Results of toxicological studies indicate that phthalates and per-/polyfluoroalkyl substances (PFAS), 2 classes of endocrine-disrupting chemicals, may alter the functioning of the hypothalamic-pituitary-adrenocortical (HPA) axis. We evaluated the associations of urinary phthalate metabolites and serum PFAS during gestation and childhood with adolescent hair cortisol concentrations (pg/mg hair) at age 12 years, an integrative marker of HPA axis activity (n = 205 mother-child pairs; Cincinnati, Ohio; enrolled 2003-2006). We used quantile-based g-computation to estimate associations between mixtures of urinary phthalate metabolites or serum PFAS and hair cortisol. We also examined whether associations of individual phthalate metabolites or PFAS with cortisol varied by the timing of exposure. We found that a 1-quartile increase in all childhood phthalate metabolites was associated with 35% higher adolescent hair cortisol (phthalate mixture psi = 0.13; 95% confidence interval: 0.03, 0.22); these associations were driven by monoethyl phthalate, monoisobutyl phthalate, and monobenzyl phthalate. We did not find evidence that phthalate metabolites during gestation or serum PFAS mixtures were related to adolescent hair cortisol concentrations. We found suggestive evidence that higher childhood concentrations of individual PFAS were related to higher and lower adolescent hair cortisol concentrations. Our results suggest that phthalate exposure during childhood may contribute to higher levels of chronic HPA axis activity.

The COVID-19 pandemic brought new emphasis on indoor air quality. However, few studies have investigated the impact of air filtration, a COVID-mitigation approach, on indoor air concentrations of semivolatile organic compounds (SVOCs). Using a quasi-experimental design, we quantified the impact of a relatively low-cost "do-it-yourself" air filter (Corsi-Rosenthal Box; CR Box) on indoor air concentrations of 42 PFAS and 24 other SVOCs. We sampled air before (October-November 2021) and during (February-March 2022) deployment of CR Boxes in 17 rooms located in an occupied Providence, Rhode Island office building. We measured sound levels in rooms with CR Boxes operating and not operating. While CR Boxes were deployed, concentrations of seven PFAS (N-EtFOSE, N-EtFOSA, FBSA, PFBS, PFHxS, PFOS, PFNA) were 28-61% lower and concentrations of five phthalates (DMP, DEP, DiBP, BBzP, DCHP) were 29-62% lower. Concentrations of five PFAS and one phthalate increased 23-44% during the intervention period, but the 95% CI of most of these estimates included the null. Daytime sound levels increased 5.0 dB when CR Boxes were operating. These results indicate that CR Boxes reduced exposure to several lower-volatility phthalates and sulfonated PFAS previously reported to be found in office building materials and products, with potentially distracting increases in sound levels.

Background: Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with lower reproductive hormones and later puberty, but epidemiological studies evaluating these associations are scarce.Objectives: We examined associations of PFAS concentrations assessed from pregnancy to adolescence with pubertal development and reproductive hormones at age 12 years.Methods: We studied 200 mother-child pairs from the HOME Study in Cincinnati, OH (enrolled: 2003-2006). We quan-tified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in pregnant women and their children at age 3, 8 and 12 years. At age 12 years, children self-assessed pubertal development using Tanner staging of pubic hair growth (males and fe -males) and breast growth (females), and age at menarche. We quantified serum concentrations of dehydroepiandros-terone sulfate, luteinizing hormone, and follicle-stimulating hormone in both sexes; estradiol in females; testosterone in males. We estimated associations of PFAS with pubertal outcomes and reproductive hormones using a combination of ordinal regression, Cox proportional-hazard regression, and linear regression. Quantile-based g-computation was used for PFAS mixture.Results: In females, adolescent PFAS concentrations and their mixture were associated with later pubic hair growth, breast maturation, and age at menarche, but there was no pattern for prenatal or other postnatal concentrations. For instance, in females, each doubling in adolescent PFAS concentrations was associated with 79 % (PFOA), 63 % (PFOS), 56 % (PFNA), and 47 % (PFHxS) lower odds of attaining a higher stage for breast growth. In addition, adoles-cent PFAS concentrations were consistently associated with lower estradiol concentrations in females. No pattern was observed for associations of PFAS concentrations with pubic hair growth or reproductive hormones in males.Conclusions: We observed associations between PFAS concentrations in adolescence and later pubertal development in females, but this could be due to reverse causation induced by excretion of PFAS through menstrual fluid.

