.93, 0.97]. The same increase in NDVI500m was also associated with 0.012 (95% CI: 0.008, 0.015) and 0.011 (95% CI: 0.007, 0.015) increases in visual acuity levels for left- and right-eye, respectively. Our results also suggested that PM1 and NO2 significantly mediated the association between NDVI500m and visual impairment. Similar effect estimates were observed for SAVI500m, and our estimates were generally robust in several sensitivity analyses. DISCUSSION: These findings suggest higher greenness surrounding schools might reduce the risk of visual impairment, possibly owing in part to lower PM1 and NO2 in vegetated areas. Further longitudinal studies with more precise greenness assessment are warranted to confirm these findings. https://doi.org/10.1289/EHP8429 [ABSTRACT FROM AUTHOR]

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may impair bone accrual and strength via endocrine disruption and nuclear receptor agonism, but human studies are primarily of adults or cross-sectional. OBJECTIVES: We assessed associations of individual PFAS and their mixture during pregnancy with child bone mineral content (BMC) and areal bone mineral density (aBMD) at age 12 y. METHODS: Among 206 mother–child pairs enrolled in a prospective cohort (2003–2006), we quantified perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in maternal serum collected during gestation or delivery. When children were age 12 y, we performed dual energy X-ray absorptiometry and calculated BMC, aBMD, and bone mineral apparent density (BMAD) 푧-scores for six skeletal sites. We estimated covariate-adjusted 푧-score differences per doubling of individual PFAS using linear regression and assessed the PFAS mixture using quantile g-computation and Bayesian kernel machine regression. We explored whether associations were modified by child's sex or mediated by whole-body lean mass. RESULTS: In covariate-adjusted models, we found that higher maternal serum concentrations of PFOA, PFNA, and the PFAS mixture were associated with lower total hip and forearm (one-third distal radius) BMC 푧-scores in children. Differences in forearm BMC 푧-scores were -0.17 [95% confidence interval (CI): -0.35, 0.01] and -0.24 (95% CI: -0.44, -0.05) per doubling of PFOA and PFNA, respectively, and -0.18 (95% CI: -0.34, -0.02) per quartile increase in the PFAS mixture. Child's sex modified PFOA associations for some skeletal sites; for example, differences in spine BMAD z-score per doubling were -0.31 (95% CI: -0.58, -0.03) among males and 0.07 (95% CI: -0.16, 0.30) among females (modification 푝= 0.04). Except for PFNA among females, these associations were not mediated by whole-body lean mass. DISCUSSION: Maternal PFAS concentrations during pregnancy may be associated with lower bone mineral accrual and strength in early adolescence [ABSTRACT FROM AUTHOR]

BACKGROUND: Drinking water chlorination by-products have been associated with adverse reproductive outcomes, although the findings for congenital malformations are still inconclusive. OBJECTIVE: We conducted a nationwide register-based prospective study to assess whether first trimester maternal exposure to the four most common trihalomethanes [total trihalomethanes (TTHM)] via municipal drinking water was associated with risk of congenital malformation among newborns. METHODS: We included all births during 2005–2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, two or fewer operating water works, and sufficient municipal TTHM monitoring data. Individual maternal first trimester exposure was obtained by linking TTHM measurements to residential information, categorized into no chlorination and <5, 5–15, and >15 μg TTHM/L. We also made chlorination treatment-specific analyses (exclusive use of chloramine or hypochlorite). Outcomes and covariates were obtained via linkage to health care and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: Based on 623,468 births and a prevalence of congenital malformation of ~2 cases/100 births, we observed associations between TTHM exposure in areas using chloramine and malformations of the nervous system (OR = 1:82; 95% CI: 1.07, 3.12), urinary system (OR = 2:06; 95% CI: 1.53, 2.78), genitals (OR = 1:77; 95% CI: 1.38, 2.26), and limbs (OR = 1:34; 95% CI: 1.10, 1.64), comparing the highest exposed category with the unexposed. No associations were observed in areas using exclusively hypochlorite as the primary water treatment method. By contrast, for malformations of the heart, a significant inverse association was observed only in areas using hypochlorite. DISCUSSION: TTHM exposure was associated with the increased risk of malformations of the nervous system, urinary system, genitals, and limbs