Early Life Exposure In Mexico To Environmental Toxicants Research Articles

Single nucleotide polymorphisms of ANKK1, DDR4, and GRIN2B genes predict behavior in a prospective cohort of Mexican children and adolescents.

Numerous studies have established associations between single nucleotide polymorphisms (SNPs) and various behavioral and neurodevelopmental conditions. This study explores the links between SNPs in candidate genes involved in central nervous system (CNS) physiology and their implications for the behavioral and emotional aspects in children and teenagers. A total of 590 participants, aged 7-15 years, from the Early Life Exposures In Mexico To Environmental Toxicants (ELEMENT) cohort study in Mexico City, underwent genotyping for at least one of 15 CNS gene-related SNPs at different timepoints. We employed multiple linear regression models to assess the potential impact of genetic variations on behavioral and cognitive traits, as measured by the Behavioral Assessment System for Children (BASC) and Conners parent rating scales. Significant associations were observed, including the rs1800497 TC genotype (ANKK1) with the Cognitive Problems/Inattention variable (p value =0.003), the rs1800955 CT genotype (DDR4) with the Emotional Lability Global index variable (p value =0.01), and the rs10492138 GA and rs7970177 TC genotypes (GRIN2B) with the Depression variable (p values 0.007 and 0.012, respectively). These finds suggest potential genetic profiles associated with "risk" and "protective" behaviors for these SNPs. Our results provide valuable insights into the role of genetic variations in neurobehavior and highlight the need for further research in the early identification and intervention in individuals at risk for these conditions.

Abstract P521: Sleep Timing and Duration in Relation to DNA Methylation in Adolescents: An Epigenome-Wide Analysis

Background: Accumulating evidence suggests that both sleep duration and sleep timing can impact metabolic health of adolescents, potentially through epigenetic modification. The objective of this study was to investigate the relationship between sleep duration and timing and DNA methylation, one type of epigenetic modification that may be responsive to changes in sleep. Methods: Cross-sectional epigenome-wide analysis of DNA methylation was conducted to identify sleep-related CpG sites in 269 females and 233 males (14.4±2.1 years on average) participating in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) cohort study. Sleep duration and midpoint on weekdays and weekends were assessed using7-day wrist actigraphy (Actigraph GTX-BT), and DNA methylation in blood leukocytes was measured using the Illumina Infinium Methylation EPIC BeadChip. Linear regression was conducted to assess the relationship between sleep variables and DNA methylation at each locus on the array (using beta values), adjusting for sex, age, maternal education, batch effects, monocytes, natural killer cells, B lymphocyte, granulocyte, and naïve CD8 T cells. A false discovery rate (FDR) using the Benjamini-Hochberg method was applied to correct for multiple testing. Sex-stratified associations were also examined. Results: The average sleep duration was 8.5±1.3 hours on weekdays and 9.1±1.3 hours on weekends, and the average sleep midpoint was 3:48AM±1.4 hours on weekdays and 4.48AM±1.3 hours on weekends. At false discovery rate <0.05, there were no significant associations at any of the 762,657 CpG sites. However, at a false discovery rate of <0.2, there were positive associations between weekday sleep duration and 4 CpG sites (i.e., longer sleep duration associated with higher % DNA methylation), including a site in or near CpG islands annotated to the gene DENND2C. Sex-stratified analyses revealed associations were more evident in males. Conclusion: Epigenome-wide analysis identified possible associations between sleep duration and multiple CpG sites, and in a sex-specific manner. Findings suggest that sleep duration may impact the epigenome in a distinct manner from sleep timing.

