Associations of prenatal exposure to phthalates and their mixture with lung function in Mexican children.

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children's lung function was evaluated at ages 8-13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV1 (ß = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (ß = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV1, ß = -0.017, 95 %CI: -0.066, 0.026; FVC, ß = -0.014, 95 %CI: -0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner.

Associations between prenatal metal and metalloid mixtures in teeth and reductions in childhood lung function.

BACKGROUND: Metal(oid)s have been cross-sectionally associated with lung function outcomes in childhood but there is limited data on their combined effects starting in utero. Child sex may further modify these effects. OBJECTIVE: Examine associations between in utero and early life exposure to metals assessed via novel dentine biomarkers and childhood lung function and explore effect modification by child sex. METHODS: Analyses included 291 children enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a longitudinal birth cohort study in Mexico City. Weekly dentine levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), and lead (Pb) were measured from 15 weeks pre-birth to 15 weeks post birth in deciduous children's teeth. Lung function was tested at ages 8-14 years and then modeled as age, height and sex adjusted z-scores. Associations were modeled using lagged weighted quantile sum (LWQS) regression to evaluate the potential for a time-varying mixture effect adjusting for maternal age and education at enrollment and exposure to environmental tobacco smoke in pregnancy. Models were also stratified by sex. RESULTS: We identified a window of susceptibility at 12-15 weeks pre-birth in which the metal mixture was associated with lower FVC z-scores in children aged 8-14 years. Cd and Mn were the largest contributors to the mixture effect (70 %). There was also some evidence of effect modification by sex, in which the mean weights and weighted correlations over the identified window was more evident in males when compared to females. In the male stratum, Cd, Mn and additionally Pb also dominated the mixture association. CONCLUSIONS: Prenatal metal(oid) exposure was associated with lower lung function in childhood. These findings underscore the need to consider both mixtures and windows of susceptibility to fully elucidate effects of prenatal metal(oid) exposure on childhood lung function.

Associations of salivary aldosterone levels during pregnancy with maternal blood pressure and birth weight-for-gestational age in a Mexico City birth cohort.

OBJECTIVE: To determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA). METHODS: We measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels. RESULTS: Log-aldosterone was positively associated with diastolic BP (ß = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (ß = -0.12, 95% CI: -0.26, 0.02) and highest (ß = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (ß = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03. CONCLUSION: Higher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.

Breastfeeding Duration and Cardiometabolic Health during Adolescence: A Longitudinal Analysis.

OBJECTIVE: To investigate the longitudinal association between breastfeeding duration and cardiometabolic health, using repeated measures study design among children and adolescents. STUDY DESIGN: This study included 634 offsprings aged 10 to 21 years (52% female) from the Early Life Exposure in Mexico to Environmental Toxicants birth cohort followed up to four time points during adolescence. Breastfeeding duration was prospectively quantified using questionnaires during early childhood. Cardiometabolic risk factors, body composition, and weight-related biomarkers were assessed as outcomes during adolescent follow-up visits. Sex-stratified linear mixed-effects models were used to model the association between quartiles of breastfeeding duration and outcomes, adjusting for age and additional covariates. RESULTS: Median breastfeeding duration was 7 months (minimum = 0, maximum = 36). Boys in the second quartile (median breastfeeding = 5 months) had lower total fat mass % (ß (SE) -3.2 (1.5) P = .037), and higher lean mass % (3.1 (1.6) P = .049) and skeletal muscle mass % (1.8 (0.8) P = .031) compared with the reference group (median breastfeeding = 2 months). A positive linear trend between breastfeeding duration and trunk lean mass % (0.1 (0.04) P = .035) was found among girls. No association was found with other cardiometabolic indicators. CONCLUSION: Despite sex-specific associations of breastfeeding duration with body composition, there was a lack of substantial evidence for the protective effects of breastfeeding against impaired cardiometabolic health during adolescence among Mexican youth. Further longitudinal studies with a robust assessment of breastfeeding are recommended.

