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.

Critical windows of perinatal particulate matter (PM2.5) exposure and preadolescent kidney function.

Air pollution exposure, especially particulate matter ≤2.5 µm in diameter (PM2.5), is associated with poorer kidney function in adults and children. Perinatal exposure may occur during susceptible periods of nephron development. We used distributed lag nonlinear models (DLNMs) to examine time-varying associations between early life daily PM2.5 exposure (periconceptional through age 8 years) and kidney parameters in preadolescent children aged 8-10 years. Participants included 427 mother-child dyads enrolled in the PROGRESS birth cohort study based in Mexico City. Daily PM2.5 exposure was estimated at each participant's residence using a validated satellite-based spatio-temporal model. Kidney function parameters included estimated glomerular filtration rate (eGFR), serum cystatin C, and blood urea nitrogen (BUN). Models were adjusted for child's age, sex and body mass index (BMI) z-score, as well as maternal education, indoor smoking report and seasonality (prenatal models were additionally adjusted for average first year of life PM2.5 exposure). We also tested for sex-specific effects. Average perinatal PM2.5 was 22.7 µg/m3 and ranged 16.4-29.3 µg/m3. Early pregnancy PM2.5 exposures were associated with higher eGFR in preadolescence. Specifically, we found that PM2.5 exposure between weeks 1-18 of gestation was associated with increased preadolescent eGFR, whereas exposure in the first 14 months of life after birth were associated with decreased eGFR. Specifically, a 5 µg/m3 increase in PM2.5 during the detected prenatal window was associated with a cumulative increase in eGFR of 4.44 mL/min/1.732 (95%CI: 1.37, 7.52), and during the postnatal window we report a cumulative eGFR decrease of -10.36 mL/min/1.732 (95%CI: -17.68, -3.04). We identified perinatal windows of susceptibility to PM2.5 exposure with preadolescent kidney function parameters. Follow-up investigating PM2.5 exposure with peripubertal kidney function trajectories and risk of kidney disease in adulthood will be critical.

Maternal carbohydrate intake during pregnancy is associated with child peripubertal markers of metabolic health but not adiposity.

OBJECTIVE: To examine the associations of trimester-specific maternal prenatal carbohydrate (CHO) intake with offspring adiposity and metabolic health during peripuberty. DESIGN: Prospective cohort study in which maternal dietary intake was collected via validated FFQ during each trimester. Offspring adiposity and metabolic biomarkers were evaluated at age 8-14 years. We used multivariable linear regression to examine associations between total energy-adjusted maternal CHO intake and offspring BMI z-score, skinfold thickness and metabolic syndrome risk z-score calculated as the average of waist circumference, fasting glucose, fasting C-peptide, TAG:HDL and systolic blood pressure + diastolic blood pressure/2. SETTING: Mexico City, Mexico. PARTICIPANTS: 237 mother-child pairs in the Early Life Exposure in Mexico to Environmental Toxicants cohort. RESULTS: We found non-linear associations of maternal CHO intake during pregnancy with offspring metabolic health during peripuberty. After adjusting for maternal age, and child age, sex and pubertal status, children whose mothers were in the fourth v. first quartile of total CHO intake during the third trimester had 0·42 (95 % CI -0·01, 0·08) ng/ml lower C-peptide and 0·10 (95 % CI -0·02, 0·22) units lower C-peptide insulin resistance (CP-IR). We found similar magnitude and direction of association with respect to net CHO intake during the first trimester and offspring C-peptide and CP-IR. Maternal CHO intake during pregnancy was not associated with offspring adiposity. CONCLUSIONS: In this study of mother-child pairs in Mexico City, children born to women in the highest quartile of CHO intake during pregnancy had lowest C-peptide and CP-IR during peripuberty. Additional research is warranted to replicate and identify mechanisms.

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.

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.

DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes.

Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, P < 0.1 was considered significant. DNAm at a locus in CCSER1 (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), P = 0.06] and emotional regulation [3.62 (-0.05, 8.69), P = 0.05]. Cg18515027 (GCNT1) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), P = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), P = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), P = 0.09]. The indirect effect was significant for cg19703494 (TRAPPC6A) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), P = 0.05]. There was also an indirect effect of cg23280166 (VPS11) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), P = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.

