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.

Análisis de la carga de enfermedad atribuible a los factores de riesgo ambientales en México en el período 1990-2021. Identificación de avances, rezagos y emergencias / Analysis of the burden of disease attributable to environmental risk factors in Mexico in the 1990-2021 period. Identification of advances, lags and emergencies

Resumen Antecedentes: Se estima que los factores de riesgo ambientales (FRA) fueron responsables en 2019 de nueve millones de muertes en el mundo. Objetivo: A partir de datos del estudio Global Burden of Disease, se analizaron indicadores de pérdida de salud asociada a la exposición a FRA en México. Material y métodos: Se analizaron números absolutos y porcentajes poblacionales de muertes y años de vida saludable (AVISA) perdidos según sexo atribuidos a FRA seleccionados en los ámbitos nacional y estatal, así como las tendencias estandarizadas por edad de 1990 a 2021. Resultados: En 2021, la contaminación por material particulado en ambiente exterior mostró la mayor mortalidad y AVISA perdidos por los FRA seleccionados (42.2 y 38.1 %, respectivamente), seguida de la exposición a plomo (20.6 y 13.4 %) y temperatura baja (19.8 y 12.3 %). Ambos indicadores han disminuido en todos los FRA seleccionados, en magnitudes diferentes entre 1991 y 2021, excepto la temperatura alta. Conclusiones: A pesar de las disminuciones en los últimos 32 años, el material particulado en ambiente exterior mostró la mayor mortalidad y AVISA perdidos, seguido de la exposición a plomo. Es fundamental fortalecer las políticas de calidad del aire y exposición a plomo en México.

Abstract Background: It is estimated that environmental risk factors (ERF) were responsible for nine million deaths worldwide in 2019. Objective: Using data from the Global Burden of Disease study, indicators of health loss associated with exposure to ERF in Mexico were analyzed. Material and methods: Absolute numbers and population percentages of deaths and disability-adjusted life years (DALY) lost attributed to selected ERFs were analyzed at the national and state level and by sex, as well as age-standardized trends from 1990 to 2021. Results: In 2021, ambient particulate matter pollution showed the highest mortality and DALYs lost attributed to selected ERFs (42.2 and 38.1% respectively), followed by lead exposure (20.6 and 13.4%) and low temperature (19.8 and 12.3%). Both indicators have decreased for all selected ERAs by different magnitudes between 1991 and 2021, except for high temperature. Conclusions: Despite decreases in the last 32 years, outdoor environment particulate matter showed the highest mortality and DALYs lost, followed by lead exposure. It is essential to strengthen air quality and lead exposure policies in Mexico.

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.

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.

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.

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

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.

Prenatal Metal Exposures and Associations with Kidney Injury Biomarkers in Children.

Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is associated with altered urine kidney injury and function biomarkers in preadolescent children. Analyses included 494 children participating in a birth cohort study in Mexico City. Concentrations of As, Cd, and Pb were measured from pregnant women in 2T blood and urine, and Hg in urine only. Kidney biomarkers were measured from children in urine at age 8-12 years. We assessed the associations between individual metals and (1) kidney biomarkers using linear regression and (2) a multi-protein kidney mixture using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney biomarkers were assessed via WQS. Within the multi-protein mixture, the association with increased urinary As was predominated by urine alpha-1-microglobulin (A1M), interferon gamma-induced protein 10 (IP10), and fatty acid binding protein 1; the association with increased urinary Cd was predominated by A1M, clusterin, and albumin. The urine metal mixture was associated with increased albumin (0.23 ng/mL; 95% confidence interval (CI): 0.10, 0.37), IP10 (0.15 ng/mL; 95% CI: 0.02, 0.28), and cystatin C (0.17 ng/mL; 95% CI: 0.04, 0.31); these associations were mainly driven by urinary As and Cd. We observed null associations between prenatal blood or urine metal mixtures and estimated glomerular filtration rate. Higher prenatal urinary metals, individually and as a mixture were associated with altered kidney injury biomarkers in children. Further research and longer participant follow-up are required to ascertain the risk of kidney disease later in life.

Prenatal and early childhood critical windows for the association of nephrotoxic metal and metalloid mixtures with kidney function.