Breastfeeding Duration and Cardiometabolic Health during Adolescence: A Longitudinal Analysis

ObjectiveTo investigate the longitudinal association between breastfeeding duration and cardiometabolic health, using repeated measures study design among children and adolescents. Study designThis study included 635 offspring aged 10 to 21 years (52% female) from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) 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. ResultsMedian breastfeeding duration was 7 months (mo) (min=0, max=36). Boys in the 2nd quartile (median breastfeeding= 5 mo) had lower total fat mass % (β (SE) -3.2 (1.5) p= 0.037), and higher lean mass % (3.1 (1.6) p= 0.049) and skeletal muscle mass % (1.8 (0.8) p= 0.031) compared with the reference group (median breastfeeding= 2 mo). A positive linear trend between breastfeeding duration and trunk lean mass % (0.1 (0.04) p= 0.035) was found among girls. No association was found with other cardiometabolic indicators. ConclusionDespite 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 exposure to phthalates, phenols, and parabens with objective and subjective measures of sleep health among Mexican women in midlife: a cross-sectional and retrospective analysis.

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 24-50years 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 26.3min 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.

DNA Methylation Is a Potential Biomarker for Cardiometabolic Health in Mexican Children and Adolescents.

DNA methylation (DNAm) is a plausible mechanism underlying cardiometabolic abnormalities, but evidence is limited among youth. This analysis included 410 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to two time points in late childhood/adolescence. At Time 1, DNAm was quantified in blood leukocytes at long interspersed nuclear elements (LINE-1), H19, and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), and at Time 2 in peroxisome proliferator-activated receptor alpha (PPAR-α). At each time point, cardiometabolic risk factors were assessed including lipid profiles, glucose, blood pressure, and anthropometry. Linear mixed effects models were used for LINE-1, H19, and 11β-HSD-2 to account for the repeated-measure outcomes. Linear regression models were conducted for the cross-sectional association between PPAR-α with the outcomes. DNAm at LINE-1 was associated with log glucose at site 1 [β = -0.029, p = 0.0006] and with log high-density lipoprotein cholesterol at site 3 [β = 0.063, p = 0.0072]. 11β-HSD-2 DNAm at site 4 was associated with log glucose (β = -0.018, p = 0.0018). DNAm at LINE-1 and 11β-HSD-2 was associated with few cardiometabolic risk factors among youth in a locus-specific manner. These findings underscore the potential for epigenetic biomarkers to increase our understanding of cardiometabolic risk earlier in life.

Urinary phthalates, phenols, and parabens in relation to sleep health markers among a cohort of Mexican adolescents

IntroductionEmerging 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 methodsIn 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. ResultsMean (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. ConclusionsHigher 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.

Sedentary patterns and cardiometabolic risk factors in Mexican children and adolescents: analysis of longitudinal data

BackgroundSedentary behavior is a modifiable risk factor for cardiometabolic health; however, the assessment of total sedentary time may not capture youth’s highly active and interrupted activity patterns. This study examined the associations between sedentary activity patterns and cardiometabolic risk factors among Mexican youth, who have a disproportionate burden of metabolic diseases, using a repeated measure design out of a longitudinal data.Methods570 subjects in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, who were followed up to three-time points during adolescence, were included. Bout duration, and frequency and percentages of waking time spent in specific intensities of activity, were quantified using ActiGraph wGT3X-BT wrist accelerometers. Self-reported questionnaires were used to query the usual duration of different sedentary behaviors. Outcomes were fasting lipid profile, markers for glucose homeostasis, anthropometry, and blood pressure. Associations were modeled using linear mixed-effects models, and isotemporal substitution approach was additionally used to assess the effect of replacing objectively assessed sedentary activity with other activity intensities, adjusting for potential confounders.ResultsEach hour of self-reported screen-based time was positively associated with diastolic blood pressure (mm Hg) [β = 0.30, 95% confidence interval (95% CI) = 0.10, 0.51], and an hour of other sedentary time was associated with log serum glucose (mg/dL) [β = 0.01, 95% CI = 0.004, 0.017]. Substitution models showed that replacing 5% of sedentary time with moderate to vigorous physical activity (MVPA) was associated with lower waist circumference (cm) [β = − 1.35, 95% CI = − 1.91, − 0.79] and log serum triglycerides (mg/dL) [β = − 0.11, 95% CI = − 0.18, − 0.03]. Substituting one uninterrupted sedentary bout with light activity was associated with lower insulin (μIU/mL) [β = − 0.06, 95% CI = − 0.10, − 0.02].ConclusionsSedentary time was associated with cardiometabolic risk factors in Mexican youth in a context-specific manner. Replacing sedentary time with higher intensities was associated with improvements in some cardiometabolic markers.