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.

Adolescent sleep timing and dietary patterns in relation to DNA methylation of core circadian genes: a pilot study of Mexican youth.

Mistimed sleep/wake and eating patterns put shift workers at increased risk for cardiometabolic disease, and epigenetic modification of circadian genes has been proposed as a mechanism. Although not as extreme as shift workers, adolescents often have delayed sleep timing and irregular eating patterns. The aim was to assess whether sleep midpoints - median of bed and wake time - and dietary patterns in adolescents were associated with DNA methylation of circadian genes. The study population included 142 Mexican youth (average age of 14.0 (SD = 2.0) years, 49% male). Average sleep midpoint over weekdays was estimated with actigraphy. Diet was assessed with a semi-quantitative food frequency questionnaire, and three dietary patterns were derived from principal component analysis, a Plant-based & lean proteins pattern, a Meat & starchy pattern, and an Eggs, milk & refined grain pattern. DNA methylation was quantified in blood leukocytes with the Infinium MethylationEPIC BeadChip, and data from 548 CpG sites within 12 circadian genes were examined. Linear regression analyses, adjusted for sex, age, and % monocytes, showed that later sleep timing was associated with higher DNA methylation of several circadian genes, notably with RORB, PER1, CRY2, and NR1D1. Each of the dietary patterns examined was also related to circadian gene DNA methylation, but the Eggs, milk & refined grain pattern ('breakfast' pattern) had the clearest evidence of relationships with circadian genes, with inverse associations (lower DNA methylation) across all 12 genes. Findings suggest that timing-related sleep and eating behaviours among adolescents could result in epigenetic modification of clock genes.

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.

Early Gestational Exposure to High-Molecular-Weight Phthalates and Its Association with 48-Month-Old Children's Motor and Cognitive Scores.

In utero phthalate exposure has been associated with neurodevelopmental disorders, nevertheless, trimester-specific susceptibility remains understudied. Our aim was to identify susceptible windows to the effects of gestational High-Molecular-Weight Phthalates (HMWP) exposure on 48 months' neurodevelopment. We measured six HMWP metabolites (MEHP, MEHHP, MEOHP, MECPP, MBzP and MCPP) in urine samples collected during each trimester from women in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 218). We assessed children's motor (MS), cognitive (GCI) and memory (MeS) abilities using McCarthy Scales of Children's Abilities (MSCA). We used linear regression models to examine associations between trimester-specific phthalate metabolites and MSCA scores, adjusted for sex, gestational age, breastfeeding, and maternal IQ. Although phthalate concentrations were similar across trimesters, first and second trimester phthalates were inversely associated with MS and GCI, with first trimester associations with MS being the strongest and statistically significant. Stronger associations were seen with MS and GCI among boys compared to girls, however interaction terms were not statistically significant. Our results suggest that early gestation is a sensitive window of exposure to HMWP for neurodevelopment, particularly in boys. Regulations on phthalate content in food as well as pregnancy consumption guidelines are necessary to protect future generations.

Association of ambient PM2·5 exposure with maternal bone strength in pregnant women from Mexico City: a longitudinal cohort study.

