Faculty Bibliography

This study examined the association of gestational diabetes mellitus (GDM), prenatal, and postnatal maternal depressive symptoms with externalizing, internalizing, and autism spectrum problems on the Preschool Child Behavior Checklist in 2379 children aged 4.12 ± 0.60 (48% female; 47% White, 32% Black, 15% Mixed Race, 4% Asian, <2% American Indian/Alaskan Native, <2% Native Hawaiian; 23% Hispanic). Data were collected from the NIH Environmental influences on Child Health Outcomes (ECHO) Program from 2009-2021. GDM, prenatal, and postnatal maternal depressive symptoms were each associated with increased child externalizing and internalizing problems. GDM was associated with increased autism behaviors only among children exposed to perinatal maternal depressive symptoms above the median level. Stratified analyses revealed a relation between GDM and child outcomes in males only.

BACKGROUND:Complex systems models of breast cancer have previously focused on prediction of prognosis and clinical events for individual women. There is a need for understanding breast cancer at the population level for public health decision-making, for identifying gaps in epidemiologic knowledge and for the education of the public as to the complexity of this most common of cancers. METHODS AND FINDINGS:We developed an agent-based model of breast cancer for the women of the state of California using data from the U.S. Census, the California Health Interview Survey, the California Cancer Registry, the National Health and Nutrition Examination Survey and the literature. The model was implemented in the Julia programming language and R computing environment. The Paradigm II model development followed a transdisciplinary process with expertise from multiple relevant disciplinary experts from genetics to epidemiology and sociology with the goal of exploring both upstream determinants at the population level and pathophysiologic etiologic factors at the biologic level. The resulting model reproduces in a reasonable manner the overall age-specific incidence curve for the years 2008-2012 and incidence and relative risks due to specific risk factors such as BRCA1, polygenic risk, alcohol consumption, hormone therapy, breastfeeding, oral contraceptive use and scenarios for environmental toxin exposures. CONCLUSIONS:The Paradigm II model illustrates the role of multiple etiologic factors in breast cancer from domains of biology, behavior and the environment. The value of the model is in providing a virtual laboratory to evaluate a wide range of potential interventions into the social, environmental and behavioral determinants of breast cancer at the population level.

The COVID-19 pandemic-and its associated restrictions-have changed many behaviors that can influence environmental exposures including chemicals found in commercial products, packaging and those resulting from pollution. The pandemic also constitutes a stressful life event, leading to symptoms of acute traumatic stress. Data indicate that the combination of environmental exposure and psychological stress jointly contribute to adverse child health outcomes. Within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort, a national consortium initiated to understand the effects of environmental exposures on child health and development, our objective was to assess whether there were pandemic-related changes in behavior that may be associated with environmental exposures. A total of 1535 participants from nine cohorts completed a survey via RedCap from December 2020 through May 2021. The questionnaire identified behavioral changes associated with the COVID-19 pandemic in expected directions, providing evidence of construct validity. Behavior changes reported by at least a quarter of the respondents include eating less fast food and using fewer ultra-processed foods, hair products, and cosmetics. At least a quarter of respondents reported eating more home cooked meals and using more antibacterial soaps, liquid soaps, hand sanitizers, antibacterial and bleach cleaners. Most frequent predictors of behavior change included Hispanic ethnicity and older age (35 years and older). Respondents experiencing greater COVID-related stress altered their behaviors more than those not reporting stress. These findings highlight that behavior change associated with the pandemic, and pandemic-related psychological stress often co-occur. Thus, prevention strategies and campaigns that limit environmental exposures, support stress reduction, and facilitate behavioral change may lead to the largest health benefits in the context of a pandemic. Analyzing biomarker data in these participants will be helpful to determine if behavior changes reported associate with measured changes in exposure.

