Measurement bias in caregiver-report of early childhood behavior problems across demographic factors in an ECHO-wide diverse sample.

Background: Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown. Methods: Item-level data of CBCL/1.5-5 from a large sample of young children (N = 9087) were drawn from 26 cohorts in the Environmental influences on Child Health Outcomes program. Factor analyses and the alignment method were applied to examine measurement invariance (MI) and differential item functioning (DIF) across child (age, sex, bilingual status, and neurodevelopmental disorders), and caregiver (sex, education level, household income level, depression, and language version administered) characteristics. Child race was examined in sensitivity analyses. Results: Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and Total Problems. The robust item sets, excluding the high DIF items, showed good reliability and high correlation with the original Internalizing and Total Problems scales, with lower reliability for Externalizing. Language version of CBCL administration, education level and sex of the caregiver respondent showed the most significant impact on MI, followed by child age. Sensitivity analyses revealed that child race has a unique impact on DIF over and above socioeconomic status. Conclusions: The CBCL/1.5-5, a caregiver-report measure of early childhood behavior problems, showed bias across demographic groups. Robust item sets with less DIF can measure Internalizing and Total Problems equally as well as the full item sets, with slightly lower reliability for Externalizing, and can be crosswalked to the metric of the full item set, enabling calculation of normed T scores based on more robust item sets.

US drinking water quality: exposure risk profiles for seven legacy and emerging contaminants.

BACKGROUND: Advances in drinking water infrastructure and treatment throughout the 20th and early 21st century dramatically improved water reliability and quality in the United States (US) and other parts of the world. However, numerous chemical contaminants from a range of anthropogenic and natural sources continue to pose chronic health concerns, even in countries with established drinking water regulations, such as the US. OBJECTIVE/METHODS: In this review, we summarize exposure risk profiles and health effects for seven legacy and emerging drinking water contaminants or contaminant groups: arsenic, disinfection by-products, fracking-related substances, lead, nitrate, per- and polyfluorinated alkyl substances (PFAS) and uranium. We begin with an overview of US public water systems, and US and global drinking water regulation. We end with a summary of cross-cutting challenges that burden US drinking water systems: aging and deteriorated water infrastructure, vulnerabilities for children in school and childcare facilities, climate change, disparities in access to safe and reliable drinking water, uneven enforcement of drinking water standards, inadequate health assessments, large numbers of chemicals within a class, a preponderance of small water systems, and issues facing US Indigenous communities. RESULTS: Research and data on US drinking water contamination show that exposure profiles, health risks, and water quality reliability issues vary widely across populations, geographically and by contaminant. Factors include water source, local and regional features, aging water infrastructure, industrial or commercial activities, and social determinants. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general problems, ascertaining the state of drinking water resources, and developing mitigation strategies. IMPACT STATEMENT: Drinking water contamination is widespread, even in the US. Exposure risk profiles vary by contaminant. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general public health problems, ascertaining the state of drinking water resources, and developing mitigation strategies.

Prenatal Exposure to Nonpersistent Environmental Chemicals and Postpartum Depression.

Importance: Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored. Objective: To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms. Design, Setting, and Participants: This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022. Exposures: Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples. Main Outcomes and Measures: Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions. Results: Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results. Conclusions and Relevance: Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.

Preterm Birth and Metal Mixture Exposure among Pregnant Women from the Navajo Birth Cohort Study.

