A surge in food insecurity during the COVID-19 pandemic in a cohort in Mexico City.

BACKGROUND: The COVID-19 pandemic has not only caused tremendous loss of life and health but has also greatly disrupted the world economy. The impact of this disruption has been especially harsh in urban settings of developing countries. We estimated the impact of the pandemic on the occurrence of food insecurity in a cohort of women living in Mexico City, and the socioeconomic characteristics associated with food insecurity severity. METHODS: We analyzed data longitudinally from 685 women in the Mexico City-based ELEMENT cohort. Food insecurity at the household level was gathered using the Latin American and Caribbean Food Security Scale and measured in-person during 2015 to 2019 before the pandemic and by telephone during 2020-2021, in the midst of the pandemic. Fluctuations in the average of food insecurity as a function of calendar time were modeled using kernel-weighted local polynomial regression. Fixed and random-effects ordinal logistic regression models of food insecurity were fitted, with timing of data collection (pre-pandemic vs. during pandemic) as the main predictor. RESULTS: Food insecurity (at any level) increased from 41.6% during the pre-pandemic period to 53.8% in the pandemic stage. This increase was higher in the combined severe-moderate food insecurity levels: from 1.6% pre-pandemic to 16.8% during the pandemic. The odds of severe food insecurity were 3.4 times higher during the pandemic relative to pre-pandemic levels (p<0.01). Socioeconomic status quintile (Q) was significantly related to food insecurity (Q2 OR = 0.35 p<0.1, Q3 OR = 0.48 p = 0.014, Q4 OR = 0.24 p<0.01, and Q5 OR = 0.17 p<0.01), as well as lack of access to social security (OR = 1.69, p = 0.01), and schooling (OR = 0.37, p<0.01). CONCLUSIONS: Food insecurity increased in Mexico City households in the ELEMENT cohort as a result of the COVID-19 pandemic. These results contribute to the body of evidence suggesting that governments should implement well-designed, focalized programs in the context of economic crisis such as the one caused by COVID-19 to prevent families from the expected adverse health and well-being consequences associated to food insecurity, especially for the most vulnerable.

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.

Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring.

Although toxicology uses animal models to represent real-world human health scenarios, a critical translational gap between laboratory-based studies and epidemiology remains. In this study, we aimed to understand the toxicoepigenetic effects on DNA methylation after developmental exposure to two common toxicants, the phthalate di(2-ethylhexyl) phthalate (DEHP) and the metal lead (Pb), using a translational paradigm that selected candidate genes from a mouse study and assessed them in four human birth cohorts. Data from mouse offspring developmentally exposed to DEHP, Pb, or control were used to identify genes with sex-specific sites with differential DNA methylation at postnatal day 21. Associations of human infant DNA methylation in homologous mouse genes with prenatal DEHP or Pb were examined with a meta-analysis. Differential methylation was observed on 6 cytosines (adjusted-p < 0.05) and 90 regions (adjusted-p < 0.001). This translational approach offers a unique method that can detect conserved epigenetic differences that are developmentally susceptible to environmental toxicants.

Sensitive development windows of prenatal air pollution and cognitive functioning in preschool age Mexican children.

Introduction: Neurotoxicity resulting from air pollution is of increasing concern. Considering exposure timing effects on neurodevelopmental impairments may be as important as the exposure dose. We used distributed lag regression to determine the sensitive windows of prenatal exposure to fine particulate matter (PM2.5) on children's cognition in a birth cohort in Mexico. Methods: Analysis included 553 full-term (≥37 weeks gestation) children. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatiotemporal model. McCarthy Scales of Children's Abilities (MSCA) were used to assess children's cognitive function at 4-5 years old (lower scores indicate poorer performance). To identify susceptibility windows, we used Bayesian distributed lag interaction models to examine associations between prenatal PM2.5 levels and MSCA. This allowed us to estimate vulnerable windows while testing for effect modification. Results: After adjusting for maternal age, socioeconomic status, child age, and sex, Bayesian distributed lag interaction models showed significant associations between increased PM2.5 levels and decreased general cognitive index scores at 31-35 gestation weeks, decreased quantitative scale scores at 30-36 weeks, decreased motor scale scores at 30-36 weeks, and decreased verbal scale scores at 37-38 weeks. Estimated cumulative effects (CE) of PM2.5 across pregnancy showed significant associations with general cognitive index (CE^ = -0.35, 95% confidence interval [CI] = -0.68, -0.01), quantitative scale (CE^ = -0.27, 95% CI = -0.74, -0.02), motor scale (CE^ = -0.25, 95% CI = -0.44, -0.05), and verbal scale (CE^ = -0.2, 95% CI = -0.43, -0.02). No significant sex interactions were observed. Conclusions: Prenatal exposure to PM2.5, particularly late pregnancy, was inversely associated with subscales of MSCA. Using data-driven methods to identify sensitive window may provide insight into the mechanisms of neurodevelopmental impairment due to pollution.

