Nan Li1, George D Papandonatos2, Antonia M Calafat3, Kimberly Yolton4, Bruce P Lanphear5, Aimin Chen6, Joseph M Braun7. 1. Department of Epidemiology, Brown University, 121 South Main Street, Providence, RI, United States. Electronic address: nan_li1@brown.edu. 2. Department of Biostatistics, Brown University, 121 South Main Street, Providence, RI, United States. 3. National Center for Environmental Health, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, United States. 4. Department of Pediatrics, Division of General and Community Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH, United States. 5. Child and Family Research Institute, British Columbia Children's Hospital, 950 West 28th Ave, Vancouver, British Columbia, Canada; Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada. 6. Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, 160 Panzeca Way, Cincinnati, OH, United States. 7. Department of Epidemiology, Brown University, 121 South Main Street, Providence, RI, United States.
Abstract
BACKGROUND: Early-life phthalate exposures may adversely affect children's neurodevelopment by disrupting thyroid function, reducing gonadal hormone levels, or altering fatty acid concentrations in the brain. This study aimed to identify periods of heightened susceptibility during gestation, infancy, and childhood to the impact of phthalates on children's cognitive abilities. METHODS: We used data from 253 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio), a longitudinal pregnancy and birth cohort. We quantified urinary concentrations of 11 phthalate metabolites in samples collected twice during gestation and 6 times during study visits when children were aged 1-8 years using a modified method of on-line solid phase extraction coupled with isotope dilution-high performance liquid chromatography-tandem mass spectrometry. We assessed children's intelligence (IQ) at ages 5 and 8 years using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV, respectively. We estimated covariate-adjusted associations between a 1-standard deviation increase in log10-transformed urinary phthalate metabolite concentrations at each visit and children's IQ, adjusting for demographic, perinatal, and child factors; we tested for differences in these associations across visits using multiple informant models. RESULTS: Associations between some phthalate metabolites and IQ varied by visit (phthalate x visit interaction p-values<0.20). The sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), mono(3-carboxypropyl) phthalate, and monoethyl phthalate at age 3 years, and monobenzyl phthalate at 16 weeks gestation and child ages 3, 5, and 8 years were inversely associated with children's full-scale IQ. For example, each 1-standard deviation increase in ΣDEHP at age 3 was associated with a 1.9-point decrease in full-scale IQ (95% confidence interval: -3.7, -0.2). Mono-n-butyl phthalate and mono-isobutyl phthalate at age 4 years were positively associated with children's full-scale IQ. CONCLUSION: Urinary concentrations of several phthalate metabolites at age 3 years, compared to other time periods, were more strongly associated with decreased cognitive abilities in these children.
BACKGROUND: Early-life phthalate exposures may adversely affect children's neurodevelopment by disrupting thyroid function, reducing gonadal hormone levels, or altering fatty acid concentrations in the brain. This study aimed to identify periods of heightened susceptibility during gestation, infancy, and childhood to the impact of phthalates on children's cognitive abilities. METHODS: We used data from 253 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio), a longitudinal pregnancy and birth cohort. We quantified urinary concentrations of 11 phthalate metabolites in samples collected twice during gestation and 6 times during study visits when children were aged 1-8 years using a modified method of on-line solid phase extraction coupled with isotope dilution-high performance liquid chromatography-tandem mass spectrometry. We assessed children's intelligence (IQ) at ages 5 and 8 years using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV, respectively. We estimated covariate-adjusted associations between a 1-standard deviation increase in log10-transformed urinary phthalate metabolite concentrations at each visit and children's IQ, adjusting for demographic, perinatal, and child factors; we tested for differences in these associations across visits using multiple informant models. RESULTS: Associations between some phthalate metabolites and IQ varied by visit (phthalate x visit interaction p-values<0.20). The sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), mono(3-carboxypropyl) phthalate, and monoethyl phthalate at age 3 years, and monobenzyl phthalate at 16 weeks gestation and child ages 3, 5, and 8 years were inversely associated with children's full-scale IQ. For example, each 1-standard deviation increase in ΣDEHP at age 3 was associated with a 1.9-point decrease in full-scale IQ (95% confidence interval: -3.7, -0.2). Mono-n-butyl phthalate and mono-isobutyl phthalate at age 4 years were positively associated with children's full-scale IQ. CONCLUSION: Urinary concentrations of several phthalate metabolites at age 3 years, compared to other time periods, were more strongly associated with decreased cognitive abilities in these children.
