Prenatal exposure to multiple metallic and metalloid trace elements and the risk of bacterial sepsis in extremely low gestational age newborns: A prospective cohort study

Background Prenatal exposures to metallic and metalloid trace elements have been linked to altered immune function in animal studies, but few epidemiologic studies have investigated immunological effects in humans. We evaluated the risk of bacterial sepsis (an extreme immune response to bacterial infection) in relation to prenatal metal/metalloid exposures, individually and jointly, within a US-based cohort of infants born extremely preterm. Methods We analyzed data from 269 participants in the US-based ELGAN cohort, which enrolled infants delivered at <28 weeks' gestation (2002–2004). Concentrations of 8 trace elements—including 4 non-essential and 4 essential—were measured using inductively coupled plasma tandem mass spectrometry in umbilical cord tissue, reflecting in utero fetal exposures. The infants were followed from birth to postnatal day 28 with bacterial blood culture results reported weekly to detect sepsis. Discrete-time hazard and quantile g-computation models were fit to estimate associations for individual trace elements and their mixtures with sepsis incidence. Results Approximately 30% of the extremely preterm infants developed sepsis during the follow-up period (median follow-up: 2 weeks). After adjustment for potential confounders, no trace element was individually associated with sepsis risk. However, there was some evidence of a non-monotonic relationship for cadmium, with hazard ratios (HRs) for the second, third, and fourth (highest) quartiles being 1.13 (95% CI: 0.51–2.54), 1.94 (95% CI: 0.87–4.32), and 1.88 (95% CI: 0.90–3.93), respectively. The HRs for a quartile increase in concentrations of all 8 elements, all 4 non-essential elements, and all 4 essential elements were 0.92 (95% CI: 0.68–1.25), 1.19 (95% CI: 0.92–1.55), and 0.77 (95% CI: 0.57–1.06). Cadmium had the greatest positive contribution whereas arsenic, copper, and selenium had the greatest negative contributions to the mixture associations. Conclusions We found some evidence that greater prenatal exposure to cadmium was associated with an increased the risk of bacterial sepsis in extremely preterm infants. However, this risk was counteracted by a combination of arsenic, copper, and selenium. Future studies are needed to confirm these findings and to evaluate the potential for nutritional interventions to prevent sepsis in high-risk infants

The interplay between environmental exposures and COVID-19 risks in the health of children

Abstract Background An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. Objectives To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. Methods An international group of researchers interested in children’s environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. Discussion Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a “dirty” environment in conveying protection – an example of the “hygiene hypothesis”; and what are the long term health effects of SARS-Cov-2 infection in early life. Conclusion A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario

Associations between placental CpG methylation of metastable epialleles and childhood body mass index across ages one, two and ten in the Extremely Low Gestational Age Newborns (ELGAN) cohort

The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that in utero and early life conditions can disrupt normal fetal development and program susceptibility to later-life disease. Metastable epialleles are genomic loci in which CpG methylation patterning is responsive to maternal diet and conserved across time and tissues. Thus, these sites could serve as ‘signatures’ of gestational environment conditions. Here, we sought to determine if methylation of metastable epialleles was associated with changes in childhood body mass index (BMI) z-scores across ages one, two and ten in the Extremely Low Gestational Age Newborns (ELGAN) cohort. CpG methylation of 250 probes (corresponding to 111 genes) within metastable epiallele regions was measured in placental tissue. Linear mixed effects models were fit to evaluate the overall and sex-stratified associations between methylation and changes in BMI z-score over time. In total, 26 probes were associated (p < 0.05) with changes in BMI z-score overall, including probes within Mesoderm Specific Transcript (MEST) and Histone Deacetylase 4 (HDAC4), which have previously been associated with childhood obesity and adipogenesis. Sex-stratified analyses revealed a significant association, after adjusting for multiple comparisons (q < 0.05), within female placentas for one probe annotated to the imprinted gene PLAG1 Like Zinc Finger 1 (PLAGL1). These findings suggest epigenetic marks may be involved in programming susceptibility to obesity in utero and highlight the potential to use placental tissues in predicting growth rate trajectories among premature infants

