Prenatal exposure to phthalates and childhood wheeze and asthma in the progress cohort.

INTRODUCTION: Prenatal phthalate exposure may influence lung development and lead to wheezing and asthma in childhood, and these associations may vary by sex. Despite ubiquity of exposure, there is limited epidemiologic data on these associations in Latin America. METHODS: We assessed 593 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort in Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine. Report of ever wheeze, wheeze in the past 12 months (current wheeze) and ever asthma were obtained using a validated survey when children were 4 and 6 years of age. We examined individual associations with modified Poisson models. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. All models were adjusted for child's sex, maternal age and education at enrollment, and parity. RESULTS: In Poisson models, a doubling of mono (carboxy-isononyl) phthalate (MCNP) during the 2nd trimester was associated with higher risk of wheeze (RR: 1.14, 95 % CI: 1.01, 1.29), and asthma (RR: 1.44, 95 % CI: 1.05, 1.97) at 4 years of age. Higher concentrations of the sum of di-isononyl phthalate metabolites (∑DiNP) during the 2nd trimester were also associated with asthma at 4 years of age (RR: 1.30, 95 % CI: 1.04, 1.61). Mixture associations of phthalate metabolite concentrations during the 2nd trimester and asthma at 4 years of age were stronger in males (BWQS, OR: 1.94, 95 % CI: 0.90, 4.60; 90 % CrI: 1.04, 3.73) compared to females (BWQS, OR: 1.23, 95 % CI: 0.56, 2.88; 90 % CrI: 0.61, 2.55). Additionally, we observed stronger inverse associations between prenatal phthalate mixtures during the 3rd trimester and current wheeze at 4 and 6 years of age in females (BWQS, OR: 0.54, 90 % CrI: 0.35, 0.82; OR: 0.45, 90 % CrI: 0.22, 0.84) compared to males (BWQS, OR: 0.95, 90 % Cri: 0.68, 1.35; OR: 0.97, 90 % CrI: 0.59, 1.54). CONCLUSIONS: Prenatal phthalate metabolite concentrations were associated with respiratory outcomes in childhood, with some evidence of sex specific effects. Future work investigating phthalate exposure and wheeze trajectories/lung function will be important for understanding how these may predict later disease.

Associations between psychosocial stress, child's anxiety, and lung function in mid-childhood.

BACKGROUND: Reducing the risk of respiratory disease during the plastic stages of lung development could have long-term health impacts. Psychosocial stress has been previously linked to adverse childhood respiratory outcomes, but the influence of child's anxiety and sex differences has not been completely elucidated. OBJECTIVE: To evaluate the association among maternal stress, child anxiety, and lung function in children and to explore differences by sex. METHODS: Cross-sectional analyses included 294 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) birth cohort in Mexico City. Children's lung function was tested once at ages 8 to 13 years of age, and height- and sex-adjusted z-scores were estimated for forced vital capacity, forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity and forced expiratory flow between 25% and 75%. Maternal stress was assessed through the Crisis in Family Systems-Revised (CRISYS-R) survey, used to report negative life events experienced in the past 6 months and dichotomized at the median (<3 and ≥3). Child's self-reported anxiety was assessed using the Revised Children's Manifest Anxiety Scale short form and dichotomized at the clinically relevant cutoff (T-score ≥ 60). The association among maternal stress, child anxiety, and lung function outcomes was evaluated using linear models. Effect modification by sex was evaluated with interaction terms and in stratified analyses. RESULTS: We did not find any association between maternal stress and any lung function outcome. Clinically elevated child anxiety symptoms were associated with lower forced expiratory volume in 1 second (ß = -0.36, 95% CI -0.69 to -0.02). We found no evidence of effect modification by sex. CONCLUSION: Results highlight the importance of considering childhood mental health in relation to lung function outcomes.

Development of 24-hour rhythms in cortisol secretion across infancy: a systematic review and meta-analysis of individual participant data.

