Neighborhood Opportunities and Disparities in Child Health Outcomes: A Nationwide US Multi-Cohort Study

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Awardee: Izzuddin Aris (Oken Cohort)

An increasing body of research has shown that the quality of neighborhoods where children reside may be an important determinant of their experiences and outcomes during childhood, as well as of their well-being in adulthood. The overall goal of this proposal is to examine the extent to which neighborhood environments could contribute to health inequalities in children. The proposed work will be the largest study examining associations of neighborhood indices with child health outcomes, and it will focus on longitudinal rather than cross-sectional associations. It will examine both positive and negative attributes of neighborhood conditions that may promote or inhibit healthy child development. The main aims of the proposal are to:

Aim 1: Characterize publicly available metrics of neighborhood disadvantage (Area Deprivation Index, Social Vulnerability Index) and opportunity (Child Opportunity Index) among children in ECHO cohorts

Aim 2: Investigate the extent to which metrics of neighborhood disadvantage and opportunity are related to child health (such as obesity, asthma, and cardiometabolic health) and health disparities.

Development of an analytical framework for multivariate mediation analysis of the prenatal exposome, endogenous lipid mediators, and infant neurodevelopment

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Awardee: Max Aung (Alshawabkeh Cohort)

Early measures of neurodevelopment in the first year of life yield promising opportunities to detect and intervene in neurological disorders and mitigate their long-term effects. The overall goal of this proposal is to leverage innovative developments in early measures of infant neurodevelopment by exploring non-nutritive suck, a measure of global sensory and motor development, and infrared eye tracking to evaluate cognitive development. The main aims of the proposal are to:

Aim 1: Estimate the extent to which maternal biomarkers of lipid metabolism mediate the relationship between prenatal exposure to toxicants (phthalates, phenols, and perfluorinated alkyl substances [PFAS]) and infant neurodevelopmental parameters (non-nutritive suck and infrared eye tracking)

Aim 2: Develop a methodological framework for multivariate mediation analysis that evaluates complex combinations of toxicants within a multi-pollutant mixture.

Investigation of Environmental Injustice as a Risk Factor for Neurodevelopmental Disorders

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Awardee: Aisha Dickerson (Newschaffer Cohort)

Although some previous studies have shown associations between geospatially-assigned exposures and adverse neurodevelopment, results for these studies have been conflicting and most have focused on only one exposure source. Thus, there is a gap in knowledge related to co-occurring exposures and risk for neurodevelopmental disorders. The overall goal of this proposal is to investigate the importance of co-occurring environmental and psychosocial exposures for risk of neurodevelopmental disorders. The main aims of the proposal are to:

Aim 1: Utilize machine learning strategies to analyze how geographically-assigned co-exposures correlate with biological markers of toxicant exposures

Aim 2: Investigate race and sociodemographic differences in exposure sources and biological measures as a function of environmental justice issues and health disparities

Aim 3: Examine how these hazardous environmental exposures interact with both area-based and individual-level psychosocial stressors to alter associations with multiple neurodevelopmental outcomes (autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], and intellectual disability [ID]).

School vs. Home Environmental Exposure and Respiratory Outcomes

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Awardee: Stephanie Lovinsky-Desir (Gern Cohort)

Most epidemiologic air pollution studies estimate exposures based on participants’ home addresses. However, school-aged children spend over 25% of their days in school. The overall goal of this proposal is to leverage existing ECHO resources and ECHO-funded projects to extend the Decentralized and Reproducible Geomarker Assessment for Multi-Site Studies (DeGAUSS) system to school addresses for children. Machine-learning techniques will be used to determine which environmental exposures in the school vs. home environments are more strongly associated with respiratory health outcomes. The main aims of the proposal are to:

Aim 1: Characterize air pollution exposures at the school and home environment based on geographic information systems indicators

Aim 2: Determine the association between school and home exposures and respiratory outcomes.

