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.

Associations between psychosocial stress, child's anxiety, and lung function in mid-childhood.

BACKGROUND: Reducing the risk of respiratory disease during the plastic stages of lung development could have long-term health impacts. Psychosocial stress has been previously linked to adverse childhood respiratory outcomes, but the influence of child's anxiety and sex differences has not been completely elucidated. OBJECTIVE: To evaluate the association among maternal stress, child anxiety, and lung function in children and to explore differences by sex. METHODS: Cross-sectional analyses included 294 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) birth cohort in Mexico City. Children's lung function was tested once at ages 8 to 13 years of age, and height- and sex-adjusted z-scores were estimated for forced vital capacity, forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity and forced expiratory flow between 25% and 75%. Maternal stress was assessed through the Crisis in Family Systems-Revised (CRISYS-R) survey, used to report negative life events experienced in the past 6 months and dichotomized at the median (<3 and ≥3). Child's self-reported anxiety was assessed using the Revised Children's Manifest Anxiety Scale short form and dichotomized at the clinically relevant cutoff (T-score ≥ 60). The association among maternal stress, child anxiety, and lung function outcomes was evaluated using linear models. Effect modification by sex was evaluated with interaction terms and in stratified analyses. RESULTS: We did not find any association between maternal stress and any lung function outcome. Clinically elevated child anxiety symptoms were associated with lower forced expiratory volume in 1 second (ß = -0.36, 95% CI -0.69 to -0.02). We found no evidence of effect modification by sex. CONCLUSION: Results highlight the importance of considering childhood mental health in relation to lung function outcomes.

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.

Prenatal maternal pesticide exposure in relation to sleep health of offspring during adolescence.

STUDY OBJECTIVES: The neurobiological processes involved in establishing sleep regulation are vulnerable to environmental exposures as early as seven weeks of gestation. Studies have linked in utero pesticide exposure to childhood sleep-disordered breathing. However, the impact of in utero pesticide exposure on the sleep health of adolescents remains unexplored. MATERIALS AND METHODS: Data from 137 mother-adolescent pairs from a Mexico City cohort were analyzed. We used maternal urinary 3-phenoxybenzoic acid (3-PBA, pyrethroid metabolite) and 3, 5, 6-trichloro-2-pyridinol (TCPy, chlorpyrifos metabolite) from trimester three to estimate in utero pesticide exposure. Among adolescents, we obtained repeated measures of objectively assessed sleep duration, midpoint, and fragmentation using wrist-actigraphy devices for 7 consecutive days in 2015 and 2017. Unstratified and sex-stratified associations between maternal urinary 3-PBA and TCPy and adolescent sleep measures were examined using generalized linear mixed models (GLMMs). We also examined the interactive effects of maternal pesticide exposure and offspring sex on sleep outcomes. RESULTS: 3-PBA and TCPy were detected in 44.4% and 93% of urine samples, respectively. Adjusted findings demonstrated that higher exposure to maternal TCPy was associated with longer sleep duration and later sleep timing. Findings from interaction tests between maternal pesticide exposure and offspring sex were not statistically significant, although adjusted sex-stratified findings showed that the association between TCPy with duration and midpoint was evident only among female offspring. To illustrate, those in the highest tertile of exposure had a 59 minute (95% CI: 12.2, 104.8) (p, trend = 0.004) longer sleep duration and a 0.6 hour (95% CI: 0.01, 1.3) (p, trend = 0.01) later sleep midpoint. We found no significant associations between 3-PBA and sleep outcomes. CONCLUSION: Within a cohort of mother-adolescent pairs, we found associations between maternal prenatal pesticide exposure and longer sleep duration and later sleep timing among adolescent offspring. Further, this association may be female-specific.

Domain-specific effects of prenatal fluoride exposure on child IQ at 4, 5, and 6-12 years in the ELEMENT cohort.