In response to COVID-19, attention was drawn to indoor air quality and interventions to mitigate airborne COVID-19 transmission. Of developed interventions, Corsi-Rosenthal (CR) boxes, a do-it-yourself indoor air filter, may have potential co-benefits of reducing indoor air contaminant levels. We employed non-targeted and suspect screening analysis (NTA and SSA) to detect and identify volatile and semi-volatile organic contaminants (VOCs and SVOCs) that decreased in indoor air following installation of CR boxes. Using a natural experiment, we sampled indoor air before and during installation of CR boxes in 17 rooms inside an occupied office building. We measured VOCs and SVOCs using gas chromatography (GC) high resolution mass spectrometry (HRMS) with electron ionization (EI) and liquid chromatography (LC) HRMS in negative and positive electrospray ionization (ESI). We examined area count changes during vs. before operation of the CR boxes using linear mixed models. Transformed (log2) area counts of 71 features significantly decreased by 50-100% after CR boxes were installed (False Discovery Rate (FDR) p-value < 0.2). Of the significantly decreased features, four chemicals were identified with Level 1 confidence, 45 were putatively identified with Level 2-4 confidence, and 22 could not be identified (Level 5). Identified and putatively identified features (Level ≥4) that declined included disinfectants (n = 1), fragrance and/or food chemicals (n = 9), nitrogen-containing heterocyclic compounds (n = 4), organophosphate esters (n = 1), polycyclic aromatic hydrocarbons (n = 8), polychlorinated biphenyls (n = 1), pesticides/herbicides/insecticides (n = 18), per- and polyfluorinated alkyl substances (n = 2), phthalates (n = 3), and plasticizers (n = 2).

Per- and polyfluoroalkyl substance (PFAS) exposure has been linked to DNA methylation changes in neonates and adults. We previously reported that prenatal PFAS exposure may have a durable impact on DNA methylation from birth to adolescence. However, few studies have examined the association of postnatal PFAS exposure with alterations in DNA methylation. We examined the associations of lifetime postnatal PFAS mixture exposure with leukocyte DNA methylation in 154 adolescents from the HOME Study (2003-2006; Cincinnati, Ohio). Lifetime postnatal PFAS mixture exposure was estimated using latent profile analysis of four PFAS concentrations measured at birth, and ages 3, 8, and 12 years. We measured DNA methylation in peripheral leukocytes at 12 years using the Illumina HumanMethylation EPIC BeadChip. We estimated covariate-adjusted associations between postnatal PFAS mixture concentrations and DNA methylation measures using linear regression, and used KEGG enrichment analysis to identify molecular pathways. Four significant differentially methylated positions were observed in the higher vs. lower PFAS profile (FDR p-value <0.05). These PFAS-associated CpG sites annotated to gene regions related to various cancers, cognition, and cardiometabolic health. We identified 17 pathways (FDR p-value <0.05), which indicates possible mechanism linking PFAS exposure to several health effects.

BACKGROUND:Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent. OBJECTIVES:We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) z-scores and risk of overweight/obesity in eight U.S. cohorts. METHODS:We used data from 1,391 mother-child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999-2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI z-scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI z-scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations. RESULTS:We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI z-scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI z-scores (β=0.07; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [relative risk (RR)=1.10; 95% CI: 1.04, 1.16] and N-methyl perfluorooctane sulfonamido acetic acid (RR=1.06; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose-response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex. DISCUSSION:In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI z-score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. https://doi.org/10.1289/EHP11545.