BACKGROUND: Preterm birth (PTB), defined as birth before 37 wk gestation, is associated with hypertension, diabetes, inadequate prenatal care, unemployment or poverty, and metal exposure. Indigenous individuals are more likely to have maternal risk factors associated with PTB compared with other populations in the United States; however, the role of environmental metals on PTB among pregnant Indigenous women remains uncertain. Previous research identified associations between PTB and individual metals, but there is limited investigation on metal mixtures and this birth outcome. OBJECTIVES: We used a mixtures analysis framework to investigate the association between metal mixtures and PTB among pregnant Indigenous women from the Navajo Birth Cohort Study (NBCS). METHODS: Maternal urine and blood samples were collected at the time of study enrollment and analyzed for metals by inductively coupled plasma dynamic reaction cell mass spectrometry. Bayesian Profile Regression was used to identify subgroups (clusters) of individuals with similar patterns of coexposure and to model association with PTB. RESULTS: Results indicated six subgroups of maternal participants with distinct exposure profiles, including one group with low exposure to all metals and one group with total arsenic, cadmium, lead, and uranium concentrations exceeding representative concentrations calculated from the National Health and Nutrition Examination Survey (NHANES). Compared with the reference group (i.e., the lowest exposure subgroup), the subgroup with the highest overall exposure had a relative risk of PTB of 2.9 times (95% credible interval: 1.1, 6.1). Exposures in this subgroup were also higher overall than NHANES median values for women 14-45 years of age. DISCUSSION: Given the wide range of exposures and elevated PTB risk for the most exposed subgroups in a relatively small study, follow-up investigation is recommended to evaluate associations between metal mixture profiles and other birth outcomes and to test hypothesized mechanisms of action for PTB and oxidative stress caused by environmental metals. https://doi.org/10.1289/EHP10361.

Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities.

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.

COVID-19 Stress and Child Behavior: Examining Discrimination and Social Support in Racially Diverse ECHO Cohorts.

OBJECTIVE: To examine the additive or moderating influences of caregiver COVID-19-related stress, social support, and discrimination on children's behavior problems across racially diverse populations. METHOD: In this Environmental influences on Child Health Outcomes (ECHO) cohort study (N = 1,999 caregiver/child pairs), we operationalized caregiver COVID-19-related stress in 2 ways: first, as the number of stressors (eg, financial concerns, social distancing); and second, as the level of pandemic-related traumatic stress symptoms reported via questionnaires administered between April 2020 and August 2022. At the same assessment visit, caregivers also reported their current levels of discrimination, and a subsample (n = 968) reported their emotional and instrumental support. Either concurrently or at a later assessment visit, caregivers reported on their children's internalizing and externalizing behavior problems using the Child Behavior Checklist for Ages 6-18 (CBCL/6-18). RESULTS: Multivariable analyses controlling for maternal education, marital status, child age, and child sex revealed that COVID-19-related stress (caregiver stressors and symptoms) and discrimination were positively associated, and that perceived support was negatively associated with child internalizing and externalizing behavior problems. Unexpectedly, neither emotional nor instrumental support attenuated the relationship between caregiver COVID-19-related stressors nor traumatic stress symptoms and child behavior problems. In the subset of Black American participants, caregiver perceived discrimination moderated the relationship between caregiver COVID-19 traumatic stress symptoms and child internalizing problems, such that the association was stronger at higher levels of discrimination. CONCLUSION: Our findings highlight the potential importance of relieving caregiver stress and increasing caregiver social support to optimize children's behavioral outcomes.

An adjusted partial least squares regression framework to utilize additional exposure information in environmental mixture data analysis.

In a large-scale environmental health population study that is composed of subprojects, often different fractions of participants out of the total enrolled have measures of specific outcomes. It's conceptually reasonable to assume the association study would benefit from utilizing additional exposure information from those with a specific outcome not measured. Partial least squares regression is a practical approach to determine the exposure-outcome associations for mixture data. Like a typical regression approach, however, the partial least squares regression requires that each data observation must have both complete covariate and outcome for model fitting. In this paper, we propose novel adjustments to the general partial least squares regression to estimate and examine the association effects of individual environmental exposure to an outcome within a more complete context of the study population's environmental mixture exposures. The proposed framework takes advantage of the bilinear model structure. It allows information from all participants, with or without the outcome values, to contribute to the model fitting and the assessment of association effects. Using this proposed framework, incorporation of additional information will lead to smaller root mean square errors in the estimation of association effects, and improve the ability to assess the significance of the effects.

Meteorological data source comparison-a case study in geospatial modeling of potential environmental exposure to abandoned uranium mine sites in the Navajo Nation.