BACKGROUND: In adults, cortisol levels show a pronounced 24-hour rhythm with a peak in the early morning. It is unknown at what age this early-morning peak in cortisol emerges during infancy, hampering the establishment of optimal dosing regimens for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency. Therefore, we aimed to characterize daily variation in salivary cortisol concentration across the first year of life. METHODS: We conducted a systematic review followed by an individual participant data meta-analysis of studies reporting on spontaneous (i.e., not stress induced) salivary cortisol concentrations in healthy infants aged 0-1 year. A one-stage approach using linear mixed-effects modelling was used to determine the interaction between age and time of day on cortisol concentrations. FINDINGS: Through the systematic review, 54 eligible publications were identified, reporting on 29,177 cortisol observations. Individual participant data were obtained from 15 study cohorts, combining 17,079 cortisol measurements from 1,904 infants. The morning/evening cortisol ratio increased significantly from 1.7 (95% CI: 1.3-2.1) at birth to 3.7 (95% CI: 3.0-4.5) at 6-9 months (p < 0.0001). Cosinor analysis using all available data revealed the gradual emergence of a 24-hour rhythm during infancy. INTERPRETATION: The early-morning peak in cortisol secretion gradually emerges from birth onwards to form a stable morning/evening ratio from age 6-9 months. This might have implications for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency.

Associations of prenatal exposure to phthalates and their mixture with lung function in Mexican children.

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children's lung function was evaluated at ages 8-13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV1 (ß = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (ß = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV1, ß = -0.017, 95 %CI: -0.066, 0.026; FVC, ß = -0.014, 95 %CI: -0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner.

Associations between prenatal metal and metalloid mixtures in teeth and reductions in childhood lung function.

BACKGROUND: Metal(oid)s have been cross-sectionally associated with lung function outcomes in childhood but there is limited data on their combined effects starting in utero. Child sex may further modify these effects. OBJECTIVE: Examine associations between in utero and early life exposure to metals assessed via novel dentine biomarkers and childhood lung function and explore effect modification by child sex. METHODS: Analyses included 291 children enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a longitudinal birth cohort study in Mexico City. Weekly dentine levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), and lead (Pb) were measured from 15 weeks pre-birth to 15 weeks post birth in deciduous children's teeth. Lung function was tested at ages 8-14 years and then modeled as age, height and sex adjusted z-scores. Associations were modeled using lagged weighted quantile sum (LWQS) regression to evaluate the potential for a time-varying mixture effect adjusting for maternal age and education at enrollment and exposure to environmental tobacco smoke in pregnancy. Models were also stratified by sex. RESULTS: We identified a window of susceptibility at 12-15 weeks pre-birth in which the metal mixture was associated with lower FVC z-scores in children aged 8-14 years. Cd and Mn were the largest contributors to the mixture effect (70 %). There was also some evidence of effect modification by sex, in which the mean weights and weighted correlations over the identified window was more evident in males when compared to females. In the male stratum, Cd, Mn and additionally Pb also dominated the mixture association. CONCLUSIONS: Prenatal metal(oid) exposure was associated with lower lung function in childhood. These findings underscore the need to consider both mixtures and windows of susceptibility to fully elucidate effects of prenatal metal(oid) exposure on childhood lung function.

Association Between Changes in Sleep, Nap Duration and Bone Mineral Density in Mexican Adults.

Studies have found associations between sleep, nap duration, and bone mineral density (BMD). However, the longitudinal relationship between sleep, nap duration, and BMD has not been explored. We evaluated the association between the change in sleep and nap duration and BMD in Mexican adults. Data come from 1,337 adult participants of the Health Workers Cohort Study (341 were men and 996 were women, including 450 women < 45 years old and 546 ≥ 45 years old), with two study waves. At each wave, sleep and nap duration was assessed using self-administered questionnaires and BMD in g/cm2 was determined by dual X-ray absorptiometry. We used fixed-effect regression models stratified by sex and adjusted for BMI, diet, physical activity, vitamin supplements, and hormone replacement therapy. Women who changed from < 7 to ≥ 7 h/day of sleep from baseline to follow-up were associated with increases in the total hip (ß = 0.012 g/cm2; 95% CI: 0.002, 0.022) and lumbar spine BMD (ß = 0.024 g/cm2; 95% CI: 0.009, 0.039). Furthermore, most of these associations were observed in women ≥ 45 years. For women, a changing from 0 to > 60 min/day of napping was associated with a significant increase in total hip BMD of 0.012 g/cm2 (95% CI: 0.004, 0.024) and lumbar spine BMD of 0.027 g/cm2 (95% CI: 0.009, 0.045). No significant associations were observed for men. Our results suggest that increased sleep and nap duration are associated with gains in BMD in Mexican women, emphasizing sleep's role in promoting bone health and supporting established recommendations.