Studies suggest perinatal infection with SARS-CoV-2 can induce adverse birth outcomes, but studies published to date have substantial limitations. We therefore conducted an observational study of 211 births occurring between January 2020-September 2021 in three urban cohorts participating in the Environmental Influences on Child Health Outcomes Program. Serology was assessed for IgG, IgM and IgA antibodies to nucleocapsid, S1 spike, S2 spike, and receptor-binding domain. There were no differences in gestational age (GA), birth weight, preterm birth (PTB) or low birth weight (LBW) among seropositive mothers. However, the few (n = 9) IgM seropositive mothers had children with lower BW (434g, 95% CI: 116-752), BW Z score-for-GA (0.73 SD, 95% CI 0.10-1.36) and were more likely to deliver preterm (OR 8.75, 95% CI 1.22-62.4). Though there are limits to interpretation, the data support efforts to prevent SARS-CoV-2 infections in pregnancy.

UNLABELLED:Accelerating evidence confirms the contribution of per- and polyfluoroalkyl substances (PFAS) to disease burden and disability across the lifespan. Given that policy makers raise the high cost of remediation and of substituting PFAS with safer alternatives in consumer products as barriers to confronting adverse health outcomes associated with PFAS exposure, it is important to document the costs of inaction even in the presence of uncertainty. We therefore quantified disease burdens and related economic costs due to legacy PFAS exposures in the US in 2018. We leveraged systematic reviews and used meta-analytic inputs whenever possible, identified previously published exposure-response relationships, and calculated PFOA- and PFOS-attributable increases in 13 conditions. These increments were then applied to census data to determine total annual PFOA- and PFOS-attributable cases of disease, from which we calculated economic costs due to medical care and lost productivity using previously published cost-of-illness data. We identified PFAS-attributable disease costs in the US of $5.52 billion across five primary disease endpoints shown to be associated with PFAS exposure in meta-analyses. This estimate represented the lower bound, with sensitivity analyses revealing as much as $62.6 billion in overall costs. While further work is needed to assess probability of causation and establish with greater certainty effects of the broader category of PFAS, the results confirm further that public health and policy interventions are still necessary to reduce exposure to PFOA and PFOS and their endocrine-disrupting effects. This study demonstrates the large potential economic implications of regulatory inaction. SUPPLEMENTARY INFORMATION/UNASSIGNED:The online version contains supplementary material available at 10.1007/s12403-022-00496-y.

OBJECTIVE/UNASSIGNED:Ongoing pediatric cohort studies offer opportunities to investigate the impact of the COVID-19 pandemic on children's health. With well-characterized data from tens of thousands of US children, the Environmental influences on Child Health Outcomes (ECHO) Program offers such an opportunity. METHODS/UNASSIGNED:ECHO enrolled children and their caregivers from community- and clinic-based pediatric cohort studies. Extant data from each of the cohorts were pooled and harmonized. In 2019, cohorts began collecting data under a common protocol, and data collection is ongoing with a focus on early life environmental exposures and five child health domains: birth outcomes, neurodevelopment, obesity, respiratory, and positive health. In April of 2020, ECHO began collecting a questionnaire designed to assess COVID-19 infection and the pandemic's impact on families. We describe and summarize the characteristics of children who participated in the ECHO Program during the COVID-19 pandemic and novel opportunities for scientific advancement. RESULTS/UNASSIGNED:= 13,725) was diverse by child age (31% early childhood, 41% middle childhood, and 16% adolescence up to age 21), sex (49% female), race (64% White, 15% Black, 3% Asian, 2% American Indian or Alaska Native, <1% Native Hawaiian or Pacific Islander, 10% Multiple race and 2% Other race), Hispanic ethnicity (22% Hispanic), and were similarly distributed across the four United States Census regions and Puerto Rico. CONCLUSION/UNASSIGNED:ECHO data collected during the pandemic can be used to conduct solution-oriented research to inform the development of programs and policies to support child health during the pandemic and in the post-pandemic era.