Prenatal exposure to metal mixtures and childhood temporal processing in the PROGRESS Birth Cohort Study: Modification by childhood obesity.

Children are frequently exposed to various biological trace metals, some essential for their development, while others can be potent neurotoxicants. Furthermore, the inflammatory and metabolic conditions associated with obesity may interact with and amplify the impact of metal exposure on neurodevelopment. However, few studies have assessed the potential modification effect of body mass index (BMI). As a result, we investigated the role of child BMI phenotype on the relationship between prenatal exposure to metal mixtures and temporal processing. Leveraging the PROGRESS birth cohort in Mexico City, children (N = 563) aged 6-9 years completed a Temporal Response Differentiation (TRD) task where they had to hold a lever down for 10-14 s. Blood and urinary metal (As, Pb, Cd, and Mn) measurements were collected from mothers in the 2nd and 3rd trimesters. Child BMI z-scores were dichotomized to normal (between -2 and +0.99) and high (≥1.00). Covariate-adjusted weighted quantile sum (WQS) regression models were used to estimate and examine the combined effect of metal biomarkers (i.e., blood and urine) on TRD measures. Effect modification by the child's BMI was evaluated using 2-way interaction terms. Children with a high BMI and greater exposure to the metal mixture during prenatal development exhibited significant temporal processing deficits compared to children with a normal BMI. Notably, children with increased exposure to the metal mixture and higher BMI had a decrease in the percent of tasks completed (ß = -10.13; 95 % CI: -19.84, -0.42), number of average holds (ß = -2.15; 95 % CI: -3.88, -0.41), longer latency (ß = 0.78; 95 % CI: 0.13, 1.44), and greater variability in the standard deviation of the total hold time (ß = 2.08; 95 % CI: 0.34, 3.82) compared to normal BMI children. These findings implicate that high BMI may amplify the effect of metals on children's temporal processing. Understanding the relationship between metal exposures, temporal processing, and childhood obesity can provide valuable insights for developing targeted environmental interventions.

Prenatal metal exposures and childhood gut microbial signatures are associated with depression score in late childhood.

BACKGROUND: Childhood depression is a major public health issue worldwide. Previous studies have linked both prenatal metal exposures and the gut microbiome to depression in children. However, few, if any, have studied their interacting effect in specific subgroups of children. OBJECTIVES: Using an interpretable machine-learning method, this study investigates whether children with specific combinations of prenatal metals and childhood microbial signatures (cliques or groups of metals and microbes) were more likely to have higher depression scores at 9-11 years of age. METHODS: We leveraged data from a well-characterized pediatric longitudinal birth cohort in Mexico City and its microbiome substudy (n = 112). Eleven metal exposures were measured in maternal whole blood samples in the second and third trimesters of pregnancy. The gut microbial abundances were measured at 9-11-year-olds using shotgun metagenomic sequencing. Depression symptoms were assessed using the Child Depression Index (CDI) t-scores at 9-11 years of age. We used Microbial and Chemical Exposure Analysis (MiCxA), which combines interpretable machine-learning into a regression framework to identify and estimate joint associations of metal-microbial cliques in specific subgroups. Analyses were adjusted for relevant covariates. RESULTS: We identified a subgroup of children (11.6 % of the sample) characterized by a four-component metal-microbial clique that had a significantly high depression score (15.4 % higher than the rest) in late childhood. This metal-microbial clique consisted of high Zinc in the second trimester, low Cobalt in the third trimester, a high abundance of Bacteroides fragilis, a high abundance of Faecalibacterium prausnitzii. All combinations of cliques (two-, three-, and four-components) were significantly associated with increased log-transformed t-scored CDI (ß = 0.14, 95%CI = [0.05,0.23], P < 0.01 for the four-component clique). SIGNIFICANCE: This study offers a new approach to chemical-microbial analysis and a novel demonstration that children with specific gut microbiome cliques and metal exposures during pregnancy may have a higher likelihood of elevated depression scores.