ECHO-wide platform for studying mother-to-infant vertical transmission of microbiota

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Awardee: Noel Mueller (Jacobson – ECHO Data Analysis Center)

There is increasing consensus that the assemblage of microorganisms living in and on our bodies, otherwise known as the human microbiome, work symbiotically with their human hosts to maintain immune and metabolic health. These microbial communities, also called microbiota, are seeded at birth. This proposal will explore how maternal intestinal and vaginal microbiota affect infant intestinal microbiota, and whether delivery mode and perinatal antibiotic use influence mother-to-infant microbiota transmission, using data from five ECHO cohorts. Cesarean-section and late pregnancy antibiotics have been associated with child obesity and asthma, and it is hypothesized that disrupted mother-to-infant microbiota transmission at birth drive these associations. Optimizing newborn microbiota colonization may be a potential intervention target to improve child health. The proposal aims to:

Aim 1: Examine the extent of mother-to-infant microbial transmission, using whole genome shotgun sequencing

Aim 2: Determine if C-section and antibiotic use interrupt mother-to-infant microbial transmission, using whole genome shotgun sequencing and 16S rRNA gene sequencing

Aim 3: Determine the presence of maternal intestinal and vaginal microbiota in the infant beyond the first few months of life, using 16S rRNA gene sequencing.

Exposure to mixtures of non-persistent endocrine disruptors in relation to childhood obesity and neurodevelopment

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Awardee: Dorothy Nakiwala (Dabelea Cohort)

Exposures to phthalates and synthetic phenols are extremely common among pregnant women in the US and around the world. The chemicals include bisphenols, dichlorophenols, benzophenone-3, triclosan, triclocarban and parabens. These short-lived chemicals are ubiquitous in household and consumer products. Chronic exposure to the chemicals may produce adverse health effects for both the mother and her developing fetus. The overall goal of this proposal is to assess the joint and overall effects of prenatal phthalates and phenolic exposures on childhood metabolic disease risk and neurodevelopment in the eligible ECHO cohorts. The main aims of the proposal are to:

Aim 1: Determine the association between prenatal exposure to a mixture of environmental phthalates and phenols and child neurobehavioral outcomes assessed in early and middle childhood

Aim 2: Assess the association between prenatal exposure to a mixture of environmental phthalates and phenols and the outcomes of child obesity and metabolic outcomes during early and middle childhood

Aim 3: Expand the approaches developed in Aims 1 and 2 to a larger set of eligible cohort studies in the ECHO program.

Exploring the Relationship Between Fear of Maternal Morbidity and Perinatal Physical and Emotional Health in Black Women

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Awardee: Candice Norcott (Hipwell Cohort)

Black women are approximately four times more likely to die from pregnancy-related causes than their white counterparts. They are also twice as likely as white women to experience severe maternal morbidity. A large body of research provides support for the hypothesis that these disparities are related to racism and discrimination; a hypothesis that has gained traction with increased public media exposure of racism in perinatal health care. To date, Black patients are left with little to no guidance on how to manage the risks they face when they become pregnant. The patient-provider relationship is an optimal platform to collaboratively work to understand risks, how they apply on the individual level, and support positive perinatal health outcomes. This proposal aims to examine the effect of maternal awareness of racial maternal health disparities on cortisol reactivity during pregnancy using data from the Pittsburgh Girls Study ECHO cohort, and to create an educational platform to improve patient-provider communication in obstetrics and gynecology. The main aims of the proposal are to:

Aim 1: Test the association between experiences of discrimination, awareness of racial disparities in pregnancy health outcomes, and examine how coping style and patient-provider communication moderate the relationship between awareness and stress

Aim 2: Use qualitative data from Black women and obstetric providers to develop an educational platform to inform patient-provider communication around maternal health for Black women.