Endocrine-disrupting chemicals (EDCs) are a prime concern for the environment and health globally. Research shows that in developing countries such as India both the environment and human populations are severely exposed to EDCs and consequently experience rising incidents of adverse health effects such as diabetes and cancers. In this paper, we discuss the current EDC management approach in India, critically assess its limitations, and describe opportunities for potential improvements. Foremost, current EDC management actions and interventions in India are fragmented and outdated, and far behind the modern and comprehensive approaches adopted in the European Union and other developed countries. Strong and well-planned actions are required on various fronts of science, policy, commerce, and public engagement. These actions include the adoption of a dedicated and modern regulatory framework for managing EDCs, enhancing capacity and infrastructure for EDC monitoring in the environment and human population, employing public-private partnership programs for not only managing EDCs but also in the sectors that indirectly contribute toward the mismanagement of EDCs in the country, and raising awareness on EDCs and promoting health-preserving consumption habits among the public. As India hosts a large proportion of the global human population and biodiversity, the success or failure of its actions will substantially affect the direction of global efforts to manage EDCs and set an example for other developing countries.

OBJECTIVE:, suggesting that elevated suPAR levels may reflect a heightened inflammatory response in preeclamptic pregnancies rather than serving as a pre-clinical indicator. No data currently exist on the trajectory of suPAR across pregnancy. In the present study, we investigated if and how plasma suPAR levels change across gestation and examined whether this change and the levels in each trimester varied between women with and without HDP. STUDY DESIGN/METHODS:Participants included pregnant individuals enrolled in the [study name removed for blinding], a prospective birth cohort designed to study an array of exposures and conditions relevant to maternal and child health. Maternal blood was collected at up to three time points during pregnancy and plasma suPAR levels were analyzed by enzyme-linked immunosorbent assay. Information on maternal HDP was abstracted from electronic medical records. Study participants with suPAR data in any trimester and information about HDP were eligible for inclusion (n=393); 64 non-HDP participants who had chronic hypertension (n=5), gestational diabetes mellitus (n=55), lupus (n=1), type 1 diabetes (n=1) or type 2 diabetes (n=2) were excluded, resulting in a final analytic sample of 329. The study was approved by the Institutional Review Board of the [institution removed for blinding] and all participants provided written informed consent. We first regressed suPAR levels on gestational age at the time of sample collection to assess change over the course of pregnancy. We did this for the sample overall and stratified by HDP status. Among the subset of participants with repeated measures, we used paired Wilcoxon signed-rank tests to assess the within-person change in suPAR across trimesters in both groups. Finally, we used Wilcoxon signed-rank tests to assess whether suPAR levels in each trimester and averaged over pregnancy were different among participants with and without HDP. RESULTS:and ranged from 16.8-50.1; 44% of the sample was overweight or obese defined by a BMI ≥ 25. The majority had at least a high school degree (90.1%) and reported never smoking cigarettes (92.9%). Participants with HDP (n=44) were older and had higher BMI; other participant characteristics did not significantly vary by HDP status. suPAR levels did not significantly differ between those with and without HDP at any gestational timepoint (Table 1), although the association was marginal when considering the third trimester such that those with HDP had higher suPAR levels (2.43 ng/mL vs. 2.12 ng/mL, p=0.11). In the sample overall, suPAR levels decreased by 1.1% per week of advancing gestation (p-value< 0.001); however, when stratified by HDP status, suPAR levels only significantly decreased among those without HDP (1.2% per week, p<0.001), while remaining more stable among the cases (0.8% per week, p=0.17) (Figure 1). This finding was also apparent when examining the subset of participants with repeated measures. Among those with paired samples that did not have HDP, the median suPAR level in early gestation (2.79 ng/mL) was significantly higher than late gestation (2.30 ng/mL) with a p-value <0.001 and large effect size r=0.634. In contrast, among those with paired samples and HDP, the median suPAR level in early gestation (2.37 ng/mL) was not significantly different than late gestation (2.45 ng/mL) with a p-value=0.578 and small effect size r=0.256. It is notable however that the sample size of participants with repeated measures and HDP was small (n=7) and the timing of HDP onset was variable across participants. CONCLUSIONS:Although HDP is a primary cause of morbidity and mortality in pregnancy, predictive biomarkers are lacking. suPAR levels decrease with advancing gestation among healthy women, but remain stable in women with HDP, which may reflect a heightened inflammatory state. Additional research is needed to understand how suPAR correlates with other biomarkers of HDP and whether stable suPAR levels can predict HDP accurately in clinical practice.