Is adiposity related to repeat measures of blood leukocyte DNA methylation across childhood and adolescence?

Epigenetic modifications such as DNA methylation may influence gene expression and phenotypes, including obesity in childhood. The directionality of this relationship is nevertheless unclear, and some evidence suggests that adiposity modifies the epigenome, rather than the other way around. In this pilot study, we utilize data from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study to examine whether measures of adiposity in childhood and early adolescence are associated with repeated measures of blood leukocyte DNA methylation at LINE-1 repetitive elements and two genes implicated in growth and adiposity: H19 and HSD11B2. Longitudinal epigenetic data were generated from cord blood and blood from follow-up visits in early and late adolescence. We assessed interactions between age and measures of body mass index (BMI) at 5 years of age and weight, BMI and waist circumference in early adolescence to infer whether adiposity deflects age-related DNA methylation changes throughout childhood. Applying linear mixed-effects models, we found an inverse association between measures of childhood BMI (kg/m2 ) and early-teen weight (kg) with repeat measures of H19 DNA methylation. We did not observe any statistically significant associations (p-value <.05) between any anthropometric measures and DNA methylation at LINE-1 or HSD11B2. We did not demonstrate statistically significant evidence in support of deflection of age-related DNA methylation trajectories by adiposity-related measures (age by adiposity interaction term). Given the pilot nature of this study, the relationships between repeat measures of DNA methylation and adiposity-measures across childhood merit further exploration in larger study populations.

The combined associations of mercury exposure and DNA methylation with sustained attention in children

BACKGROUND AND AIM: Attention deficit disorder (ADHD) is one of the world’s most common neurodevelopmental disorders, yet the etiology is not well-understood. Childhood DNA methylation (DNAm) patterns and exposure to methylmercury have both been implicated in the development of ADHD, though simultaneous assessments of these factors are rare. This study leverages the ELEMENT (Early Life Exposures in Mexico to Environmental Toxicants) cohort to identify the associations of childhood mercury exposure and DNAm with sustained attention in adolescence, and how these associations differ by sex. METHODS: Total mercury was measured in hair and urine from ELEMENT participants aged 6-12, reflecting organic and inorganic sources respectively. Children were followed on average 5.6 years, when adolescent DNAm was quantified in blood leukocytes via the Infinium EPIC array. Conners Continuous Performance Test (CPT3) was used to quantify measures of inattention, impulsivity, sustained attention, and vigilance. Linear regression was used to assess relationships between mercury biomarkers and CPT3 outcomes (N=399). In an epigenome-wide association study, we examined associations between adolescent DNAm and CPT3 performance (N=517). All analyses were adjusted for age, sex, socioeconomic status, and response style in adolescence. RESULTS: Childhood hair and specific gravity-adjusted urine mercury averaged 0.62&amp;#xb1;0.03 µg/g and 1.09&amp;#xb1;0.14 µg/L, respectively. Relationships between mercury levels and attention varied by mercury biomarker and CPT3 variable. Hair mercury, for instance, was associated with reduced inattentiveness (β=-0.021(SE=0.0095), p=0.027); urine mercury was not (β=-0.0045(SE=0.0078), p=0.57). Sex modified associations; for instance, urine mercury exposure was related to decreased vigilance in males (β=1.31(SE=0.65), p=0.045), but not in females (β=-0.20(SE=0.81), p=0.80). Lastly, DNAm at certain genes was associated with CPT3 scores. For example, DNAm at a loci in ZNF814 (Zinc Finger Protein-814) was related to increased sustained attention (β=0.97(SE=0.17), q=0.012). CONCLUSIONS: Both DNAm and mercury exposure are associated with adolescent CPT3 performance. KEYWORDS: mercury, sustained attention, DNA methylation, ADHD

Trimester-specific phthalate exposures in pregnancy are associated with circulating metabolites in children.