in areas exclusively using chloramine. An association between chloramine-related chlorination by-products and congenital malformations has not previously been highlighted and needs further attention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to per- and polyfluoroalkyl substances (PFAS), a prevalent class of persistent pollutants, may increase the risk of type 2 diabetes. OBJECTIVE: We examined associations between PFAS exposure and glucose metabolism in youth. METHODS: Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; 푛=310) participated in annual visits for an average of 3.3±2.9 y. Generalizability of findings were tested in young adults from the Southern California Children's Health Study (CHS; 푛=135) who participated in a clinical visit with a similar protocol. At each visit, oral glucose tolerance tests were performed to estimate glucose metabolism and b-cell function via the insulinogenic index. Four PFAS were measured at baseline using liquid chromatography–high-resolution mass spectrometry; high levels were defined as concentrations >66th percentile. RESULTS: In females from the SOLAR, high perfluorohexane sulfonate (PFHxS) levels (=2.0 ng/mL) were associated with the development of dysregulated glucose metabolism beginning in late puberty. The magnitude of these associations increased postpuberty and persisted through 18 years of age. For example, postpuberty, females with high PFHxS levels had 25-mg/dL higher 60-min glucose (95% CI: 12, 39 mg/dL; 푝<0.0001), 15-mg/dL higher 2-h glucose (95% CI: 1, 28 mg/dL; 푝=0:04), and 25% lower b-cell function (푝=0.02) compared with females with low levels. Results were largely consistent in the CHS, where females with elevated PFHxS levels had 26-mg/dL higher 60-min glucose (95% CI: 6.0, 46 mg/dL; 푝=0.01) and 19-mg/dL higher 2-h glucose, which did not meet statistical significance (95% CI: –1, 39 mg/dL; 푝=0.08). In males, no consistent associations between PFHxS and glucose metabolism were observed. No consistent associations were observed for other PFAS and glucose metabolism. DISCUSSION: Youth exposure to PFHxS was associated with dysregulated glucose metabolism in females, which may be due to changes in b-cell function. These associations appeared during puberty and were most pronounced postpuberty. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lead can adversely affect child health across a wide range of exposure levels. We describe the distribution of blood lead levels (BLLs) in U.S. children ages 1–11 y by selected sociodemographic and housing characteristics over a 40-y period. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) II (1976–1980), NHANES III (Phase 1: 1988–1991 and Phase II: 1991–1994), and Continuous NHANES (1999–2016) were used to describe the distribution of BLLs (in micrograms per deciliter; 1 μg/dL=0.0483 μmol/L) in U.S. children ages 1–11 y from 1976 to 2016. For all children with valid BLLs (푛=27,122), geometric mean (GM) BLLs [95% confidence intervals (CI)] and estimated prevalence ≥5 μg/dL (95% CI) were calculated overall and by selected characteristics, stratified by age group (1–5 y and 6–11 y). RESULTS: The GM BLL in U.S. children ages 1-5 y declined from 15:2 μg/dL (95% CI: 14.3, 16.1) in 1976-1980 to 0:83 μg/dL (95% CI: 0.78, 0.88) in 2011-2016, representing a 94.5% decrease over time. For children ages 6-11 y, GM BLL declined from 12.7 μg/dL (95% CI: 11.9, 13.4) in 1976-1980 to 0.60μg/dL (95% CI: 0.58, 0.63) in 2011-2016, representing a 95.3% decrease over time. Even so, for the most recent period (2011-2016), estimates indicate that approximately 385,775 children ages 1-11 y had BLLs greater than or equal to the CDC blood lead reference value of 5 μg/dL. Higher GM BLLs were associated with non-Hispanic Black race/ethnicity, lower family income-to-poverty-ratio, and older housing age. DISCUSSION: Overall, BLLs in U.S. children ages 1–11 y have decreased substantially over the past 40 y. Despite these notable declines in population exposures to lead over time, higher GM BLLs are consistently associated with risk factors such as race/ethnicity, poverty, and housing age that can be used to target blood lead screening efforts. [ABSTRACT FROM AUTHOR]

The article discusses a 2022 study on the impact of long-term ambient air pollution on childhood eczema in the U.S. Topics covered include the link of long-term ambient nitrogen dioxide (NO2) concentrations with eczema incidence in the first year of life, and eczema's association with increased risk for multiple atopic diseases like food allergy, asthma and allergic rhinitis. Also noted is the increased risk for allergic diseases if there are exposures that increase eczema risk.