Authors: Anderson J M Andrade; Simone W Grande; Chris E Talsness; Christine Gericke; Konstanze Grote; Andrea Golombiewski; Anja Sterner-Kock; Ibrahim Chahoud Journal: Toxicology Date: 2006-08-22 Impact factor: 4.221
Authors: Martha M Téllez-Rojo; Alejandra Cantoral; David E Cantonwine; Lourdes Schnaas; Karen Peterson; Howard Hu; John D Meeker Journal: Sci Total Environ Date: 2013-06-05 Impact factor: 7.963
Authors: Megan E Romano; Melissa N Eliot; R Thomas Zoeller; Andrew N Hoofnagle; Antonia M Calafat; Margaret R Karagas; Kimberly Yolton; Aimin Chen; Bruce P Lanphear; Joseph M Braun Journal: Int J Hyg Environ Health Date: 2018-03-23 Impact factor: 5.840
Authors: Robin M Whyatt; Xinhua Liu; Virginia A Rauh; Antonia M Calafat; Allan C Just; Lori Hoepner; Diurka Diaz; James Quinn; Jennifer Adibi; Frederica P Perera; Pam Factor-Litvak Journal: Environ Health Perspect Date: 2011-09-06 Impact factor: 9.031
Authors: Nan Li; Yun Liu; George D Papandonatos; Antonia M Calafat; Charles B Eaton; Karl T Kelsey; Kim M Cecil; Heidi J Kalkwarf; Kimberly Yolton; Bruce P Lanphear; Aimin Chen; Joseph M Braun Journal: Environ Int Date: 2021-01-06 Impact factor: 9.621
Authors: Christine T Loftus; Nicole R Bush; Drew B Day; Yu Ni; Frances A Tylavsky; Catherine J Karr; Kurunthachalam Kannan; Emily S Barrett; Adam A Szpiro; Sheela Sathyanarayana; Kaja Z LeWinn Journal: Environ Int Date: 2021-02-06 Impact factor: 9.621
Authors: Jenny L Carwile; Shravanthi M Seshasayee; Katherine A Ahrens; Russ Hauser; Jorge E Chavarro; Abby F Fleisch Journal: Environ Res Date: 2021-09-25 Impact factor: 6.498
Authors: Michiel A van den Dries; Mònica Guxens; Suzanne Spaan; Kelly K Ferguson; Elise Philips; Susana Santos; Vincent W V Jaddoe; Akhgar Ghassabian; Leonardo Trasande; Henning Tiemeier; Anjoeka Pronk Journal: Environ Health Perspect Date: 2020-07-27 Impact factor: 9.031
Authors: Marisa A Patti; Melissa Eliot; Nan Li; Kimberly Yolton; Bruce P Lanphear; Aimin Chen; Joseph M Braun Journal: Environ Epidemiol Date: 2022-03-15
Authors: Angela Giuliani; Mariachiara Zuccarini; Angelo Cichelli; Haroon Khan; Marcella Reale Journal: Int J Environ Res Public Health Date: 2020-08-05 Impact factor: 3.390
Authors: Carly Hyland; Ana M Mora; Katherine Kogut; Antonia M Calafat; Kim Harley; Julianna Deardorff; Nina Holland; Brenda Eskenazi; Sharon K Sagiv Journal: Environ Health Perspect Date: 2019-10-25 Impact factor: 9.031
Authors: Agnieszka Jankowska; Linda Nazareth; Dorota Kaleta; Kinga Polanska Journal: Int J Environ Res Public Health Date: 2021-12-09 Impact factor: 3.390