Prenatal phthalates exposures have been related to adiposity in peripuberty in a sex-specific fashion. Untargeted metabolomics analysis to assess circulating metabolites offers the potential to characterize biochemical pathways by which early life exposures influence the development of cardiometabolic risk during childhood and adolescence, prior to becoming evident in clinical markers. Among mother-child dyads from the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, we measured 9 phthalate metabolites and bisphenol A in maternal spot urine samples obtained during each trimester of pregnancy, corrected for urinary specific gravity and natural log-transformed. In 110 boys and 124 girls aged 8-14 years, we used a mass-spectrometry based untargeted metabolomics platform to measure fasting serum metabolites, yielding 572 annotated metabolites. We estimated the associations between trimester-specific urinary toxicants and each serum metabolite, among all children or stratified by sex and adjusting for child age, BMI z-score, and pubertal onset. We accounted for multiple comparisons using a 10% false discovery rate (q<0.1). Associations between exposures and metabolites were observed among all children and in sex-stratified analyses (q<0.1). First trimester MEP, MiBP, and MCPP were associated with decreased 2-deoxy-D-glucose among all children. Among girls, third trimester concentrations of MECPP, MEHHP, MEHP, and MCPP were associated with 15, 13, 1, and 10 metabolites, respectively, including decreased choline and increased acylcarnitines and saturated FAs (FA). Among boys, third trimester MIBP was positively associated with 9 features including long chain saturated FAs, and second trimester MBzP was inversely associated with thyroxine. Metabolomics biomarkers may reflect sex- and exposure timing-specific responses to prenatal phthalate exposures manifesting in childhood that may not be detected using standard clinical markers of cardiometabolic risk.

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

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

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

ObjectivePrenatal 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. MethodsWe 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. ResultsThe 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. ConclusionThe 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.

Diet Quality Scores and Cardiometabolic Risk Factors in Mexican Children and Adolescents: A Longitudinal Analysis.

There is limited evidence for the effects of diet on cardiometabolic profiles during the pubertal transition. We collected repeated measures of diet quality and cardiometabolic risk factors among Mexican youth. This analysis included 574 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to three time points. Dietary Approaches to Stop Hypertension (DASH), alternate Mediterranean Diet (aMedDiet), and Children’s Dietary Inflammatory Index (C-DIITM) scores were computed from food frequency questionnaires. Higher DASH and aMedDiet scores reflect a higher diet quality, and lower C-DII scores reflect an anti-inflammatory diet. Cardiometabolic risk factors were lipid profile, glucose homeostasis, blood pressure, and waist circumference. Linear mixed models were used between quartiles of each diet score and outcomes. Compared to the first quartile, the fourth DASH quartile was inversely associated with log serum insulin (μIU/mL) [β = −0.19, p = 0.0034] and log-Homeostatic Model Assessment of Insulin Resistance [β = −0.25, p = 0.0008]. Additionally, log serum triglycerides (mg/dL) was linearly associated with aMedDiet score [β = −0.03, p = 0.0022]. Boys in the highest aMedDiet quartile had higher serum high-density lipoprotein cholesterol (mg/dL) [β = 4.13, p = 0.0034] compared to the reference quartile. Higher diet quality was associated with a better cardiometabolic profile among Mexican youth.