Early Lead Exposure Associated with Molar Hypomineralization.

Purpose: The purpose of this study was to determine the association between prenatal and early life exposure to lead and the presence of molar hypomineralization (MH) in a group of Mexican children. Methods: A subset of participants of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENTS) cohort study was examined for the presence of molar hypomineralization using European Academy of Pedi- atric Dentistry (EAPD) criteria. Prenatal lead exposure was assessed by K-ray fluorescence measurements of patella and tibia lead and by maternal blood lead levels by trimester and averaged over trimesters. Postnatal exposure was assessed by levels of maternal blood lead at delivery and child blood lead at 12 and 24 months. Results: A subset of 506 subjects from the ELEMENT cohorts (nine to 18 years old) were examined for MH; 87 subjects (17.2 percent) had MH. Maternal blood lead levels in the third trimester (odds ratio [OR] equals 1.08; 95 percent confidence interval [95% CI] equals 1.02 to 1.15) and averaged over three trimesters (OR equals 1.10; 95% CI equals 1.02 to 1.19) were significantly associated with MH status. None of the maternal bone lead or the child's blood lead parameters was significantly associated with the presence of MH (P>0.05). Conclusions: This study documents a significant association between prenatal lead exposure especially in late pregnancy and the odds of molar hypomineralization.

Maternal urinary fluoride during pregnancy and birth weight and length: Results from ELEMENT cohort study.

Epidemiological studies assessing prenatal fluoride exposure and anthropometry at birth are scarce, inconsistent and with methodological limitations. The aim of this study was to evaluate associations between maternal urinary fluoride (MUF) at each trimester of pregnancy and birth weight and length in 536 mother-child pairs in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort study. MUF (mg/L) was measured using microdiffusion/fluoride-specific electrode from at least one trimester of pregnancy. Non-linear associations were assessed through segmented regression models (MUF and birth weight Z-score) and we used linear regression models for MUF and birth length Z-score. Models were adjusted for potential confounders including urinary creatinine concentrations as a covariate. Non-creatinine adjusted MUF levels at each trimester of pregnancy were 0.81, 0.86, and 0.82 mg/L, mean concentrations for first, second and third trimester, respectively. For birth weight, we identified a MUF breakpoint at 0.99, 0.68 and 0.58 mg/L, for first, second and third trimester of pregnancy, respectively. In the first trimester, an increase of 1 mg/L in MUF concentrations ≥0.99 mg/L was associated with an increase in weight Z-score at birth (ß = 0.79; 95% CI: 0.10, 1.48; p = 0.02). Second trimester MUF (≥0.68 mg/L) was marginally associated with birth weight decrease (ß = -0.25; 95% CI: -0.55, 0.04; p = 0.09) and third trimester MUF (≥0.58 mg/L) was significantly associated with birth weight decrease (ß = -0.33; 95% CI: -0.63, -0.03; p = 0.03). We observed a linear and significant association between MUF and Z-score of length at birth only for the first trimester of pregnancy (ß = 0.55; 95% CI: 0.07, 1.04; p < 0.02). Prenatal fluoride exposure was associated with birthweight z-score with different susceptibility windows. Our findings reinforce the hypothesis that maternal fluoride exposure may affect birth anthropometry.

Third-Trimester Maternal Dietary Patterns Are Associated with Sleep Health among Adolescent Offspring in a Mexico City Cohort.