Occupational Exposures and Cardiac Structure and Function: ECHO-SOL (Echocardiographic Study of Latinos)

Background Our objective was to determine associations of occupational exposures with cardiac structure and function in Hispanic/Latino adults. Methods and Results Employed participants were included (n=782; 52% women, mean age 52.9 years). Occupational exposures to burning wood, vehicle exhaust, solvents, pesticides, and metals at the current and longest-held job were assessed by questionnaire. Survey multivariable linear regression analyses were used to model the relationship of each self-reported exposure with echocardiographic measures of cardiac structure and function. Exposure to burning wood at the current job was associated with decreased left ventricular (LV) ejection fraction (-3.1%; standard error [SE], 1.0 [ =0.002]). When the analysis was restricted to exposure at the longest-held job, occupational exposure to burning wood was associated with increased LV diastolic volume (6.7 mL; SE, 1.6 [ <0.0001]), decreased LV ejection fraction (-2.7%; SE, 0.6 [ <0.0001]), worse LV global longitudinal strain (1.0%; SE, 0.3 [ =0.0009]), and decreased right ventricular fractional area change (-0.02; SE, 0.004 [ <0.001]). Exposure to pesticides was associated with worse average global longitudinal strain (0.8%; SE, 0.2 [ <0.0001]). Exposure to metals was associated with worse global longitudinal strain in the 2-chamber view (1.0%; SE, 0.5 [ =0.04]), increased stroke volume (3.6 mL; SE, 1.6 [ =0.03]), and increased LV mass indexed to BSA (9.2 g/m ; SE, 3.8 [ =0.01]) or height (4.4 g/m ; SE, 1.9 [ =0.02]). Conclusions Occupational exposures to burning wood, vehicle exhaust, pesticides, and metals were associated with abnormal parameters of LV and right ventricular systolic function. Reducing exposures to toxic chemicals and particulates in the workplace is a potential opportunity to prevent cardiovascular disease in populations at risk

Association of occupational exposures with cardiovascular disease among US Hispanics/Latinos

ObjectiveCardiovascular disease (CVD) is a leading cause of mortality and morbidity in the USA. The role of occupational exposures to chemicals in the development of CVD has rarely been studied even though many agents possess cardiotoxic properties. We therefore evaluated associations of self-reported exposures to organic solvents, metals and pesticides in relation to CVD prevalence among diverse Hispanic/Latino workers.MethodsCross-sectional data from 7404 employed individuals, aged 18–74 years, enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were analysed. Participants from four US cities provided questionnaire data and underwent clinical examinations, including ECGs. CVD was defined as the presence of at least one of the following: coronary heart disease, atrial fibrillation, heart failure or cerebrovascular disease. Prevalence ratios reflecting the relationship between each occupational exposure and CVD as well as CVD subtypes were calculated using Poisson regression models.ResultsHispanic/Latino workers reported exposures to organic solvents (6.5%), metals (8.5%) and pesticides (4.7%) at their current jobs. Overall, 6.1% of participants had some form of CVD, with coronary heart disease as the most common (4.3%) followed by cerebrovascular disease (1.0%), heart failure (0.8%) and atrial fibrillation (0.7%). For individuals who reported working with pesticides, the prevalence ratios for any CVD were 2.18 (95% CI 1.34 to 3.55), coronary heart disease 2.20 (95% CI 1.31 to 3.71), cerebrovascular disease 1.38 (95% CI 0.62 3.03), heart failure 0.91 (95% CI 0.23 to 3.54) and atrial fibrillation 5.92 (95% CI 1.89 to 18.61) after adjustment for sociodemographic, acculturation, lifestyle and occupational characteristics. Metal exposures were associated with an almost fourfold (3.78, 95% CI 1.24 to 11.46) greater prevalence of atrial fibrillation. Null associations were observed for organic solvent exposures.ConclusionsOur results suggest that working with metals and pesticides could be risk factors for CVD among Hispanic/Latino workers. Further work is needed to evaluate these relationships prospectively

