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Introduction: Epigenetic aging, a marker of biological aging measured by DNA methylation, may be affected by behaviors, including sleep and physical activity. However, investigations of physical activity and sleep with epigenetic aging among pediatric populations are scant and have not accounted for correlated behaviors., Methods: The study population included 472 Mexico City adolescents (52% female). Blood collection and 7-d wrist actigraphy (Actigraph GTX-BT) occurred during a follow-up visit when participants were 14.5 (2.09) yr. Leukocyte DNA methylation was measured with the Infinium MethylationEPIC array after bisulfite conversion, and nine epigenetic clocks were calculated. Sleep versus wake time was identified through a pruned dynamic programing algorithm, and physical activity was processed with Chandler cutoffs. Kmeans clustering was used to select actigraphy-assessed physical activity and sleep behavior clusters. Linear regression analyses were used to evaluate adjusted associations between the clusters and epigenetic aging., Results: There were three unique clusters: "Short sleep/high sedentary behavior," "Adequate sleep duration and late sleep timing/low moderate or vigorous physical activity (MVPA)," and "Adequate sleep duration/high MVPA." Compared with the "Adequate duration/high MVPA," adolescents with "Adequate duration and late sleep timing/low MVPA" had more accelerated aging for the GrimAge clock ( β = 0.63; 95% confidence interval, 0.07-1.19). In pubertal-stratified analyses, more mature adolescents in the "Adequate sleep duration and late sleep timing/low MVPA group" had accelerated epigenetic aging. In contrast, females in the "Short sleep/high sedentary" group had decelerated epigenetic aging for the Wu pediatric clock., Conclusions: Associations between behavior clusters and epigenetic aging varied by pubertal status and sex. Contrary results in the Wu clock suggest the need for future research on pediatric-specific clocks., (Copyright © 2024 by the American College of Sports Medicine.)

Endocrine-disrupting chemicals (EDCs) may impact sleep during the menopausal transition by altering sex hormones. However, these studies are scarce among Latin American women. This investigation utilized cross-sectional and retrospective data from midlife women enrolled in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study to examine associations between exposure to EDCs (phthalates, phenols, and parabens) and sleep health measures. For cross-sectional analyses, single spot urine samples were collected between 2017-2019 from a pilot sample of women (N = 91) of midlife age to estimate the urinary concentration of individual phthalates, phenols, and parabens and to calculate the summary concentration of phthalate mixtures. Seven-day nightly sleep duration, midpoint, and fragmentation were obtained from wrist-actigraphy devices and estimated from the actigraphy data using a pruned dynamic programming algorithm. Self-reported poor sleep quality was assessed by one item from the Pittsburgh Sleep Quality Index (PSQI). We examined associations between urinary summary phthalate mixtures, phthalate metabolites, phenol, and paraben analytes with each sleep measure using linear or logistic (to compute odds of poor sleep quality only) regression models adjusted for specific gravity, age, and socioeconomic status. We ran similar regression models for retrospective analyses (N = 74), except that urine exposure biomarker data were collected in 2008 when women were 24-50 years old. At the 2017-2019 midlife visit, 38% reported poor sleep quality. Cross-sectionally, EDCs were associated with longer sleep duration, earlier sleep timing, and more fragmented sleep. For example, every 1-unit IQR increase in the phenol triclosan was associated with a 26.3 min per night (95% CI: 10.5, 42.2; P < 0.05) longer sleep duration and marginally associated with 0.2 decimal hours (95% CI: -0.4, 0.0; P < 0.10) earlier sleep midpoint; while every 1-unit IQR increase in the phthalate metabolite MEHP was associated with 1.1% higher sleep fragmentation (95% CI: 0.1, 2.1; P < 0.05). Retrospective study results generally mirrored cross-sectional results such that EDCs were linked to longer sleep duration, earlier sleep timing, and more fragmented sleep. EDCs were not significantly associated with odds of self-reported poor sleep quality. Results from cross-sectional and retrospective analyses revealed that higher exposure to EDCs was predictive of longer sleep duration, earlier sleep timing, and more fragmented sleep among midlife women., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Emerging research has shed light on the potential impact of environmental toxicants on sleep health, however, it remains unclear if these associations exist during adolescence and whether associations differ by sex. This study aimed to examine associations between phthalates, parabens, and phenols on adolescent sleep health using cross-sectional data from 470 participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study., Material and Methods: In 2015, spot urine samples were analyzed for exposure biomarkers of 14 phthalate metabolites, seven phenol, and four paraben analytes. Over seven consecutive days, sleep duration, midpoint, and fragmentation were assessed with wrist-actigraphy. We examined associations between summary phthalates, individual phthalate metabolites, and phenol and paraben analytes with mean weekday sleep duration, midpoint, and fragmentation using linear regression models adjusted for specific-gravity and sex, age, pubertal status, smoking and alcohol behavior, physical activity, and screen time., Results: Mean (SD) age was 13.8 (2.1) years; 53.5 % were female. Σ Plastic - summary measure for toxicants from plastic sources - and Σ DEHP and its metabolites, were associated with longer sleep duration in the unstratified sample. To illustrate, every 1-unit log increase in Σ DEHP was associated with 7.7 min (95 % CI: 0.32, 15.1; p < 0.05) longer duration. Summary measures of toxicants from plastic sources, personal care products, anti-androgenic toxicants, and multiple individual phthalates, phenols, and parabens were associated with later midpoint. The midpoint associations were largely female-specific. There were no associations with sleep fragmentation., Conclusions: Higher EDC exposure may be related to longer sleep duration and later sleep timing during adolescence, and associations may vary by toxicant and according to sex., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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 ( 5 mC + 5 hmC ) and 5mC only; 5hmC is estimated by subtraction., Results: Participants were 51% male, and mean maternal blood lead levels (BLL) were 6.43 ± 5.16 μ g / dL in Trimester 1 (T1), 5.66 ± 5.21 μ g / dL in Trimester 2 (T2), and 5.86 ± 4.34 μ g / 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 ( β = - 0.37 , p = 0.03 ) and 5hmC in NINJ2 ( β = 0.49 , p = 0.003 ); T2 BLLs with 5mC in HCN2 ( β = 0.37 , p = 0.03 ) and 5hmC in NINJ2 ( β = 0.27 , p = 0.008 ); and T3 BLLs with 5mC in HCN2 ( β = 0.50 , p = 0.01 ) and NINJ2 ( β = - 0.35 , p = 0.004 ) and 5hmC in NINJ2 ( β = 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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zamora, Jansen, Tamayo-Ortiz, Goodrich, Sánchez, Watkins, Tamayo-Orozco, Téllez-Rojo, Mercado-García, Baylin, Meeker and Peterson.)

