Gillian England-Mason1, Melody N Grohs2, Jess E Reynolds3, Amy MacDonald4, David Kinniburgh4, Jiaying Liu5, Jonathan W Martin6, Catherine Lebel3, Deborah Dewey7. 1. Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada. 2. Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada; Department of Neuroscience, Cumming School of Medicine, University of Calgary, Calgary, Canada. 3. Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada; Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Canada; Hotchkiss Brain Institute, Calgary, Canada. 4. Alberta Centre for Toxicology, University of Calgary, Calgary, Canada. 5. Department of Laboratory Medicine and Pathology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canada. 6. Department of Laboratory Medicine and Pathology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canada; Science for Life Laboratory, Department of Analytical Chemistry and Environmental Sciences, Stockholm University, Stockholm, Sweden. 7. Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada; Hotchkiss Brain Institute, Calgary, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada. Electronic address: dmdewey@ucalgary.ca.
Abstract
BACKGROUND: Previous research reports associations between prenatal exposure to phthalates and childhood behavior problems; however, the neural mechanisms that may underlie these associations are relatively unexplored. OBJECTIVE: This study examined microstructural white matter as a possible mediator of the associations between prenatal phthalate exposure and behavior problems in preschool-aged children. METHODS: Data are from a subsample of a prospective pregnancy cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study (n = 76). Mother-child pairs were included if mothers provided a second trimester urine sample, if the child completed a successful magnetic resonance imaging (MRI) scan at age 3-5 years, and if the Child Behavior Checklist was completed within 6 months of the MRI scan. Molar sums of high (HMWP) and low molecular weight phthalates (LMWP) were calculated from levels in urine samples. Associations between prenatal phthalate concentrations, fractional anisotropy (FA) and mean diffusivity (MD) in 10 major white matter tracts, and preschool behavior problems were investigated. RESULTS: Maternal prenatal phthalate concentrations were associated with MD of the right inferior fronto-occipital fasciculus (IFO), right pyramidal fibers, left and right uncinate fasciculus (UF), and FA of the left inferior longitudinal fasciculus (ILF). Mediation analyses showed that prenatal exposure to HMWP was indirectly associated with Internalizing (path ab = 0.09, CI.95 = 0.02, 0.20) and Externalizing Problems (path ab = 0.09, CI.95 = 0.01, 0.19) through MD of the right IFO, and to Internalizing Problems (path ab = 0.11, CI.95 = 0.01, 0.23) through MD of the right pyramidal fibers. DISCUSSION: This study provides the first evidence of childhood neural correlates of prenatal phthalate exposure. Results suggest that prenatal phthalate exposure may be related to microstructural white matter in the IFO, pyramidal fibers, UF, and ILF. Further, MD of the right IFO and pyramidal fibers may transmit childhood risk for behavioral problems.
BACKGROUND: Previous research reports associations between prenatal exposure to phthalates and childhood behavior problems; however, the neural mechanisms that may underlie these associations are relatively unexplored. OBJECTIVE: This study examined microstructural white matter as a possible mediator of the associations between prenatal phthalate exposure and behavior problems in preschool-aged children. METHODS: Data are from a subsample of a prospective pregnancy cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study (n = 76). Mother-child pairs were included if mothers provided a second trimester urine sample, if the child completed a successful magnetic resonance imaging (MRI) scan at age 3-5 years, and if the Child Behavior Checklist was completed within 6 months of the MRI scan. Molar sums of high (HMWP) and low molecular weight phthalates (LMWP) were calculated from levels in urine samples. Associations between prenatal phthalate concentrations, fractional anisotropy (FA) and mean diffusivity (MD) in 10 major white matter tracts, and preschool behavior problems were investigated. RESULTS: Maternal prenatal phthalate concentrations were associated with MD of the right inferior fronto-occipital fasciculus (IFO), right pyramidal fibers, left and right uncinate fasciculus (UF), and FA of the left inferior longitudinal fasciculus (ILF). Mediation analyses showed that prenatal exposure to HMWP was indirectly associated with Internalizing (path ab = 0.09, CI.95 = 0.02, 0.20) and Externalizing Problems (path ab = 0.09, CI.95 = 0.01, 0.19) through MD of the right IFO, and to Internalizing Problems (path ab = 0.11, CI.95 = 0.01, 0.23) through MD of the right pyramidal fibers. DISCUSSION: This study provides the first evidence of childhood neural correlates of prenatal phthalate exposure. Results suggest that prenatal phthalate exposure may be related to microstructural white matter in the IFO, pyramidal fibers, UF, and ILF. Further, MD of the right IFO and pyramidal fibers may transmit childhood risk for behavioral problems.
Authors: Julia M Young; Benjamin R Morgan; Hilary E A Whyte; Wayne Lee; Mary Lou Smith; Charles Raybaud; Manohar M Shroff; John G Sled; Margot J Taylor Journal: Cereb Cortex Date: 2017-08-01 Impact factor: 5.357
Authors: Matthew D Albaugh; Simon Ducharme; Sherif Karama; Richard Watts; John D Lewis; Catherine Orr; Tuong-Vi Nguyen; Robert C Mckinstry; Kelly N Botteron; Alan C Evans; James J Hudziak Journal: Dev Psychopathol Date: 2016-06-14
Authors: Shaina L Stacy; George D Papandonatos; Antonia M Calafat; Aimin Chen; Kimberly Yolton; Bruce P Lanphear; Joseph M Braun Journal: Environ Int Date: 2017-07-29 Impact factor: 9.621
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: Drew B Day; Brent R Collett; Emily S Barrett; Nicole R Bush; Shanna H Swan; Ruby H N Nguyen; Adam A Szpiro; Sheela Sathyanarayana Journal: Environ Int Date: 2021-01-05 Impact factor: 13.352