Abstract P072: Association of Occupational Exposures with Cardiovascular Disease among Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos

Background: Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in the US. Acute, high-dose exposures to some solvents, metals, and pesticides can be cardiotoxic, but little is known about the cardiovascular effects of chronic, low-level exposures. Thus, we evaluated cross-sectional associations of self-reported occupational exposures to solvents, metals, and pesticides with CVD prevalence among diverse Hispanics/Latinos in the US. Methods: The analyses included baseline data from 7,404 currently employed participants, ages 18-74 years, from the HCHS/SOL. CVD was defined as the presence of one or more of the following: coronary heart disease (self-reported angina, myocardial infarction, coronary bypass surgery, balloon angioplasty, or stent placement in coronary arteries, or electrocardiogram [ECG] evidence of major Q wave abnormalities or minor Q, QS waves with ST, T abnormalities); atrial fibrillation (self-reported or ECG evidence of atrial fibrillation or flutter); heart failure (self-reported); or cerebrovascular disease (self-reported stroke or transient ischemic attack). Survey-weighted Poisson regression models were used to estimate prevalence ratios (PR) and 95% confidence intervals (CIs) for each occupational exposure, adjusted for sociodemographic (age, gender, field center, Hispanic/Latino background, health insurance), acculturation (language, years of duration in the US), lifestyle (smoking, alcohol, physical activity, diet), and occupational (full- or part-time employment) characteristics. Results: Overall, 6.1% of participants had any prevalent CVD; coronary heart disease (4.3%) was most common, followed by cerebrovascular disease (1.0%), heart failure (0.8%), and atrial fibrillation (0.7%). Current occupational exposures to solvents, metals, and pesticides were reported by 6.5%, 8.5%, and 4.7% of participants, respectively. The prevalence of any CVD (PR: 2.18, 95% CI: 1.34-3.55), coronary heart disease (PR: 2.20, 95% CI: 1.31-3.71), and atrial fibrillation (PR: 5.92, 95% CI: 1.89-18.61) were significantly elevated for participants who reported current occupational pesticide exposure compared to no exposure. Current occupational metal exposure was associated with a greater prevalence of atrial fibrillation (PR: 3.78, 95% CI: 1.24-11.46). Further adjustment for hypertension, hypercholesterolemia, diabetes, or body mass index did not appreciably change the results. Current occupational solvent exposure was not associated with CVD prevalence. Conclusions: Occupational exposure to pesticides and metals is associated with higher CVD prevalence at baseline. These cross-sectional associations do not appear to be attenuated by hypertension, hypercholesterolemia, diabetes, or obesity. Further research is needed to examine other biologic mechanisms that may underlie these associations

Accelerated epigenetic age at birth and child emotional and behavioura development in early childhood: a meta-analysis of four prospective cohort studies in ECHO

Background: ‘Epigenetic clocks’ have been developed to accurately predict chronologic gestational age and have been associated with child health outcomes in prior work. Methods: We meta-analysed results from four prospective U.S cohorts investigating the association between epigenetic age acceleration estimated using blood DNA methylation collected at birth and preschool age Childhood Behavior Checklist (CBCL) scores. Results: Epigenetic ageing was not significantly associated with CBCL total problem scores (β = 0.33, 95% CI: −0.95, 0.28) and DSM-oriented pervasive development problem scores (β = −0.23, 95% CI: −0.61, 0.15). No associations were observed for other DSM-oriented subscales. Conclusions: The meta-analysis results suggest that epigenetic gestational age acceleration is not associated with child emotional and behavioural functioning for preschool age group. These findings may relate to our study population, which includes two cohorts enriched for ASD and one preterm birth cohort.; future work should address the role of epigenetic age in child health in other study populations. Abbreviations: DNAm: DNA methylation; CBCL: Child Behavioral Checklist; ECHO: Environmental Influences on Child Health Outcomes; EARLI: Early Autism Risk Longitudinal Investigation; MARBLES: Markers of Autism Risk in Babies – Learning Early Signs; ELGAN: Extremely Low Gestational Age Newborns; ASD: autism spectrum disorder; BMI: body mass index; DSM: Diagnostic and Statistical Manual of Mental Disorders

