Neurodevelopment of HIV-Exposed and HIV-Unexposed Uninfected Children at 24 Months

Chaudhury, Sumona; Williams, Paige L.; Mayondi, Gloria; Leidner, Jean; Holding, Penny; Tepper, Vicki; Nichols, Sharon L.; Magetse, Jane; Sakoi, Maureen; Moabi, Kebaiphe; Makhema, Joseph; Mdluli, Charlotte; Jibril, Haruna; Seage, George R.; Kammerer, Betsy; Lockman, Shahin

doi:10.1542/peds.2017-0988

Cited by 67 publications

(95 citation statements)

References 31 publications

(23 reference statements)

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“…Two of the largest studies from southern Africa used the Bayley Scales of Infant and Toddler Development and had conflicting findings. In Botswana, between 2010 and 2012 when only one‐third of mothers received combination ART during pregnancy and <10% of CHEU were breastfed compared to >99% of CHU, there was little evidence of differences in neurodevelopment at 24 months of age (N = 724) . However, in the era of combination maternal ART and breastfeeding in South Africa, CHEU had higher odds of cognitive and motor, although not language, delay at 13 months of age (N = 521) .…”

Section: Discussionmentioning

confidence: 99%

“…At 12 months of age, a study from South Africa found increased odds of cognitive and motor delay . At two years of age, a study from Botswana showed expressive language delay and a study from South Africa found receptive and expressive language delay . In contrast, a study from Uganda and Malawi did not find difference in neurodevelopmental outcomes in CHEU compared to CHU aged one to five years .…”

Section: Introductionmentioning

confidence: 91%

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Early child development in children who are HIV‐exposed uninfected compared to children who are HIV‐unexposed: observational sub‐study of a cluster‐randomized trial in rural Zimbabwe

et al. 2020

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Introduction Exposure to maternal HIV may affect early child development (ECD), although previous studies have reported heterogeneous findings. We evaluated ECD among children who were HIV‐exposed uninfected (CHEU) and children who were HIV‐unexposed (CHU) recruited to the SHINE trial in rural Zimbabwe. Methods SHINE was a community‐based cluster‐randomized trial of improved infant feeding and/or improved water, sanitation and hygiene. Pregnant women were enrolled between 2012 and 2015. We assessed ECD in a sub‐study at 24 months of age, between 2016 and 2017, using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social development); MacArthur‐Bates Communicative Development Inventory (CDI) (assessing vocabulary and grammar); A‐not‐B test (assessing object permanence); and a self‐control task. Mothers and infants were tested longitudinally for HIV. We used generalized estimating equations to compare ECD scores between CHEU and CHU, accounting for the cluster‐randomized design. Primary results were adjusted for trial‐related factors that could affect measurement reliability of ECD: study nurse, age of child, calendar month of birth, sex and randomized arm. Results A total of 205 CHEU and 1175 CHU were evaluated. Mean total MDAT score was 90.6 (SD 8.7) in CHEU compared to 92.4 (9.1) in CHU (adjusted mean difference −1.3, 95% CI: −2.3, −0.3), driven mostly by differences in gross motor (−0.5, 95% CI: −0.9, −0.2) and language scores (−0.6, 95% CI: −1.1, −0.1). There was evidence that fine motor scores were lower in CHEU (adjusted mean difference −0.4, 95% CI: −0.8, 0.0) but no evidence of a difference in social scores (0.1, 95% CI: −0.2, 0.4). Mean MacArthur‐Bates CDI vocabulary score was 57.9 (SD 19.2) in CHEU compared to 61.3 (18.8) in CHU (adjusted mean difference −2.9 words, 95% CI: −5.7, −0.1). Object permanence and self‐control scores were similar between groups. Conclusions CHEU in rural Zimbabwe had total child development and vocabulary scores that were approximately 0.15 standard deviations lower than CHU at two years of age. More detailed and specific studies are now needed to unravel the reasons for developmental delay in CHEU and the likelihood that these delays persist in the longer term.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Early child development in children who are HIV‐exposed uninfected compared to children who are HIV‐unexposed: observational sub‐study of a cluster‐randomized trial in rural Zimbabwe

et al. 2020

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“…For both zidovudine‐ and lamuvidine‐exposed rodents, some studies suggested that memory and learning may be impaired at early ages . More recent clinical studies with newer ART regimens have not found such deficits in young children . Fewer data are available about specific cognitive functions in older HEU children and adolescents, but studies have found a higher frequency of reading and math impairments in HEU children compared to the general population .…”

Section: Discussionmentioning

confidence: 99%

“…A meta‐analysis on neurodevelopment in HIV‐exposed uninfected (HEU) children highlighted the limitations in the current body of literature including the heterogeneity of the patient populations between studies, limited confounders measured and variability in ART regimens. More recent studies are often limited by sample size and have mixed results .…”

Section: Introductionmentioning

confidence: 99%

In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes

et al. 2019

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Introducion With the increasing number of children exposed to HIV or antiretroviral therapy in utero, there are concerns that this population may have worse neurodevelopmental outcomes compared to those who are unexposed. The objective of this study was to systematically review the clinical and preclinical literature on the effects of in utero exposure to HIV and/or antiretroviral therapy ( ART ) on neurodevelopment. Methods We systematically searched OVID Medline, Psyc INFO and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively. Results The search yielded 3027 unique titles. Of the 255 critically reviewed full‐text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of HIV ‐exposed uninfected children compared to HIV ‐unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinical studies with ART exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction. Conclusions While the existing literature suggests that there may be some neurobehavioral differences associated with HIV and ART exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between HIV ‐exposed uninfected and HIV ‐unexposed uninfected children and using exposures consistent with current clinical care.

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“…[47] A recent study from SA found motor and cognitive delay, particularly associated with preterm birth, [51] and a study from Zambia reported a later impact on school performance. [52] However, other studies in Botswana [53] and SA [54] have not found substantial differences when compared with HIV-unexposed children, although some language impairment was demonstrated, which has also been seen in high-income settings. [55] Further research and follow-up of both CLHIV and HEU children in the current ART era is needed to determine the nature of the developmental delay as well as the long-term implications.…”

Section: Early Neurodevelopmentmentioning

confidence: 83%

The impact of health programmes to prevent vertical transmission of HIV. Advances, emerging health challenges and research priorities for children exposed to or living with HIV: Perspectives from South Africa

et al. 2019

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Neurodevelopment of HIV-Exposed and HIV-Unexposed Uninfected Children at 24 Months

Abstract: HEU children performed equally well on neurodevelopmental assessments at 24 months of age compared with HUU children. Given the global expansion of the HEU population, results suggesting no adverse impact of in-utero HIV and antiretroviral exposure on early neurodevelopment are reassuring.

Cited by 67 publications

References 31 publications

Early child development in children who are HIV‐exposed uninfected compared to children who are HIV‐unexposed: observational sub‐study of a cluster‐randomized trial in rural Zimbabwe

Early child development in children who are HIV‐exposed uninfected compared to children who are HIV‐unexposed: observational sub‐study of a cluster‐randomized trial in rural Zimbabwe

In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes

The impact of health programmes to prevent vertical transmission of HIV. Advances, emerging health challenges and research priorities for children exposed to or living with HIV: Perspectives from South Africa

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