Meteorological (MET) data is a crucial input for environmental exposure models. While modeling exposure potential using geospatial technology is a common practice, existing studies infrequently evaluate the impact of input MET data on the level of uncertainty on output results. The objective of this study is to determine the effect of various MET data sources on the potential exposure susceptibility predictions. Three sources of wind data are compared: The North American Regional Reanalysis (NARR) database, meteorological aerodrome reports (METARs) from regional airports, and data from local MET weather stations. These data sources are used as inputs into a machine learning (ML) driven GIS Multi-Criteria Decision Analysis (GIS-MCDA) geospatial model to predict potential exposure to abandoned uranium mine sites in the Navajo Nation. Results indicate significant variations in results derived from different wind data sources. After validating the results from each source using the National Uranium Resource Evaluation (NURE) database in a geographically weighted regression (GWR), METARs data combined with the local MET weather station data showed the highest accuracy, with an average R2 of 0.74. We conclude that local direct measurement-based data (METARs and MET data) produce a more accurate prediction than the other sources evaluated in the study. This study has the potential to inform future data collection methods, leading to more accurate predictions and better-informed policy decisions surrounding environmental exposure susceptibility and risk assessment.

Metal mixture exposures and multiplexed autoantibody screening in Navajo communities exposed to uranium mine wastes.

Background: Environmental exposures to metals in uranium mining wastes and drinking water were documented in more than half of the 1304 Navajo community members of the Diné Network for Environmental Health (DiNEH) Project, the first comprehensive assessment of exposures to these metals and community health on the Navajo Nation. Objective: Evaluate environmental exposures among participants who provided blood and urine samples using multiplexed autoantibody positivity as an early effect biomarker. Methods: Survey and geospatial location data, well water quality, and metals biomonitoring were used to assess exposures to mixed-metal wastes from 100 abandoned uranium waste sites. Results: We observed that the prevalence of multiplexed autoantibody positivity in 239 participants was more than double that reported for the U.S. population (27.2% v. 13.8%) even though the national prevalence was generated using a different assay, the HEp-2 cell-based antinuclear antibody test. Increased risk of multiplexed autoantibody screening positivity (OR = 3.07,95%CI 1.15-8.22) was found among DiNEH study people who lived close to uranium mine and milling wastes and consumed metals in drinking water. Associations for females were even stronger when they lived closed to contaminated uranium mining and milling sites. Anti-U1-RNP antibodies were associated with water consumption of nickel. Conclusion: Proximity to waste sites and consumption of metals in water even below current drinking water standards were associated with perturbations of immune tolerance. These findings are consistent with previous studies of autoimmunity in the local population and demonstrate that multiplexed autoantibody screening method has a potential as sentinel indicator of exposures to environmental metals. Impact statement: This is the first, community-engaged environmental health study in exposed Navajo communities that applied clinical multiplexed testing in risk assessment of environmental metals associated with abandoned, unremediated uranium mining and milling waste sites. Routine clinical autoimmunity measures could be used as early effect biomarkers of environmental metal exposures.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

Effects of COVID-19 Financial and Social Hardships on Infants' and Toddlers' Development in the ECHO Program.

BACKGROUND: The financial hardships and social isolation experienced during the COVID-19 pandemic have been found to adversely affect children's developmental outcomes. While many studies thus far have focused on school-aged children and the pandemic-related impacts on their academic skills and behavior problems, relatively less is known about pandemic hardships and associations with children's development during their early years. Using a racially and economically diverse sample, we examined whether hardships experienced during the pandemic were associated with children's development with a particular focus on communication and socioemotional development. METHODS: Participants from eight cohorts of the Environmental influences on Child Health Outcomes program provided data on pandemic-related financial and social hardships as well as child developmental outcomes. Financial hardship was defined as at least one parent experiencing job loss or change, and social hardship was defined as families' quarantining from household members or extended family and friends. The development of children under 4 was assessed longitudinally, before and during the pandemic (N = 684), using the Ages and Stages Questionnaire (ASQ). The Generalized Estimating Equations, which accounted for within-child correlation, were used for analysis. RESULTS: Families from minority backgrounds and low socioeconomic status disproportionately experienced pandemic-related hardships. Male children had higher odds of experiencing negative changes in communication and personal social skills from pre- to during-pandemic visits (ORs ranged between 2.24 and 3.03 in analysis with binary ASQ outcomes and ranged from -0.34-0.36 in analyses with ASQ z-scores, ps = 0.000). Pandemic-related hardships in the social and financial areas did not explain within-individual changes in children's developmental outcomes. CONCLUSION: Negative developmental changes from pre- to during-pandemic were found in boys, yet we did not find any associations between increased experience of pandemic-related hardships and children's development. E how pandemic hardships affect development using a larger sample size and with longer follow-up is warranted.