Placental epigenetic gestational aging in relation to maternal sociodemographic factors and smoking among infants born extremely preterm: a descriptive study

Social determinants of health (SDoH) are defined as the conditions in which people are born, grow, live, work, and age. The distribution of these conditions is influenced by underlying structural factors and may be linked to adverse pregnancy outcomes through epigenetic modifications of gestational tissues. A promising modification is epigenetic gestational age (eGA), which captures ‘biological’ age at birth. Measuring eGA in placenta, an organ critical for foetal development, may provide information about how SDoH ‘get under the skin’ during pregnancy to influence birth outcomes and ethnic/racial disparities. We examined relationships of placental eGA with sociodemographic factors, smoking, and two key clinical outcomes: Apgar scores and NICU length of stay. Using the Robust Placental Clock, we estimated eGA for placental samples from the Extremely Low Gestational Age Newborns cohort (N = 408). Regression modelling revealed smoking during pregnancy was associated with placental eGA acceleration (i.e., eGA higher than chronologic gestational age). This association differed by maternal race: among infants born to mothers racialized as Black, we observed greater eGA acceleration (+0.89 week, 95% CI: 0.38, 1.40) as compared to those racialized as white (+0.27 week, 95% CI: −0.06, 0.59). Placental eGA acceleration was also correlated with shorter NICU lengths of stay, but only among infants born to mothers racialized as Black (−0.08 d/week-eGA, 95% CI: −0.12, −0.05). Together, these observed associations suggest that interpretations of epigenetic gestational aging may be tissue-specific.</p

Arsenic in private well water and birth outcomes in the United States.

BackgroundPrenatal exposure to drinking water with arsenic concentrations &gt;50&nbsp;μg/L is associated with adverse birth outcomes, with inconclusive evidence for concentrations ≤50&nbsp;μg/L. In a collaborative effort by public health experts, hydrologists, and geologists, we used published machine learning model estimates to characterize arsenic concentrations in private wells-federally unregulated for drinking water contaminants-and evaluated associations with birth outcomes throughout the conterminous U.S.MethodsUsing several machine learning models, including boosted regression trees (BRT) and random forest classification (RFC), developed from measured groundwater arsenic concentrations of ∼20,000 private wells, we characterized the probability that arsenic concentrations occurred within specific ranges in groundwater. Probabilistic model estimates and private well usage data were linked by county to all live birth certificates from 2016 (n&nbsp;=&nbsp;3.6 million). We evaluated associations with gestational age and term birth weight using mixed-effects models, adjusted for potential confounders and incorporated random intercepts for spatial clustering.ResultsWe generally observed inverse associations with term birth weight. For instance, when using BRT estimates, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 5&nbsp;μg/L was associated with a -1.83&nbsp;g (95% CI: -3.30, -0.38) lower term birth weight after adjusting for covariates. Similarly, a 10-percentage point increase in the probability that private well arsenic concentrations exceeded 10&nbsp;μg/L was associated with a -2.79&nbsp;g (95% CI: -4.99, -0.58) lower term birth weight. Associations with gestational age were null.ConclusionIn this largest epidemiologic study of arsenic and birth outcomes to date, we did not observe associations of modeled arsenic estimates in private wells with gestational age and found modest inverse associations with term birth weight. Study limitations may have obscured true associations, including measurement error stemming from a lack of individual-level information on primary water sources, water arsenic concentrations, and water consumption patterns