BACKGROUND: Access to green space has been hypothesized to have a beneficial impact on children's mental well-being and cognitive development. The underlying mechanisms of the mental health benefits of green space are not fully understood, but different pathways have been suggested, such as the psychologically restoring capacities of green space, the ability to facilitate physical activity and social cohesion, and the mitigation of exposure to air pollution. OBJECTIVES: In this nationwide cohort study, we investigated associations between residential green space in early childhood and a clinical diagnosis of attention deficit hyperactivity disorder (ADHD). METHODS: The cohort included individuals, who were born in Denmark between 1992 and 2007 (n=814,689) and followed for a diagnosis of ADHD from age 5, during the period 1997–2016. We used the normalized difference vegetation index (NDVI) as a measure of vegetation greenness surrounding each residential address in a quadratic area of 210m×210m in which the residence was located in the center of the quadrate. Individual exposure to green space was calculated as the average of NDVI surrounding each individual's residential address (or addresses if more than one) between birth and the fifth birthday. Multilevel modeling was used to estimate the incidence rate ratios (IRRs) with 95% confidence intervals (CI) for ADHD, according to exposure level and adjusted for calendar time, age, sex, parental socioeconomic status, neighborhood level socioeconomic status, and urbanicity. RESULTS: Individuals living in areas defined by sparse green vegetation (lowest decile of NDVI) had an increased risk of developing ADHD, compared with individuals living in areas within the highest decile of NDVI (IRR=1.55; 95% CI: 1.46, 1.65). Adjusting for the known confounders attenuated the result, but the association remained (IRR=1.20; 95% CI: 1.13, 1.28). CONCLUSION: Our findings suggest that lower levels of green space in residential surroundings, during early childhood, may be associated with a higher risk of developing ADHD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vitamin D improves absorption of calcium; however, in animal studies vitamin D also increases the absorption of toxic metals, such as lead and cadmium. OBJECTIVES: We examined maternal and neonatal cord blood levels of lead, cadmium, manganese, and mercury after supplementation with vitamin D during pregnancy. METHODS: The Maternal Vitamin D for Infant Growth trial was a randomized, placebo-controlled, multi-arm study of maternal vitamin D supplementation during pregnancy in Dhaka, Bangladesh (NCT01924013). Women were randomized during their second trimester to blinded weekly doses of placebo or 4,200, 16,800, or 28,000 IU of vitamin D3 throughout pregnancy. Each group had 118–239 maternal blood specimens and 100–201 cord blood samples analyzed. Metals were measured using inductively coupled plasma mass spectrometry. Unadjusted estimates from linear regression models were expressed as percentage differences. Cord blood cadmium was analyzed as detectable or undetectable with log-binomial regression. RESULTS: Maternal cadmium, mercury, and manganese levels were nearly identical across groups. Maternal lead levels were 6.3%, 7.4%, and 6.0% higher in the treatment groups (4,200, 16,800, and 28,000 IU, respectively) vs. placebo; however, 95% confidence intervals (CIs) showed that differences from 4.1% lower to 20% higher were compatible with the data. In treatment groups (4,200, 16,800, 28,000 IU) vs. placebo, neonatal cord blood lead levels were 8.5% (95% CI: -3:5, 22), 16% (95% CI: 3.3, 30), and 11% (95% CI: 0.4, 23) higher and had higher risk of detectable cadmium, relative risk ðRRÞ= 2:2 (95% CI: 1.3, 3.7), RR = 1:4 (95% CI: 0.8, 2.5), RR = 1:7 (95% CI: 1.0, 2.9). DISCUSSION: Vitamin D supplementation from the second trimester of pregnancy did not influence maternal cadmium, mercury, or manganese levels at delivery. Vitamin D was associated with nonsignificant increases in maternal lead and with significant increases in cord blood lead and cadmium. These associations were not dose dependent. Given that there are no safe levels of metals in infants, the observed increases in cord blood lead and cadmium require further exploration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Manganese (Mn) in drinking water may increase the risk of several neurodevelopmental outcomes, including attention-deficit hyperactivity disorder (ADHD). Earlier epidemiological studies on associations between Mn exposure and ADHD-related outcomes had small sample sizes, lacked spatiotemporal exposure assessment, and relied on questionnaire data (not diagnoses)—shortcomings that we address here. OBJECTIVE: Our objective was to assess the association between exposure to Mn in drinking water during childhood and later development of ADHD. METHODS: In a nationwide population-based registry study in Denmark, we followed a cohort of 643,401 children born 1992–2007 for clinical diagnoses of ADHD. In subanalyses, we classified cases into ADHD-Inattentive and ADHD-Combined subtypes based on hierarchical categorization of International Classification of Diseases (ICD)-10 codes. We obtained Mn measurements from 82,574 drinking water samples to estimate longitudinal exposure during the first 5 y of life with high spatiotemporal resolution. We modeled exposure as both peak concentration and time-weighted average. We estimated sex-specific hazard ratios (HRs) in Cox proportional hazards models adjusted for age, birth year, socioeconomic status (SES), and urbanicity. RESULTS: We found that