Associations of salivary aldosterone levels during pregnancy with maternal blood pressure and birth weight-for-gestational age in a Mexico City birth cohort.

OBJECTIVE: To determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA). METHODS: We measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels. RESULTS: Log-aldosterone was positively associated with diastolic BP (ß = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (ß = -0.12, 95% CI: -0.26, 0.02) and highest (ß = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (ß = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03. CONCLUSION: Higher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.

Individual and joint effects of prenatal PM2.5 and maternal stress on child temperament.

Prenatal fine particulate matter (PM2.5) and maternal psychological functioning have been associated with child cognitive outcomes, though their independent and joint impacts on earlier behavioral outcomes remains less studied. We used data from 382 mother-child pairs from a prospective birth cohort in Mexico City. Temperament was measured at 24 months using the Carey Toddler Temperament Scale (TTS). Exploratory factor analysis (EFA) was used to update the factor structure of the TTS. During pregnancy, mothers completed the Crisis in Family Systems-Revised, Edinburgh Depression Scale, pregnancy-specific anxiety scale, and the Perceived Stress Scale. Pregnancy PM2.5 was assessed using estimates from a satellite-based exposure model. We assessed the association between prenatal maternal stress and PM2.5 on temperament, in both independent and joint models. Quantile g-computation was used to estimate the joint associations. Models were adjusted for maternal age, SES, education, child sex, and child age. In EFA, we identified three temperament factors related to effortful control, extraversion, and negative affect. Our main results showed that higher levels of PM2.5 and several of the maternal psychological functioning measures were related to both effortful control and negative affect in the child, both individually and as a mixture. For instance, a one quartile increase in the prenatal mixture was associated with higher negative affect scores in the child (0.34, 95% CI: 0.16, 0.53). We observed modification of these associations by maternal SES, with associations seen only among lower SES participants for both effortful control (-0.45, 95% CI: -0.70, -0.20) and negative affect outcomes (0.60, 95% CI: 0.35, 0.85). Prenatal PM2.5 and maternal psychological functioning measures were associated with toddler temperament outcomes, providing evidence for impacts of chemical and non-chemical stressors on early child health.

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.

SARS-CoV-2 seroprevalence and respiratory disease disability claims in Mexico City Metropolitan Area.

OBJECTIVE: To characterize the impact of SARS-CoV-2 infection in workers from an essential large-scale company in the Greater Mexico City Metropolitan Area using point prevalence of acute infection, point prevalence of past infection through serum antibodies and respiratory disease short-term disability claims (RD-STDC). MATERIALS AND METHODS: Four randomized surveys, three during 2020 before and one after (December 2021) vaccines' availability. OUTCOMES: point prevalence of acute infection through saliva PCR (polymerase chain reaction) testing, point prevalence of past infection through serum antibodies against Covid-19, RD-STDC and prevalence of symptoms during the previous six months. RESULTS: Prevalence of SARS-CoV-2 cases was 1.29-4.88%, on average, a quarter of participants pre-vaccination were seropositive; over half of participants with a RD-STDC had antibodies. The odds of having antibodies were 6-7 times more among workers with an RD-STDC. CONCLUSIONS: High antibody levels against Covid-19 in this study population reflects that coverage is high among workers in this industry. STDCs are a useful tool to track workplace epidemics.

Contribución de diversas fuentes de exposición a la concentración de plomo en sangre en población infantil mexicana, Ensanut 2022.