BACKGROUND: Maternal diet during gestation has been linked to infant sleep; whether associations persist through adolescence is unknown. OBJECTIVES: We explored associations between trimester-specific maternal diet patterns and measures of sleep health among adolescent offspring in a Mexico City birth cohort. METHODS: Data from 310 mother-adolescent dyads were analyzed. Maternal diet patterns were identified by principal component analysis derived from FFQs collected during each trimester of pregnancy. Sleep duration, midpoint, and fragmentation were obtained from 7-d actigraphy data when adolescents were between 12 and 20 y old. Unstratified and sex-stratified association analyses were conducted using linear regression models, adjusted for potential confounders. RESULTS: Mean ± SD age of offspring was 15.1 ± 1.9 y, and 52.3% of the sample was female. Three diet patterns were identified during each trimester of pregnancy: the Prudent Diet (PD), high in lean proteins and vegetables; the Transitioning Mexican Diet (TMD), high in westernized foods; and the High Meat & Fat Diet (HMFD), high in meats and fat products. Mean ± SD sleep duration was 8.5 ± 1.5 h/night. Most associations were found in the third trimester. Specifically, PD maternal adherence was associated with shorter sleep duration among offspring (-0.57 h; 95% CI: -0.98, -0.16 h, in the highest tertile compared with the lowest) and earlier sleep midpoint among females (-0.77 h; 95% CI: -1.3, -0.26 h). Adherence to the HMFD and TMD was nonlinearly associated with less fragmented sleep, with the latter only evident among females. CONCLUSIONS: Findings indicate that maternal dietary patterns, especially during the third trimester of pregnancy, may have long-term impacts on offspring sleep.

Dietary Influences on Urinary Fluoride over the Course of Pregnancy and at One-Year Postpartum.

Dietary factors are known to influence urinary fluoride (UF) levels in nonpregnant people. Maternal UF is used as a biomarker of fluoride exposure; however, dietary influences on UF during pregnancy are unknown. We compared UF levels and assessed the associations between UF and five select dietary influences in pregnancy vs. one-year postpartum: dietary fluoride (F), calcium intake from diet (Ca-diet), calcium intake from supplements (Ca-sup), dietary acid load (AL), and table salt use (TS) in 421 women exposed to fluoridated salt in the Mexican diet. Spot UF (mg/L) was measured by microdiffusion/fluoride-specific electrode and dilution-corrected with specific gravity (SG). Dietary variables were estimated from a validated Food Frequency Questionnaire. Comparisons among UF in pregnancy vs. one-year postpartum were performed with non-parametric tests. Associations between dietary variables and UF were assessed using random effect models (for pregnancy) and linear regression (for one-year postpartum). SG-corrected UF (median, range) during pregnancy (0.77, 0.01-4.73 mg/L) did not significantly differ from one-year postpartum (0.75, 0.15-2.62 mg/L) but did increase every 10 gestational weeks, ß = 0.05 (CI: 0.00-0.10). Different dietary influences on UF were identified at each state. Although Ca-diet and AL were not associated with UF in either state, Ca-sup decreased UF only during pregnancy, ß = - 0.012 mg/L (CI: - 0.023-0.00). Reporting TS use was associated with 12% increase in UF only at one-year postpartum (p = 0.026). These results suggest different dietary influences on UF in the pregnant state, which need consideration when using UF as a biomarker of fluoride exposure.

Prenatal and Early Childhood Exposure to Lead and Repeated Measures of Metabolic Syndrome Risk Indicators From Childhood to Preadolescence.