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

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

Recent ambient temperature and fine particulate matter (PM2.5) exposure is associated with urinary kidney injury biomarkers in children.

BACKGROUND: Limited research has examined associations between exposure to ambient temperature, air pollution, and kidney function or injury during the preadolescent period. We examined associations between exposure to ambient temperature and particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) with preadolescent estimated glomerular filtration rate (eGFR) and urinary kidney injury biomarkers. METHODS: Participants included 437 children without cardiovascular or kidney disease enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors birth cohort study in Mexico City. eGFR and urinary kidney injury biomarkers were assessed at 8-12 years. Validated satellite-based spatio-temporal models were used to estimate mean daily temperature and PM2.5 levels at each participant's residence 7- and 30-days prior to the date of visit. Linear regression and distributed lag nonlinear models (DLNM) were used to examine associations between daily mean temperature and PM2.5 exposure and kidney outcomes, adjusted for covariates. RESULTS: In single linear regressions, higher seven-day average PM2.5 was associated with higher urinary alpha-1-microglobulin and eGFR. In DLNM analyses, higher temperature exposure in the seven days prior to date of visit was associated with a decrease in urinary cystatin C of -0.56 ng/mL (95 % confidence interval (CI): -1.08, -0.04) and in osteopontin of -0.08 ng/mL (95 % CI: -0.15, -0.001). PM2.5 exposure over the seven days prior to date of visit was associated with an increase in eGFR of 1.77 mL/min/1.73m2 (95 % CI: 0.55, 2.99) and urinary cystatin C of 0.19 ng/mL (95 % CI: 0.03, 0.35). CONCLUSIONS: Recent exposure to ambient temperature and PM2.5 were associated with increased and decreased urinary kidney injury biomarkers that may reflect subclinical glomerular or tubular injury in children. Further research is required to assess environmental exposures and worsening subclinical kidney injury across development.

Associations between blood leukocyte DNA methylation and sustained attention in mid-to-late childhood.

Aims: To identify associations between DNA methylation (DNAm) across the epigenome and symptoms related to attention-deficit/hyperactivity disorder in a population of Hispanic children. Materials & methods: Among 517 participants in the ELEMENT study aged 9-18 years, we conducted an epigenome-wide association study examining associations between blood leukocyte DNAm and performance on the Conners' continuous performance test (CPT3). Results: DNAm at loci in or near ZNF814, ELF4 and OR6K6 and functional enrichment for gene pathways pertaining to ferroptosis, inflammation, immune response and neurotransmission were significantly related to CPT3 scores. Conclusion: DNAm was associated with CPT3 performance. Further analysis is warranted to understand how these genes and enriched pathways contribute to attention-deficit/hyperactivity disorder.

Early Lead Exposure Associated with Molar Hypomineralization.

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

Prenatal manganese biomarkers and operant test battery performance in Mexican children: Effect modification by child sex.