OBJETIVO: Analizar la asociación entre fuentes de exposición al plomo (FEPb) y la concentración en sangre capilar (PbS) en menores de 1 a 4 años de edad a nivel nacional y regional, así como cuantificar la contribución relativa de las distintas FEPb. Material y métodos. Se utilizaron datos de la Encuesta Nacional de Salud y Nutrición (Ensanut 2022). Las FEPb consideradas fueron uso de loza de barro vidriada con plomo (LBVPb), residencia cercana a sitios contaminados y exposición paraocupacional. Se estimaron prevalencias de intoxicación (PbS ≥ 5.0 mg/dL) y medias geométricas de PbS. Se utilizaron modelos de regresión para PbS (escala logarítmica) y la descomposición Shapley-Owen de R2 para evaluar la contribución relativa de cada FEPb. RESULTADOS: Las FEPb estudiadas explican el 6% de la variabilidad de PbS a nivel nacional; de este, el 87.3% lo explica el uso de LBVPb, el 4.2% otras FEPb ambiental y 1.3% FEPb paraocupacionales. La contribución relativa del uso de LBVPb varía entre regiones, desde 38.1 a 76.8%. Algunas regiones destacan la FEPb ambiental, pero no paraocupacional. CONCLUSIONES: Los resultados confirman que el uso de LBVPb es la principal fuente de exposición reportada y sugieren que la población no identifica las principales FEPb documentadas hasta ahora.

Intoxicación infantil por plomo en México: otras fuentes de exposición más allá del barro vidriado (Ensanut 2022).

OBJETIVO: Describir y actualizar al año 2022 la prevalencia de intoxicación por plomo (Pb) en la población infantil de 1-4 años en México y describir fuentes de exposición ambiental, paraocupacional y uso de barro vidriado (BV). Material y métodos. Estudio en una muestra de menores que participaron en la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022). Se midió la concentración de plomo en sangre (PbS) capilar. Se aplicó un cuestionario para indagar sobre fuentes de exposición a Pb. RESULTADOS: Se midió PbS en 1 158 menores de 1-4 años. La prevalencia nacional de intoxicación por Pb (≥5.0 µg/dL) fue 16.8% (IC95%:13.6,20.5). La proporción de hogares que reportó exposición a una fuente exclusiva fue de 21.2, 17.7 y 7.4% para BV, exposición ambiental y paraocupacional, respectivamente. La prevalencia de intoxicación de los expuestos a una sola fuente fue 21.5%, y esta cifra aumenta a 24.2% entre quienes reportaron exposición combinada tres tipos de fuentes. Conclusión. La prevalencia nacional de intoxicación por plomo permaneció estable con respecto a lo reportado en la Ensanut 2018-19. El uso de BV es una fuente de exposición relevante, pero no es la única. Se identificó una contribución importante por exposición ambiental y, en menor medida, de exposición paraocupacional.

The Omicron wave in Mexico: vaccine protection against progression to severe Covid-19 in SARS-CoV-2-infected workers.

OBJECTIVE: To assess the effectiveness of seven Covid-19 vaccines in preventing disease progression (DP) using data from national private sector workers during the Omicron wave in Mexico from January 2 to March 5, 2022. MATERIALS AND METHODS: This study employed an administrative retrospective cohort design, analyzing DP (hospitalization or death due to respiratory disease) among workers who filed a respiratory short-term disability claim and tested positive for SARS-CoV-2. Risk ratios (RRadj) were estimated using Poisson regression models adjusted for various factors. RESULTS: Vaccinated individuals had a lower risk of hospitalization and death compared with unvaccinated individuals. The overall RRadj for hospitalization and death were 0.36 (95%CI 0.32, 0.41) and 0.24 (0.17, 0.33), respectively. When evaluating vaccines individually, the RRadj for hospitalization were as follows Pfizer BioNTech 0.27 (95%CI 0.22, 0.33), Moderna 0.29 (95%CI 0.15, 0.57), Sinovac 0.32 (95%CI 0.25, 0.41), AstraZeneca 0.39 (95%CI 0.34, 0.46), Sputnik 0.39 (95%CI 0.28, 0.53), CanSino 0.41 (95%CI 0.24, 0.7), and Janssen 0.53 (95%CI 0.39, 0.72). The RRadj for death were as follows: Pfizer BioNTech 0.12 (95%CI 0.07, 0.19), Sputnik 0.15 (95%CI 0.06, 0.38), Sinovac 0.29 (95%CI 0.16, 0.53), AstraZeneca 0.30 (95%CI 0.20, 0.44), CanSino 0.38 (95%CI 0.1, 1.4), and Janssen 0.50 (95%CI 0.26, 0.97). CONCLUSION: Covid-19 vaccines significantly reduced the risk of severe disease during the Omicron wave in Mexico.

