Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers

IntroductionAntiretroviral therapy (ART) is considered the most effective way to prevent perinatal transmission of human immunodeficiency virus (HIV). However, there is little knowledge about the effect of ART on the brain of HIV uninfected children born to HIV infected mothers (HUC). The current st...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Yadav, Santosh K. (author)
مؤلفون آخرون: Gupta, Rakesh K. (author), Hashem, Sheema (author), Nisar, Sabah (author), Azeem, Taha (author), Bhat, Ajaz A. (author), Syed, Najeeb (author), Garg, Ravindra K. (author), Venkatesh, Vimala (author), Kamal, Madeeha (author), Fakhro, Khalid (author), Frenneaux, Michael P. (author), Haris, Mohammad (author)
التنسيق: article
منشور في: 2020
الموضوعات:
الوصول للمادة أونلاين:http://dx.doi.org/10.1016/j.bbih.2020.100039
https://www.sciencedirect.com/science/article/pii/S2666354620300041
http://hdl.handle.net/10576/16108
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author Yadav, Santosh K.
author2 Gupta, Rakesh K.
Hashem, Sheema
Nisar, Sabah
Azeem, Taha
Bhat, Ajaz A.
Syed, Najeeb
Garg, Ravindra K.
Venkatesh, Vimala
Kamal, Madeeha
Fakhro, Khalid
Frenneaux, Michael P.
Haris, Mohammad
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author_facet Yadav, Santosh K.
Gupta, Rakesh K.
Hashem, Sheema
Nisar, Sabah
Azeem, Taha
Bhat, Ajaz A.
Syed, Najeeb
Garg, Ravindra K.
Venkatesh, Vimala
Kamal, Madeeha
Fakhro, Khalid
Frenneaux, Michael P.
Haris, Mohammad
author_role author
dc.creator.none.fl_str_mv Yadav, Santosh K.
Gupta, Rakesh K.
Hashem, Sheema
Nisar, Sabah
Azeem, Taha
Bhat, Ajaz A.
Syed, Najeeb
Garg, Ravindra K.
Venkatesh, Vimala
Kamal, Madeeha
Fakhro, Khalid
Frenneaux, Michael P.
Haris, Mohammad
dc.date.none.fl_str_mv 2020-09-14T10:06:41Z
2020-02-29
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://dx.doi.org/10.1016/j.bbih.2020.100039
Yadav, S. K., Gupta, R. K., Hashem, S., Nisar, S., Azeem, T., Bhat, A. A., ... & Fakhro, K. (2020). Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers. Brain, Behavior, & Immunity-Health, 2, 100039.
2666-3546
https://www.sciencedirect.com/science/article/pii/S2666354620300041
http://hdl.handle.net/10576/16108
2
dc.language.none.fl_str_mv en
dc.publisher.none.fl_str_mv Elsevier
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Antiretroviral therapies
Human immunodeficiency virus
Diffusion tensor imaging
Neuropsychological test
Brain
dc.title.none.fl_str_mv Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers
dc.type.none.fl_str_mv Article
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
description IntroductionAntiretroviral therapy (ART) is considered the most effective way to prevent perinatal transmission of human immunodeficiency virus (HIV). However, there is little knowledge about the effect of ART on the brain of HIV uninfected children born to HIV infected mothers (HUC). The current study evaluated the brain’s microstructural integrity, and cognitive function in HUC compared to healthy children born to normal mothers (CHNM) and HIV infected children born to HIV infected mothers (HIC) to investigate the effect of in-utero exposure of ART on cerebral gray and white matter. Materials and methodsForty nine HIC, 12 HUC and 18 CHNM underwent neuropsychological (NP) assessment and a brain MRI. Diffusion tensor imaging (DTI) data was used to generate fractional anisotropy (FA) and mean diffusivity (MD) maps. Voxel wise comparison for FA and MD was performed between three groups using an analysis of covariance (ANCOVA) including age and sex as covariates, and correction for multiple comparisons (false discovery rate (FDR), p ​< ​0.05 with minimum extended cluster size, 150 voxels). NP test scores were also compared between three groups using ANOVA with Post Hoc Bonferroni multiple comparison corrections (p ​< ​0.05). Significantly changed FA and MD values in different brain regions in HIC and HUC compared to CHNM were used for correlation analysis with NP test scores using Pearson’s correlation. ResultsHIC and HUC groups showed significantly decreased NP test scores in various domain compared to CHNM. Significantly lower NP test scores was observed in HIC than those of HUC. HIC showed decreased FA and increased MD in multiple brain sites as compared to both CHNM and HUC. Decreased FA along with both increased and decreased MD in different brain regions was present in HUC compared to CHNM. Both positive and negative correlation of altered FA and MD values from different brain regions in HIC and HUC with NP test scores was observed. ConclusionThe presence of brain tissue changes and neurocognitive function deficit in absence of HIV infection in HUC indicates that ART may have a detrimental impact on the developing brain. The findings of the current study underscore the need for screening of ART exposed children for neurodevelopment and cognitive abnormalities at an early stage and call for access to early interventions, and nutritional and care programs.
