title: White Matter Microstructural Integrity and Neurobehavioral Outcome of HIV-Exposed Uninfected Neonates.
abstract: The successful implementation of prevention programs for mother-to-child human immunodeficiency virus (HIV) transmission has dramatically reduced the prevalence of infants infected with HIV while increasing that of HIV-exposed uninfected (HEU) children. Neuropsychological assessments indicate that HEU children may exhibit differences in neurodevelopment compared to unexposed children (HUU). Pathological mechanisms leading to such neurodevelopmental delays are not clear. In this observational birth cohort study we explored the integrity of regional white matter microstructure in HEU infants, shortly after birth. Microstructural changes in white matter associated with prenatal HIV exposure were evaluated in HEU infants (n = 15) and matched controls (n = 22) using diffusion tensor imaging and tract-based spatial statistics. Additionally, diffusion values were extracted and compared for white matter tracts of interest, and associations with clinical outcomes from the Dubowitz neonatal neurobehavioral tool were investigated. Higher fractional anisotropy in the middle cerebellar peduncles of HEU compared to HUU neonates was found after correction for age and gender. Scores on the Dubowitz abnormal neurological signs subscale were positively correlated with FA (r = 0.58, P = 0.038) in the left uncinate fasciculus in HEU infants. This is the first study to present data suggesting that prenatal HIV exposure without infection is associated with altered white matter microstructural integrity in the neonatal period. Longitudinal studies of HEU infants as their brains mature are necessary to understand further the significance of prenatal HIV and antiretroviral treatment exposure on white matter integrity and neurodevelopmental outcomes.
authors.affiliation: From the Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town (LTT, KAD); SU/UCT MRC Unit on Anxiety & Stress Disorders, Stellenbosch University (AR); Department of Psychiatry and Mental Health, University of Cape Town (J-PF); Department of Psychiatry, Stellenbosch University (J-PF); Department of Psychiatry and Mental Health, MRC Unit on Anxiety & Stress Disorders, University of Cape Town, Cape Town, South Africa (NK, DJS); Department of Neurology, University of California, Los Angeles, CA (RPW, KLN); and Department of Paediatrics and Child Health and MRC Unit on Child & Adolescent Health, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa (HJZ).
authors.forename: Linh T
authors.initials: LT
authors.lastname: Tran
authors.forename: Annerine
authors.initials: A
authors.lastname: Roos
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fouche
authors.forename: Nastassja
authors.initials: N
authors.lastname: Koen
authors.forename: Roger P
authors.initials: RP
authors.lastname: Woods
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Zar
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Narr
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Donald
mesh_terms: D016880:Anisotropy; D002531:Cerebellum; D056324:Diffusion Tensor Imaging; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000523:psychology; D006801:Humans; D018730:Infant Behavior; D007231:Infant, Newborn; D008297:Male; D009483:Neuropsychological Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis* / Q000821:virology; D013019:South Africa; D066127:White Matter / Q000473:pathology*
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