Exposure to phthalates in relation to sleep duration and social jetlag among adolescent boys and girls in Mexico City

BACKGROUND AND AIM: Emerging research has demonstrated the importance of environmental toxicants, such as phthalates, for sleep health, as they may disrupt neuronal sleep regulation circuitry. However, the impact of high-molecular-weight (HMW) versus low-molecular-weight (LMW) phthalates remains unknown. Among Mexican adolescents, we evaluated the association between exposure to HMW and LMW phthalates with sleep duration and social jetlag (a circadian marker that measures the discrepancy between weekend and weekday sleep duration). METHODS: Participants included 413 adolescents from the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) study. In 2015, urinary concentrations of 13 phthalates were measured from spot urine samples, and sleep duration was assessed with wrist-actigraph devices over 7consecutive days. We examined associations between phthalates with mean weekday and weekend sleep duration and social jetlag using linear regression models, adjusted for specific-gravity, sex, age, BMI z-score, total energy intake, caffeine intake, and physical activity. RESULTS:The mean (SD) age was 15.6 (2.0) years; 53.5% were girls. The mean (SD) sleep duration was 8.4 (1.2) hr/night on weekdays and 9.0 (1.3) hr/night on weekends. In adjusted models, each IQR increase in the HMW phthalate, mono-(2-ethyl-5-oxohexyl) phthalate was associated with a 13.3 minute (95%CI: -26.3, -0.41; p 0.05) lower social jetlag, and each IQR increase in mono-benzyl phthalate was associated with an 8.0 minute (95% CI: -16.8, -0.72; p 0.05) shorter sleep duration on weekends. Among LMW phthalates, we found that each IQR increase in monoethyl phthalate was associated with an 8.6 minute (95% CI: -17.9, -0.63; p 0.05) shorter sleep duration on weekends and a 15.3 minute (95% CI: -29.0, -1.6; p 0.05) lower social jetlag. CONCLUSIONS:In contrast to other literature, higher phthalate exposure was related to shorter weekend sleep duration and lower social jetlag among Mexican adolescents, sleep characteristics that may be indicative of better sleep health. KEYWORDS: phthalates; environmental epidemiology; adolescent sleep health; social jetlag, sleep duration, wrist-actigraphy

Early-life exposure to lead and antisocial behaviors during childhood and adolescence

BACKGROUND AND AIM: An association between lead (Pb) exposure and antisocial behaviors has been documented over the last decades, but the findings have been inconsistent. We aimed to estimate the association between prenatal, early-childhood, and preadolescent/adolescent (periadolescent) Pb exposure, and aggression and conduct problems in periadolescents of Mexico City. METHODS: We studied participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohorts. We used 1) maternal patella Pb at puerperium as a proxy for prenatal Pb exposure, 2) cumulative blood lead index (a summary of repeated blood Pb (BPb) measurements) between birth and 60 months of age as a measure of early-childhood Pb exposure, and 3) a single BPb measurement concurrent with behavioral evaluation as a measure of periadolescent Pb exposure. The parent-reported scales of aggression and conduct problems of the Behavioral Assessment System for Children-2nd version (BASC-2) were evaluated during periadolescence (at a mean age of 10.38 years). We estimated the association between Pb exposure at each stage and having obtained an elevated T-score (≥60) in each scale, while adjusting for household socioeconomic status, maternal education and age at delivery, child sex, and Pb exposure at previous stages. RESULTS:743, 704, and 595 participants were included in the models for prenatal, early-childhood, and periadolescent Pb exposure, respectively. On average, mothers had 10.6 years of education, and were 26.3 years old at delivery. 49% of children were female. A one-unit increase in Pb exposure during the prenatal period (1 µg/g of maternal patella Pb), but not during childhood or periadolescence, was associated with increased odds of aggression (Odds Ratio (OR)=1.021; 95% Confidence Interval (CI): 1, 1.041) and conduct problems (OR=1.019; 95% CI: 1.002, 1.037) CONCLUSIONS:Exposure to Pb during the prenatal stage, but not during childhood or adolescence, was associated with aggression and conduct problems during periadolescence in this longitudinal cohort study. KEYWORDS: Heavy metals, Neurodevelopmental outcomes, Children's environmental health