Background: Exposure to lead (Pb) during the early life stages has been associated with the development of metabolic syndrome (MetS). Longitudinal studies of Pb exposure in critical developmental windows in children are limited. Methods: Our study included 601 mother-child dyads from the PROGRESS (Programming Research in Obesity, Growth, Environment and Social Stressors) birth cohort. Blood lead levels (BLLs) were assessed during the second and third gestational trimesters, in cord blood at delivery, and at ages 1, 2, and 4 years. Bone lead levels in the patella and tibia were assessed at 1 month postpartum and evaluated in separate models. To account for cumulative exposure (prenatal, postnatal, and cumulative), we dichotomized the BLLs at each stage visit and determined the following: "higher" if a BLL was at least once above the median (HPb) and "lower" if all BLLs were below the median (LPb). We analyzed fasting glucose, HbA1c, triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (cHDL), low-density lipoprotein cholesterol (cLDL), body mass index, waist circumference (WC), body fat percentage, and systolic (SBP) and diastolic blood pressure (DBP) at two study visits between 6 and 12 years of age and created cutoff points based on the clinical guidelines for each indicator. Mixed effects models were used to analyze each outcome longitudinally for each BLL score, adjusting for child's sex, size for gestational age, child's age, maternal parity, mother's age, and socioeconomic status. Results: We observed associations for HPb exposure and TC in all stages (OR = 0.53, 95%CI = 0.32-0.86) and postnatally (OR = 0.59, 95%CI = 0.36-0.94) and for prenatal HPb and TGs (OR = 0.65, 95%CI = 0.44-0.95). HPb at all stages was associated with WC (OR = 0.27, 95%CI = 0.08-0.86), BMI (OR = 0.33, 95%CI = 0.11-0.99), SBP (OR = 0.53, 95%CI = 0.32-0.85), and DBP (OR = 0.57, 95%CI = 0.34-0.95). Pb levels in the patella were associated with cHDL (OR = 1.03, 95%CI = 1.00-1.07) and those in the tibia with TGs (OR = 0.95, 95%CI = 0.91-0.99). Conclusion: Early life exposure to Pb may alter early indicators of MetS. A follow-up of these children will allow for more definition on the impact of longer-term exposures.

Prenatal Lead (Pb) Exposure and Peripheral Blood DNA Methylation (5mC) and Hydroxymethylation (5hmC) in Mexican Adolescents from the ELEMENT Birth Cohort.

BACKGROUND: Gestational lead (Pb) exposure can adversely affect offspring health through multiple mechanisms, including epigenomic alterations via DNA methylation (5mC) and hydroxymethylation (5hmC), an intermediate in oxidative demethylation. Most current methods do not distinguish between 5mC and 5hmC, limiting insights into their individual roles. OBJECTIVE: Our study sought to identify the association of trimester-specific (T1, T2, T3) prenatal Pb exposure with 5mC and 5hmC levels at multiple cytosine-phosphate-guanine sites within gene regions previously associated with prenatal Pb (HCN2, NINJ2, RAB5A, TPPP) in whole blood leukocytes of children ages 11-18 years of age. METHODS: Participants from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohorts were selected (n=144) for pyrosequencing analysis following oxidative or standard sodium bisulfite treatment. This workflow directly quantifies total methylation (5mC+5hmC) and 5mC only; 5hmC is estimated by subtraction. RESULTS: Participants were 51% male, and mean maternal blood lead levels (BLL) were 6.43±5.16µg/dL in Trimester 1 (T1), 5.66±5.21µg/dL in Trimester 2 (T2), and 5.86±4.34µg/dL in Trimester 3 (T3). In addition, 5hmC levels were calculated for HCN2 (mean±standard deviation(SD), 2.08±4.18%), NINJ2 (G/C: 2.01±5.95; GG: 0.90±3.97), RAB5A (0.66±0.80%), and TPPP (1.11±6.67%). Furthermore, 5mC levels were measured in HCN2 (81.3±9.63%), NINJ2 (heterozygotes: 38.6±7.39%; GG homozygotes: 67.3±9.83%), RAB5A (1.41±1.21%), and TPPP (92.5±8.03%). Several significant associations between BLLs and 5mC/5hmC were identified: T1 BLLs with 5mC in HCN2 (ß=-0.37, p=0.03) and 5hmC in NINJ2 (ß=0.49, p=0.003); T2 BLLs with 5mC in HCN2 (ß=0.37, p=0.03) and 5hmC in NINJ2 (ß=0.27, p=0.008); and T3 BLLs with 5mC in HCN2 (ß=0.50, p=0.01) and NINJ2 (ß=-0.35, p=0.004) and 5hmC in NINJ2 (ß=0.45, p<0.001). NINJ2 5mC was negatively correlated with gene expression (Pearson r=-0.5, p-value=0.005), whereas 5hmC was positively correlated (r=0.4, p-value=0.04). DISCUSSION: These findings suggest there is variable 5hmC in human whole blood and that prenatal Pb exposure is associated with gene-specific 5mC and 5hmC levels at adolescence, providing evidence to consider 5hmC as a regulatory mechanism that is responsive to environmental exposures. https://doi.org/10.1289/EHP8507.