Developing a remote assessment approach to measure cognitive stimulation

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Awardee: Cindy Ola (Karr Cohort)

Cognitive stimulation, including the provision of age-appropriate learning materials and caregivers’ didactic efforts to promote child development, is critical for brain development. Cognitive stimulation is hypothesized to serve a mechanistic role in the association between socioeconomic status (SES) and developmental outcomes and has been shown to modify the effects of teratogenic exposures on neurodevelopment. Optimal assessment of cognitive stimulation involves a combination of observational and caregiver-report measures, making it impractical in many large, geographically-dispersed epidemiological cohorts, especially in the context of the COVID-19 pandemic. The overarching goal of this proposal is to streamline an existing cognitive stimulation assessment tool (Home Observation for Measurement of the Environment [HOME]) to facilitate its use in remote data collection, using data from three ECHO cohorts. To address this, the proposal aims to:

Aim 1: Reduce the item set from the 55-item HOME tool to develop a parsimonious measure of cognitive stimulation

Aim 2: To establish the feasibility and validity of a remote assessment protocol for the reduced HOME tool developed in aim 1. These assessments will combine parent-self report and smartphone video recordings of parent-child interactions, using an ecological momentary assessment approach.

Effects of Racism on Neurocognitive Development of Black Children

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Awardee: Jennifer Porter (Watson – ECHO IDeA States Pediatric Clinical Trials Network)

Family SES affects the neurodevelopmental outcomes of children, and parental education level, IQ, and likely discrimination impact SES. The overall goal of this proposal is to disentangle the effects of racism from poverty on neurocognitive outcomes of Black children. Using data from multiple ECHO cohorts, the proposed work hypothesizes that parental racial discrimination has a negative effect on early childhood neurodevelopment, independent of SES. This work fundamentally challenges the historical conceptualization of race as the underlying reason for observed health disparities, and instead seeks to provide evidence of racism as the driver of health disparities. The proposal uses the following aims to address this:

Aim 1: Assess parental racial discrimination and caregiver stress for parents of Black children and non-Hispanic white children across SES levels and between and within racial groups

Aim 2: Develop a model to examine the association between parental racial discrimination and childhood neurocognitive outcomes within and between racial and ethnic groups

Aim 3: Examine additional explanatory variables in the model developed in Aim 2.

Genetic Variation in the Placental Barrier: Impact on Child Environmental Health Studies

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Awardee: Zorimar Rivera-Núñez (O'Connor Cohort)

Placental efflux proteins (“placental transporters”) play a critical role restricting chemicals and pharmaceuticals from crossing the placenta; however, their role is understudied in perinatal environmental epidemiology. Most research currently relies on maternal prenatal concentrations as a proxy for fetal exposures, neglecting the role the placenta may play in reducing maternal-fetal transmission of chemicals. Using data from six ECHO cohorts, this proposal will examine the extent to which genetic variation in placental transporters modifies the association between maternal exposure to perfluorooctane sulfonic acid (PFOS) and infant size at birth. To improve characterization of fetal exposure, this proposal aims to:

Aim 1: Evaluate genetic variation in placental transporters (including BCRP) by race and ethnicity

Aim 2: Determine the relationship between maternal PFOS concentrations and infant birth size and assess effect modification by BCRP genotype and other transporter polymorphisms.

Social ecological assets and mental health among diverse youth: An application of the dual-factor model

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Awardee: Theda Rose (Leve Cohort)

Embracing a conceptualization of mental health that incorporates wellbeing (WB) and psychopathology (PTH) fosters a more holistic picture of youth functioning and enables researchers and practitioners to better identify protective and promotive factors that support healthy functioning among children and adolescents. Using nationwide ECHO cohorts, this proposal applies the dual-factor model to characterize mental health, including components of WB and PTH, in a diverse sample of children and adolescents. This departure from the traditional deficits-based approach will broaden the understanding of mental health and allow clinicians to better identify protective factors supporting healthy functioning. The proposed work aims to:

Aim 1: Identify profiles of WB and PTH using the dual model approach

Aim 2: Describe associations between the mental health profiles identified in aim 1 and socio-ecological domains (e.g., family, peer, school)

Aim 3: Explore whether the associations in aim 2 vary by race/ethnicity, sex, and age group.