Subpopulations of children with multiple chronic health outcomes in relation to chemical exposures in the ECHO-PATHWAYS consortium

Drew B. Day; Kaja Z. LeWinn; Catherine J. Karr; Christine T. Loftus; Kecia N. Carroll; Nicole R. Bush; Qi Zhao; Emily S. Barrett; Shanna H. Swan; Ruby H.N. Nguyen; Leonardo Trasande; Paul E. Moore; Ako Adams Ako; Nan Ji; Chang Liu; Adam A. Szpiro; Sheela Sathyanarayana

Environment International (Mar 2024)

Subpopulations of children with multiple chronic health outcomes in relation to chemical exposures in the ECHO-PATHWAYS consortium

Drew B. Day,
Kaja Z. LeWinn,
Catherine J. Karr,
Christine T. Loftus,
Kecia N. Carroll,
Nicole R. Bush,
Qi Zhao,
Emily S. Barrett,
Shanna H. Swan,
Ruby H.N. Nguyen,
Leonardo Trasande,
Paul E. Moore,
Ako Adams Ako,
Nan Ji,
Chang Liu,
Adam A. Szpiro,
Sheela Sathyanarayana

Affiliations

Drew B. Day: Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, 1920 Terry Avenue, Seattle, Washington 98101, USA; Corresponding author at: M/S Cure-3, PO Box 5371, Seattle, WA 98145.
Kaja Z. LeWinn: Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, 675 18th Street, San Francisco, CA 94143, USA
Catherine J. Karr: Department of Environmental and Occupational Health, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105, USA; Department of Epidemiology, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105, USA; Department of Pediatrics, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105, USA
Christine T. Loftus: Department of Environmental and Occupational Health, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105, USA
Kecia N. Carroll: Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA
Nicole R. Bush: Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, 675 18th Street, San Francisco, CA 94143, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
Qi Zhao: Department of Preventive Medicine, Division of Preventive Medicine, University of Tennessee Health Science Center, 66 North Pauline Street, Memphis, TN 38163, USA
Emily S. Barrett: Department of Biostatistics and Epidemiology, Rutgers School of Public Health, 683 Hoes Lane West, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA
Shanna H. Swan: Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA
Ruby H.N. Nguyen: Department of Epidemiology and Community Health, University of Minnesota, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455, USA
Leonardo Trasande: Department of Pediatrics, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA
Paul E. Moore: Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, 2200 Children’s Way, Nashville, TN 37232, USA
Ako Adams Ako: Department of Pediatrics, Children’s Hospital at Montefiore, 3415 Bainbridge Avenue, Bronx, NY 10467, USA
Nan Ji: Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
Chang Liu: Department of Psychology, Washington State University, Johnson Tower, Pullman, WA 99164, USA
Adam A. Szpiro: Department of Biostatistics, University of Washington, 3980 15th Avenue NE, Seattle, WA 98195, USA
Sheela Sathyanarayana: Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, 1920 Terry Avenue, Seattle, Washington 98101, USA; Department of Environmental and Occupational Health, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105, USA; Department of Epidemiology, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105, USA; Department of Pediatrics, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105, USA

Journal volume & issue: Vol. 185
p. 108486

Abstract

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A multimorbidity-focused approach may reflect common etiologic mechanisms and lead to better targeting of etiologic agents for broadly impactful public health interventions. Our aim was to identify clusters of chronic obesity-related, neurodevelopmental, and respiratory outcomes in children, and to examine associations between cluster membership and widely prevalent chemical exposures to demonstrate our epidemiologic approach. Early to middle childhood outcome data collected 2011–2022 for 1092 children were harmonized across the ECHO-PATHWAYS consortium of 3 prospective pregnancy cohorts in six U.S. cities. 15 outcomes included age 4–9 BMI, cognitive and behavioral assessment scores, speech problems, and learning disabilities, asthma, wheeze, and rhinitis. To form generalizable clusters across study sites, we performed k-means clustering on scaled residuals of each variable regressed on study site. Outcomes and demographic variables were summarized between resulting clusters. Logistic weighted quantile sum regressions with permutation test p-values associated odds of cluster membership with a mixture of 15 prenatal urinary phthalate metabolites in full-sample and sex-stratified models. Three clusters emerged, including a healthier Cluster 1 (n = 734) with low morbidity across outcomes; Cluster 2 (n = 192) with low IQ and higher levels of all outcomes, especially 0.4–1.8-standard deviation higher mean neurobehavioral outcomes; and Cluster 3 (n = 179) with the highest asthma (92 %), wheeze (53 %), and rhinitis (57 %) frequencies. We observed a significant positive, male-specific stratified association (odds ratio = 1.6; p = 0.01) between a phthalate mixture with high weights for MEP and MHPP and odds of membership in Cluster 3 versus Cluster 1. These results identified subpopulations of children with co-occurring elevated levels of BMI, neurodevelopmental, and respiratory outcomes that may reflect shared etiologic pathways. The observed association between phthalates and respiratory outcome cluster membership could inform policy efforts towards children with respiratory disease. Similar cluster-based epidemiology may identify environmental factors that impact multi-outcome prevalence and efficiently direct public policy efforts.

Published in Environment International

ISSN: 0160-4120 (Print)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/environment-international

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