Exposure to Phenols, Phthalates, and Parabens and Development of Metabolic Syndrome Among Mexican Women in Midlife.

Background: Evidence suggests exposure to endocrine-disrupting chemicals (EDCs) can influence Metabolic Syndrome (MetS) risk in adults, but it is unclear if EDCs impact women during midlife. We examined if EDCs measured in adult women were predictive of MetS and its components 9 years later. Methods: We measured urinary phthalate metabolites, phenols, and parabens collected in 2008 among 73 females from the ELEMENT study. MetS and its components (Abdominal Obesity, Hypertriglyceridemia, Cholesterolemia, Hypertension, and Hyperglycemia) were assessed in 2017. We regressed log-transformed EDC concentrations on MetS and MetS components using logistic regression, adjusting for age and physical activity. Results: At follow-up, the mean (SD) age was 46.6 (6.3) years; the prevalence of MetS was 34.3%. Sum of dibutyl phthalate metabolites (ΣDBP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP) were associated with an increased odds of hypertriglyceridemia. 2,5-dichlorophenol (2,5 DCP) and 2,4-dichlorophenol (2,4 DCP) were associated with increased odds of hypertriglyceridemia. The odds of hypertension were 4.18 (95% CI: 0.98, 17.7, p < 0.10) and 3.77 (95% CI: 0.76, 18.62, p < 0.10) times higher for every IQR increase in MCOP and propyl paraben, respectively. The odds of hyperglycemia were 0.46 (95% CI: 0.18, 1.17 p < 0.10) times lower for every IQR increase in the sum of di-2-ethylhexyl phthalate metabolites (ΣDEHP), and the odds of abdominal obesity were 0.70 (95% CI: 0.40, 1.21, p < 0.10) lower for every IQR increase in the concentration of triclosan. Conclusion: We found EDCs measured in 2008 were marginally predictive of hypertriglyceridemia and hypertension 9 years later. Results suggest that lower exposure to certain toxicants was related to lower markers of metabolic risk among midlife women.

Association between cumulative childhood blood lead exposure and hepatic steatosis in young Mexican adults.

BACKGROUND: Exposure to environmental toxicants may play a role in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD). Cumulative exposure to lead (Pb) has chronic and permanent effects on liver function. Pediatric populations are vulnerable to the toxic effects of Pb, even at low exposure levels. The purpose of the study was to estimate the association between cumulative Pb exposure during childhood and hepatic steatosis biomarkers in young Mexican adults. METHODS: A subsample of 93 participants from the ELEMENT cohort were included in this study. Childhood blood samples were collected annually from ages 1-4 years and were used to calculate the Cumulative Childhood Blood Lead Levels (CCBLL). Hepatic steatosis during adulthood was defined as an excessive accumulation of hepatic triglycerides (>5%) determined using Magnetic Resonance Imaging (MRI). Liver enzymes were also measured at this time, and elevated liver enzyme levels were defined as ALT (≥30 IU/L), AST (≥30 IU/L), and GGT (≥40 IU/L). Adjusted linear regression models were fit to examine the association between CCBLL (quartiles) and the hepatic steatosis in young adulthood. RESULTS: In adulthood, the mean age was 21.4 years, 55% were male. The overall prevalence of hepatic steatosis by MRI was 19%. Elevate levels of the enzymes ALT, AST, and GGT were present in 25%, 15%, and 17% of the sample, respectively. We found a positive association between the highest quartile of CCBLL with the steatosis biomarkers of hepatic triglycerides (Q4 vs. Q1: ß = 6.07, 95% CI: 1.91-10.21), elevated ALT (Q4 vs. Q1: ß = 14.5, 95% CI: 1.39-27.61) and elevated AST (Q4 vs. Q1: ß = 7.23, 95% CI: 0.64-13.82). No significant associations were found with GGT. CONCLUSIONS: Chronic Pb exposure during early childhood is associated with a higher levels of hepatic steatosis biomarkers and hepatocellular injury in young adulthood. More actions should be taken to eliminate sources of Pb during the first years of life.