INTRODUCTION: As renal development and maturation processes begin in utero and continue through early childhood, sensitive developmental periods arise during which metal exposures can program subclinical nephrotoxicity that manifests later in life. We used novel dentine biomarkers of established nephrotoxicants including arsenic (As), cadmium (Cd), lead (Pb), chromium (Cr), and lithium (Li), and their mixtures, to identify critical windows of exposure-associated kidney function alterations in preadolescents. METHODS: Participants included 353 children in the Programming Research in Obesity Growth, Environment and Social Stressors (PROGRESS) longitudinal birth cohort study based in Mexico City. Estimated glomerular filtration rate (eGFR) was assessed in 8-12 year old children using serum cystatin C measures. Pre- and postnatal metal(loid) concentrations were assessed in weekly increments by analyzing deciduous teeth with laser ablation-inductively coupled plasma-mass spectrometry. We used reverse distributed lag models (rDLMs) and lagged Weighted Quantile Sum (L-WQS) regression to examine time-varying associations between weekly perinatal metal(loid) exposure or metal(loid) mixtures and preadolescent eGFR while adjusting for age, sex, BMI z-score, SES and prenatal tobacco smoke exposure. RESULTS: We identified a critical window of susceptibility to Pb exposure, in the late 3rd trimester (5 weeks prior to birth) during which higher Pb exposure was associated with children's increased eGFR. When all elements were assessed as a mixture, we identified late 2nd/early 3rd trimester (weeks 8-17 of gestation) as a window of vulnerability associated with decreased eGFR, with Li and Cr contributing the greatest weights to the association. When stratified by sex, we observed stronger effects among boys than girls. CONCLUSIONS: Using tooth-matrix biomarkers, we identified discrete developmental exposure windows wherein Pb and metal(loid) mixtures were associated with altered preadolescent kidney function.

Intermediate- and long-term associations between air pollution and ambient temperature and glycated hemoglobin levels in women of child bearing age.

BACKGROUND: Air pollution has been linked to obesity while higher ambient temperatures typically reduce metabolic demand in a compensatory manner. Both relationships may impact glucose metabolism, thus we examined the association between intermediate- and long-term exposure to fine particulate matter (PM2.5) and ambient temperature and glycated hemoglobin(HbA1c), a longer-term marker of glucose control. METHODS: We assessed 3-month, 6-month, and 12-month average air pollution and ambient temperature at 1-km2 spatial resolution via satellite remote sensing models (2013-2019), and assessed HbA1c at four, six, and eight years postpartum in women enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City. PM2.5 and ambient temperature were matched to participants' addresses and confirmed by GPS tracker. Using linear mixed-effects models, we examined the association between 3-month, 6-month, and 12-month average PM2.5 and ambient temperature with repeated log-transformed HbA1c values. All models included a random intercept for each woman and were adjusted for calendar year, season, and individual-level confounders (age, marital status, smoking, alcohol consumption level, and education level). RESULTS: We analyzed 1,265 HbA1c measurements of 484 women. Per 1 µg/m3 increase in 3-month and 6-month PM2.5, HbA1c levels increased by 0.28% (95% confidence interval (95 %CI): 0.14, 0.42%) and 0.28% (95 %CI: 0.04, 0.52%) respectively. No association was seen for 12-month average PM2.5. Per 1 °C increase in ambient temperature, HbA1c levels decreased by 0.63% (95 %CI: -1.06, -0.21%) and 0.61% (95 %CI: -1.08, -0.13%), while the 12-month average again is not associated with HbA1c. CONCLUSIONS: Intermediate-term exposure to PM2.5 and ambient temperature are associated with opposing changes in HbA1c levels, in this region of high PM2.5 and moderate temperature fluctuation. These effects, measurable in mid-adult life, may portend future risk of type 2 diabetes and possible heart disease.

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

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

Early childhood fluoride exposure and preadolescent kidney function.