BACKGROUND: Manganese (Mn) is essential to healthy neurodevelopment, but both Mn deficiency and over-exposure have been linked to prefrontal cortex (PFC) impairments, the brain region that regulates cognitive and neurobehavioral processes responsible for spatial memory, learning, motivation, and time perception. These processes facilitated by attention, inhibitory control, working memory, and cognitive flexibility are often sexually dimorphic and complex, driven by multiple interconnected neurologic and cognitive domains. OBJECTIVE: We investigated the role of child sex as an effect modifier of the association between prenatal Mn exposure and performance in an operant testing battery (OTB) that assessed multiple cognitive and behavioral functional domains. METHODS: Children (N = 575) aged 6-8 years completed five OTB tasks. Blood and urinary Mn measurements were collected from mothers in the 2nd and 3rd trimesters. Multiple regression models estimated the association between Mn biomarkers at each trimester with OTB performance while adjusting for socio-demographic covariates. Covariate-adjusted weighted quantile sum (WQS) regression models were used to estimate the association of a Mn multi-media biomarker (MMB) mixture with OTB performance. Interaction terms were used to estimate modification effect by child sex. RESULTS: Higher blood Mn exposure was associated with better response rates (more motivation) on the progressive ratio task and higher overall accuracy on the delayed matching-to-sample task. In the WQS models, the MMB mixture was associated with better response rates (more motivation) on the progressive ratio task. Additionally, for the linear and WQS models, we observed a modification effect by child sex in the progressive ratio and delayed matching-to-sample tasks. Higher prenatal Mn biomarker levels were associated with improved task performance for girls and reduced performance in boys. CONCLUSION: Higher prenatal blood Mn concentrations and the MMB mixture predicted improved performance on two of five operant tasks. Higher prenatal Mn concentrations regulated executive functions in children in a sexually dimorphic manner. Higher prenatal Mn exposure is associated with improved performance on spatial memory and motivation tasks in girls, suggesting that Mn's nutritional role is sexually dimorphic, and should be considered when making dietary and/or environmental intervention recommendations.

Cross-sectional associations between phthalates, phenols, and parabens with metabolic syndrome risk during early-to-mid adolescence among a cohort of Mexican youth.

BACKGROUND: Epidemiological studies on children and adults have linked toxicants from plastics and personal care products to metabolic disruption. Yet, the impact of endocrine-disrupting chemicals (EDCs) on adolescent metabolic syndrome (MetS) risk during early and mid-adolescence is unclear. METHODS: To examine the links between exposure to EDCs and MetS risk and its components, cross-sectional data from 344 Mexican youth in early-to-mid adolescence (10-17 years) were analyzed. Urinary biomarker concentrations of phthalates, phenol, and paraben analytes were measured from a single spot urine sample collected in 2015; study personnel obtained anthropometric and metabolic measures. We examined associations between summary phthalates and metabolites, phenol, and paraben analytes with MetS risk z-scores using linear regression, adjusted for specific gravity, sex, age, pubertal status, smoking, alcohol intake, physical activity level, and screen time. As a secondary aim, mediation analysis was conducted to evaluate the role of hormones in the association between summary phthalates with lipids and MetS risk z-scores. RESULTS: The mean (SD) age was 13.2 (1.9) years, and 50.9% were female. Sex-stratified analyses revealed associations between summary phthalates and lipids ratio z-scores, including Σ DEHP [ß = 0.21 (95% CI: 0.04, 0.37; p < 0.01)], phthalates from plastic sources (Σ Plastic) [ß = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], anti-androgenic phthalates (Σ AA) [ß = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], and individual phthalate metabolites (MEHHP, MEOHP, and MECPP) among males. Among females, BPA [ß = 0.24 (95% CI: 0.03, 0.44; p < 0.05)] was positively associated with lipids ratio z-score and one phenol (2,5 DCP) [ß = 0.09 (95% CI: 0.01, 0.18); p < 0.05)] was associated with increased waist circumference z-score. Results showed no evidence of mediation by hormone concentrations in the association between summary phthalates with lipids ratio or MetS risk z-scores. CONCLUSION: Higher EDC exposure was positively associated with serum lipids during adolescence, particularly among males.

Sex-specific association between prenatal manganese exposure and working memory in school-aged children in Mexico city: An exploratory multi-media approach.

