Childhood Exposures to Environmental Chemicals and Neurodevelopmental Outcomes in Congenital Heart Disease

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Nov 17

PMID 36395323

Authors

J William Gaynor

Nancy B Burnham

Richard F Ittenbach

Marsha Gerdes

Judy C Bernbaum

Elaine Zackai

Daniel J Licht

William W Russell

Erin E Zullo

Thomas Miller

Hakon Hakonarson

Kayan A Clarke

Gail P Jarvik

Antonia M Calafat

Asa Bradman

David C Bellinger

Frederick M Henretig

Eric S Coker

Affiliations

Soon will be listed here.

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.

Citing Articles

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Gaynor J, Moldenhauer J, Zullo E, Burnham N, Gerdes M, Bernbaum J JAMA Netw Open. 2024; 7(5):e2412291.

PMID: 38805228 PMC: 11134212. DOI: 10.1001/jamanetworkopen.2024.12291.

Anesthesia and Sedation Exposure and Neurodevelopmental Outcomes in Infants Undergoing Congenital Cardiac Surgery: A Retrospective Cohort Study.

Simpao A, Randazzo I, Chittams J, Burnham N, Gerdes M, Bernbaum J Anesthesiology. 2023; 139(4):393-404.

PMID: 37440275 PMC: 10527982. DOI: 10.1097/ALN.0000000000004684.

References

Ramirez V, Galvez-Ontiveros Y, Gonzalez-Domenech P, Baca M, Rodrigo L, Rivas A . Role of endocrine disrupting chemicals in children's neurodevelopment. Environ Res. 2021; 203:111890. DOI: 10.1016/j.envres.2021.111890. View

Cory-Slechta D . Studying toxicants as single chemicals: does this strategy adequately identify neurotoxic risk?. Neurotoxicology. 2005; 26(4):491-510. DOI: 10.1016/j.neuro.2004.12.007. View

Nattel S, Adrianzen L, Kessler E, Andelfinger G, Dehaes M, Cote-Corriveau G . Congenital Heart Disease and Neurodevelopment: Clinical Manifestations, Genetics, Mechanisms, and Implications. Can J Cardiol. 2017; 33(12):1543-1555. DOI: 10.1016/j.cjca.2017.09.020. View

von Rettberg H, Hannman T, Subotic U, Brade J, Schaible T, Waag K . Use of di(2-ethylhexyl)phthalate-containing infusion systems increases the risk for cholestasis. Pediatrics. 2009; 124(2):710-6. DOI: 10.1542/peds.2008-1765. View

Dorea J . Multiple low-level exposures: Hg interactions with co-occurring neurotoxic substances in early life. Biochim Biophys Acta Gen Subj. 2018; 1863(12):129243. DOI: 10.1016/j.bbagen.2018.10.015. View

Li N, Papandonatos G, Calafat A, Yolton K, Lanphear B, Chen A . Gestational and childhood exposure to phthalates and child behavior. Environ Int. 2020; 144:106036. PMC: 7572811. DOI: 10.1016/j.envint.2020.106036. View

Berger K, Coker E, Rauch S, Eskenazi B, Balmes J, Kogut K . Prenatal phthalate, paraben, and phenol exposure and childhood allergic and respiratory outcomes: Evaluating exposure to chemical mixtures. Sci Total Environ. 2020; 725:138418. PMC: 7255953. DOI: 10.1016/j.scitotenv.2020.138418. View

Lee D, Kim M, Lim Y, Lee N, Hong Y . Prenatal and postnatal exposure to di-(2-ethylhexyl) phthalate and neurodevelopmental outcomes: A systematic review and meta-analysis. Environ Res. 2018; 167:558-566. DOI: 10.1016/j.envres.2018.08.023. View

Coker E, Liverani S, Ghosh J, Jerrett M, Beckerman B, Li A . Multi-pollutant exposure profiles associated with term low birth weight in Los Angeles County. Environ Int. 2016; 91:1-13. DOI: 10.1016/j.envint.2016.02.011. View

10.

Navaranjan G, Takaro T, Wheeler A, Diamond M, Shu H, Azad M . Early life exposure to phthalates in the Canadian Healthy Infant Longitudinal Development (CHILD) study: a multi-city birth cohort. J Expo Sci Environ Epidemiol. 2019; 30(1):70-85. DOI: 10.1038/s41370-019-0182-x. View

11.

Verstraete S, Vanhorebeek I, Covaci A, Guiza F, Malarvannan G, Jorens P . Circulating phthalates during critical illness in children are associated with long-term attention deficit: a study of a development and a validation cohort. Intensive Care Med. 2015; 42(3):379-392. DOI: 10.1007/s00134-015-4159-5. View

12.

Antonelli J, Wilson A, Coull B . Multiple exposure distributed lag models with variable selection. Biostatistics. 2022; 25(1):1-19. PMC: 10724118. DOI: 10.1093/biostatistics/kxac038. View

13.

Minatoya M, Kishi R . A Review of Recent Studies on Bisphenol A and Phthalate Exposures and Child Neurodevelopment. Int J Environ Res Public Health. 2021; 18(7). PMC: 8036555. DOI: 10.3390/ijerph18073585. View

14.

Sarigiannis D, Papaioannou N, Handakas E, Anesti O, Polanska K, Hanke W . Neurodevelopmental exposome: The effect of in utero co-exposure to heavy metals and phthalates on child neurodevelopment. Environ Res. 2021; 197:110949. DOI: 10.1016/j.envres.2021.110949. View

15.

Olsen I, Lawson M, Ferguson A, Cantrell R, Grabich S, Zemel B . BMI curves for preterm infants. Pediatrics. 2015; 135(3):e572-81. DOI: 10.1542/peds.2014-2777. View

16.

Davis M, Wade E, Restrepo P, Roman-Esteva W, Bravo R, Kuklenyik P . Semi-automated solid phase extraction method for the mass spectrometric quantification of 12 specific metabolites of organophosphorus pesticides, synthetic pyrethroids, and select herbicides in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2013; 929:18-26. DOI: 10.1016/j.jchromb.2013.04.005. View

17.

Liverani S, Hastie D, Azizi L, Papathomas M, Richardson S . PReMiuM: An R Package for Profile Regression Mixture Models Using Dirichlet Processes. J Stat Softw. 2016; 64(7):1-30. PMC: 4905523. DOI: 10.18637/jss.v064.i07. View

18.

Coker E, Gunier R, Bradman A, Harley K, Kogut K, Molitor J . Association between Pesticide Profiles Used on Agricultural Fields near Maternal Residences during Pregnancy and IQ at Age 7 Years. Int J Environ Res Public Health. 2017; 14(5). PMC: 5451957. DOI: 10.3390/ijerph14050506. View

19.

Lubin J, Colt J, Camann D, Davis S, Cerhan J, Severson R . Epidemiologic evaluation of measurement data in the presence of detection limits. Environ Health Perspect. 2004; 112(17):1691-6. PMC: 1253661. DOI: 10.1289/ehp.7199. View

20.

Sears C, Lanphear B, Calafat A, Chen A, Skarha J, Xu Y . Lowering Urinary Phthalate Metabolite Concentrations among Children by Reducing Contaminated Dust in Housing Units: A Randomized Controlled Trial and Observational Study. Environ Sci Technol. 2020; 54(7):4327-4335. PMC: 7494216. DOI: 10.1021/acs.est.9b04898. View