BACKGROUND: Early-life renal maturation is susceptible to nephrotoxic environmental chemicals. Given the widespread consumption of fluoride and the global obesity epidemic, our main aim was to determine whether childhood fluoride exposure adversely affects kidney function in preadolescence, and if adiposity status modifies this association. METHODS: Our study included 438 children from the PROGRESS cohort. Urinary fluoride (uF) was assessed at age 4 by diffusion analysis; outcomes studied included estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), selected kidney proteins and blood pressure measured at age 8-12 years. We modeled the relationship between uF and outcomes, and adjusted for body mass index (BMI), age, sex, and socioeconomic status. RESULTS: The median uF concentration was 0.67 µg/mL. We observed null associations between 4-year uF and preadolescent eGFR, although effect estimates were in the expected inverse direction. A single unit increase in ln-transformed uF was associated with a 2.2 mL/min decrease in cystatin C-based eGFR (95% CI: 5.8, 1.4; p = 0.23). We observed no evidence of sex-specific effects or effect modification by BMI status. Although uF was not associated with BMI, among children with obesity, we observed an inverse association (ß: 4.8; 95% CI: 10.2, 0.6; p = 0.08) between uF and eGFR. CONCLUSIONS: Low-level fluoride exposure in early childhood was not associated with renal function in preadolescence. However, given the adverse outcomes of chronic fluoride consumption it is possible that the preadolescent age was too young to observe any effects. Longitudinal follow-up in this cohort and others is an important next step.

Association between prenatal metal exposure and adverse respiratory symptoms in childhood.

INTRODUCTION: Manganese and lead have been cross-sectionally associated with adverse respiratory outcomes in childhood but there is limited data on their combined effects starting in utero. We examined associations between in utero exposure to metals and childhood respiratory symptoms. METHODS: We assessed 633 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) birth cohort in Mexico City. Blood manganese (BMn) and lead (BPb) were measured in mothers at 2nd and 3rd trimester. Ever wheeze, current wheeze and asthma diagnosis were ascertained at 4-5 and 6-7 year visits through the International Study of Asthma and Allergies in Childhood survey. Logistic mixed model regression was used to assess the association between prenatal metals and respiratory outcomes in children across the 4-5 and 6-7 year visits. Covariates included mother's age, education and asthma, environmental tobacco smoke, child's sex and assessment time. RESULTS: In adjusted models, higher 2nd trimester BPb had a significant association with elevated odds of ever wheeze (Odds Ratio (OR): 1.97, 95% CI: 1.05, 3.67). BMn at 2nd trimester was associated with decreased (OR: 0.06, 95% CI: 0.01, 0.35) odds of current wheeze. We did not find any statistically significant associations with 3rd trimester blood metals. CONCLUSION: Prenatal exposure to Pb was associated with higher odds of ever wheeze while Mn was negatively associated with odds of current wheeze. These findings underscore the need to consider prenatal metal exposure, including low exposure levels, in the study of adverse respiratory outcomes.

Nephrotoxic Metal Mixtures and Preadolescent Kidney Function.

Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4-6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8-10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and -2.6% (95% CI: -5.1%, -0.1%) and -3.3% (95% CI: -6.5%, -0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses.

Relationships of beverage consumption and actigraphy-assessed sleep parameters among urban-dwelling youth from Mexico.

OBJECTIVE: To examine whether usual beverage intake was associated with sleep timing, duration and fragmentation among adolescents. DESIGN: Usual beverage intake was assessed with a FFQ. Outcomes included sleep duration, midpoint (median of bed and wake times) and fragmentation, assessed with 7-d actigraphy. Sex-stratified linear regression was conducted with sleep characteristics as separate outcomes and quantiles of energy-adjusted beverage intake as exposures, accounting for age, maternal education, physical activity and smoking. SETTING: Mexico City. PARTICIPANTS: 528 adolescents residing in Mexico City enrolled in a longitudinal cohort. RESULTS: The mean age (sd) was 14·4 (2·1) years; 48 % were male. Among males, milk and water consumption were associated with longer weekday sleep duration (25 (95 % CI 1, 48) and 26 (95 % CI 4, 47) more minutes, in the 4th compared to the 1st quartile); and higher 100 % fruit juice consumption was related to earlier weekday sleep timing (-22 (95 % CI -28, 1) minutes in the 1st compared to the last quantile; P = 0·03). Among females, soda was associated with higher sleep fragmentation (1·6 (95 % CI 0·4, 2·8) % in the 4th compared to the 1st), and coffee/tea consumption was related to shorter weekend sleep duration (-23 (95 % CI -44, 2) minutes in the 4th compared to the 1st). CONCLUSIONS: Among females, adverse associations with sleep were observed for caffeinated drinks, while males with higher consumption of healthier beverage options (water, milk and 100 % juice) had evidence of longer and earlier-timed sleep. Potential mechanisms involving melatonin and tryptophan should be further investigated.

