Prenatal metal(loid) mixtures and birth weight for gestational age: A pooled analysis of three cohorts participating in the ECHO program

Background: A growing number of studies have identified both toxic and essential metals which influence fetal growth. However, most studies have conducted single-cohort analyses, which are often limited by narrow exposure ranges, and evaluated metals individually. The objective of the current study was to conduct an environmental mixture analysis of metal impacts on fetal growth, pooling data from three geographically and demographically diverse cohorts in the United States participating in the Environmental Influences on Child Health Outcomes program. Methods: The pooled sample (N = 1,002) included participants from the MADRES, NHBCS, and PROTECT cohorts. Associations between seven metals (antimony, cadmium, cobalt, mercury, molybdenum, nickel, tin) measured in maternal urine samples collected during pregnancy (median: 16.0 weeks gestation) and birth weight for gestational age z-scores (BW for GA) were investigated using Bayesian Kernel Machine Regression (BKMR). Models were also stratified by cohort and infant sex to investigate possible heterogeneity. Chromium and uranium concentrations fell below the limits of detection for most participants and were evaluated separately as binary variables using pooled linear regression models. Results: In the pooled BKMR analysis, antimony, mercury, and tin were inversely and linearly associated with BW for GA, while a positive linear association was identified for nickel. The inverse association between antimony and BW for GA was observed in both males and females and for all three cohorts but was strongest for MADRES, a predominantly low-income Hispanic cohort in Los Angeles. A reverse j-shaped association was identified between cobalt and BW for GA, which was driven by female infants. Pooled associations were null for cadmium, chromium, molybdenum, and uranium, and BKMR did not identify potential interactions between metal pairs. Conclusions: Findings suggest that antimony, an understudied metalloid, may adversely impact fetal growth. Cohort- and/or sex-dependent associations were identified for many of the metals, which merit additional investigation

Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children’s health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO’s rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children

Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. OBJECTIVES: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. METHODS: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. RESULTS: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of formula presented [95% confidence interval (CI): formula presented ], formula presented (95% CI: formula presented ), formula presented (95% CI: formula presented ), formula presented (95% CI: formula presented , 0.06), and formula presented (95% CI: formula presented ), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: formula presented (95% CI: 0.38, 0.83), formula presented (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [formula presented ; 95% highest posterior density (HPD): formula presented ] and decreased odds of large-for-gestational-age (formula presented ; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. DISCUSSION: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723

Maternal tobacco smoking and offspring autism spectrum disorder or traits in ECHO cohorts

Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72–1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02–2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73–4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. Lay Summary: Evidence on the association between maternal prenatal smoking and the child's risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results

Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm

Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Exposures: Premature birth (<37 weeks' gestation). Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models

International pooled study on diet and bladder cancer: the bladder cancer, epidemiology and nutritional determinants (BLEND) study: Design and baseline characteristics

Background: In 2012, more than 400,000 urinary bladder cancer cases occurred worldwide, making it the 7th most common type of cancer. Although many previous studies focused on the relationship between diet and bladder cancer, the evidence related to specific food items or nutrients that could be involved in the development of bladder cancer remains inconclusive. Dietary components can either be, or be activated into, potential carcinogens through metabolism, or act to prevent carcinogen damage. Methods/design: The BLadder cancer, Epidemiology and Nutritional Determinants (BLEND) study was set up with the purpose of collecting individual patient data from observational studies on diet and bladder cancer. In total, data from 11,261 bladder cancer cases and 675,532 non-cases from 18 case-control and 6 cohort studies from all over the world were included with the aim to investigate the association between individual food items, nutrients and dietary patterns and risk of developing bladder cancer. Discussion: The substantial number of cases included in this study will enable us to provide evidence with large statistical power, for dietary recommendations on the prevention of bladder cancer

Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium.

Development Psychopathology in context: famil

Intake of alpha-linolenic acid and other fatty acids in relation to the risk of bladder cancer: results from the New Hampshire case-control study.

The role of dietary fat in bladder cancer aetiology is currently unclear due to few studies, equivocal findings and a lack of information on important dietary fatty acids. The aim of the present study was to investigate the association between the intake of major dietary fats and fatty acids and the risk of bladder cancer. A case-control study was conducted in New Hampshire, USA. Dietary data were collected from 322 cases and 239 controls, and OR and 95 % CI were calculated using unconditional logistic regression. Adjustment was made for potential confounders: sex, age, smoking status, pack-years smoked, cholesterol and energy intake. Statistically significant reduced odds of bladder cancer were observed for high intakes (highest quartile v. lowest quartile) of alpha-linolenic acid (ALA) (OR 0.26, 95 % CI 0.10, 0.65; P for trend = 0.01) and vegetable fat (OR 0.39, 95 % CI 0.18, 0.86; P for trend = 0.03). Borderline statistically significant reduced odds were detected for polyunsaturated fat (OR 0.43, 95 % CI 0.19, 0.98; P for trend = 0.07) and linoleic acid (OR 0.43, 95 % CI 0.19, 0.96; P for trend = 0.06). These fats and fatty acids were highly correlated and following adjustment for each other, the only potential inverse association to remain was for ALA. The present findings suggest that ALA may have a protective role against developing bladder cancer; however, further investigation and replication in other epidemiological studies are required. Future research should focus on the type, source and quantities of different dietary fatty acids consumed