OBJECTIVE: Prenatal exposure to fluoride has been associated with adverse neurodevelopmental outcomes. However, the neuropsychological profile of fluoride's developmental neurotoxicity at low levels and the stability of this relationship across childhood has not been characterized. We investigated the longitudinal and domain specific effect of prenatal fluoride exposure on IQ among children ages 4, 5, and 6-12 years in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort. METHODS: We measured the average of maternal urinary fluoride at each trimester of pregnancy adjusted for creatinine (MUFCRE). Children were administered the McCarthy Scales of Children's Abilities at ages 4 (N = 386) and 5 (N = 308), and the Wechsler Abbreviated Scale of Intelligence at age 6-12 (N = 278). We used generalized estimating equation (GEE) models to estimate the population averaged effect of MUFCRE concentration on longitudinal General Cognitive Index (GCI)/Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores (N = 348). We tested for possible interactions between MUFCRE and child sex as well as for MUFCRE and time point on children's IQ. All models controlled for relevant available covariates. RESULTS: The mean/median MUFCRE concentration was 0.90/0.83 mg/L (SD = 0.39; IQR, 0.64-1.11 mg/L). A 0.5 mg/L increase in MUFCRE predicted an average 2.12-point decrease in GCI/FSIQ (95% CI: -3.49, -0.75) and 2.63-point decrease in PIQ (95% CI: -3.87, -1.40). MUFCRE was marginally associated with VIQ across time (B = -1.29, 95% CI: -2.60, 0.01). No interactions between MUFCRE and child sex or MUFCRE and time were observed. CONCLUSION: The negative association between prenatal fluoride exposure and longitudinal IQ was driven by decrements in non-verbal intelligence (i.e. PIQ), suggesting that visual-spatial and perceptual reasoning abilities may be more impacted by prenatal fluoride exposure as compared to verbal abilities.

Prenatal lead exposure and childhood lung function: Influence of maternal cortisol and child sex.

INTRODUCTION: Maternal hypothalamic-pituitary-adrenal (HPA) axis disruption in pregnancy may contribute to the programming of childhood respiratory disease and may modify the effect of chemical toxins, like lead (Pb), on lung development. Child sex may further modify these effects. We sought to prospectively examine associations between maternal HPA axis disruption, prenatal Pb and childhood lung function and explore potential effect modification by maternal cortisol and child sex on the association between prenatal Pb and lung function outcomes. MATERIALS AND METHODS: Analyses included 222 mothers and children enrolled in a longitudinal birth cohort study in Mexico City. Maternal diurnal salivary cortisol was assessed in pregnancy; cortisol awakening response (CAR) and diurnal slope were calculated. Blood Pb was measured during the second trimester of pregnancy. Post-bronchodilator lung function was tested at ages 8-11 years. Associations were modeled using generalized linear models with interaction terms, adjusting for covariates. RESULTS: A higher (flatter) diurnal slope was associated with lower FEV1/FVC ratio (ß: 0.433, 95%CI [-0.766, -0.101]). We did not find any main effect associations between prenatal Pb and lung function outcomes. We report an interaction between Pb and cortisol in relation to FEV1/FVC and FEF25-75% (pinteraction<0.05 for all). Higher prenatal Pb was associated with reduced FEV1/FVC only in children whose mothers had a high CAR. Higher prenatal Pb was also associated with reduced FEV1/FVC and FEF25-75% in mothers with a flatter diurnal slope. A 3-way interaction between prenatal Pb, CAR and sex on FEV1/FVC, indicated that boys born to women with high CAR and higher prenatal Pb levels had lower FEV1/FVC ratios (pinteraction = 0.067). CONCLUSIONS: Associations between prenatal Pb and childhood lung function were modified by disrupted maternal cortisol in pregnancy and child sex. These findings underscore the need to consider complex interactions to fully elucidate effects of prenatal Pb exposure on childhood lung function.

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.

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.

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.

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.

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.

[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.

Association between prenatal particulate air pollution exposure and telomere length in cord blood: Effect modification by fetal sex.

INTRODUCTION: In utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM2.5) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM2.5 effects and explore sex differences. METHODS: Women who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models. RESULTS: In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM2.5 exposure during early pregnancy (4-9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14-19 and 34-36 weeks in which increased PM2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM2.5 and shortened LTL were stronger in girls when compared to boys. CONCLUSIONS: Increased PM2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms.

Fluoride exposure and pubertal development in children living in Mexico City.

BACKGROUND: 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. METHODS: We conducted a cross-sectional study of 157 boys and 176 girls at age 10-17 years living in Mexico City. We used ion-selective electrode-based diffusion methods to assess fluoride levels in urine, adjusting for urinary specific gravity. Pubertal stages were evaluated by a trained physician. Associations of fluoride with pubertal stages and age at menarche were studied using ordinal regression and Cox proportional-hazard regression, respectively. RESULTS: In the entire sample, the geometric mean and interquartile range (IQR) of urinary fluoride (specific gravity adjusted) were 0.59 mg/L and 0.31 mg/L, respectively. In boys, our analysis showed that a one-IQR increase in urinary fluoride was associated with later pubic hair growth (OR = 0.71, 95% CI: 0.51-0.98, p = 0.03) and genital development (OR = 0.71, 95% CI: 0.53-0.95, p = 0.02). No significant associations were found in girls, although the direction was negative. CONCLUSIONS: Childhood fluoride exposure, at the levels observed in our study, was associated with later pubertal development among Mexican boys at age 10-17 years. Further research is needed to confirm these findings.