exposure to increasing levels of Mn in drinking water was associated with an increased risk of ADHD-Inattentive subtype, but not ADHD-Combined subtype. After adjusting for age, birth year, and SES, females exposed to high levels of Mn (i.e., >100µg/L) at least once during their first 5 y of life had an HR for ADHD-Inattentive subtype of 1.51 [95% confidence interval (CI): 1.18, 1.93] and males of 1.20 (95% CI: 1.01, 1.42) when compared with same-sex individuals exposed to <5µg/L. When modeling exposure as a time-weighted average, sex differences were no longer present. DISCUSSION: Mn in drinking water was associated with ADHD, specifically the ADHD-Inattentive subtype. Our results support earlier studies suggesting a need for a formal health-based drinking water guideline value for Mn. Future Mn-studies should examine ADHD subtype-specific associations and utilize direct subtype measurements rather than relying on ICD-10 codes alone. [ABSTRACT FROM AUTHOR]

BACKGROUND: Perfluoroalkyl substances (PFAS) are a group of widely used persistent chemicals with suspected immunotoxic effects. OBJECTIVES: The present study aimed to examine the association between infant PFAS exposure and antibody responses to measles vaccination as well as morbidity in a low-income country. METHODS: In a randomized controlled trial, children from Guinea-Bissau, West Africa, were followed from inclusion (4–7 months of age) through 2 years of age. Half the children received two measles vaccinations (at inclusion and at 9 months of age), and the other half received only one (at 9 months of age). In a subset of 237 children, six PFAS were quantified in serum at inclusion, and measles antibody concentrations were assessed at inclusion and at approximately 9 months and 2 years of age. At inclusion and at the 9-month visit, mothers were interviewed about infant morbidity. RESULTS: All but one child had detectable serum concentrations of all six PFAS, although levels were lower than seen elsewhere. A doubling in perfluorooctane sulfonic acid (PFOS) and perfluorodecanoic acid (PFDA) were associated with 21% (95% CI: 2, 37%) and 25% (95% CI: 1, 43%), respectively, lower measles antibody concentrations at the 9-month visit among the children who had received a measles vaccine at inclusion. Elevated serum PFAS concentrations were also associated with reduced prevaccination measles antibody concentrations and increased morbidity. DISCUSSION: The present study documents that PFAS exposure has reached West Africa and that infants show PFAS-associated increases in morbidity and decreases in measles-specific antibody concentrations before and after vaccination. These findings support the evidence on PFAS immunotoxicity at comparatively low serum concentrations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester. OBJECTIVE: We examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age. METHOD: The study sample consisted of 1,282 mother-child pairs participating in the Generation R Study, a population-based birth cohort in Rotterdam, Netherlands (enrollment 2002-2006). We measured maternal urinary concentrations of 18 phthalate metabolites and 8 bisphenols at <18, 18-25, and >25 wks of gestation. Child nonverbal IQ was measured at 6 years of age using the Snijders-Oomen Nonverbal Intelligence Test-Revised. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged prenatal exposure across pregnancy. RESULTS: Higher urinary concentrations of phthalate metabolites during early pregnancy were associated with lower child nonverbal IQ score [e.g., B per 10-fold increase in summed low-molecular weight phthalates = -1.7 (95% CI: -3.1, -0.3)]. This association remained unchanged when adjusted for mid and late pregnancy exposures. We also observed an inverse association between late pregnancy di-n-octyl phthalate (DNOP) exposure and nonverbal IQ. Maternal urinary concentrations of bisphenols were not associated with child nonverbal IQ. There was no effect estimate modification by sex. CONCLUSIONS: We did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. [ABSTRACT FROM AUTHOR]

BACKGROUND: Perfluoroalkyl acids (PFAA) are repellants that cross the placental barrier, enabling interference with fetal programming. Maternal PFAA concentrations have been associated with offspring obesity and dyslipidemia in childhood and adulthood, but this association has not been studied in infancy. OBJECTIVES: We investigated associations between maternal PFAA concentrations and repeated markers of adiposity and lipid metabolism in infancy. METHODS: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAA: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 649 women. Offspring were examined at birth (n=613) and at 3 months (n=602) and 18 months (n=503) of age. Total cholesterol, LDL, HDL, and triglyceride were evaluated at 3 months (n=262) and 18 months (n=198) of age. Mixed effects linear regression models estimated associations between PFAA and standardized (SDS) body mass index (BMI), ponderal index, and waist circumference. Associations between PFAA and body fat% (BF%) and plasma lipids SDS at 3 months and 18 months of age were investigated with linear regression models. RESULTS: PFNA and PFDA were associated with higher BMI SDS [adjusted β=0.26; 95% confidence interval (CI): 0.03, 0.49 and β=0.58; 95% CI: -0.03, 1.19, respectively, for 1-ng/mL increases] and ponderal index SDS (β=0.36; 95% CI: 0.13, 0.59 and β=1.02; 95% CI: 0.40, 1.64, respectively) at 3 and 18 months of age (pooled) in girls. Corresponding estimates for boys were closer to the null but not significantly different from estimates for girls. In