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; program collaborators for Environmental influences on Child Health Outcomes

doi:10.1016/j.envint.2024.108486

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

Environ Int. 2024 Mar:185:108486. doi: 10.1016/j.envint.2024.108486. Epub 2024 Feb 8.

Authors

Drew B Day¹, Kaja Z LeWinn², Catherine J Karr³, Christine T Loftus⁴, Kecia N Carroll⁵, Nicole R Bush⁶, Qi Zhao⁷, Emily S Barrett⁸, Shanna H Swan⁹, Ruby H N Nguyen¹⁰, Leonardo Trasande¹¹, Paul E Moore¹², Ako Adams Ako¹³, Nan Ji¹⁴, Chang Liu¹⁵, Adam A Szpiro¹⁶, Sheela Sathyanarayana¹⁷; program collaborators for Environmental influences on Child Health Outcomes

Affiliations

¹ Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, 1920 Terry Avenue, Seattle, Washington 98101, USA. Electronic address: drew.day@seattlechildrens.org.
² Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, 675 18th Street, San Francisco, CA 94143, USA.
³ 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.
⁴ Department of Environmental and Occupational Health, University of Washington, 4245 Roosevelt Way NE, Seattle, WA 98105, USA.
⁵ 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.
⁶ 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.
⁷ Department of Preventive Medicine, Division of Preventive Medicine, University of Tennessee Health Science Center, 66 North Pauline Street, Memphis, TN 38163, USA.
⁸ 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.
⁹ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
¹⁰ Department of Epidemiology and Community Health, University of Minnesota, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455, USA.
¹¹ Department of Pediatrics, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA.
¹² Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN 37232, USA.
¹³ Department of Pediatrics, Children's Hospital at Montefiore, 3415 Bainbridge Avenue, Bronx, NY 10467, USA.
¹⁴ 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.
¹⁵ Department of Psychology, Washington State University, Johnson Tower, Pullman, WA 99164, USA.
¹⁶ Department of Biostatistics, University of Washington, 3980 15th Avenue NE, Seattle, WA 98195, USA.
¹⁷ 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.

Abstract

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.

Keywords: Asthma; Behavior; Clustering; Multi-morbidity; Multi-outcome; Phthalates.

MeSH terms

Asthma* / epidemiology
Asthma* / urine
Child
Child, Preschool
Environmental Exposure / adverse effects
Environmental Pollutants* / adverse effects
Environmental Pollutants* / urine
Female
Humans
Male
Outcome Assessment, Health Care
Phthalic Acids* / adverse effects
Phthalic Acids* / urine
Pregnancy
Prospective Studies
Respiratory Sounds / etiology
Rhinitis*

Substances

phthalic acid
Phthalic Acids
Environmental Pollutants

Abstract

MeSH terms

Substances

Grants and funding