Validity of Self-Assessed Sexual Maturation Against Physician Assessments and Hormone Levels.

OBJECTIVE: To compare self-report and physician assessments of sexual maturation against serum hormone markers to evaluate the hypothesis that the validity of self-assessed sexual maturation is underestimated in traditional validation studies. STUDY DESIGN: We adapted a self-assessment instrument that 248 Mexican children and adolescents, aged 8-13 years, completed. The participants were examined by a trained pediatrician and provided fasting blood samples for measurement of reproductive hormones (eg, testosterone, estradiol, sex hormone-binding globulin, inhibin B) and other hormones (eg, C-peptide, insulin-like growth factor 1, leptin, dehydroepiandrosterone sulfate) known to change during adolescence. Spearman correlations (r) were calculated among the average rank of all hormones and self-assessed and physician-assessed Tanner stage. The method of triads was used to assess the validity of self-reports by estimating correlations between self-assessments and true but unobservable sexual maturation based on all available data. Bootstrap sampling was used to construct 95% CIs. RESULTS: The validity of self-reported genitalia staging for boys was modest (r = 0.50; 95% CI, 0.31-0.65) and inferior to physician assessment (r = 0.75; 95% CI, 0.56-0.93). Breast stage was well reported (r = 0.89; 95% CI, 0.79-0.97) and superior to physician assessment (r = 0.80; 95% CI, 0.70-0.89). Pubic hair stage reported by boys (r = 0.91; 95% CI, 0.79-0.99) and girls (r = 0.99; 95% CI, 0.96-1.00) was superior to physician assessment (r = 0.79; 95% CI, 0.57-0.97 and r = 0.91; 95% CI, 0.83-0.97, respectively). CONCLUSION: Self-assessment can be validly used in epidemiologic studies for evaluating sexual maturation in children; however, physician assessment may be necessary for accurate assessment of genitalia development in boys.

Exposure to phthalates is associated with lipid profile in peripubertal Mexican youth.

Animal models indicate that endocrine disrupting chemicals (EDCs) affect circulating lipid concentrations by interfering with hepatic fatty acid oxidation. Little is known of the relationship between EDC exposure and lipid profile in humans. We measured bisphenol A (BPA) and 9 phthalate metabolites in maternal urine collected at up to three time points during pregnancy as a measure of in utero exposure, and in the child's urine at 8-14 years as a measure of concurrent, peripubertal exposure among 248 participants of a Mexico City pre-birth cohort. We used linear regression to examine relations of BPA and phthalate exposure with peripubertal serum lipids, while also adjusting for child age, sex, and specific gravity. While in utero EDC exposure was not associated with lipid profile, higher concurrent levels of mono-3-carboxypropyl phthalate (MCPP), monoethyl phthalate (MEP), and dibutyl phthalate metabolites (DBP) corresponded with lower total cholesterol and low-density lipoprotein (LDL-C) in boys; e.g., an interquartile range increment in MCPP corresponded with 7.4% (2.0%, 12.8%) lower total cholesterol and 12.7% (3.8%, 21.6%) lower LDL-C. In girls, higher urinary di-2-ethylhexyl phthalate metabolites (ΣDEHP) correlated with lower LDL-C (-7.9% [-15.4%, -0.4%]). Additional longitudinal research is needed to determine whether these associations persist beyond adolescence.

Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls.

BACKGROUND: Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. METHODS: We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes. RESULTS: Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester was associated with 25% higher DHEA-S (95%CI: 4.7-47%). In IQR increase in mean mono-2-ethylhexyl phthalate (MEHP) levels across pregnancy was associated with lower odds of having a Tanner Stage >1 for breast development (OR = 0.32, 95%CI: 0.11-0.95), while MEHP in the third trimester was associated with higher odds of having a Tanner Stage >1 for pubic hair development (OR = 3.76, 95%CI: 1.1-12.8). Results from secondary analyses were consistent with findings from our main analysis. CONCLUSION: These findings suggest that female reproductive development may be more vulnerable to the effects of phthalate or BPA exposure during specific critical periods of in utero development. This highlights the need for comprehensive characterizations of in utero exposure and consideration of windows of susceptibility in developmental epidemiological studies. Future research should consider repeated measures of in utero phthalate and BPA exposure within each trimester and across pregnancy.

The association of lead exposure during pregnancy and childhood anthropometry in the Mexican PROGRESS cohort.

