Childhood exposures to environmental chemicals and neurodevelopmental outcomes in congenital heart disease

J William Gaynor, Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Nancy B. Burnham, Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Richard F. Ittenbach, Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
Marsha Gerdes, Department of Psychology, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Judy C. Bernbaum, Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Elaine Zackai, Division of Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Daniel J. Licht, Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
William W. Russell, Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Erin E. Zullo, Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Thomas Miller, Maine Medical CenterFollow
Hakon Hakonarson, The Center for Applied Genomics, The Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Kayan A. Clarke, Department of Environmental and Global Health, University of Florida, Gainesville, FL, United States of America.
Gail P. Jarvik, Departments of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington Medical Center, Seattle, WA, United States of America.
Antonia M. Calafat, Division of Laboratory Sciences, National Center for Environmental Health, Atlanta, GA, United States of America.
Asa Bradman, Department of Public Health, University of California, Merced, Merced, CA, United States of America.
David C. Bellinger, Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA and Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
Frederick M. Henretig, Emergency Medicine, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Eric S. Coker, Department of Environmental and Global Health, University of Florida, Gainesville, FL, United States of America.

Document Type

Article

Publication Date

11-17-2022

Institution/Department

Pediatrics, Cardiology

Journal Title

PloS one

MeSH Headings

Infant; Humans; Child, Preschool; Prospective Studies; Bayes Theorem; Heart Defects, Congenital (chemically induced, surgery); Parabens; Phenols; Biomarkers

Abstract

BACKGROUND: Children with congenital heart defects have an increased risk of neurodevelopmental disability. The impact of environmental chemical exposures during daily life on neurodevelopmental outcomes in toddlers with congenital heart defects is unknown. METHODS: This prospective study investigated the impacts of early childhood exposure to mixtures of environmental chemicals on neurodevelopmental outcomes after cardiac surgery. Outcomes were assessed at 18 months of age using The Bayley Scales of Infant and Toddler Development-III. Urinary concentrations of exposure biomarkers of pesticides, phenols, parabens, and phthalates, and blood levels of lead, mercury, and nicotine were measured at the same time point. Bayesian profile regression and weighted quantile sum regression were utilized to assess associations between mixtures of biomarkers and neurodevelopmental scores. RESULTS: One-hundred and forty infants were enrolled, and 110 (79%) returned at 18 months of age. Six biomarker exposure clusters were identified from the Bayesian profile regression analysis; and the pattern was driven by 15 of the 30 biomarkers, most notably 13 phthalate biomarkers. Children in the highest exposure cluster had significantly lower adjusted language scores by -9.41 points (95%CI: -17.2, -1.7) and adjusted motor scores by -4.9 points (-9.5, -0.4) compared to the lowest exposure. Weighted quantile sum regression modeling for the overall exposure-response relationship showed a significantly lower adjusted motor score (β = -2.8 points [2.5th and 97.5th percentile: -6.0, -0.6]). The weighted quantile sum regression index weights for several phthalates, one paraben, and one phenol suggest their relevance for poorer neurodevelopmental outcomes. CONCLUSIONS: Like other children, infants with congenital heart defects are exposed to complex mixtures of environmental chemicals in daily life. Higher exposure biomarker concentrations were associated with significantly worse performance for language and motor skills in this population.

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