Dietary fluoride intake over the course of pregnancy in Mexican women.

OBJECTIVE: To estimate dietary fluoride intake (F) over the course of pregnancy and the overall adjusted difference in dietary F intake by pregnancy stages and levels of compliance with dietary recommendations. DESIGN: Secondary data analysis from a longitudinal pregnancy cohort study in a population exposed to fluoridated salt. Women were followed during the early, middle and late stages of their pregnancy (n 568). The dietary intake of recommended prenatal nutrients according to Mexican dietary guidelines and F intake (mg/d) was estimated with a validated FFQ. Data were summarised with descriptive statistics. Levels of F intake were compared with the USA's Institute of Medicine adequate intake (AI) of 3 mg/d for pregnancy. Adjusted differences in F intake by pregnancy stages and levels of compliance with recommendations were estimated using random effects models. SETTING: Mexico City. PARTICIPANTS: Women participating in the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) project, from 2001 to 2003. RESULTS: Median dietary F intake throughout pregnancy ranged from 0·64 (interquartile range (IQR) 0·38) in the early to 0·70 (IQR 0·42) in the middle, and 0·72 (IQR 0·44) mg/d in the late stage (0·01 mg F/kg per d). Corresponding adjusted intakes of F were 0·72 (95 % CI 0·70, 0·74), 0·76 (95 % CI 0·74, 0·77) and 0·80 (95 % CI 0·78, 0·82) mg/d. Women who were moderately and highly compliant with Mexican dietary recommendations ingested, on average, 0·04 and 0·14 mg F/d more than non-compliant women (P < 0·005). CONCLUSIONS: Dietary F intake was below current AI, was greater with the progression of pregnancy and in women who were moderately and highly compliant with dietary recommendations.

Prenatal and early life exposure to particulate matter, environmental tobacco smoke and respiratory symptoms in Mexican children.

BACKGROUND: Exposure to particulate matter <2.5 µm in diameter (PM2.5) and environmental tobacco smoke (ETS) are associated with respiratory morbidity starting in utero. However, their potential synergistic effects have not been completely elucidated. Here, we examined the joint effects of prenatal and early life PM2.5 and prenatal ETS exposure on respiratory outcomes in children. MATERIAL AND METHODS: We studied 536 mother-child dyads in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study in Mexico City. Exposure to PM2.5 was estimated using residence in pregnancy and child's first year of life with a satellite-based spatio-temporal model. ETS exposure was assessed by caregiver's report of any smoker in the household during the second or third trimester. Outcomes included report of ever wheeze and wheeze in the past 12 months (current wheeze) assessed when children were 6-8 years old considered in separate models. Associations were modeled using distributed lag models (DLM) with daily PM2.5 averages for pregnancy and the first year of life, adjusting for child's sex, birth weight z-score, mother's age and education at enrollment, maternal asthma, season of conception and stratified by prenatal ETS exposure (yes/no). RESULTS: We identified a sensitive window from gestational week 14 through postnatal week 18 during which PM2.5 was associated with higher risk of ever wheeze at age 6-8 years. We also observed a critical window of PM2.5 exposure between postnatal weeks 6-39 and higher risk of current wheeze. We found significant associations between higher prenatal and early life PM2.5 exposure and higher cumulative risk ratios of ever wheeze (RR:3.76, 95%CI [1.41, 10.0] per 5 µg/m3) and current wheeze in the past year (RR:7.91, 95%CI [1.5, 41.6] per 5 µg/m3) only among children born to mothers exposed to ETS in pregnancy when compared to mothers who were not exposed. CONCLUSIONS: Exposure to prenatal ETS modified the association between prenatal and early life PM2.5 exposure and respiratory outcomes at age 6-8 years. It is important to consider concurrent chemical exposures to more comprehensively characterize children's environmental risk. Interventions aimed at decreasing passive smoking might mitigate the effects of ambient air pollution.