Lead exposure during pregnancy remains a public health problem with potential lifelong impacts on children's growth and development. Mexico is unique in that stunting and obesity are both major public health concerns in children. This situation might be exacerbated by lead exposure which remains more common in Mexico than in the United States due in part to the use of lead glazed pottery in food preparation and storage. Our objective is to determine how lead exposure during pregnancy is associated with children's growth parameters, including height, weight, body mass index and percentage body fat measured between ages 4-6 years old in a Mexico City pregnancy cohort. Blood lead was collected in the 2nd and 3rd trimester of pregnancy as well as at delivery. Bone lead was assessed in mothers as a long term exposure biomarker. We performed multivariable linear regression analyses to assess the association between each of these lead exposure biomarkers and child anthropometry. We found a significant negative association between maternal 3rd trimester blood lead concentration and offspring height for age (ß-0.10; 95% CI -0.19, -0.01), and a negative association between maternal 3rd trimester blood lead concentration and weight for age (ß-0.11; 95% CI -0.22,-0.003). Our results in this Mexican population add to previous findings of an association of lead and decreased stature and weight in early childhood. Ongoing follow-up and longitudinal analyses may help elucidate how this impacts growth trajectory and other children's health outcomes.

Impact of phthalate and BPA exposure during in utero windows of susceptibility on reproductive hormones and sexual maturation in peripubertal males.

BACKGROUND: Phthalates and BPA are endocrine disrupting chemicals (EDCs) widely used in consumer products. Evidence suggests that phthalate and BPA exposure alters steroid hormone levels in adults, while in utero exposure has been associated with altered fetal reproductive development in boys. However, the impact of exposure during distinct critical windows of in utero development on hormone concentrations and sexual maturation during the pubertal transition has not been examined. The objective of this study was to assess trimester-specific in utero phthalate and BPA exposure in relation to measures of reproductive development among peripubertal boys in a Mexico City birth cohort. METHODS: We measured maternal urinary phthalate metabolites and BPA during the first, second, and third trimesters of pregnancy. We measured serum levels of testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation (Tanner staging and testicular volume) among male children at age 8-14 years (n = 109). Linear and logistic regression were used to investigate trimester-specific in utero exposure as predictors of peripubertal hormone levels and sexual maturation, respectively. In sensitivity analyses we evaluated estimated exposure at 7 weeks gestation and rates of change in exposure across pregnancy in relation to outcomes. RESULTS: Exposure to phthalates during the third trimester was associated with reduced odds of having a Tanner stage >1 for pubic hair development (e.g. MBzP OR = 0.18 per interquartile range (IQR) increase; 95% CI:0.03-0.97) and higher peripubertal SHBG levels (e.g. MBzP 15.2%/IQR; 95% CI:3.2-28%), while first and second trimester phthalates were not. In contrast, exposure to DEHP during the first trimester was associated with higher estradiol (11%/IQR; 95% CI:1.5-22%), while second or third trimester DEHP exposure was not. Sensitivity analyses yielded similar findings. CONCLUSIONS: Associations between in utero phthalate and BPA exposure and peripubertal measures of male reproductive development are dependent on the timing of that exposure during gestation. These findings suggest that future epidemiological studies relating in utero EDC exposure to pubertal outcomes should consider windows of susceptibility.

Lead in candy consumed and blood lead levels of children living in Mexico City.

BACKGROUND: Recent studies have shown that lead exposure continues to pose a health risk in Mexico. Children are a vulnerable population for lead effects and Mexican candy has been found to be a source of exposure in children. There are no previous studies that estimates lead concentrations in candy that children living in Mexico City consume and its association with their blood lead level. OBJECTIVES: To evaluate whether there is an association between reported recent consumption of candies identified to have lead, and blood lead levels among children in Mexico City. METHODS: A subsample of 171 children ages 2-6 years old, from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort study was assessed between June 2006 and July 2007. The candy reported most frequently were analyzed for lead using ICP-MS. The total weekly intake of lead through the consumption of candy in the previous week was calculated. Capillary blood lead levels (BLL) were measured using LeadCare (anodic stripping voltammetry). RESULTS: Lead concentrations ≥0.1ppm, the FDA permitted level (range: 0.13-0.7ppm) were found in 6 samples out of 138 samples from 44 different brands of candy. Median BLL in children was 4.5µg/dl. After adjusting for child's sex, age, BMI, maternal education & occupation, milk consumption, sucking the candy wrapper, use of lead-glazed pottery, child exposure behavior, living near a lead exposure site and use of folk remedies, an increase of 1µg of lead ingested through candy per week was associated with 3% change (95% CI: 0.1%, 5.2%) in BLL. CONCLUSIONS: Although lead concentrations in candy were mostly below the FDA permitted level, high lead concentrations were detected in 4% of the candy samples and 12% of brands analyzed. Although candy intake was modestly associated with children's BLL, lead should not be found in consumer products, especially in candy that children can consume due to the well documented long-lasting effect of lead exposure.