boys and girls (combined), PFNA and PFDA were associated with BF% at age 3 months (for 1-ng/mL PFDA, β=0.40; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months (β=1.06; 95% CI: 0.08, 2.03) (n=83). DISCUSSION: Prenatal PFAA were positively associated with longitudinal markers of adiposity and higher total cholesterol in infancy. These findings deserve attention in light of rising rates of childhood overweight conditions and dyslipidemia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Air pollution has been related to brain structural alterations, but a relationship with white matter microstructure is unclear. OBJECTIVES: We assessed whether pregnancy and childhood exposures to air pollution are related to white matter microstructure in preadolescents. METHODS: We used data of 2,954 children from the Generation R Study, a population-based birth cohort from Rotterdam, Netherlands (2002–2006). Concentrations of 17 air pollutants including nitrogen oxides (NOX), particulate matter (PM), and components of PM were estimated at participants’ homes during pregnancy and childhood using land-use regression models. Diffusion tensor images were obtained at child’s 9–12 years of age, and fractional anisotropy (FA) and mean diffusivity (MD) were computed. We performed linear regressions adjusting for socioeconomic and lifestyle characteristics. Single-pollutant analyses were followed by multipollutant analyses using the Deletion/Substitution/Addition (DSA) algorithm. RESULTS: In the single-pollutant analyses, higher concentrations of several air pollutants during pregnancy or childhood were associated with significantly lower FA or higher MD (p<0.05). In multipollutant models of pregnancy exposures selected by DSA, higher concentration of fine particles was associated with significantly lower FA [-0.71 (95% CI: -1.26, -0.16) per 5 µg/m³ fine particles] and higher concentration of elemental silicon with significantly higher MD [0.06 (95% CI: 0.01, 0.11) per 100 ng/m³ silicon]. Multipollutant models of childhood exposures selected by DSA indicated significant associations of NOX with FA [-0.14 (95% CI: -0.23, -0:04) per 20-µg/m³ NOX increase], and of elemental zinc and the oxidative potential of PM with MD [0.03 (95% CI: 0.01, 0.04) per 10-ng=m3 zinc increase and 0.07 (95% CI: 0.00, 0.44) per 1-nmol DTT/min/m³ oxidative potential increase]. Mutually adjusted models of significant exposures during pregnancy and childhood indicated significant associations of silicon during pregnancy, and zinc during childhood, with MD. DISCUSSION: Exposure in pregnancy and childhood to air pollutants from tailpipe and non-tailpipe emissions were associated with lower FA and higher MD in white matter of preadolescents. [ABSTRACT FROM AUTHOR]

Background: Pregnant women and children are especially vulnerable to exposures to food contaminants, and a balanced diet during these periods is critical for optimal nutritional status. Objectives: Our objective was to study the association between diet and measured blood and urinary levels of environmental contaminants in mother–child pairs from six European birth cohorts (n=818 mothers and 1,288 children). Methods: We assessed the consumption of seven food groups and the blood levels of organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and heavy metals and urinary levels of phthalate metabolites, phenolic compounds, and organophosphate pesticide (OP) metabolites. Organic food consumption during childhood was also studied. We applied multivariable linear regressions and targeted maximum likelihood based estimation (TMLE). Results: Maternal high (=4?times/week) versus low (<2?times/week) fish consumption was associated with 15% higher PCBs [geometric mean (GM) ratio=1.15; 95% confidence interval (CI): 1.02, 1.29], 42% higher perfluoroundecanoate (PFUnDA) (GM?ratio=1.42; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (GM?ratio=1.89; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (GM?ratio=4.87; 95% CI: 2.57, 9.23) levels. In children, high (=3?times/week) versus low (<1.5?times/week) fish consumption was associated with 23% higher perfluorononanoate (PFNA) (GM?ratio=1.23; 95% CI: 1.08, 1.40), 36% higher PFUnDA (GM?ratio=1.36; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (GM?ratio=1.37; 95% CI: 1.22, 1.54), and >200% higher Hg and As [GM?ratio=3.87 (95% CI: 1.91, 4.31) and GM?ratio=2.68 (95% CI: 2.23, 3.21)] concentrations. Using TMLE analysis, we estimated that fish consumption within the recommended 2–3 times/week resulted in lower PFAS, Hg, and As compared with higher consumption. Fruit consumption was positively associated with OP metabolites. Organic food consumption was negatively associated with OP metabolites. DISCUSSION: Fish consumption is related to higher PFAS, Hg, and As exposures. In addition, fruit consumption is a source of exposure to OPs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Telomere length is a molecular marker of biological aging. OBJECTIVE: Here we investigated whether early-life exposure to residential air pollution was associated with leukocyte telomere length (LTL) at 8 y of age. METHODS: In a multicenter European birth cohort study, HELIX (Human Early Life Exposome) (n=1,396), we estimated prenatal and 1-y childhood exposure to nitrogen dioxide (NO2), particulate matter with aerodynamic diameter ≤2:5 lm (PM2:5), and proximity to major roads. Average relative LTL was measured using quantitative real-time polymerase chain reaction (qPCR). Effect estimates of the association between LTL and prenatal, 1-y childhood air pollution, and proximity to major roads were calculated