Objective: To evaluate whether sleep duration, timing, and variability were associated with inflammatory cytokines in a cohort of Mexico City adolescents. Methods: The analytic sample comprised > 500 adolescents who were part of an ongoing longitudinal study in Mexico City. At two time points during mid-to-late puberty (average age 14, n = 391) and late -to-post puberty (average age 16, n = 345), adolescents completed a follow-up visit that included 7-day wrist actigraphy and clinical assessment of plasma inflammatory cytokines (high-sensitivity C-reactive protein, Interleukin 10, Interleukin 6, and Tumor Necrosis Factor alpha). Sleep characteristics included weekday and weekend sleep duration and midpoint (median of bed and wake time), as well as sleep variability (SD of sleep duration across 7 days) and social jetlag (midpoint difference from weekdays to weekends). At each time point, multivariable linear regression models were run with log inflammatory levels as the outcome and categories of sleep characteristics as predictors, while adjusting for potential confounders (specific to each model). Analyses were run unstratified and sex-stratified. Results: In the mid-to-late pubertal visit, weekday sleep duration was inversely associated with natural log hs-CRP after adjustment (Q4 vs Q1: 0 =-0.41, 95% Confidence Interval (CI)-0.81 to-0.01) and later sleep midpoint was positively associated with log hs-CRP (Q4 vs Q1: 0 = 0.55, 95% CI 0.13 to 0.97). Sleep duration variability was associated with higher IL-10 among boys, while in girls social jetlag was associated with higher IL-10 and weekend sleep duration was inversely associated with IL-6. At the late-to -post pubertal visit, there were few associations except for a positive association between weekday sleep duration and hs-CRP among boys (0 = 0.60, 95% CI 0.04 to 1.16) and a non-linear positive association between social jetlag and hs-CRP among girls (0 = 0.80, 95% CI 0.22 to 1.37 comparing 2 to 3 h of social jetlag vs < 1 h). . Conclusion: Later timing, shorter duration, and inconsistency of sleep were related to higher levels of inflammatory biomarkers, but associations were more evident at the mid-to-late pubertal visit than the late-to-post pubertal visit. (C) 2022 Elsevier B.V. All rights reserved.

Background: DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation. Objectives: We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003–2006; Cincinnati, Ohio). Methods: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children’s age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999–2002; Boston, Massachusetts) to replicate significant associations. Results: After adjusting for covariates, 435 cytosine–guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q<0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children’s age. Discussion: In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118

ResumenEn el 2019, en seguimiento a un taller dirigido por el Global Health Studies del Fogarty International Center sobre el tema de la prevención de la obesidad infantil y las sinergias de investigación que surgen a través de las colaboraciones transfronterizas, convocamos a un grupo de expertos de Estados Unidos y Latinoamérica para que realizaran una revisión narrativa de la literatura epidemiológica sobre el papel obesogénico de los químicos disruptores endócrinos (EDC, por sus siglas en inglés) en la etiología de la obesidad infantil entre la juventud latina de Estados Unidos y Latinoamérica. Además de resumir y sintetizar los resultados de las investigaciones sobre este tema publicados en la última década, contextualizamos los hallazgos dentro de un marco bioconductual de curso de vida para identificar relaciones exposición‐desenlace impulsadas por resultados de investigación, identificar inconsistencias y deficiencias de la literatura actual, y discutir el papel de las regulaciones políticas, todo con el objetivo de identificar posibles vías para la prevención temprana de la obesidad en las poblaciones hispanas/latinas.

BACKGROUND:Per- and polyfluoroalkyl substances (PFAS) may adversely influence cardiometabolic risk. However, few studies have examined if the timing of early life PFAS exposure modifies their relation to cardiometabolic risk. We examined the influence of gestational and childhood PFAS exposure on adolescents' cardiometabolic risk. METHODS:We quantified concentrations of four PFAS (perfluorooctanoate [PFOA], perfluorooctane sulfonate [PFOS], perfluorononanoate [PFNA], and perfluorohexane sulfonate [PFHxS]) in sera collected during pregnancy, at birth, and at ages 3, 8, and 12 years from 221 mother-child pairs in the HOME Study (enrolled 2003-06, Cincinnati, Ohio). We measured cardiometabolic risk factors using physical examinations, fasting serum biomarkers, and dual-energy X-ray absorptiometry scans at age 12 years. Cardiometabolic risk summary scores were calculated by summing age- and sex-standardized z-scores for individual cardiometabolic risk factors. We used multiple informant models to estimate covariate-adjusted associations of serum PFAS concentrations (log2-transformed) at each visit with cardiometabolic risk scores and their individual components, and tested for differences in associations across visits. RESULTS:The associations of serum PFOA concentrations with cardiometabolic risk scores differed across visits (P for heterogeneity = 0.03). Gestational and cord serum PFOA concentrations were positively associated with cardiometabolic risk scores (βs and 95% confidence intervals [95% CIs]: gestational 0.8 [0.0, 1.6]; cord 0.9 [-0.1, 1.9] per interquartile range increase). These positive associations were primarily driven by homeostatic model assessment for insulin resistance index (β = 0.3 [0.1, 0.5]) and adiponectin to leptin ratio (β = -0.5 [-1.0, 0.0]). Other individual cardiometabolic risk factors associated with gestational PFOA included insulin and waist circumference. Gestational and cord PFHxS were also associated with higher cardiometabolic risk scores (βs: gestational 0.9 [0.2, 1.6]; cord 0.9 [0.1, 1.7]). CONCLUSION:In this cohort of children with higher gestational PFOA exposure, fetal exposure to PFOA and PFHxS was associated with unfavorable cardiometabolic risk in adolescence.

Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations.

Background: Bisphenol A (BPA) is a suspected obesogen that has been associated with adiposity in children. Bisphenol S (BPS), a structural analog of BPA, is used as a BPA substitute and may have similar health effects as BPA. However, few studies have examined whether BPS is associated with childhood adiposity. Methods: We quantified urinary BPA and BPS concentrations in 212 children age 8 years from the HOME Study, a prospective pregnancy and birth cohort study that enrolled pregnant women in Cincinnati, Ohio (2003–2006). We assessed children’s adiposity by bioelectric impedance at age 8 years (n = 212), and by anthropometry and dual-energy X-ray absorptiometry at age 12 years (n = 181). We measured serum adipocytokine concentrations at age 12 years (n = 155). Using multivariable linear regression, we estimated covariate-adjusted associations of BPA and BPS with adiposity measures at ages 8 and 12 years and adipocytokine concentrations at age 12 years. Results: Each 10-fold increase in urinary BPA concentrations were inversely associated with percent body fat at age 8 years [β = −1.2, 95% confidence interval (CI) = −3.4, 1.0] and 12 years (β = −1.6, 95% CI = −4.0, 0.9). In contrast, urinary BPS concentrations were positively associated with percent body fat at age 8 years (β = 1.1, 95% CI = −0.6, 2.7), but not at 12 years (β = 0.1, 95% CI = −1.7, 1.8). Urinary BPA and BPS concentrations were not associated with serum adiponectin or leptin concentrations. Conclusions: We did not observe evidence that urinary BPA or BPS concentrations during childhood were associated with greater child adiposity at ages 8 and 12 years in this cohort.

Background: Several animal studies have suggested that fluoride exposure may increase the levels of cardio-metabolic risk factors, but little is known about whether fluoride exposure is associated with such risk in humans. Objectives: We examined the cross-sectional association between peripubertal exposure to fluoride and markers of cardiometabolic risk in 280 girls and 256 boys at age 10-18 years living in Mexico City. Methods: We measured plasma fluoride concentration using a microdiffusion method. We collected data on anthropometry including BMI, waist circumference (WC) and trunk fat percentage. We measured serum markers of cardiometabolic risk, including fasting glucose, insulin and lipids. All the indicators of outcome were converted to age- and sex-specific z-scores. We also calculated a summary cardiometabolic risk score for each participant. Multivariable linear regression models were used to examine these associations. Results: The geometric mean (95% confidence interval (CI)) of plasma fluoride was 0.21 mu mol/L (0.20, 0.23 mu mol/L) in the total sample. In girls, plasma fluoride concentrations were associated with higher z-scores for all the individual markers (except for lipids) and for the combined cardiometabolic risk score (risk score: beta=1.28, 95% CI: 0.57-2.00, p-sex interaction=0.02)), adjusting for covariates. No associations were found in boys. Conclusions: We found that higher peripubertal fluoride exposure at the levels observed in this study population was significantly associated with increased levels of cardiometabolic risk factors in Mexican girls but not boys. Future studies with a longitudinal design are needed to confirm our findings and further elucidate the role of fluoride in cardiometabolic risk.

