Association of in utero HIV exposure with child brain structure and language development: a South African birth cohort study.

Antiretroviral therapy Brain structure HIV Language Magnetic resonance imaging Neurodevelopment

Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
22 Mar 2024
Historique:
received: 04 08 2023
accepted: 01 02 2024
medline: 23 3 2024
pubmed: 23 3 2024
entrez: 23 3 2024
Statut: epublish

Résumé

There is a growing population of children with in utero HIV exposure who are at risk of poor neurodevelopmental outcomes despite avoiding HIV infection. However, the underlying neurobiological pathways are not understood and neuroimaging studies are lacking. We aimed to investigate the cortical brain structure of children who are HIV-exposed and uninfected (HEU) compared to HIV-unexposed (HU) children and to examine the relationship with neurodevelopment. The Drakenstein Child Health birth cohort study enrolled pregnant women from a high HIV prevalence area in South Africa with longitudinal follow-up of mother-child pairs. High-resolution magnetic resonance imaging scans from 162 children (70 HEU; 92 HU) were acquired at 2-3 years of age. All HEU children were born to mothers taking antiretroviral therapy. Measures of brain structure (cortical thickness and surface area) in the prefrontal cortex regions were extracted from T1-weighted images and compared between groups using multivariate analysis of variance and linear regression. Child development, assessed using the Bayley Scales of Infant and Toddler Development-III, was correlated with cortical structure, and mediation analyses were performed. Analyses demonstrated an association between HIV exposure and cortical thickness across the prefrontal cortex (p = 0.035). Children who were HEU had thicker cortices in prefrontal regions, with significantly greater cortical thickness in the medial orbitofrontal cortex (mOFC) bilaterally compared to HU children (3.21 mm versus 3.14 mm, p = 0.009, adjusted effect size 0.44 [95% CI 0.12 to 0.75]). Estimates held across multiple sensitivity analyses. There were no group differences in cortical surface area. Language scores, which were lower in HEU versus HU children (81.82 versus 86.25, p = 0.011, effect size - 0.44 [95% CI - 0.78 to - 0.09]), negatively correlated with prefrontal cortical thickness in both groups. Cortical thickness in the mOFC mediated the relationship between HIV exposure and poor language outcomes (Sobel test p = 0.032). In this cohort study, exposure to HIV during pregnancy was associated with altered cortical structure in early life. Our findings indicate that differences in cortical thickness development in the prefrontal region in children who are HEU may be a pathway leading to language impairment. Longitudinal studies are needed to determine the lasting impact.

Sections du résumé

BACKGROUND BACKGROUND
There is a growing population of children with in utero HIV exposure who are at risk of poor neurodevelopmental outcomes despite avoiding HIV infection. However, the underlying neurobiological pathways are not understood and neuroimaging studies are lacking. We aimed to investigate the cortical brain structure of children who are HIV-exposed and uninfected (HEU) compared to HIV-unexposed (HU) children and to examine the relationship with neurodevelopment.
METHODS METHODS
The Drakenstein Child Health birth cohort study enrolled pregnant women from a high HIV prevalence area in South Africa with longitudinal follow-up of mother-child pairs. High-resolution magnetic resonance imaging scans from 162 children (70 HEU; 92 HU) were acquired at 2-3 years of age. All HEU children were born to mothers taking antiretroviral therapy. Measures of brain structure (cortical thickness and surface area) in the prefrontal cortex regions were extracted from T1-weighted images and compared between groups using multivariate analysis of variance and linear regression. Child development, assessed using the Bayley Scales of Infant and Toddler Development-III, was correlated with cortical structure, and mediation analyses were performed.
RESULTS RESULTS
Analyses demonstrated an association between HIV exposure and cortical thickness across the prefrontal cortex (p = 0.035). Children who were HEU had thicker cortices in prefrontal regions, with significantly greater cortical thickness in the medial orbitofrontal cortex (mOFC) bilaterally compared to HU children (3.21 mm versus 3.14 mm, p = 0.009, adjusted effect size 0.44 [95% CI 0.12 to 0.75]). Estimates held across multiple sensitivity analyses. There were no group differences in cortical surface area. Language scores, which were lower in HEU versus HU children (81.82 versus 86.25, p = 0.011, effect size - 0.44 [95% CI - 0.78 to - 0.09]), negatively correlated with prefrontal cortical thickness in both groups. Cortical thickness in the mOFC mediated the relationship between HIV exposure and poor language outcomes (Sobel test p = 0.032).
CONCLUSIONS CONCLUSIONS
In this cohort study, exposure to HIV during pregnancy was associated with altered cortical structure in early life. Our findings indicate that differences in cortical thickness development in the prefrontal region in children who are HEU may be a pathway leading to language impairment. Longitudinal studies are needed to determine the lasting impact.

Identifiants

pubmed: 38519887
doi: 10.1186/s12916-024-03282-6
pii: 10.1186/s12916-024-03282-6
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

129

Subventions

Organisme : Wellcome Trust
ID : 203525/Z/16/Z
Pays : United Kingdom
Organisme : Academy of Medical Sciences
ID : NAF002/1001
Pays : United Kingdom
Organisme : NIAAA NIH HHS
ID : R21AA023887
Pays : United States
Organisme : NIAAA NIH HHS
ID : U24 AA014811
Pays : United States
Organisme : Medical Research Council
ID : MR/R010161/1
Pays : United Kingdom

Informations de copyright

© 2024. The Author(s).

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Auteurs

Catherine J Wedderburn (CJ)

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa. catherine.wedderburn@uct.ac.za.
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK. catherine.wedderburn@uct.ac.za.
The Neuroscience Institute, University of Cape Town, Cape Town, South Africa. catherine.wedderburn@uct.ac.za.

Shunmay Yeung (S)

Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.

Sivenesi Subramoney (S)

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.

Jean-Paul Fouche (JP)

The Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa.

Shantanu H Joshi (SH)

Departments of Neurology, Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.

Katherine L Narr (KL)

Departments of Neurology, Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.

Andrea M Rehman (AM)

MRC International Statistics & Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK.

Annerine Roos (A)

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
The Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
SA MRC Unit On Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.

Diana M Gibb (DM)

MRC Clinical Trials Unit, University College London, London, UK.

Heather J Zar (HJ)

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
SA MRC Unit On Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.

Dan J Stein (DJ)

The Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa.
SA MRC Unit On Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.

Kirsten A Donald (KA)

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
The Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Classifications MeSH