Use of Lead-glazed Ceramics and Bone Health in Adult Women

BACKGROUND AND AIM: One of the main sources of lead (Pb) exposure in Mexico is the use of lead-glazed ceramics (PbC). Exposure to Pb is associated with a decrease in bone mineral density (BMD) and bone mass in adults. Our aim was to evaluate the association between use of PbC and bone health in adult women. METHODS: Our cross-sectional study comprised 101 women from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort. Women reported the use of PbC (yes/no) in the past 3 months. BMD was measured by dual-energy X-ray absorptiometry and bone matrix by ultrasound (speed of sound; SOS). We used z-scores from BDM and SOS to create quantity (normal bone: both z-scores between -1 and 1; less abundant (LA): both -1; and more abundant (MA): both 1) and quality (normal bone: absolute difference between z-scores ≤.5 standard deviations (SD); rigid bone(RB): BMD .5 SD of SOS; softer bone (SB): SOS z-score .5 SD of BMD) indexes for cortical and trabecular bone. Multinomial logistic regressions (normal bone as reference outcome category) were performed to estimate the association between use of PbC and the quantity and quality of cortical and trabecular bone, adjusting for age, menopause, socioeconomic status, physical activity, body mass index and gynoid adiposity. RESULTS:Use of PbC was associated with lower odds of MA cortical bone (OR: 0.28, p=0.05 ) and marginally significant odds of cortical SB (OR: 0.31 p=0.1). Null associations were found for the rest of the bone indexes, however the direction of the estimates were opposite with trabecular bone being 1 whereas cortical bone estimates were 1. CONCLUSIONS:Findings from this pilot study suggest that use of PbC, as a proxy of lead exposure, may influence bone health in midlife and should be examined using a lead biomarker and in a larger sample. KEYWORDS: lead-glazed ceramics, bone health, women

A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children.

As a guide to establishing a safe exposure level for fluoride exposure in pregnancy, we applied benchmark dose modeling to data from two prospective birth cohort studies. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Maternal urinary fluoride concentrations (U-F, in mg/L, creatinine-adjusted) were measured in urine samples obtained during pregnancy. Children were assessed for intelligence quotient (IQ) at age 4 (n = 211) and between six and 12 years (n = 287) in the ELEMENT cohort, and three to four years (n = 407) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to assess the association of maternal U-F concentrations with children's IQ measures. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) and benchmark concentration levels (BMCLs). No deviation from linearity was detected in the dose-response relationships, but boys showed lower BMC values than girls. Using a linear slope for the joint cohort data, the BMC for maternal U-F associated with a 1-point decrease in IQ scores was 0.31 mg/L (BMCL, 0.19 mg/L) for the youngest boys and girls in the two cohorts, and 0.33 mg/L (BMCL, 0.20 mg/L) for the MIREC cohort and the older ELEMENT children. Thus, the joint data show a BMCL in terms of the adjusted U-F concentrations in the pregnant women of approximately 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in pregnant women.

Plasma Fatty Acid Biomarkers of Dairy Consumption Are Associated With Sex-Dependent Effects on MetS Components in Mexican Adolescents