Per- and polyfluoroalkyl substances (PFAS) exposure may increase adiposity and obesity risk in children. However, no studies have extended these findings into adolescence or identified periods of heightened susceptibility. We estimated associations of repeated pre- and postnatal serum PFAS concentrations with adolescent adiposity and risk of overweight/obesity. We studied 212 mother-offspring pairs from the HOME Study. We quantified serum concentrations of four PFAS in mothers at ∼16 week gestation and their children at birth and ages 3, 8, and 12 years. We assessed adiposity at 12 years using anthropometry and dual-energy X-ray absorptiometry. Using multiple informant models, we estimated covariate-adjusted associations of an interquartile range (IQR) increase in log2-transformed PFAS for each time period with adiposity measures and tested differences in these associations. Serum perfluorooctanoate (PFOA) and perfluorohexane sulfonate (PFHxS) concentrations during pregnancy were associated with modest increases in central adiposity and risk of overweight/obesity, but there was no consistent pattern for postnatal concentrations. We observed nonlinear associations between PFOA in pregnancy and some measures of adiposity. Overall, we observed a pattern of modest positive associations of gestational PFOA and PFHxS concentrations with central adiposity and the risk of obesity in adolescents, while no pattern was observed for postnatal PFAS concentrations.

Background: Prenatal and early childhood lead exposures have been associated with reduced weight in infants and young children, while studies that have examined such associations in children during peripubescence are rare. Objectives: We investigated the associations of prenatal and early-life exposure to lead with indices of adiposity in peripubertal children living in Mexico City. Methods: Maternal bone lead (as a proxy for cumulative fetal exposure) was assessed at 1 month postpartum. Blood samples were obtained from children annually from 1 to 4 years. Multivariable linear regression models were used to examine the association between each lead biomarker and BMI z-score, waist circumference, sum of skinfolds and body fat percentage in 248 children aged 8-16 years. Results: After adjusting for covariates, maternal patella lead was associated with lower child BMI z-score (beta = - 0.02, 95% CI: 0.03, - 0.01, p = 0.004), waist circumference (beta = - 0.12 cm, 95% CI: 0.22, - 0.03, p = 0.01), sum of skinfolds (beta = - 0.29 mm, 95% CI: 0.50, - 0.08, p = 0.007) and body fat percentage (beta = - 0.09%, 95% CI: 0.17, -0.01, p = 0.03). No significant associations were detected from the postnatal exposure period. Conclusions: We observed a significant and inverse association of prenatal lead exposure with body composition in Mexican children, suggesting the potential role of early lead exposure in the fetal programming of child growth. Further research on the biological mechanisms underlying these associations is needed.

Background: Sources of fluoride exposure for Mexicans include foods, beverages, fluoridated salt, and naturally fluoridated water. There are no available data describing fluoride content of foods and beverages consumed in Mexico. Objective: To measure the content of fluoride in foods and beverages typically consumed and to compare their content to that of those from the United States and the United Kingdom. Methods: Foods and beverages reported as part of the Mexican Health and Nutrition Survey (n = 182) were purchased in the largest supermarket chains and local markets in Mexico City. Samples were analyzed for fluoride, at least in duplicate, using a modification of the hexamethyldisiloxane microdiffusion method. Value contents were compared to those from the US Department of Agriculture and UK fluoride content tables. Results: The food groups with the lowest and highest fluoride content were eggs (2.32 µg/100 g) and seafood (371 µg/100 g), respectively. When estimating the amount of fluoride per portion size, the lowest content corresponded to eggs and the highest to fast foods. Meats and sausages, cereals, fast food, sweets and cakes, fruits, dairy products, legumes, and seafood from Mexico presented higher fluoride contents than similar foods from the United States or the United Kingdom. Drinks and eggs from the United States exhibited the highest contents, while this was the case for pasta, soups, and vegetables from the United Kingdom. Conclusion: The majority of items analyzed contained higher fluoride contents than their US and UK counterparts. Data generated provide the first and largest table on fluoride content, which will be useful for future comparisons and estimations.