Assessing the real-world effectiveness of five SARS-CoV-2 vaccines in a cohort of Mexican pensioners: a nationwide nested test-negative design study.

Background: Despite the extensive distribution of COVID-19 vaccines across Latin America, research on their real-world performance remains limited. We aimed to evaluate the effectiveness of five vaccines (BNT162b2, AZD1222, CoronaVac, Gam-COVID-Vac, and Ad5-nCoV) in a cohort of 2,559,792 pensioners covered by the Mexican Institute of Social Security. Methods: We conducted a nested test-negative design study on 28,271 individuals tested for SARS-CoV-2 infection between April and November 2021, accounting for 29,226 separate episodes. We used mixed-effects logistic regression models to estimate the vaccine effectiveness (VE) in fully vaccinated individuals for symptomatic infection, hospitalization, severe disease, and death. Findings: The median age of the study population was 70 years (interquartile range 65-76) and 76.4% (21,598/28,271) were male. VE rates were 56.3%, 75.3%, 79.7%, and 79.8% against symptomatic infection (95% confidence interval [CI]: 53.5-59.0), hospitalization (95% CI: 73.4-77.0), severe disease (95% CI: 78.0-81.3), and death (95% CI: 78.1-81.4), respectively. When evaluating vaccines individually, all showed moderate to high VE, with the best being BNT162b2 (symptomatic infection, 69.8%, 95% CI: 67.3-72.0; hospitalization, 84.1%, 95% CI: 82.5-85.6; severe disease, 88.2%, 95% CI: 86.7-89.5; and death, 88.3%, 95% CI: 86.9-89.6) and Gam-COVID-Vac (symptomatic infection, 70.0%, 95% CI: 64.8-74.4; hospitalization, 86.8%, 95% CI: 83.7-89.3; severe disease, 91.9%, 95% CI: 89.4-93.9; and death, 92.0%, 95% CI: 89.5-93.9). Interpretation: All five SARS-CoV-2 vaccines available for this population showed moderate to high levels of protection against COVID-19 and its progression to severe outcomes. Funding: Fundación IMSS, México.

Short-term exposure to PM2.5 and 1.5 million deaths: a time-stratified case-crossover analysis in the Mexico City Metropolitan Area.