Cross-cultural applicability of eye-tracking in assessing attention to emotional faces in preschool-aged children.

Humans show an attention bias toward emotional versus neutral information, which is considered an adaptive pattern of information processing. Deviations from this pattern have been observed in children with socially withdrawn behaviors, with most research being conducted in controlled settings among children from urban areas. The goal of the current study was to examine the cross-cultural applicability of two eye-tracking-based measures in assessing attention biases and their relations to children's symptoms of socially withdrawn behaviors in two independent and diverse samples of preschool children. The cross-cultural comparison was conducted between the Navajo Birth Cohort study (NBCS), an indigenous cohort with relatively low socioeconomic status (SES), and the Illinois Kids Development study (IKIDS), a primarily Non-Hispanic White and high SES cohort. Children in both cohorts completed eye-tracking tasks with pictures of emotional faces, and mothers reported on children's symptoms of socially withdrawn behaviors. Results showed that general patterns of attention biases were mostly the same across samples, reflecting heightened attention toward emotional versus neutral faces. The differences across two samples mostly involved the magnitude of attention biases. NBCS children were slower to disengage from happy faces when these emotional faces were paired with neutral faces. Additionally, socially withdrawn children in the NBCS sample showed a pattern of attentional avoidance for emotional faces. The comparability of overall patterns of attention biases provides initial support for the cross-cultural applicability of the eye-tracking measures and demonstrates the robustness of these methods across clinical and community settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neurodevelopmental profiles of 4-year-olds in the Navajo Birth Cohort Study.

Objective: Native American children disproportionally face many risk factors for poor developmental outcomes; these factors include poverty, environmental toxicant exposure, and limited medical, and intervention services. To understand these risks, comprehensive documentation of developmental and behavioral phenotypes are needed. In the current descriptive study, we assessed the neurodevelopment of young Diné (Navajo) children using standardized assessment instruments in combination with expert clinician judgment. Methods: As part of an ongoing, population-based, prospective birth cohort study, we conducted comprehensive neurodevelopmental assessments of 138, 3-5-year-old, Diné children residing on or near the Navajo Nation. We report results from standardized parent reports, psychiatric examinations, and direct assessments of children's language, cognitive, adaptive, and social-emotional development, as well as best estimate clinical diagnoses. Results: Forty-nine percent of our sample met DSM-5 criteria for a neurodevelopmental disorder (NDD) diagnosis. Language and speech sound disorders were most common, although autism spectrum disorder (ASD) was also elevated compared to the general population. Though language performance was depressed amongst all groups of children with, and without, NDDs, those meeting criteria for certain NDDs performed significantly lower on all language measures, when compared to those without. Social-emotional, behavioral, and nonverbal cognitive ability were in the average range overall. Conclusions: Diné children in our study were found to have a high percentage of clinically significant developmental delays. Overall, children presented with a pervasive pattern of depressed language performance across measures, irrespective of diagnosis (or no diagnosis), while other domains of functioning were similar to normative samples. Findings support the need to identify appropriate intervention and educational efforts for affected youth, while also exploring the causes of the specific developmental delays. However, longitudinal studies are necessary to establish best practices for identifying delays and delineating resilience factors to optimize development of Diné children.

COVID-19 Pandemic Experiences and Symptoms of Pandemic-Associated Traumatic Stress Among Mothers in the US.