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among boys in Mexico City.

BACKGROUND: Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone concentrations and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. METHODS: Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone concentrations [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8-14, 10-18 years). We used linear regression to independently examine urinary metal concentrations in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume. RESULTS: In utero and prepubertal concentrations of some urinary metals were associated with increased concentrations of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits. CONCLUSION: These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.

Lead Concentrations in Mexican Candy: A Follow-Up Report.

Background: Lead is a neurotoxic metal potentially affecting the developing brain. Children are particularly susceptible since they can absorb between 50% and 100% of ingested lead. There is no safe level for lead, therefore preventing exposure is crucial. We previously reported a positive association between lead concentrations found in candy and concurrent blood lead levels in Mexican children. This first report garnered media and the general public's attention. Objective: To conduct a follow-up study to assess lead concentrations in candy brands that we previously reported with concentrations ≥0.1ppm the U.S. Food and Drug Administration's recommended maximum lead level in candy likely to be consumed frequently by small children. Methods: In 2018 we analyzed 50 additional candy samples. Lead concentrations were analyzed by an inductively coupled plasma mass spectrometer and lead content per candy unit was calculated. Findings: We found concentrations were typically low, with a marked decrease from prior levels (2008). Nevertheless two candy units had concentrations of 0.1 ppm of lead. Conclusions: Candy may have lead concentrations up to 0.1 ppm and 1.2 µg per unit. This is a concern because candies are exported and consumed in many countries worldwide potentially resulting in human exposure. Continued public health surveillance is needed to protect populations especially vulnerable to lead exposure, especially children.

Trends and Patterns of Phthalates and Phthalate Alternatives Exposure in Pregnant Women from Mexico City during 2007-2010.

Phthalates are associated with several adverse health outcomes, but few studies have evaluated phthalate exposures in Mexican populations, particularly pregnant women. Between 2007 and 2011, 948 pregnant women from Mexico City were recruited as part of the PROGRESS cohort. We quantified 17 metabolites of phthalates and phthalate alternatives in urine samples collected during the second and third trimesters and examined temporal trends of metabolite concentrations, within-person reproducibility, and relations of individual metabolites with sociodemographic, lifestyle, and occupational factors. Concentrations of mono-2-ethyl-5-carboxypentyl terephthalate, a metabolite of the alternative phthalate di-2-ethylhexyl terephthalate, increased monotonically from 2007 to 2010 (31% per year; 95% confidence interval = 23 and 39%). We observed moderate to high correlations among metabolites collected at the same visit, but there was high variability between second and third trimester phthalate metabolite concentrations (intraclass correlation coefficients = 0.17-0.35). In general, higher socioeconomic status was associated with higher phthalate concentrations. Some metabolites were associated with maternal age and education, but no consistent patterns were observed. Women working in the home and those who worked in administration had higher concentrations of several phthalate metabolites relative to students, professionals, and those in customer service. Biomonitoring efforts are warranted to investigate present and future exposure trends and patterns.

[Analysis of the national distributionof lead poisoning in 1-4 year-old children.Implications for Mexican public policy]. / Análisis de la distribución nacionalde intoxicación por plomo en niños de 1 a 4 años. Implicaciones parala política pública en México.