using multiple linear mixed models with a random cohort effect and adjusted for relevant covariates. RESULTS: LTL was inversely associated with prenatal and 1-y childhood NO2 and PM2:5 exposures levels. Each standard deviation (SD) increase in prenatal NO2 was associated with a −1:5% (95% CI: −2:8, −0:2) change in LTL. Prenatal PM2:5 was nonsignificantly associated with LTL (−0:7% per SD increase; 95% CI: −2:0, 0.6). For each SD increment in 1-y childhood NO2 and PM2:5 exposure, LTL shortened by −1:6% (95% CI: −2:9, −0:4) and −1:4% (95% CI: −2:9, 0.1), respectively. Each doubling in residential distance to nearest major road during childhood was associated with a 1.6% (95% CI: 0.02, 3.1) lengthening in LTL. CONCLUSION: Lower exposures to air pollution during pregnancy and childhood were associated with longer telomeres in European children at 8 y of age. These results suggest that reductions in traffic-related air pollution may promote molecular longevity, as exemplified by telomere length, from early life onward. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effects of weather on diarrhea could influence the health impacts of climate change. Children have the highest diarrhea incidence, especially in India, where many lack safe water and sanitation. OBJECTIVES: In a prospective cohort of 1,284 children under 5 y of age from 900 households across 25 villages in rural Tamil Nadu, India, we examined whether high temperature and heavy rainfall was associated with increased all-cause diarrhea and water contamination. METHODS: Seven-day prevalence of diarrhea was assessed monthly for up to 12 visits from January 2008 to April 2009, and hydrogen sulfide (H2S) presence in drinking water, a fecal contamination indicator, was tested in a subset of households. We estimated associations between temperature and rainfall exposures and diarrhea and H2S using binomial regressions, adjusting for potential confounders, random effects for village, and autoregressive-1 error terms for study week. RESULTS: There were 259 cases of diarrhea. The prevalence of diarrhea during the 7 d before visits was 2.95 times higher (95% CI: 1.99, 4.39) when mean temperature in the week before the 7-d recall was in the hottest versus the coolest quartile of weekly mean temperature during 1 December 2007 to 15 April 2009. Diarrhea prevalence was 1.50 times higher when the 3 weeks before the diarrhea recall period included ≥1 d (vs. 0 d) with rainfall of >16:82 mm (95% CI: 1.12, 2.02), and 2.60 times higher (95% CI: 1.55, 4.36) for heavy rain weeks following a 60-d dry period. The H2S prevalence in household water was not associated with heavy rain prior to sample collection. CONCLUSIONS: The results suggest that, in rural Tamil Nadu, heavy rainfall may wash pathogens that accumulate during dry weather into child contact. Higher temperatures were positively associated with diarrhea 1-3 weeks later. Our findings suggest that diarrhea morbidity could worsen under climate change without interventions to reduce enteric pathogen transmission through multiple pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic cadmium exposure has been associated with osteotoxicity in adults, but little is known concerning its effects on early growth, which has been shown to be impaired by cadmium. OBJECTIVES: Our objective was to assess the impact of early-life cadmium exposure on bone-related biomarkers and anthropometry at 9 y of age. METHODS: For 504 children in a mother-child cohort in Bangladesh, cadmium exposure was assessed by concentrations in urine (U-Cd, long-term exposure) and erythrocytes (Ery-Cd, ongoing exposure) at 9 and 4.5 y of age, and in their mothers during pregnancy. Biomarkers of bone remodeling [urinary deoxypyridinoline (DPD), urinary calcium, plasma parathyroid hormone, osteocalcin, vitamin D3, insulin-like growth factor (IGF) 1, IGF binding protein 3, thyroid stimulating hormone] were measured at 9 y of age. RESULTS: In multivariable-adjusted linear models, a doubling of concurrent U-Cd was associated with a mean increase in osteocalcin of 2:7ng=mL (95% CI: 0.042, 5.9) and in urinary DPD of 22 nmol=L (95% CI: 12, 32). In a combined exposure model, a doubling of maternal Ery-Cd was associated with a mean increase in urinary DPD of 15 nmol =L (95% CI: -0:047, 30). Stratifying the osteocalcin model by gender (pinteraction = 0.001), a doubling of concurrent U-Cd was associated with a mean decrease in osteocalcin of -4:3 ng=mL (95% CI: -8:5, -0:080) in boys and a mean increase of 9:4 ng=mL (95% CI: 5.4, 13) in girls. The same pattern was seen with U-Cd at 4.5 y of age (pinteraction = 0.016). Children's U-Cd and Ery- Cd, concurrent and at 4.5 y of age, were inversely associated with vitamin D3. CONCLUSIONS: Childhood cadmium exposure was associated with several bone-related biomarkers and some of the associations differed by gender. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to triclosan, an endocrine disrupting chemical, may affect thyroid hormone homeostasis and adversely affect neurodevelopment. OBJECTIVE: Using a longitudinal pregnancy and birth cohort, we investigated associations between triclosan exposures during different time windows, and cognitive test scores at 8 y of age in 198 children from the HOME Study. METHODS: We quantified triclosan in urine samples from mother-child pairs up to nine times between the second trimester of gestation and 8 y of age. The Wechsler Intelligence Scale for Children-IV [i.e., Full-Scale Intelligence Quotient (IQ)] assessment was administered to HOME Study children at 8 y of age. We estimated covariate-adjusted triclosan-IQ associations at each visit. We also tested whether associations between triclosan concentrations and cognitive test scores varied among exposure at different time periods. RESULTS: Full-Scale IQ was not significantly associated with urinary triclosan concentrations during gestation or childhood but was significantly associated with a 10-fold increase in maternal urinary triclosan concentration at delivery [-4:5 points (95% CI: -7:0, -2:0)]. Perceptual Reasoning Index (PRI) scores were significantly decreased in association with urinary triclosan concentrations at delivery and at 2 y of age. Associations between repeated triclosan concentrations and cognitive test scores significantly varied among exposure at different time periods for Full-Scale IQ, PRI, Verbal Comprehension Index, and Working Memory (triclosan-visit interaction p=0:04). CONCLUSION: Urinary triclosan concentrations at delivery, but not during mid to late pregnancy and childhood, were associated with significantly lower children's cognitive test scores at 8 y of age in this cohort of U.S. children. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is growing concern that phthalate exposures may have an impact on child neurodevelopment. Prenatal exposure to phthalates has been linked with externalizing behaviors and executive functioning defects suggestive of an attention-deficit hyperactivity disorder (ADHD) phenotype. OBJECTIVES: We undertook an investigation into whether prenatal exposure to phthalates was associated with clinically confirmed ADHD in a population-based nested case-control study of the Norwegian Mother and Child Cohort (MoBa) between the years 2003 and 2008. METHODS: Phthalate metabolites were measured in maternal urine collected at midpregnancy. Cases of ADHD (n=297) were obtained through linkage between MoBa and the Norwegian National Patient Registry. A random sample of controls (n=553) from the MoBa population was obtained. RESULTS: In multivariable adjusted coexposure models, the sum of di-2-ethylhexyl phthalate metabolites (κ DEHP) was associated with a monotonically increasing risk of ADHD. Children of mothers in the highest quintile of κ DEHP had almost three times the odds of an ADHD diagnosis as those in the lowest [OR=2:99 (95% CI: 1.47, 5.49)]. When κ DEHP was modeled as a log-linear (natural log) term, for each log-unit increase in exposure, the odds of ADHD increased by 47% [OR =1:47 (95% CI: 1.09, 1.94)]. We detected no significant modification by sex or mediation by prenatal maternal thyroid function or by preterm delivery. CONCLUSIONS: In this population-based case-control study of clinical ADHD, maternal urinary concentrations of DEHP were monotonically associated with increased risk of ADHD. Additional research is needed to evaluate potential mechanisms linking phthalates to ADHD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have reported some evidence of adverse effects of organochlorine exposures on child development, but the results have been inconsistent, and few studies have evaluated associations with child behavior. OBJECTIVE: We investigated the association between prenatal and early-life exposures to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1- dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) and behaviors in children between 5 and 9 y of age. METHODS: In the Biopersistent organochlorines in diet and human fertility: Epidemiologic studies of time to pregnancy and semen quality in Inuit and European populations (INUENDO) cohort, consisting of mother-child pairs from Greenland and Ukraine (n = 1,018), maternal serum PCB-153 and p,p'-DDE concentrations were measured during pregnancy, and cumulative postnatal exposures during the first 12 months after delivery were estimated using a pharmacokinetic model. Parents completed the Strengths and Difficulties Questionnaire (SDQ), and children's behaviors were dichotomized as abnormal (high) versus normal/borderline for five SDQ subscales and the total difficulties score. RESULTS: The total difficulties score, an overall measure of abnormal behavior, was not clearly associated with pre- or postnatal exposures to PCB-153 or to p,p'-DDE. However, pooled adjusted odds ratios (ORs) for high conduct problem scores with a doubling of exposure were 1.19 (95% CI: 0.99, 1.42) and 1.16 (95% CI: 0.96, 1.41) for pre- and postnatal PCB-153, respectively, and 1.25 (95% CI: 1.04, 1.51) and 1.24 (95% CI: 1.01, 1.51) for pre- and postnatal p,p'-DDE, respectively. Corresponding ORs for high hyperactivity scores were 1.24 (95% CI: 0.94, 1.62) and 1.08 (95% CI: 0.81, 1.45) for pre- and postnatal PCB-153, respectively, and 1.43 (95% CI: 1.06, 1.92) and 1.27 (95% CI: 0.93, 1.73) for pre- and postnatalp,p'-DDE, respectively. CONCLUSION: Prenatal and early postnatal exposures to p,p'-DDE and PCB-153 were associated with a higher prevalence of abnormal scores for conduct and hyperactivity at 5-9 y of age in our study population. These findings provide further support for the importance of minimizing organochlorine exposures to young children and to women of childbearing age. [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: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑ DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 [ABSTRACT FROM AUTHOR]