Introduction: Mercury intoxication is known to be associated with adverse symptoms of fatigue and sleep disturbances, but whether low-level mercury exposure could affect sleep remains unclear. In particular, children may be especially vulnerable to both mercury exposures and to poor sleep. We sought to examine associations between mercury levels and sleep disturbances in Mexican youth., Methods: The study sample comprised 372 youth from the Early Life Exposures to Environmental Toxicants (ELEMENT) cohort, a birth cohort from Mexico City. Sleep (via 7-day actigraphy) and concurrent urine mercury were assessed during a 2015 follow-up visit. Mercury was also assessed in mid-childhood hair, blood, and urine during an earlier study visit, and was considered a secondary analysis. We used linear regression and varying coefficient models to examine non-linear associations between Hg exposure biomarkers and sleep duration, timing, and fragmentation. Unstratified and sex-stratified analyses were adjusted for age and maternal education., Results: During the 2015 visit, participants were 13.3 ± 1.9 years, and 48% were male. There was not a cross-sectional association between urine Hg and sleep characteristics. In secondary analysis using earlier biomarkers of Hg, lower and higher blood Hg exposure was associated with longer sleep duration among girls only. In both boys and girls, Hg biomarker levels in 2008 were associated with later adolescent sleep midpoint (for Hg urine in girls, and for blood Hg in boys). For girls, each unit log Hg was associated with 0.2 h later midpoint (95% CI 0 to 0.4), and for boys each unit log Hg was associated with a 0.4 h later sleep midpoint (95% CI 0.1 to 0.8)., Conclusions: There were mostly null associations between Hg exposure and sleep characteristics among Mexican children. Yet, in both boys and girls, higher Hg exposure in mid-childhood (measured in urine and blood, respectively) was related to later sleep timing in adolescence., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Study Objectives: Sleep deprivation and low sleep quality are widespread among adolescents, and associate with obesity risk. Plausible mediators include diet and physical activity. Another potential interrelated pathway, as yet unexplored in adolescents, could involve epigenetic modification of metabolism genes., Methods: In a cohort of 351 Mexico City adolescents (47% male; mean [SD] age = 14 [2] years), 7-day actigraphy was used to assess average sleep duration, sleep fragmentation, and movement index. DNA isolated from blood leukocytes was bisulfite-converted, amplified, and pyrosequenced at four candidate regions. Linear mixed models evaluated sex-stratified associations between sleep characteristics (split into quartiles [Q]) and DNA methylation of each region, adjusted for potential confounders., Results: Mean sleep duration was 8.5 [0.8] hours for boys and 8.7 [1] hours for girls. There were sex-specific associations between sleep duration and LINE-1 (long interspersed nuclear element) methylation. Boys with longer sleep duration (Q4) had lower LINE-1 methylation than boys in the 3rd quartile reference category, while girls with both longer and shorter sleep duration had higher LINE-1 methylation compared to Q3. Longer sleep duration was associated with higher H19 methylation among girls (comparing highest to third quartile, -0.9% [-2.2, 0.5]; p, trend = 0.047). Sleep fragmentation was inversely associated with peroxisome proliferator-activated receptor alpha (PPARA) methylation among girls (comparing highest to lowest fragmentation quartile, 0.9% [0.1 to 1.8]). Girls also showed an inverse association between sleep fragmentation and hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2; Q4 to Q1, 0.6% [-1.2%, 0%])., Conclusions: Sleep duration and fragmentation in adolescents show sex-specific associations with leukocyte DNA methylation patterns of metabolism genes., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 D 1 MFT and D 4 MFT at adolescence., Results: Maternal second and third trimester and cumulative early childhood Pb exposure were positively associated with peri-pubertal D 1 MFT 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 D 1 MFT count, and 3rd trimester Pb exposure was associated with a 1.50 times (1.18, 1.90) higher D 1 MFT 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., (Copyright © 2018. Published by Elsevier B.V.)