OBJECTIVE: To estimate de magnitude of Pb poisoning (≥5µg/dL blood) in 1-4 year old children and to identify the contribution of lead-glazed ceramics use (LGC) as a source of exposure in the 32 Mexican states. MATERIALS AND METHODS: Using the results from a sample of capillary blood lead (BPb) we estimated the prevalence of Pb poisoning, it's association with LGC and national distribution. RESULTS: The national prevalence of Pb poisoning was 17.4% representing 1.4 million children. The prevalence was 30.7% among LGC users and 11.8% in non-users. In 17 states the prevalence of Pb poisoning was ≥10%, in 11 states between 5-10%, and in 4 states <5%. CONCLUSIONS: There is a geographic differential distribution of the problem; confirming the association with LGC and estimating the contribution of other Pb exposure sources. This information offers a guide to implement preven-tion and control actions in Mexico.

OBJETIVO: Estimar la magnitud de intoxicación por plomo (Pb) (≥5µg/dL en sangre) en niños de 1 a 4 años e identificar la contribución del uso de loza de barro vidriado con Pb (LBVPb) como fuente de exposición en los 32 estados de México. MATERIAL Y MÉTODOS: Muestra de Pb en sangre (PbS) capilar de niños participantes en la Encuesta Nacional de Salud y Nutrición 2018-2019. Se estimó la prevalencia de intoxicación, su asociación con LBVPb y distribución nacional. RESULTADOS: La prevalencia nacional de intoxicación fue 17.4%, lo cual representa 1.4 millones de niños. Esta preva-lencia fue 30.7% entre usuarios de LBVPb y 11.8% entre no usuarios. En 17 estados la prevalencia de intoxicación es ≥10%; en 11 es ≥5-10% y en 4 es <5%. CONCLUSIONES: Existe una distribución diferencial geográfica del problema; se confirma la asociación con LBVPb y se estima la contribución de otras fuentes de exposición. Esta información ofrece una guía para implementar acciones de prevención y control en México.

Análisis de la distribución nacional de intoxicación por plomo en niños de 1 a 4 años. Implicaciones para la política pública en México / Analysis of the national distribution of lead poisoning in 1-4 year-old children. Implications for Mexican public policy

Resumen: Objetivo: Estimar la magnitud de intoxicación por plomo (Pb) (≥5μg/dL en sangre) en niños de 1 a 4 años e identificar la contribución del uso de loza de barro vidriado con Pb (LBVPb) como fuente de exposición en los 32 estados de México. Material y métodos: Muestra de Pb en sangre (PbS) capilar de niños participantes en la Encuesta Nacional de Salud y Nutrición 2018-2019. Se estimó la prevalencia de intoxicación, su asociación con LBVPb y distribución nacional. Resultados: La prevalencia nacional de intoxicación fue 17.4%, lo cual representa 1.4 millones de niños. Esta prevalencia fue 30.7% entre usuarios de LBVPb y 11.8% entre no usuarios. En 17 estados la prevalencia de intoxicación es ≥10%; en 11 es ≥5-10% y en 4 es <5%. Conclusiones: Existe una distribución diferencial geográfica del problema; se confirma la asociación con LBVPb y se estima la contribución de otras fuentes de exposición. Esta información ofrece una guía para implementar acciones de prevención y control en México.

Abstract: Objective: To estimate de magnitude of Pb poisoning (≥5μg/dL blood) in 1-4 year old children and to identify the contribution of lead-glazed ceramics use (LGC) as a source of exposure in the 32 Mexican states. Materials and methods: Using the results from a sample of capillary blood lead (BPb) we estimated the prevalence of Pb poisoning, it's association with LGC and national distribution. Results: The national prevalence of Pb poisoning was 17.4% representing 1.4 million children. The prevalence was 30.7% among LGC users and 11.8% in non-users. In 17 states the prevalence of Pb poisoning was ≥10%, in 11 states between 5-10%, and in 4 states <5%. Conclusions: There is a geographic differential distribution of the problem; confirming the association with LGC and estimating the contribution of other Pb exposure sources. This information offers a guide to implement prevention and control actions in Mexico.

Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project.

PURPOSE: The Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother-child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes. PARTICIPANTS: n=1643 mother-child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico. FINDINGS TO DATE: Maternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling. FUTURE PLANS: As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures. TRIAL REGISTRATION NUMBER: NCT00558623.