It remains unclear whether manganese (Mn) exposure affects working memory (WM) in a sexually dimorphic manner. Further, no gold standard media exists to measure Mn, suggesting a combined blood and urinary Mn index may better capture the totality of exposure. We investigated the modification effect of child sex on the influence of prenatal Mn exposure on WM in school-age children, exploring two methodological frameworks to integrate exposure estimates across multiple exposure biomarkers. Leveraging the PROGRESS birth cohort in Mexico City, children (N = 559) ages 6-8 completed the between errors and strategy measures of the CANTAB Spatial Working Memory (SWM) task. Mn levels were assayed in blood and urine of mothers during the 2nd and 3rd trimesters and in umbilical cord blood from mothers and children at delivery. Weighted quantile sum regression estimated the association of a multi-media biomarker (MMB) mixture with SWM. We applied a confirmatory factor analysis to similarly quantify a latent blood Mn burden index. We then used an adjusted linear regression to estimate the Mn burden index with SWM measures. Interaction terms were used to estimate the modification effect by child sex for all models. Results showed that the between-errors-specific MMB mixture (i.e., this model demonstrates the impact of the MMB mixture on the between-error scores.) was associated (ß = 6.50, 95% CI: 0.91, 12.08) with fewer between errors for boys and more between errors for girls. The strategy-specific MMB mixture (i.e., this model demonstrates the impact of the MMB mixture on the strategy scores) was associated (ß = -1.36, 95% CI: 2.55, - 0.18) with less efficient strategy performance for boys and more efficient strategy performance for girls. A higher Mn burden index was associated (ß = 0.86, 95% CI: 0.00, 1.72) with more between errors in the overall sample. The vulnerability to prenatal Mn biomarkers on SWM differs in the directionality by child sex. An MMB mixture and composite index of body burden are stronger predictors than a single biomarker for Mn exposure on WM performance.

Prenatal exposure to metals and concentration thereof in umbilical cord blood in a Mexico City cohort.

BACKGROUND: In Mexico, there is a paucity of evidence on the magnitude of prenatal exposure to metals. OBJECTIVE: To estimate the concentration of arsenic, cadmium, manganese and lead in umbilical cord blood (UCB) and its association with maternal blood concentrations during pregnancy and delivery. MATERIAL AND METHODS: Metal concentration in maternal blood was analyzed during pregnancy (n = 901), delivery (n = 732) and in UCB (n = 512) from participants of the PROGRESS cohort residing in Mexico City. The association between concentrations in UCB and maternal biomarkers was analyzed using generalized linear models, adjusted for relevant covariates. RESULTS: Mean concentrations (µg/L) of lead, arsenic and manganese in UCB were 27.14 (25.28-29.14), 0.77 (0.71-0.84) and 42.60 (40.45-44.83), respectively. Cadmium concentration could not be estimated because 86.2% of measurements were below the detection limit. Lead and manganese concentrations in UCB were significantly associated with maternal biomarkers during pregnancy and delivery; at delivery, association was only observed with arsenic. CONCLUSIONS: Prenatal exposure to toxic metals in sensitive periods of organogenesis shows a neglected public health problem. Biomonitoring of the population and establishment of regulations aimed at providing care to vulnerable populations is required.

ANTECEDENTES: En México es exigua la evidencia sobre la exposición prenatal a metales. OBJETIVO: Estimar la concentración de arsénico, cadmio, manganeso y plomo en sangre de cordón umbilical (SCU), y su asociación con las concentraciones en sangre materna durante el embarazo y parto. MATERIAL Y MÉTODOS: Se analizó la concentración de los metales en sangre materna durante el embarazo (n = 901), parto (n = 732) y en la SCU (n = 512) de participantes de la cohorte PROGRESS, residentes en la Ciudad de México. Se estimó la asociación entre la concentración en SCU y los biomarcadores maternos mediante modelos lineales generalizados, ajustados por covariables relevantes. RESULTADOS: La media (µg/L) de plomo, arsénico y manganeso en SCU fue 27.14 (25.28-29.14), 0.77 (0.71-0.84) y 42.60 (40.45-44.83), respectivamente. El valor del cadmio no se pudo estimar porque 86.2 % de las mediciones fueron inferiores al límite de detección. Las concentraciones de plomo y manganeso en SCU se asociaron significativamente a los biomarcadores maternos durante el embarazo y el parto; solo se observó asociación con arsénico en el parto. CONCLUSIONES: La exposición prenatal a metales tóxicos en periodos sensibles de la organogénesis evidencia un problema de salud pública desatendido. Se requiere un biomonitoreo poblacional y establecer regulación dirigida a proveer atención a población vulnerable.

