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White matter microstructure mediates the association between prenatal exposure to phthalates and behavior problems in
Gillian England-Mason1, Melody N Grohs2, Jess E Reynolds3
1Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Canada; Owerko Centre, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.
Insights
Prenatal phthalate exposure may impact childhood behavior by altering white matter development. This study found associations between phthalates, white matter integrity, and behavioral issues in preschoolers.
Area of Science:
- Neuroscience
- Environmental Health
- Developmental Psychology
Background:
- Previous research links prenatal phthalate exposure to childhood behavior problems.
- Neural mechanisms underlying this association remain largely unexplored.
Purpose of the Study:
- To investigate microstructural white matter as a mediator between prenatal phthalate exposure and behavioral problems in preschoolers.
- To examine associations between phthalate concentrations and white matter integrity.
Main Methods:
- Utilized data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study (n=76).
- Assessed prenatal phthalate exposure via maternal urine samples.
- Evaluated child brain white matter microstructure using MRI (fractional anisotropy and mean diffusivity).
- Quantified child behavior problems using the Child Behavior Checklist.
Main Results:
- Prenatal phthalate concentrations correlated with white matter integrity in several tracts, including the inferior fronto-occipital fasciculus (IFO) and uncinate fasciculus (UF).
- Mediation analyses indicated that high molecular weight phthalates (HMWP) were indirectly associated with Internalizing and Externalizing Problems through mean diffusivity (MD) of the right IFO and right pyramidal fibers.
Conclusions:
- This study presents the first evidence of neural correlates of prenatal phthalate exposure in children.
- Findings suggest prenatal phthalate exposure may affect white matter microstructure (IFO, pyramidal fibers, UF, ILF).
- MD of the right IFO and pyramidal fibers may mediate the risk for behavioral problems in children exposed to phthalates prenatally.
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.
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