ObjectivesThis study investigates the association between plasma fatty acids (FAs) related to dairy intake and dairy portions with Metabolic Syndrome (MetS) components in Mexican adolescents. MethodsA total of 311 participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort were included in this cross-sectional analysis. Fasting blood samples were collected to assess the concentration of FAs in plasma. Dairy intake was assessed using a 7-day recall Food Frequency Questionnaire to determinate dairy servings per day. The following dairy biomarkers were used in analysis: pentadecanoic acid (C15:0), heptadecanoic acid (C17:0), and trans-palmitoleic acid (t-C16:1n-7). MetS components included waist circumference (WC), blood pressure, HDL-cholesterol, triglycerides, glucose, and insulin. Linear regression models stratified by sex were fit to explore the association between plasma FAs tertiles and dairy portions (low fat/high fat) with MetS components as continuous variables, adjusted by age, socioeconomic status, sedentary behavior, BMI, pubertal status, and energy intake. ResultsThe mean age was 14.0 years (SD ± 2.0) and 50.6% were male. Significant associations between tertiles of dairy FAs and MetS components were found. In females, C17:0 (T2 vs T1: β = –2.0; 95% CI: –3.0, –0.1) and t-C16:1n-7 (T3 vs T1: β –3.1; 95% CI: –4.8, –1.1) were negatively associated with WC. Similarly, in males, t-C16:1n-7 was negatively associated with WC (T2 vs T1: β = –2.0; 95% CI: 4.1, –0.04, P = 0.05) and insulin (T2 vs T1: β –4.1; 95% CI: –7.1, –0.7). In female C17:0 was also negatively associated with HDL (T2 vs T1: β = –3.9; 95% CI: –7.4, –0.2). In contrast, C15:0 in females (T3 v2 T1: β = 44.5; 95% CI: 22.5, 66.5) and t-C16:1n-7 in male (T3 vs T1: β = 21.2; 95% CI: 1.7, 40.6) was related to increased triglycerides. High fat dairy portions were negatively associated with WC (β –0.86; 95% CI: –1.4, –0.28) in female. In contrast, low fat dairy portions were negatively associated with HDL-C (β –1.7; 95% CI: –3.4, –0.1). ConclusionsOur results suggest that adolescent dairy intake, assessed through FAS levels, may be associated in different ways with cardiovascular risk factors, and that associations are sex-dependent. Funding SourcesThe study is supported by National Institutes of Health. FAs analysis was funded by the University of Michigan Momentum Center.

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 () for pyrosequencing analysis following oxidative or standard sodium bisulfite treatment. This workflow directly quantifies total methylation () and 5mC only; 5hmC is estimated by subtraction.Results:Participants were 51% male, and mean maternal blood lead levels (BLL) were in Trimester 1 (T1), in Trimester 2 (T2), and in Trimester 3 (T3). In addition, 5hmC levels were calculated for HCN2 (, ), NINJ2 (G/C: ; GG: ), RAB5A (), and TPPP (). Furthermore, 5mC levels were measured in HCN2 (), NINJ2 (heterozygotes: ; GG homozygotes: ), RAB5A (), and TPPP (). Several significant associations between BLLs and 5mC/5hmC were identified: T1 BLLs with 5mC in HCN2 (, ) and 5hmC in NINJ2 (, ); T2 BLLs with 5mC in HCN2 (, ) and 5hmC in NINJ2 (, ); and T3 BLLs with 5mC in HCN2 (, ) and NINJ2 (, ) and 5hmC in NINJ2 (, ). NINJ2 5mC was negatively correlated with gene expression (Pearson , ), whereas 5hmC was positively correlated (, ).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

An Efficient Segmentation Algorithm to Estimate Sleep Duration from Actigraphy Data

Sleep duration is a recognized determinant of mental health, obesity and cardiovascular disease, cognition, and memory across the lifespan. Due to convenience and cost, sleep duration is often measured through self-report; yet, self-reported sleep duration can be highly biased. Actigraphy is a viable alternative as an objective measure of sleep. To analyze this actigraphy data, various sleep evaluation algorithms have been developed using regression methods, with coefficients constructed on minute-by-minute data measured at a specific device placement (wrist or hip). Because activity counts per minute may be affected by various factors in the study (e.g., type of device, sampling frequencies), regression-based algorithms developed within specific populations may not be generalizable to wider use. To address these concerns, we propose a new learning method to obtain robust and consistent sleep duration estimates. First, we identify temporal segments via pruned dynamic programming; then, we develop a calling algorithm with individual-specific thresholds and capture sleep periods. Our proposed method is motivated by and demonstrated in the Multi-Ethnic Study of Atherosclerosis (MESA) Sleep study and the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) study.