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 24-50 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.

Concentración de metales en sangre de cordón umbilical debido a exposición prenatal en una cohorte de la Ciudad de México / Prenatal exposure to metals and concentration thereof in umbilical cord blood in a Mexico City cohort

Resumen Antecedentes: En México es exigua la evidencia sobre la exposición prenatal a metales. Objetivo: Estimar la concentración de arsénico, cadmio, manganeso y plomo en sangre de cordón umbilical (SCU), y su asociación con las concentraciones en sangre materna durante el embarazo y parto. Material y métodos: Se analizó la concentración de los metales en sangre materna durante el embarazo (n = 901), parto (n = 732) y en la SCU (n = 512) de participantes de la cohorte PROGRESS, residentes en la Ciudad de México. Se estimó la asociación entre la concentración en SCU y los biomarcadores maternos mediante modelos lineales generalizados, ajustados por covariables relevantes. Resultados: La media (μg/L) de plomo, arsénico y manganeso en SCU fue 27.14 (25.28-29.14), 0.77 (0.71-0.84) y 42.60 (40.45-44.83), respectivamente. El valor del cadmio no se pudo estimar porque 86.2 % de las mediciones fueron inferiores al límite de detección. Las concentraciones de plomo y manganeso en SCU se asociaron significativamente a los biomarcadores maternos durante el embarazo y el parto; solo se observó asociación con arsénico en el parto. Conclusiones: La exposición prenatal a metales tóxicos en periodos sensibles de la organogénesis evidencia un problema de salud pública desatendido. Se requiere un biomonitoreo poblacional y establecer regulación dirigida a proveer atención a población vulnerable.

Abstract Background: In Mexico, there is a paucity of evidence on the magnitude of prenatal exposure to metals. Objective: To estimate the concentration of arsenic, cadmium, manganese and lead in umbilical cord blood (UCB) and its association with maternal blood concentrations during pregnancy and delivery. Material and methods: Metal concentration in maternal blood was analyzed during pregnancy (n = 901), delivery (n = 732) and in UCB (n = 512) from participants of the PROGRESS cohort residing in Mexico City. The association between concentrations in UCB and maternal biomarkers was analyzed using generalized linear models, adjusted for relevant covariates. Results: Mean concentrations (μg/L) of lead, arsenic and manganese in UCB were 27.14 (25.28-29.14), 0.77 (0.71-0.84) and 42.60 (40.45-44.83), respectively. Cadmium concentration could not be estimated because 86.2% of measurements were below the detection limit. Lead and manganese concentrations in UCB were significantly associated with maternal biomarkers during pregnancy and delivery; at delivery, association was only observed with arsenic. Conclusions: Prenatal exposure to toxic metals in sensitive periods of organogenesis shows a neglected public health problem. Biomonitoring of the population and establishment of regulations aimed at providing care to vulnerable populations is required.

Sleep duration and timing are prospectively linked with insulin resistance during late adolescence.

OBJECTIVE: The aim of this study was to evaluate whether short sleep duration or later sleep timing is a risk factor for insulin resistance (IR) in late adolescence. METHODS: Mexico City adolescents enrolled in a longitudinal birth cohort (ELEMENT) took part in two study visits during peri-puberty that occurred approximately 2 years apart. IR was assessed with serum glucose and insulin. Four groups were defined using puberty-specific cut points: no IR over the follow-up period, transition from normal to IR, transition from IR to normal, and IR at both time points. Baseline sleep assessments were measured with 7-day wrist actigraphy. Multinomial logistic regression models were used to evaluate associations between sleep duration and timing with homeostatic model assessment of insulin resistance categories, adjusting for age, sex, and baseline pubertal status. RESULTS: Adolescents who were ≥ 1 hour below the sleep duration recommendations-for-age were 2.74 times more likely to develop IR (95% CI: 1.0-7.4). Similarly, adolescents who were in the latest category of sleep midpoint (>4:33 a.m.) were more likely than those with earliest midpoints (1 a.m.-3 a.m.) to develop IR (odds ratio = 2.63, 95% CI: 1.0-6.7). Changes in adiposity over follow-up did not mediate sleep and IR. CONCLUSIONS: Insufficient sleep duration and late sleep timing were associated with development of IR over a 2-year period in late adolescence.