BACKGROUND: Pregnancy is associated with deteriorations in maternal bone strength and heightened susceptibility to bone fractures. We aimed to investigate whether ambient particulate matter (PM)2·5 concentrations were associated with bone strength during pregnancy. METHODS: In this longitudinal cohort study, we analysed longitudinal data from women participating in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort in Mexico City, Mexico. Eligible women were aged 18 years or older, at less than 20 weeks' gestation at the time of recruitment, planning to stay in Mexico City for the next 3 years, without heart or kidney disease, did not use steroids or anti-epileptic drugs, were not daily consumers of alcohol, and had access to a telephone. Daily ambient PM2·5 concentrations were estimated from a spatio-temporal model that was based on the individual's address. Trabecular bone strength was measured using quantitative ultrasound from the radius of the middle finger and cortical bone strength from the proximal phalanx of the middle finger, during the second trimester, third trimester, and 1 and 6 months post partum. Bone strength T scores were modelled with PM2·5 concentrations using linear mixed models and distributed lag models. FINDINGS: Adjusting for multiple exposure windows, each 10 ug/m3 increase in PM2·5 exposure concentrations in the first trimester was associated with a 0·18 SD decrease (95% CI -0·35 to -0·01; p=0·033) in ultrasound speed-of-sound (SOS) T score of trabecular bone strength from the second trimester until 6 months post partum. Similarly, each 10 µg/m3 increase in third trimester PM2·5 exposure was associated with a 0·18 SD decrease (-0·36 to -0·01; p=0·044) in the SOS T score of trabecular bone strength from the third trimester until 6 months post partum. PM2·5 exposure in the first month post partum was associated with a 0·20 SD decline (-0·39 to -0·01; p=0·043) in cortical bone strength until 6 months post partum. INTERPRETATION: Ambient PM2·5 exposure during and after pregnancy was associated with diminished trabecular and cortical bone strength. Early pregnancy PM2·5 exposure was associated with a greater decline in bone strength later during pregnancy. Late pregnancy and early post-partum exposures adversely affected the post-partum bone strength recovery. Technological and policy solutions to reduce PM2·5 pollution could improve public health by reducing bone fracture risk. FUNDING: US National Institute of Environmental Health Sciences.

Exposure to Endocrine-Disrupting Chemicals During Pregnancy Is Associated with Weight Change Through 1 Year Postpartum Among Women in the Early-Life Exposure in Mexico to Environmental Toxicants Project.

Background: The postpartum period may be a vulnerable life stage for a woman's cardiometabolic health. We examined associations of exposure to common endocrine-disrupting chemicals (EDCs) during pregnancy with weight from delivery through 1 year postpartum among 199 women in Mexico City. Materials and Methods: During each trimester of pregnancy, we collected a urine sample to assay bisphenol A (BPA), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and monoethyl phthalate (MEP). We calculated summary scores for di-2-ethylhexyl phthalate metabolites (ΣDEHP) and dibutyl phthalate metabolites (ΣDBP). We calculated the geometric mean of each EDC across pregnancy for use in the analysis. At delivery and three additional times during the first year postpartum, we measured the women's weight. We used mixed-effects linear regression models to estimate associations of each EDC with weight at delivery (kg) and weight change (kg/year) from delivery through 1 year postpartum. Covariates included urinary specific gravity, maternal age, parity, height, first trimester body mass index, and gestational age at enrollment. Results: Mean ± standard deviation weight change during the first postpartum year was -0.49 ± 4.04 kg. The EDCs were inversely associated with weight at delivery, but positively associated with weight change through 1 year postpartum. For example, each interquartile range of urinary ΣDEHP corresponded with 1.38 (95% confidence interval: 0.44-2.33) kg lower weight at delivery and 1.01 (0.41--1.61) kg/year slower rate of weight loss. We observed similar associations for other EDCs. Conclusions: Prenatal exposure to EDCs is associated with lower weight at delivery, but slower rate of weight loss through the first postpartum year.

Onset and tempo of sexual maturation is differentially associated with gestational phthalate exposure between boys and girls in a Mexico City birth cohort.

Phthalates are endocrine disrupting compounds commonly found in consumer products, exposure to which may influence reproductive maturation. Effects from exposure in utero on the onset and progression of sexual development are understudied. We examined longitudinal associations between gestational phthalate exposure and sexual maturation at two points in adolescence (8-14, 9-18 years). Gestational exposure was quantified using the geometric mean of 3 trimester-specific urinary phthalate metabolite measurements. Sexual maturation was assessed using Tanner stages and menarche onset for girls and Tanner stages and testicular volume for boys. Generalized estimating equations for correlated ordinal multinomial responses were used to model relationships between phthalates and odds of transitioning to the next Tanner stage, while generalized additive (GA) mixed models were used to assess the odds of menarche. All models were adjusted for child age (centered around the mean), BMI z-score, change in BMI between visits, time (years) between visits (ΔT), and interactions between ΔT and mean-centered child age and the natural log of exposure metabolite concentration. Among girls, a doubling of gestational MBzP concentrations was associated with increased odds of being at a higher Tanner stage for breast development at 8-14 years (OR = 4.62; 95% CI: 1.38, 15.5), but with slower progression of breast development over the follow-up period (OR = 0.65 per year; 95% CI: 0.46, 0.92) after adjustment for child age and BMI z-score. Similar results were found for ∑DEHP levels and breast development. In boys, a doubling of gestational MBP concentrations was associated with lower odds of being at a higher Tanner stage for pubic hair growth at 8-14 years (OR = 0.37; 95% CI: 0.14, 0.95) but with faster progression (OR: 1.28; 95% CI: 0.97, 1.69). These results indicate that gestational phthalate exposures may impact the onset and progression of sexual development, and that these relationships differ between boys and girls.