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identifier_str_mv Yadav, S. K., Gupta, R. K., Hashem, S., Nisar, S., Azeem, T., Bhat, A. A., ... & Fakhro, K. (2020). Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers. Brain, Behavior, & Immunity-Health, 2, 100039.
2666-3546
2
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publishDate 2020
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spelling Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothersYadav, Santosh K.Gupta, Rakesh K.Hashem, SheemaNisar, SabahAzeem, TahaBhat, Ajaz A.Syed, NajeebGarg, Ravindra K.Venkatesh, VimalaKamal, MadeehaFakhro, KhalidFrenneaux, Michael P.Haris, MohammadAntiretroviral therapiesHuman immunodeficiency virusDiffusion tensor imagingNeuropsychological testBrainIntroductionAntiretroviral therapy (ART) is considered the most effective way to prevent perinatal transmission of human immunodeficiency virus (HIV). However, there is little knowledge about the effect of ART on the brain of HIV uninfected children born to HIV infected mothers (HUC). The current study evaluated the brain’s microstructural integrity, and cognitive function in HUC compared to healthy children born to normal mothers (CHNM) and HIV infected children born to HIV infected mothers (HIC) to investigate the effect of in-utero exposure of ART on cerebral gray and white matter. Materials and methodsForty nine HIC, 12 HUC and 18 CHNM underwent neuropsychological (NP) assessment and a brain MRI. Diffusion tensor imaging (DTI) data was used to generate fractional anisotropy (FA) and mean diffusivity (MD) maps. Voxel wise comparison for FA and MD was performed between three groups using an analysis of covariance (ANCOVA) including age and sex as covariates, and correction for multiple comparisons (false discovery rate (FDR), p ​< ​0.05 with minimum extended cluster size, 150 voxels). NP test scores were also compared between three groups using ANOVA with Post Hoc Bonferroni multiple comparison corrections (p ​< ​0.05). Significantly changed FA and MD values in different brain regions in HIC and HUC compared to CHNM were used for correlation analysis with NP test scores using Pearson’s correlation. ResultsHIC and HUC groups showed significantly decreased NP test scores in various domain compared to CHNM. Significantly lower NP test scores was observed in HIC than those of HUC. HIC showed decreased FA and increased MD in multiple brain sites as compared to both CHNM and HUC. Decreased FA along with both increased and decreased MD in different brain regions was present in HUC compared to CHNM. Both positive and negative correlation of altered FA and MD values from different brain regions in HIC and HUC with NP test scores was observed. ConclusionThe presence of brain tissue changes and neurocognitive function deficit in absence of HIV infection in HUC indicates that ART may have a detrimental impact on the developing brain. The findings of the current study underscore the need for screening of ART exposed children for neurodevelopment and cognitive abnormalities at an early stage and call for access to early interventions, and nutritional and care programs.This study was funded by Department of Science and Technology (SR/CSI/02/2 0 10, G), New Delhi, India. Sidra Medicine provided data processing platform. This work was supported by funding from Sidra Medicine to Mohammad Haris (50610110002), Santosh Kumar Yadav (5011043002) and Ajaz A. Bhat (5011041002).Elsevier2020-09-14T10:06:41Z2020-02-29Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.bbih.2020.100039Yadav, S. K., Gupta, R. K., Hashem, S., Nisar, S., Azeem, T., Bhat, A. A., ... & Fakhro, K. (2020). Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers. Brain, Behavior, & Immunity-Health, 2, 100039.2666-3546https://www.sciencedirect.com/science/article/pii/S2666354620300041http://hdl.handle.net/10576/161082enhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/161082025-06-11T19:08:33Z
spellingShingle Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers
Yadav, Santosh K.
Antiretroviral therapies
Human immunodeficiency virus
Diffusion tensor imaging
Neuropsychological test
Brain
status_str publishedVersion
title Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers
title_full Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers
title_fullStr Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers
title_full_unstemmed Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers
title_short Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers
title_sort Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers
topic Antiretroviral therapies
Human immunodeficiency virus
Diffusion tensor imaging
Neuropsychological test
Brain
url http://dx.doi.org/10.1016/j.bbih.2020.100039
https://www.sciencedirect.com/science/article/pii/S2666354620300041
http://hdl.handle.net/10576/16108