CONTEXT:Several cross-sectional studies have assessed the association of lead exposure with type 2 diabetes and cardiometabolic risk factors in adults; however, studies of such associations in childhood are rare.OBJECTIVE:We assessed the prospective associations of prenatal exposure to lead with type 2 diabetes and cardiometabolic risk factors in children.DESIGN:The Early Life Exposure in Mexico to Environmental Toxicants is a birth cohort study of pregnant women and their offspring.SETTING:Public hospitals in Mexico City.PATIENTS OR OTHER PARTICIPANTS:Women were recruited during pregnancy; their offspring were recruited for a follow-up visit at age 10 to 18 years (n = 369).MAIN OUTCOME MEASURES:We measured fasting serum markers of type 2 diabetes and cardiometabolic risk factors in children, including fasting glucose, insulin, and lipids. The index of insulin resistance was calculated.RESULTS:The geometric mean of maternal blood lead levels (BLLs) during pregnancy was 4.3 µg/dL (95% confidence interval [CI]): 4.0-4.6 µg/dL) in the entire sample. In boys, those with maternal BLLs ≥ 5 µg/dL (compared with those with BLLs < 5 µg/dL) had significantly lower z scores for total cholesterol (β = -0.41, 95% CI: -0.71, -0.12), high-density lipoprotein cholesterol (β = -0.32, 95% CI: -0.59, -0.05), and low-density lipoprotein cholesterol (β = -0.52, 95% CI: -0.81, -0.22), adjusting for covariates. No associations were detected in girls.CONCLUSIONS:In our study, we found that higher prenatal exposure to lead was associated with lower levels of cholesterol in children following a sex-specific pattern. Further studies with a larger sample size that examine whether sex is a potential modifier are needed to confirm our findings.

Previous animal and ecological studies have provided evidence for an earlier sexual maturation in females in relation to fluoride exposure; however, no epidemiological studies have examined the association between fluoride exposure and pubertal development in both boys and girls using individual-level biomarkers of fluoride. Capitalizing on an ongoing Mexican birth cohort study, we examined the association between concurrent urinary fluoride levels and physical markers of pubertal development in children.

BACKGROUND:Previous studies have examined the association between blood lead levels and pubertal timing in adolescent girls; however, the evidence is lacking on the role of lead exposure during sensitive developmental periods on sexual maturation. OBJECTIVES:To examine the association of prenatal and early childhood lead exposure with pubertal stages among 264 boys and 283 girls aged 9.8-18.0 years in Mexico City. METHODS:We measured maternal bone lead (a proxy for cumulative fetal exposure to lead from maternal bone stores mobilized during pregnancy) at 1 month postpartum. Blood lead was measured annually from 1 to 4 years. Pubertal stage was assessed by a pediatrician. We examined the association between lead and pubertal stages of breast, pubic hair and genitalia using ordinal regression. Age at menarche was evaluated using Cox proportional-hazard models. RESULTS:Multivariate models showed that maternal patella lead and early childhood blood lead were inversely associated with breast growth (patella OR = 0.72, 95% CI: 0.51-1.00; blood OR = 0.70, 95% CI: 0.53-0.93) in girls. Girls with maternal patella lead in the 3rd tertile and child blood lead in the 2nd tertile had a later age at menarche compared with girls in the 1st tertile (patella HR = 0.60, 95% CI: 0.41-0.88; blood HR = 0.65, 95% CI 0.46-0.91). Additionally, early childhood blood lead was negatively associated with pubic hair growth (OR = 0.68, 95% CI: 0.51-0.90) in girls. No associations were found in boys. CONCLUSIONS:These data suggest that higher prenatal and early childhood exposure to lead may be associated with delayed pubertal development in girls but not boys. Our findings are consistent with previous analyses and reinforce the reproductive effects of lead for girls.

Alterations in pubertal timing have been associated with long-term health outcomes. While a few reports have shown that dietary intake of selenium is associated with fertility and testosterone levels in men, no human studies have considered the association between selenium and pubertal development in children. We examined the cross-sectional association of childhood dietary intake of selenium with pubertal development among 274 girls and 245 boys aged 10-18 years in Mexico City. Multiple logistic and ordinal regression models were used to capture the association between energy-adjusted selenium intake (below Recommended Dietary Allowance (RDA) vs. above RDA) and stages of sexual maturity in children, adjusted for covariates. We found that boys with consumption of selenium below the RDA had lower odds of a higher stage for pubic hair growth (odds ratio (OR) = 0.51, 95% confidence interval (95% CI): 0.27-0.97) and genital development (OR = 0.53, 95% CI: 0.28-0.99) as well as a lower probability of having matured testicular volume (OR = 0.37, 95% CI: 0.15-0.88) compared with boys who had adequate daily dietary intake of selenium (above RDA). No associations were found in girls. According to our results, it is possible that inadequate consumption of selenium may be associated with later pubertal development in boys, suggesting a sex-specific pattern. Future work with a larger sample size and measures of selenium biomarkers is needed to confirm our findings and improve understanding of the role of this mineral in children's sexual development.