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White Matter Microstructural Integrity and Neurobehavioral Outcome of HIV-Exposed Uninfected Neonates
Linh T Tran1, Annerine Roos, Jean-Paul Fouche
1From 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).
Insights
Prenatal exposure to human immunodeficiency virus (HIV) without infection may alter white matter microstructure in newborns. This early change in brain development warrants further investigation in HIV-exposed uninfected (HEU) children.
Area of Science:
- Neuroscience
- Developmental Biology
- Radiology
Background:
- Prevention programs have reduced mother-to-child HIV transmission, increasing HIV-exposed uninfected (HEU) children.
- HEU children may show neurodevelopmental differences compared to HIV-unexposed, uninfected (HUU) children.
- Mechanisms behind potential neurodevelopmental delays in HEU infants are unclear.
Purpose of the Study:
- To investigate white matter microstructure integrity in HEU infants shortly after birth.
- To explore associations between prenatal HIV exposure and neonatal white matter microstructural changes.
- To correlate microstructural findings with neonatal neurobehavioral outcomes.
Main Methods:
- Observational birth cohort study comparing HEU infants (n=15) and matched HUU controls (n=22).
- Diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) to evaluate white matter microstructure.
- Analysis of diffusion values in specific white matter tracts and correlation with Dubowitz neonatal neurobehavioral assessment.
Main Results:
- HEU neonates exhibited higher fractional anisotropy (FA) in the middle cerebellar peduncles compared to HUU neonates.
- FA in the left uncinate fasciculus of HEU infants positively correlated with abnormal neurological signs.
- This is the first study indicating altered white matter microstructure in neonates with prenatal HIV exposure.
Conclusions:
- Prenatal HIV exposure, even without infection, is associated with altered white matter microstructural integrity in the neonatal period.
- Early microstructural changes in HEU infants suggest potential long-term neurodevelopmental implications.
- Longitudinal studies are crucial to understand the impact of prenatal HIV and antiretroviral treatment on brain development in HEU children.
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.
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