title: White matter deficits mediate effects of prenatal alcohol exposure on cognitive development in childhood.
abstract: Fetal alcohol spectrum disorders comprise the spectrum of cognitive, behavioral, and neurological impairments caused by prenatal alcohol exposure (PAE). Diffusion tensor imaging (DTI) was performed on 54 children (age 10.1 ± 1.0 years) from the Cape Town Longitudinal Cohort, for whom detailed drinking histories obtained during pregnancy are available: 26 with full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 15 nonsyndromal heavily exposed (HE), and 13 controls. Using voxelwise analyses, children with FAS/PFAS showed significantly lower fractional anisotropy (FA) in four white matter (WM) regions and higher mean diffusivity (MD) in seven; three regions of FA and MD differences (left inferior longitudinal fasciculus (ILF), splenium, and isthmus) overlapped, and the fourth FA cluster was located in the same WM bundle (right ILF) as an MD cluster. HE children showed lower FA and higher MD in a subset of these regions. Significant correlations were observed between three continuous alcohol measures and DTI values at cluster peaks, indicating that WM damage in several regions is dose dependent. Lower FA in the regions of interest was attributable primarily to increased radial diffusivity rather than decreased axonal diffusivity, suggesting poorer axon packing density and/or myelination. Multiple regression models indicated that this cortical WM impairment partially mediated adverse effects of PAE on information processing speed and eyeblink conditioning. Hum Brain Mapp 37:2943-2958, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.|Department of Human Biology, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
authors.forename: Jia
authors.identifier: 0000-0002-0443-5904
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Human Biology, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.|Department of Psychiatry and Mental Health, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.|Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Sandra W
authors.initials: SW
authors.lastname: Jacobson
authors.affiliation: MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.|Department of Human Biology, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.|African Institute for Mathematical Sciences, Muizenberg, Western Cape, South Africa.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Taylor
authors.affiliation: Department of Psychiatry and Mental Health, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Molteno
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Dodge
authors.affiliation: Department of Psychology, University of Delaware, Newark, Delaware.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Stanton
authors.affiliation: Department of Human Biology, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.|Department of Psychiatry and Mental Health, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.|Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Jacobson
authors.affiliation: MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.|Department of Human Biology, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
authors.forename: Ernesta M
authors.initials: EM
authors.lastname: Meintjes
mesh_terms: D002648:Child; D002657:Child Development / Q000187:drug effects*; D003071:Cognition; D056324:Diffusion Tensor Imaging; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D006801:Humans; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
keywords: IQ; diffusion tensor imaging; eyeblink conditioning; fetal alcohol spectrum disorders; prenatal alcohol exposure