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.

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.

Prenatal lead exposure and childhood lung function: Influence of maternal cortisol and child sex.

INTRODUCTION: Maternal hypothalamic-pituitary-adrenal (HPA) axis disruption in pregnancy may contribute to the programming of childhood respiratory disease and may modify the effect of chemical toxins, like lead (Pb), on lung development. Child sex may further modify these effects. We sought to prospectively examine associations between maternal HPA axis disruption, prenatal Pb and childhood lung function and explore potential effect modification by maternal cortisol and child sex on the association between prenatal Pb and lung function outcomes. MATERIALS AND METHODS: Analyses included 222 mothers and children enrolled in a longitudinal birth cohort study in Mexico City. Maternal diurnal salivary cortisol was assessed in pregnancy; cortisol awakening response (CAR) and diurnal slope were calculated. Blood Pb was measured during the second trimester of pregnancy. Post-bronchodilator lung function was tested at ages 8-11 years. Associations were modeled using generalized linear models with interaction terms, adjusting for covariates. RESULTS: A higher (flatter) diurnal slope was associated with lower FEV1/FVC ratio (ß: 0.433, 95%CI [-0.766, -0.101]). We did not find any main effect associations between prenatal Pb and lung function outcomes. We report an interaction between Pb and cortisol in relation to FEV1/FVC and FEF25-75% (pinteraction<0.05 for all). Higher prenatal Pb was associated with reduced FEV1/FVC only in children whose mothers had a high CAR. Higher prenatal Pb was also associated with reduced FEV1/FVC and FEF25-75% in mothers with a flatter diurnal slope. A 3-way interaction between prenatal Pb, CAR and sex on FEV1/FVC, indicated that boys born to women with high CAR and higher prenatal Pb levels had lower FEV1/FVC ratios (pinteraction = 0.067). CONCLUSIONS: Associations between prenatal Pb and childhood lung function were modified by disrupted maternal cortisol in pregnancy and child sex. These findings underscore the need to consider complex interactions to fully elucidate effects of prenatal Pb exposure on childhood lung function.

Changes in Depressive Symptoms, Stress and Social Support in Mexican Women during the COVID-19 Pandemic.

The aim of this study was to examine changes in depression, stress and social support levels before and during the COVID-19 pandemic in women living in Mexico City. We studied 466 women enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study who completed the Edinburgh Depression Scale (EDS) questionnaire prior (2018-2019) and during the lockdown period of the pandemic (May-November 2020). Psychosocial stress and social support for both time periods were ascertained using the Crisis in Family Systems (CRISYS) questionnaire and the Social Support Network (SSN) Scale, respectively. Associations between stress, social support and change in EDS score/depression were analyzed using generalized linear models adjusting for covariates. Higher stress (>median) during the pandemic was associated with an increase in EDS score (ß: 2.13; 95% CI (1.06, 3.19), p < 0.001), and higher odds of depression (OR: 3.75; 95% CI (2.17, 6.50), p < 0.001), while social support was associated with lower odds of depression (OR: 0.56, 95% CI (0.32, 0.97), p = 0.037). Higher levels of stress during the pandemic were associated with depression. Social support may act as a buffer for the effects of psychosocial stress. Future studies should examine the long-term effects of stress associated with the pandemic on mental and overall health.

Prenatal and early life exposure to particulate matter, environmental tobacco smoke and respiratory symptoms in Mexican children.

BACKGROUND: Exposure to particulate matter <2.5 µm in diameter (PM2.5) and environmental tobacco smoke (ETS) are associated with respiratory morbidity starting in utero. However, their potential synergistic effects have not been completely elucidated. Here, we examined the joint effects of prenatal and early life PM2.5 and prenatal ETS exposure on respiratory outcomes in children. MATERIAL AND METHODS: We studied 536 mother-child dyads in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study in Mexico City. Exposure to PM2.5 was estimated using residence in pregnancy and child's first year of life with a satellite-based spatio-temporal model. ETS exposure was assessed by caregiver's report of any smoker in the household during the second or third trimester. Outcomes included report of ever wheeze and wheeze in the past 12 months (current wheeze) assessed when children were 6-8 years old considered in separate models. Associations were modeled using distributed lag models (DLM) with daily PM2.5 averages for pregnancy and the first year of life, adjusting for child's sex, birth weight z-score, mother's age and education at enrollment, maternal asthma, season of conception and stratified by prenatal ETS exposure (yes/no). RESULTS: We identified a sensitive window from gestational week 14 through postnatal week 18 during which PM2.5 was associated with higher risk of ever wheeze at age 6-8 years. We also observed a critical window of PM2.5 exposure between postnatal weeks 6-39 and higher risk of current wheeze. We found significant associations between higher prenatal and early life PM2.5 exposure and higher cumulative risk ratios of ever wheeze (RR:3.76, 95%CI [1.41, 10.0] per 5 µg/m3) and current wheeze in the past year (RR:7.91, 95%CI [1.5, 41.6] per 5 µg/m3) only among children born to mothers exposed to ETS in pregnancy when compared to mothers who were not exposed. CONCLUSIONS: Exposure to prenatal ETS modified the association between prenatal and early life PM2.5 exposure and respiratory outcomes at age 6-8 years. It is important to consider concurrent chemical exposures to more comprehensively characterize children's environmental risk. Interventions aimed at decreasing passive smoking might mitigate the effects of ambient air pollution.