Prenatal blood lead levels and reduced preadolescent glomerular filtration rate: Modification by body mass index.

BACKGROUND: For the developing kidney, the prenatal period may represent a critical window of vulnerability to environmental insults resulting in permanent nephron loss. Given that the majority of nephron formation is complete in the 3rd trimester, we set out to test whether 1) prenatal lead exposure is associated with decreased preadolescent kidney function and 2) whether preadolescent obesity acts synergistically with early life lead exposure to reduce kidney function. METHODS: Our study included 453 mother-child pairs participating in the PROGRESS birth cohort. We assessed prenatal blood lead levels (BLLs) in samples collected in the 2nd and 3rd trimesters and at delivery, as well as tibial and patellar bone lead measures assessed one-month postpartum. Preadolescent estimated glomerular filtration rate (eGFR) was derived from serum levels of creatinine and/or cystatin C measured at age 8-12 years. We applied linear regression to assess the relationship between prenatal bone and BLL with preadolescent eGFR, and adjusted for covariates including age, sex, BMI z-score, indoor tobacco smoke exposure, and socioeconomic status. We also examined sex-specific associations and tested for effect modification by BMI status. RESULTS: We observed null associations between prenatal lead exposure and eGFR. However, in interaction analyses we found that among overweight children, there was an inverse association between BLL (assessed at 2nd and 3rd trimester and at delivery) and preadolescent eGFR. For example, among overweight participants, a one ln-unit increase in 2nd trimester BLL was associated with a 10.5 unit decrease in cystatin C-based eGFR (95% CI: -18.1, -2.8; p = 0.008). Regardless of lead exposure, we also observed null relationships between BMI z-score and eGFR overall, as well as among overweight participants. However, among participants with preadolescent obesity, we observed a significant 5.9-unit decrease in eGFR. We observed no evidence of sex-specific effects. CONCLUSIONS: Our findings, if confirmed in other studies, suggest a complex interplay between the combined adverse effects of adiposity and perinatal lead exposure as they relate to adolescent kidney function. Future studies will assess kidney function and adiposity trajectories through adolescence to better understand environmental risk factors for kidney function decline.

Exosomal miRNAs in urine associated with children's cardiorenal parameters: a cross-sectional study.

Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4-6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q < 0.1. Specifically, three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio and one with decreased estimated glomerular filtration rate. Conclusions: These results highlight urinary exo-miRs as early-life biomarkers of children's cardiorenal health.

Prenatal maternal phthalate exposures and child lipid and adipokine levels at age six: A study from the PROGRESS cohort of Mexico City.

BACKGROUND: Prenatal phthalate exposures may affect processes that underlie offspring cardiometabolic health, but findings from studies examining these associations are conflicting. We examined associations between biomarkers of phthalate exposures during pregnancy with child lipid and adipokine levels. METHODS: Data were from 463 mother-child pairs in the PROGRESS cohort of Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine samples and created an average pregnancy measure using the geometric mean. We evaluated the 15 metabolites as nine biomarkers, including four metabolite molar sums. We measured fasting serum triglycerides, non-HDL cholesterol, leptin, and adiponectin in children at the six-year follow-up visit (mean = 6.8 years). We estimated associations using linear regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) and assessed effect modification by sex. RESULTS: In BKMR and WQS models, higher concentrations of the total mixture of phthalate biomarkers were associated with lower triglycerides (ß = -3.7% [-6.5, -0.78] per 1 unit increase in WQS biomarker index) and non-HDL cholesterol (ß = -2.0 [-3.7, -0.25] ng/ml per increase in WQS biomarker index). Associations between individual biomarkers and child outcomes were largely null. We observed some evidence of effect modification by child sex for mono-3-carboxypropyl phthalate (ß = 19.4% [1.26, 40.7] per doubling of phthalate) and monobenzyl phthalate (ß = -7.6% [-14.4, -0.23]) in girls for adiponectin. CONCLUSIONS: Individual prenatal phthalate biomarkers were not associated with child lipid or adipokine levels. Contrary to our hypothesis, the total phthalate mixture was associated with lower child triglycerides and non-HDL cholesterol.