Blood manganese levels during pregnancy and postpartum depression: A cohort study among women in Mexico.

BACKGROUND: Occupational studies have shown an association between elevated Mn exposure and depressive symptoms. Blood Mn (BMn) naturally rises during pregnancy due to mobilization from tissues, suggesting it could contribute to pregnancy and postpartum depressive symptoms. OBJECTIVES: To assess the association between BMn levels during pregnancy and postpartum depression (PPD), creating opportunities for possible future interventions. METHODS: We studied 561 women from the reproductive longitudinal Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort in Mexico City. BMn was measured at the 2nd and 3rd trimesters, as well as delivery. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD symptoms at 12-months postpartum. We used a generalized linear model assuming a Poisson distribution to assess the association between BMn levels and PPD, with adjustments for age, stress and depressive symptoms during pregnancy, education, socioeconomic status, and contemporaneous blood lead levels. RESULTS: The mean ±â€¯standard deviation (SD) EPDS score at 12-months postpartum was 6.51 ±â€¯5.65, and 17.11% of women met the criteria for possible PPD (score ≥ 13). In adjusted models, BMn during the 3rd trimester (ß: 0.13, 95% CI: 0.04-0.21) and BMn levels averaged at the 2nd and 3rd trimester (ß: 0.14, 95% CI: 0.02-0.26) had a positive association with EPDS scores at 12 months postpartum. BMn at the 2nd trimester (ß: 0.07, 95% CI: -0.09-0.22) and delivery (ß: 0.03, 95% CI: -0.04-0.10) had a non-significant positive association with EPDS scores at 12-months postpartum. Stress and depressive symptoms during pregnancy was associated with higher EPDS scores at 12-months postpartum in all of the adjusted models but were only significant when either BMn during 3rd trimester or BMn averaged across 2nd and 3rd trimester was assessed as the exposure. DISCUSSION: Our results demonstrate that elevated BMn levels during pregnancy predict PPD symptoms and could be a potential pathway for intervention and prevention of PPD.

Particulate air pollution exposure during pregnancy and postpartum depression symptoms in women in Mexico City.

BACKGROUND: Postpartum depression (PPD), which affects up to 1 in 5 mothers globally, negatively impacts the health of both mothers and children. Exposure to ambient air pollution has been linked to depressive symptoms in animal models and human studies, but the relationship between air pollution and PPD has not been widely studied. METHODS: In a birth cohort in Mexico City (509 mothers with available data), we examined the association between exposure to particulate matter ≤2.5 µm in diameter (PM2.5) with symptoms of psychological dysfunction at 1 and 6 months postpartum. Daily PM2.5 estimates were derived from a hybrid satellite-based spatio-temporally resolved model and averaged over pregnancy and the first year postpartum. Edinburgh Postnatal Depression Scale (EPDS) scores at 1 and 6 months were used to assess the relationship between PM2.5 exposure and probable PPD (EPDS score ≥13) using relative risk regression and symptoms of anhedonia, depression, and anxiety (derived from EPDS subscales) using negative binomial regression. RESULTS: A 5-µg/m3 increase in average PM2.5 exposure during pregnancy was associated with an increased risk of PPD at 6 months (RR = 1.59; 95% CI: 1.11 to 2.28) and of late-onset PPD (no PPD at 1 month, PPD at 6 months) (RR = 2.58; 95% CI: 1.40 to 4.73) in covariate-adjusted models. No association was observed between PM2.5 exposure in the first year postpartum and PPD. Average PM2.5 exposure during pregnancy was also associated with increased 6-month EPDS subscale symptom scores for anhedonia (p = 0.03) and depression (p = 0.04). CONCLUSION: Our results suggest that in women in Mexico City, particulate matter exposure during pregnancy is positively associated with PPD and symptoms of anhedonia and depression at 6 months postpartum. Future studies should examine mechanisms linking air pollution and other environmental exposures during pregnancy with postpartum psychological functioning.