Importance: The primary outcomes of the COVID-19 pandemic on the mental health of women with children remain largely unknown. Objectives: To identify and describe clusters of mothers of children participating in the Environmental influences on Child Health Outcomes (ECHO) Program that characterize pandemic-associated hardships, coping mechanisms, and behaviors, and to evaluate associations between pandemic-associated hardships, coping strategies, and behavior changes with pandemic-associated traumatic stress symptoms. Design, Setting, and Participants: This multicenter cohort study investigated experiences during the COVID-19 pandemic between April 2020 and August 2021 among maternal caregivers of children participating in the ECHO Program. Data from self-identified mothers of ECHO-enrolled children from 62 US cohorts were included in analyses. Data were analyzed from November 2021 to July 2022. Exposures: The primary exposures were pandemic-associated changes in mothers' health, health care utilization, work and finances, coping strategies, and health-associated behaviors. Exposures were assessed via a self-reported questionnaire designed by ECHO investigators. Main Outcomes and Measures: The primary outcome was the total symptoms score of pandemic-associated traumatic stress (PTS), defined as the number of items endorsed at least sometimes or more frequently, from a 10-item self-report measure. Results: The study surveyed 11 473 mothers (mean [SD] age, 37.8 [7.4] years; 342 American Indian [2.98%], 378 Asian [3.29%], 1701 Black [14.83%], and 7195 White [62.71%]; 2184 with Hispanic/Latina ethnicity [19.04%]) and identified 2 clusters that best characterized their COVID-19 pandemic experiences-one characterized by higher life disruptions (eg, to work and health care), higher social isolation, more coping behaviors to mitigate the outcomes of the pandemic, and more changes to their health behavior routines (high change [1031 mothers]) and the other characterized by lower changes (low change [3061 mothers]). The high change cluster was more socioeconomically advantaged and reported higher PTS (mean [SD] number of symptoms, 3.72 [2.44] vs 2.51 [2.47]). Across both clusters, higher pandemic-associated hardships, coping mechanisms, and behavior changes were associated with higher PTS, and these associations were greater in the low change cluster. Conclusions and Relevance: In this study of more than 11 000 US mothers, associations between socioeconomic factors, stressful life events, and mental health sequelae were complex. Accordingly, programs, policies, and practices targeting mental health during public health crises such as the COVID-19 pandemic should consider the range and configuration of hardships in designing the most effective interventions to mitigate long-term outcomes.

Environmental uranium exposures and cytokine profiles among mother-newborn baby pairs from the Navajo Βirth Cohort Study.

The Navajo Nation was heavily mined for uranium (U) during the cold-war leading to a legacy of >1100 abandoned U mining, milling and associated waste sites. The Navajo Birth Cohort Study was initiated to assess the effect of non-occupational legacy exposure to U during pregnancy on birth outcomes and child development. We report that 92% of babies with detectable urine U at birth were born from mothers who had urine U concentrations greater than national norms during pregnancy, indicative of prenatal exposure to U. To assess immune alterations associated with U exposure on both mothers and babies, we investigated associations between cytokine profiles and maternal U and associations of these measures with cytokine profiles in babies. Effect sizes for the differences in cytokine profiles were more evident among babies than mothers. Overall, there were seven cytokines (IFN-γ, IL-1ß, IL-2, IL-4, IL-10, GM-CSF, and TNF-α), for which the effect size for babies with higher than the national U concentrations was medium to large (ORs of 2.21 (1.08-4.52) through 1.71(0.76-3.83). In contrast, only three cytokines (IL-8, IL-12p70, and TNF-α) had effect sizes which almost reached medium strength (ORs of 1.64 (0.74-4.05) through 1.36 (0.65-2.87) in mothers with U above national norms. The effects of prenatal exposures to uranium and associated alterations in systemic immune responses resulting from U exposure could impact both maternal health as well as healthy child development through induction of inflammation, autoimmunity or other chronic diseases related to immune dysfunction that may affect long-term health.

A mass-balance approach to evaluate arsenic intake and excretion in different populations.

Unless a toxicant builds up in a deep compartment, intake by the human body must on average balance the amount that is lost. We apply this idea to assess arsenic (As) exposure misclassification in three previously studied populations in rural Bangladesh (n = 11,224), Navajo Nation in the Southwestern United States (n = 619), and northern Chile (n = 630), under varying assumptions about As sources. Relationships between As intake and excretion were simulated by taking into account additional sources, as well as variability in urine dilution inferred from urinary creatinine. The simulations bring As intake closer to As excretion but also indicate that some exposure misclassification remains. In rural Bangladesh, accounting for intake from more than one well and rice improved the alignment of intake and excretion, especially at low exposure. In Navajo Nation, comparing intake and excretion revealed home dust as an important source. Finally, in northern Chile, while food-frequency questionnaires and urinary As speciation indicate fish and shellfish sources, persistent imbalance of intake and excretion suggests imprecise measures of drinking water arsenic as a major cause of exposure misclassification. The mass-balance approach could prove to be useful for evaluating sources of exposure to toxicants in other settings.