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 11ß-hydroxysteroid dehydrogenase type 2 (11ß-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 11ß-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 [ß = -0.029, p = 0.0006] and with log high-density lipoprotein cholesterol at site 3 [ß = 0.063, p = 0.0072]. 11ß-HSD-2 DNAm at site 4 was associated with log glucose (ß = -0.018, p = 0.0018). DNAm at LINE-1 and 11ß-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.

Prenatal dietary patterns in relation to adolescent offspring adiposity and adipokines in a Mexico City cohort.

Maternal diet during pregnancy has been associated with obesity among offspring. The extent to which trimester-specific dietary patterns are associated with markers of adiposity during adolescence remains unclear. We examined associations between prenatal diet patterns with adolescent offspring measures of adiposity and adipokines in 384 mother-adolescent dyads from the Mexico City ELEMENT cohort. Trimester-specific diet patterns were derived from principal component analysis of food frequency questionnaire data. Adolescent anthropometry and serum leptin and adiponectin were measured at 10-17 years. Three maternal diet patterns were identified: Prudent Diet (PD), high in fish and vegetables, the High Meat and Fat Diet (HMFD), high in pork and processed meats, and the Transitioning Mexican Diet (TMD), high in corn tortillas and sugar-sweetened beverages. Multiple linear regression was used to estimate sex-stratified associations among quartiles of diet patterns with adiposity and adipokines, adjusting for maternal marital status, education, and parity. First trimester TMD was associated with greater anthropometric measures and higher leptin in females, while third trimester HMFD was associated higher body fat percentage, triceps thickness, waist circumference, and leptin, but lower adiponectin among males. Contrary to expectation, there were positive associations between the trimester 1 PD pattern and anthropometric measurements in females, and for trimester 2 HMFD and TMD patterns with adipokines among males. Findings suggest maternal diet patterns may influence offspring adiposity markers during adolescence in a sex-specific manner.

Perinatal Lead Exposure Promotes Sex-Specific Epigenetic Programming of Disease-Relevant Pathways in Mouse Heart.

Environmental contaminants such as the metal lead (Pb) are associated with cardiovascular disease, but the underlying molecular mechanisms are poorly understood. In particular, little is known about how exposure to Pb during early development impacts the cardiac epigenome at any point across the life course and potential differences between sexes. In a mouse model of human-relevant perinatal exposures, we utilized RNA-seq and Enhanced Reduced Representation Bisulfite Sequencing (ERRBS) to investigate the effects of Pb exposure during gestation and lactation on gene expression and DNA methylation, respectively, in the hearts of male and female mice at weaning. For ERRBS, we identified differentially methylated CpGs (DMCs) or differentially methylated 1000 bp regions (DMRs) based on a minimum absolute change in methylation of 10% and an FDR < 0.05. For gene expression data, an FDR < 0.05 was considered significant. No individual genes met the FDR cutoff for gene expression; however, we found that Pb exposure leads to significant changes in the expression of gene pathways relevant to cardiovascular development and disease. We further found that Pb promotes sex-specific changes in DNA methylation at hundreds of gene loci (280 DMCs and 99 DMRs in males, 189 DMCs and 121 DMRs in females), and pathway analysis revealed that these CpGs and regions collectively function in embryonic development. In males, differential methylation also occurred at genes related to immune function and metabolism. We then investigated whether genes exhibiting differential methylation at weaning were also differentially methylated in hearts from a cohort of Pb-exposed mice at adulthood. We found that a single gene, Galnt2, showed differential methylation in both sexes and time points. In a human cohort investigating the influence of prenatal Pb exposure on the epigenome, we also observed an inverse association between first trimester Pb concentrations and adolescent blood leukocyte DNA methylation at a locus in GALNT2, suggesting that this gene may represent a biomarker of Pb exposure across species. Together, these data, across two time points in mice and in a human birth cohort study, collectively demonstrate that Pb exposure promotes sex-specific programming of the cardiac epigenome, and provide potential mechanistic insight into how Pb causes cardiovascular disease.