BACKGROUND: Satellite-based PM2.5 predictions are being used to advance exposure science and air-pollution epidemiology in developed countries; including emerging evidence about the impacts of PM2.5 on acute health outcomes beyond the cardiovascular and respiratory systems, and the potential modifying effects from individual-level factors in these associations. Research on these topics is lacking in low and middle income countries. We aimed to explore the association between short-term exposure to PM2.5 with broad-category and cause-specific mortality outcomes in the Mexico City Metropolitan Area (MCMA), and potential effect modification by age, sex, and SES characteristics in such associations. METHODS: We used a time-stratified case-crossover study design with 1,479,950 non-accidental deaths from the MCMA for the period of 2004-2019. Daily 1 × 1 km PM2.5 (median = 23.4 µg/m3; IQR = 13.6 µg/m3) estimates from our satellite-based regional model were employed for exposure assessment at the sub-municipality level. Associations between PM2.5 with broad-category (organ-system) and cause-specific mortality outcomes were estimated with distributed lag conditional logistic models. We also fit models stratifying by potential individual-level effect modifiers including; age, sex, and individual SES-related characteristics namely: education, health insurance coverage, and job categories. Odds ratios were converted into percent increase for ease of interpretation. RESULTS: PM2.5 exposure was associated with broad-category mortality outcomes, including all non-accidental, cardiovascular, cerebrovascular, respiratory, and digestive mortality. A 10-µg/m3 PM2.5 higher cumulative exposure over one week (lag06) was associated with higher cause-specific mortality outcomes including hypertensive disease [2.28% (95%CI: 0.26%-4.33%)], acute ischemic heart disease [1.61% (95%CI: 0.59%-2.64%)], other forms of heart disease [2.39% (95%CI: -0.35%-5.20%)], hemorrhagic stroke [3.63% (95%CI: 0.79%-6.55%)], influenza and pneumonia [4.91% (95%CI: 2.84%-7.02%)], chronic respiratory disease [2.49% (95%CI: 0.71%-4.31%)], diseases of the liver [1.85% (95%CI: 0.31%-3.41%)], and renal failure [3.48% (95%CI: 0.79%-6.24%)]. No differences in effect size of associations were observed between age, sex and SES strata. CONCLUSIONS: Exposure to PM2.5 was associated with non-accidental, broad-category and cause-specific mortality outcomes beyond the cardiovascular and respiratory systems, including specific death-causes from the digestive and genitourinary systems, with no indication of effect modification by individual-level characteristics.

Urban Stress and its Association with Symptoms of Depression, Fatigue, and Sleep Disruption in Women in Mexico City.

Women in urban neighborhoods often face disproportionately higher levels of environmental and social stressors; however, the health effects from urban stressors remains poorly understood. We aimed to evaluate the association between urban stress and symptoms of depression, fatigue, and sleep disruption in a cohort of 460 women in Mexico City. To assess urban stress, women were administered the Urban Annoyances (Nuisances Environnementales) scale. Six constructs were summarized to create an overall index. Depressive symptoms were assessed using the Edinburgh Depression Scale; the Patient-Reported Outcomes Information System scales were used to assess sleep disruption and fatigue. Linear regression models were used to estimate the association with continuous symptoms comparing women with high urban stress to those with lower levels. Models were adjusted for socioeconomic status, education, age, social support, and previous depressive symptoms. High urban stress was associated with greater depressive symptoms (ß: 1.77; 95%CI: 0.83, 2.71), fatigue (ß: 2.47; 95%CI: 0.87, 4.07), and sleep disruption (ß: 2.14; 95%CI: 0.54, 3.73). Urban stress plays an important role in women's psychological and physical health, highlighting the importance of including these measures in environmental health studies. Urban interventions, such as promoting alternative transport options, should additionally be addressed to improve health of urban populations.

Calcium supplementation and body mass index modify associations between prenatal phthalate exposure and perinatal bone ultrasound measures among pregnant women.

Phthalates have endocrine activity that may interfere with bone health, particularly during pregnancy and the early postpartum period, when bone resorption increases. We evaluated associations between prenatal phthalate exposure and perinatal bone health among 289 mothers in the ELEMENT birth cohort in Mexico City who were randomized upon recruitment to receive 1,200 mg daily calcium supplementation or placebo throughout pregnancy. Spot urine samples at up to three timepoints during pregnancy were assayed for 9 phthalate metabolites. Bone integrity was assessed by quantitative ultrasound speed of sound (SOS) measurements of the phalange and distal radius at 3, 6, and 8 months of pregnancy and 1, 3, 7, and 12 months postpartum. Geometric means of specific gravity-corrected phthalate concentrations were used as overall measures of prenatal exposure. Linear mixed effect models estimated associations between phthalate exposure and repeated perinatal bone SOS measures, adjusting for age, pre-pregnancy body mass index (BMI), education, parity, calcium supplementation, and month of pregnancy/postpartum. Effect modification by calcium supplementation and BMI were assessed in sensitivity analyses. An interquartile range increase in MEP and MiBP increased pregnancy phalange z-scores (ß: 0.11; 95%CI: 0.003, 0.31 and ß: 0.15; 95%CI: 0.00,0.42, respectively). Higher concentrations of several phthalate metabolites resulted in lower SOS measures among women who received calcium supplements (compared to placebo group) but higher SOS measures among women with a BMI≥25 (compared to BMI<25). These results suggest that phthalate exposure may interfere with bone remodeling during pregnancy, and that consideration of effect modifiers is paramount to fully understand the effects of environmental exposures on bone health.