Efficacy of Air Filtration and Education Interventions on Indoor Fine Particulate Matter and Child Lower Respiratory Tract Infections among Rural U.S. Homes Heated with Wood Stoves: Results from the KidsAIR Randomized Trial.

BACKGROUND: Millions of rural U.S. households are heated with wood stoves. Wood stove use can lead to high indoor concentrations of fine particulate matter [airborne particles ≤2.5µm in aerodynamic diameter (PM2.5)] and is associated with lower respiratory tract infection (LRTI) in children. OBJECTIVES: We assessed the impact of low-cost educational and air filtration interventions on childhood LRTI and indoor PM2.5 in rural U.S. homes with wood stoves. METHODS: The Kids Air Quality Interventions for Reducing Respiratory Infections (KidsAIR) study was a parallel three-arm (education, portable air filtration unit, control), post-only randomized trial in households from Alaska, Montana, and Navajo Nation (Arizona and New Mexico) with a wood stove and one or more children <5 years of age. We tracked LRTI cases for two consecutive winter seasons and measured indoor PM2.5 over a 6-d period during the first winter. We assessed results using two analytical frameworks: a) intervention efficacy on LRTI and PM2.5 (intent-to-treat), and b) association between PM2.5 and LRTI (exposure-response). RESULTS: There were 61 LRTI cases from 14,636 child-weeks of follow-up among 461 children. In the intent-to-treat analysis, children in the education arm [odds ratio (OR)=0.98; 95% confidence interval (CI): 0.35, 2.72] and the filtration arm (OR=1.23; 95% CI: 0.46, 3.32) had similar odds of LRTI vs. control. Geometric mean PM2.5 concentrations were similar to control in the education arm (11.77% higher; 95% CI: -16.57, 49.72) and air filtration arm (6.96% lower; 95% CI: -30.50, 24.55). In the exposure-response analysis, odds of LRTI were 1.45 times higher (95% CI: 1.02, 2.05) per interquartile range (25 µg/m3) increase in mean indoor PM2.5. DISCUSSION: We did not observe meaningful differences in LRTI or indoor PM2.5 in the air filtration or education arms compared with the control arm. Results from the exposure-response analysis provide further evidence that biomass air pollution adversely impacts childhood LRTI. Our results highlight the need for novel, effective intervention strategies in households heated with wood stoves. https://doi.org/10.1289/EHP9932.

Best Practices for Conducting Clinical Trials With Indigenous Children in the United States.

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children's participation in state-of-the-art clinical trials.

Indoor fine particulate matter and demographic, household, and wood stove characteristics among rural US homes heated with wood fuel.

Household heating using wood stoves is common practice in many rural areas of the United States (US) and can lead to elevated concentrations of indoor fine particulate matter (PM2.5 ). We collected 6-day measures of indoor PM2.5 during the winter and evaluated household and stove-use characteristics in homes at three rural and diverse study sites. The median indoor PM2.5 concentration across all homes was 19 µg/m3 , with higher concentrations in Alaska (median = 30, minimum = 4, maximum = 200, n = 10) and Navajo Nation homes (median = 29, minimum = 3, maximum = 105, n = 23) compared with Montana homes (median = 16, minimum = 2, maximum = 139, n = 59). Households that had not cleaned the chimney within the past year had 65% higher geometric mean PM2.5 compared to those with chimney cleaned within 6 months (95% confidence interval [CI]: -1, 170). Based on a novel wood stove grading method, homes with low-quality and medium-quality stoves had substantially higher PM2.5 compared to homes with higher-quality stoves (186% higher [95% CI: 32, 519] and 161% higher; [95% CI:27, 434], respectively). Our findings highlight the need for, and complex nature of, regionally appropriate interventions to reduce indoor air pollution in rural wood-burning regions. Higher-quality stoves and behavioral practices such as regular chimney cleaning may help improve indoor air quality in such homes.