Perception of parents' physical activity as a positive model on physical activity of adolescents.

Physical activity (PA) promotes an adequate level of health in adolescents. The PA behaviors moderation is led by the adolescents' perception of their parents. We suppose that higher adolescents' perception of their parents' physical activity influences the physical activity spent in adolescents. The objective of this study was to determine the association between adolescents' perception of their parents' PA practice with adolescent's PA in a sample of public schools in the Morelos state of Mexico. We analyzed the information of 4625 adolescents from the baseline of a cohort study of students in public schools in Mexico. We evaluated adolescents' perceptions of their parents PA and PA practice of the adolescents. A logistic regression analysis stratified by sex was carried out to evaluate the association between adolescents' perceptions of their parents PA, and adolescents' PA. We found that the PA of female adolescents was associated with their perceptions' of both parents' PA (OR = 2.48; IC95% 1.84-3.35). Adolescents' perceptions of their mother's PA was associated with their PA (daughters OR = 1.69; IC95% 1.33-2.15; sons OR = 1.87 IC95% 1.41-2.45). In conclusion, adolescents' perceptions of their parents' PA practice were associated with higher adolescents' PA. Higher adolescents' perception of their parents PA may play an important role as a positive model for the adolescent's PA practice (p < 0.001). Finally, parental PA and the perceptions that adolescents have of their parents' PA must be considered in devising general PA programs.

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.

Dietary Intake of Selenium in Relation to Pubertal Development in Mexican Children.

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.

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.

The associations between lead exposure at multiple sensitive life periods and dental caries risks in permanent teeth.

BACKGROUND: Dental caries is an important public health problem in Mexico, a country also faced with high exposure to toxicants including lead (Pb). METHODS: Participants were 386 children living in Mexico City. Prenatal (trimester 1-3), early-childhood (12, 24, 36, and 48 months of age) and peri-pubertal (10-18 years of age) blood Pb levels were quantified using graphite-furnace atomic-absorption spectroscopy. Maternal patella and tibia bone Pb at 1 month postpartum were quantified with K X-ray fluorescence instrument. Dental caries presence was evaluated using decayed, missing, and filled teeth (DMFT) scores. Peri-pubertal sugar sweetened beverage (SSB) intake was estimated using a 116-item, interview-administered semi-quantitative food frequency questionnaire (FFQ). Total energy adjusted daily SSB intake was generated using the residual approach. Zero inflated negative binomial (ZINB) Poisson regression models were used to examine the associations between Pb with D1MFT and D4MFT at adolescence. RESULTS: Maternal second and third trimester and cumulative early childhood Pb exposure were positively associated with peri-pubertal D1MFT scores in unadjusted ZINB models (2nd trimester: RR = 1.17 (1.00, 1.37); 3rd trimester: RR = 1.20 (1.03, 1.40); early childhood: RR = 1.22 (1.02, 1.48)). These effect sizes were attenuated and no longer statistically significant after adjusting for covariates. When stratified by high/low SSB intake, a one unit increase of log-transformed 2nd trimester Pb exposure was associated with a 1.41 times (1.06, 1.86) higher D1MFT count, and 3rd trimester Pb exposure was associated with a 1.50 times (1.18, 1.90) higher D1MFT count among those with higher than median peri-pubertal SSB. Associations among those with lower SSB intake were roughly half those of the higher group and not statistically significant. CONCLUSIONS: Pb exposure during sensitive developmental periods was not statistically significantly associated with caries risk after accounting for confounders among our cohort. However, evidence from stratified analysis suggested a Pb-caries association among children with high SSB intake.