Lead Exposure Can Affect Early Childhood Development and Could Be Aggravated by Stunted Growth: Perspectives from Mexico.

BACKGROUND: Lead can affect early childhood development (ECD) differentially due to nutritional deficiencies that lead to stunted growth, defined as being at least two standard deviations below the average height-for-age. These deficiencies are more frequent among children living in rural locations or with lower socioeconomic status (SES); however, studies at a population level are scarce worldwide. Early childhood development plays a crucial role in influencing a child's health and wellbeing throughout life. Therefore, the aim of this study was to analyze how stunted growth can modify the association between lead exposure and ECD in children from disadvantaged communities. METHODS: Data were analyzed from the 2018 National Health and Nutrition Survey in localities with fewer than 100,000 inhabitants in Mexico (ENSANUT-100K). Capillary blood lead (BPb) levels were measured using a LeadCare II device and dichotomized as detectable (cutoff point ≥ 3.3 µg/dL) and non-detectable. As a measure of ECD, language development was assessed in n = 1394 children, representing 2,415,000 children aged 12-59 months. To assess the association between lead exposure and language z-scores, a linear model was generated adjusted by age, sex, stunted growth, maternal education, socioeconomic status, area, region (north, center, south), and family care characteristics; afterwards, the model was stratified by stunted growth. RESULTS: Fifty percent of children had detectable BPb and 15.3% had stunted growth. BPb showed a marginal inverse association with language z-scores (ß: -0.08, 95% CI: -0.53, 0.36). Children with detectable BPb and stunted growth had significantly lower language z-scores (ß: -0.40, 95% CI: -0.71, -0.10) than those without stunted growth (ß: -0.15, 95% CI: -0.36, 0.06). CONCLUSIONS: Children with stunted growth are more vulnerable to the adverse effects of lead exposure. These results add to previous research calling for action to reduce lead exposure, particularly in children with chronic undernutrition.

Associations between early-life exposure to PM2.5 and reductions in childhood lung function in two North American longitudinal pregnancy cohort studies.

Data integration of epidemiologic studies across different geographic regions can provide enhanced exposure contrast and statistical power to examine adverse respiratory effects of early-life exposure to particulate matter <2.5 microns in diameter (PM2.5). Methodological tools improve our ability to combine data while more fully accounting for study heterogeneity. Methods: Analyses included children enrolled in two longitudinal birth cohorts in Boston, Massachusetts, and Mexico City. Propensity score matching using the 1:3 nearest neighbor with caliper method was used. Residential PM2.5 exposure was estimated from 2 months before birth to age 6 years using a validated satellite-based spatiotemporal model. Lung function was tested at ages 6-11 years and age, height, race, and sex adjusted z scores were estimated for FEV1, FVC, FEF25-75%, and FEV1/FVC. Using distributed lag nonlinear models, we examined associations between monthly averaged PM2.5 levels and lung function outcomes adjusted for covariates, in unmatched and matched pooled samples. Results: In the matched pooled sample, PM2.5 exposure between postnatal months 35-44 and 35-52 was associated with lower FEV1 and FVC z scores, respectively. A 5 µg/m3 increase in PM2.5 was associated with a reduction in FEV1 z score of 0.13 (95% CI = -0.26, -0.01) and a reduction in FVC z score of 0.13 (95% CI = -0.25, -0.01). Additionally PM2.5 during postnatal months 23-39 was associated with a reduction in FEF25-75% z score of 0.31 (95% CI = -0.57, -0.05). Conclusions: Methodological tools enhanced our ability to combine multisite data while accounting for study heterogeneity. Ambient PM2.5 exposure in early childhood was associated with lung function reductions in middle childhood.