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among boys in Mexico City.

BACKGROUND: Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone concentrations and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. METHODS: Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone concentrations [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8-14, 10-18 years). We used linear regression to independently examine urinary metal concentrations in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume. RESULTS: In utero and prepubertal concentrations of some urinary metals were associated with increased concentrations of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits. CONCLUSION: These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.

Fine particulate matter exposure and lipid levels among children in Mexico city.

BACKGROUND: Studies have identified associations between air pollution and lipid levels in adults, suggesting a mechanism by which air pollution contributes to cardiovascular disease. However, little is known about the association between early life air pollution exposure and lipid levels in children. METHODS: Participants included 465 mother-child pairs from a prospective birth cohort in Mexico City. Daily particulate matter <2.5 µm in diameter (PM2.5) predictions were estimated using a satellite-based exposure model and averaged over trimesters, the entire pregnancy, and the first year of life. We assessed associations with several lipid measures at 4-6 years of age, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Linear regression models were used to estimate change in lipid levels with each interquartile range increase in PM2.5. We additionally assessed if associations between PM2.5 and lipid levels varied across lipid quantiles using quantile regression. Models were adjusted for maternal education, body mass index, and age, child's age at study visit, prenatal environmental tobacco smoke, and season of conception. RESULTS: PM2.5 exposure during the third trimester was associated with increases in childhood total cholesterol, LDL-C, and non-HDL-C, and decreases in HDL-C and triglycerides. There was additionally an increasing trend in the effect estimate across higher quantiles of total cholesterol, LDL-C, and non-HDL-C during the third trimester and entire pregnancy period. There were no consistent associations for first year of life exposures. CONCLUSION: In this longitudinal birth cohort in Mexico City, associations between prenatal PM2.5 and childhood lipid (total cholesterol, LDL-C, non-HDL-C) levels were greater for children at higher lipid quantiles.

Maternal Prenatal Psychosocial Stress and Prepregnancy BMI Associations with Fetal Iron Status.

BACKGROUND: Iron accrued in utero is critical for fetal and infant neurocognitive development. Psychosocial stress and obesity can each suppress fetal iron accrual. Their combined effects and differences by fetal sex are not known. In an observational pregnancy cohort study in Mexico City, we investigated associations of maternal prenatal life stressors, psychological dysfunction, and prepregnancy BMI with fetal iron status at delivery. OBJECTIVES: We hypothesized that greater maternal prenatal psychosocial stress and prepregnancy overweight and obesity are associated with lower cord blood ferritin and hemoglobin (Hb), with stronger associations in boys than girls. METHODS: Psychosocial stress in multiple domains of life stress (negative life events, perceived stress, exposure to violence) and psychological dysfunction symptoms (depression, generalized anxiety, and pregnancy-specific anxiety) were assessed with validated questionnaires during pregnancy. Prepregnancy BMI was predicted with a validated equation and categorized as normal/overweight/obese. Cord blood ferritin and Hb associations with prenatal psychosocial stress and BMI were modeled in multivariable linear regressions adjusted for maternal age, socioeconomic status, child sex, and prenatal iron supplementation. Interactions with child sex and 3-way stress-overweight/obesity-sex interactions were tested with product terms and likelihood ratio tests. RESULTS: In 493 dyads, median (IQR) cord blood ferritin and Hb concentrations were 185 µg/L (126-263 g/dL) and 16 g/dL (14.7-17.1 g/dL), respectively. Ferritin was lower in infants of mothers with higher prenatal perceived stress (-23%; 95% CI: -35%, -9%), violence exposure (-28%; 95% CI: -42%, -12%), anxiety symptoms (-16%; 95% CI: -27%, -4%), and obesity (-17%; 95% CI: -31%, 0.2%). Interaction models suggested sex differences and synergism between maternal stress and overweight/obesity. No associations were observed between stress or BMI and Hb. CONCLUSIONS: Multiple prenatal psychosocial stressors and excess prepregnancy BMI were each inversely associated with fetal iron status at birth. Pregnancies and infants at elevated risk of impaired fetal iron accrual may be identifiable according to observed synergism between maternal stress and obesity and differential associations with fetal iron status by infant sex.