IMPORTANCE/UNASSIGNED:Physical and social neighborhood attributes may have implications for children's growth and development patterns. The extent to which these attributes are associated with body mass index (BMI) trajectories and obesity risk from childhood to adolescence remains understudied. OBJECTIVE/UNASSIGNED:To examine associations of neighborhood-level measures of opportunity and social vulnerability with trajectories of BMI and obesity risk from birth to adolescence. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from 54 cohorts (20 677 children) participating in the Environmental Influences on Child Health Outcomes (ECHO) program from January 1, 1995, to January 1, 2022. Participant inclusion required at least 1 geocoded residential address and anthropometric measure (taken at the same time or after the address date) from birth through adolescence. Data were analyzed from February 1 to June 30, 2022. EXPOSURES/UNASSIGNED:Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) linked to geocoded residential addresses at birth and in infancy (age range, 0.5-1.5 years), early childhood (age range, 2.0-4.8 years), and mid-childhood (age range, 5.0-9.8 years). MAIN OUTCOMES AND MEASURES/UNASSIGNED:BMI (calculated as weight in kilograms divided by length [if aged <2 years] or height in meters squared) and obesity (age- and sex-specific BMI ≥95th percentile). Based on nationwide distributions of the COI and SVI, Census tract rankings were grouped into 5 categories: very low (<20th percentile), low (20th percentile to <40th percentile), moderate (40th percentile to <60th percentile), high (60th percentile to <80th percentile), or very high (≥80th percentile) opportunity (COI) or vulnerability (SVI). RESULTS/UNASSIGNED:Among 20 677 children, 10 747 (52.0%) were male; 12 463 of 20 105 (62.0%) were White, and 16 036 of 20 333 (78.9%) were non-Hispanic. (Some data for race and ethnicity were missing.) Overall, 29.9% of children in the ECHO program resided in areas with the most advantageous characteristics. For example, at birth, 26.7% of children lived in areas with very high COI, and 25.3% lived in areas with very low SVI; in mid-childhood, 30.6% lived in areas with very high COI and 28.4% lived in areas with very low SVI. Linear mixed-effects models revealed that at every life stage, children who resided in areas with higher COI (vs very low COI) had lower mean BMI trajectories and lower risk of obesity from childhood to adolescence, independent of family sociodemographic and prenatal characteristics. For example, among children with obesity at age 10 years, the risk ratio was 0.21 (95% CI, 0.12-0.34) for very high COI at birth, 0.31 (95% CI, 0.20-0.51) for high COI at birth, 0.46 (95% CI, 0.28-0.74) for moderate COI at birth, and 0.53 (95% CI, 0.32-0.86) for low COI at birth. Similar patterns of findings were observed for children who resided in areas with lower SVI (vs very high SVI). For example, among children with obesity at age 10 years, the risk ratio was 0.17 (95% CI, 0.10-0.30) for very low SVI at birth, 0.20 (95% CI, 0.11-0.35) for low SVI at birth, 0.42 (95% CI, 0.24-0.75) for moderate SVI at birth, and 0.43 (95% CI, 0.24-0.76) for high SVI at birth. For both indices, effect estimates for mean BMI difference and obesity risk were larger at an older age of outcome measurement. In addition, exposure to COI or SVI at birth was associated with the most substantial difference in subsequent mean BMI and risk of obesity compared with exposure at later life stages. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, residing in higher-opportunity and lower-vulnerability neighborhoods in early life, especially at birth, was associated with a lower mean BMI trajectory and a lower risk of obesity from childhood to adolescence. Future research should clarify whether initiatives or policies that alter specific components of neighborhood environment would be beneficial in preventing excess weight in children.