BACKGROUND: Prior studies suggest neurodevelopmental impacts of polybrominated diphenyl ethers (PBDEs), but few have examined diagnosed developmental disorders. OBJECTIVES: Our aim was to determine whether prenatal exposure to brominated flame retardants (BFRs) is associated with autism spectrum disorder (ASD) or intellectual disability without autism (ID). METHODS: We conducted a population-based case-control study including children with ASD (n=545) and ID (n=181) identified from the California Department of Developmental Services and general population (GP) controls (n=418) from state birth certificates. ASD cases were matched to controls by sex, birth month, and birth year. Concentrations of 10 BFRs were measured in maternal second trimester serum samples stored from routine screening. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses. RESULTS: Geometric mean concentrations of five of the six congeners with ≥55% of samples above the limit of detection were lower in mothers of children with ASD or ID than in controls. In adjusted analyses, inverse associations with several congeners were found for ASD relative to GP (e.g., quartile 4 vs. 1, BDE-153: AOR=0:56, 95% CI: 0.38, 0.84). When stratified by child sex (including 99 females with ASD, 77 with ID, and 73 with GP), estimates were consistent with overall analyses in boys, but in the opposite direction among girls, particularly for BDE-28 and -47 (AOR=2:58, 95% CI: 0.86, 7.79 and AOR=2:64, 95% CI: 0.97, 7.19, respectively). Similar patterns overall and by sex were observed for ID. CONCLUSIONS: Contrary to expectation, higher PBDE concentrations were associated with decreased odds of ASD and ID, though not in girls. These findings require confirmation but suggest potential sexual dimorphism in associations with prenatal exposure to BFRs. [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: Elemental sulfur, "the oldest of all pesticides," is the most heavily used agricultural pesticide in California and Europe. Sulfur is considered relatively safe and is used in both conventional and organic farming systems. Adverse respiratory effects have been reported in applicators and animals, but the effect on residential populations, and especially on children living in proximity to fields treated with elemental sulfur, is not known. OBJECTIVES: We evaluated associations between residential proximity to elemental sulfur applications and respiratory symptoms and spirometry of children living in an agricultural community. METHODS: Participants were enrolled in the CHAMACOS longitudinal birth cohort. We collected respiratory symptomatology for 347 children at 7 y of age and measured spirometry on a subset of 279. Of these, estimations of proximity to sulfur application and relevant covariate data were available for 237 and 205 children for whom we had symptomatology information and FEV1 measurements, respectively. Data from the California Pesticide Use Reporting System were used to estimate the amount of elemental sulfur applied within 0.5, 1, and 3 km of a child's residence during the week, month, and 12 mo prior to pulmonary evaluation. Regression models controlled for maternal smoking during pregnancy; season of birth; PM2.5 (particulate matter ≤2.5 mm in aerodynamic diameter); breast feeding duration; child's sex, age, and height; technician; and other covariates. RESULTS: Adverse associations with respiratory outcomes were found for sulfur applications within 0.5- and 1-km radii. Specifically, asthma medication usage and respiratory symptoms increased [OR=3.51; 95% confidence interval (CI): 1.50, 8.23, p=0.004; OR=2.09; 95% CI: 1.27, 3.46, p=0.004, respectively] and FEV1 decreased (β=-0.143; 95% CI: -0.248, -0.039, p=0.008) per 10-fold increase in the estimated amount of sulfur used within 1 km of child residence during the year prior to pulmonary evaluation. CONCLUSIONS: This study suggests that elemental sulfur use, allowed in both organic and conventional farming, in close proximity to residential areas, may adversely affect children's respiratory health. [ABSTRACT FROM AUTHOR]

BACKGROUND: The association of ozone exposure with respiratory outcomes has been investigated in epidemiologic studies mainly including asthmatic children. The findings reported had methodological gaps and inconsistencies. OBJECTIVES: We aimed to investigate effects of personal ozone exposure on various respiratory outcomes in school-age children generally representative of the population during their normal activities. METHODS: We conducted a panel study in a representative sample of school-age children in the two major cities of Greece, Athens and Thessaloniki. We followed 188, 10-to 11-y-old, elementary school students for 5 wk spread throughout the 2013-2014 academic year, during which ozone was measured using personal samplers. At the end of each study week, spirometry was performed by trained physicians, and the fractional concentration of nitric oxide in exhaled air (FeNO) was measured. Students kept a daily time-activity-symptom diary and measured PEF (peak expiratory flow) using peak flow meters. Mixed models accounting for repeated measurements were applied. RESULTS: An increase of 10 µg/m³ in weekly ozone concentration was associated with a decrease in FVC (forced vital capacity) and FEV1 (forced expiratory volume in 1 s) of 0:03 L [95% confidence interval (CI): -0:05, -0:01] and 0:01 L (95% CI: -0:03, 0.003) respectively. The same increase in exposure was associated with a 11.10% (95% CI: 4.23, 18.43) increase in FeNO and 19% (95% CI: -0:53, 42.75) increase in days with any symptom. The effect estimates were robust to PM10 adjustment. No inverse association was found between ozone exposure and PEF. CONCLUSIONS: The study provides evidence that airway inflammation and the frequency of respiratory symptoms increase, whereas lung function decreases with increased ozone exposure in schoolchildren. [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]