In-utero exposure to antiretrovirals and neurodevelopment among HIV-exposed-uninfected children in Botswana

Chaudhury, Sumona; Mayondi, Gloria; Williams, Paige L.; Leidner, Jean; Shapiro, Roger; Diseko, Modiegi; Ajibola, Gbolahan; Holding, Penny; Tepper, Vicki; Makhema, Joseph; Petlo, Chipo; Seage, George R.; Lockman, Shahin; Kammerer, Betsy

doi:10.1097/qad.0000000000001790

Cited by 20 publications

(24 citation statements)

References 33 publications

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“…In a US cohort study, language outcomes were affected by specific antiretrovirals (including atazanavir associated with late language emergence at 1 year of age and tenofovir with speech impairment at 3 years but not 5 years of age) 19 . In Botswana, no effect of monotherapy versus triple ART therapy on developmental outcomes was observed, 27 although efavirenz exposure was associated with lower receptive language scores at 2 years of age compared with non-efavirenz-containing therapies 28 . A study from Uganda and Malawi found no increased developmental risk associated with maternal ART 8 .…”

Section: Discussionmentioning

confidence: 99%

Neurodevelopment of HIV-exposed uninfected children in South Africa: outcomes from an observational birth cohort study

Wedderburn

Yeung

Rehman

et al. 2019

The Lancet Child & Adolescent Health

129

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Background HIV infection is known to cause developmental delay, but the effects of HIV exposure without infection during pregnancy on child development are unclear. We compared the neurodevelopmental outcomes of HIV-exposed uninfected and HIV-unexposed children during their first 2 years of life. Methods Pregnant women (>18 years of age) at 20-28 weeks' gestation were enrolled into the Drakenstein Child Health cohort study while attending routine antenatal appointments at one of two peri-urban community-based clinics in Paarl, South Africa. Livebirths born to enrolled women during follow-up were included in the birth cohort. Mothers and infants received antenatal and postnatal HIV testing and antiretroviral therapy per local guidelines. Developmental assessments on the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), were done in a subgroup of infants at 6 months of age, and in the full cohort at 24 months of age, with assessors masked to HIV exposure status. Mean raw scores and the proportions of children categorised as having a delay (scores <-2 SDs from the reference mean) on BSID-III were compared between HIV-exposed uninfected and HIV-unexposed children. Findings 1225 women were enrolled between March 5, 2012, and March 31, 2015. Of 1143 livebirths, 1065 (93%) children were in follow-up at 6 months and 1000 (87%) at 24 months. Two children were diagnosed with HIV infection between birth and 24-month follow-up and were excluded from the analysis. BSID-III assessments were done in 260 (24%) randomly selected children (61 HIV-exposed uninfected, 199 HIV-unexposed) at 6 months and in 732 (73%) children (168 HIV-exposed uninfected, 564 HIV-unexposed) at 24 months. All HIV-exposed uninfected children were exposed to antiretrovirals (88% to maternal triple antiretroviral therapy). BSID-III outcomes did not significantly differ between HIV-exposed uninfected and HIV-unexposed children at 6 months. At 24 months, HIV-exposed uninfected children scored lower than HIV-unexposed for receptive language (adjusted mean difference-1•03 [95% CI-1•69 to-0•37]) and expressive language (-1•17 [-2•09 to-0•24]), whereas adjusted differences in cognitive (-0•45 [-1•32 to 0•43]), fine motor (0•09 [-0•49 to 0•66]), and gross motor (-0•41 [-1•09 to 0•27]) domain scores between groups were not significant. Correspondingly, the proportions of HIV-exposed uninfected children with developmental delay were higher than those of HIV-unexposed children for receptive language (adjusted odds ratio 1•96 [95% CI 1•09 to 3•52]) and expressive language (2•14 [1•11 to 4•15]). Interpretation Uninfected children exposed to maternal HIV infection and antiretroviral therapy have increased odds of receptive and expressive language delays at 2 years of age. Further long-term work is needed to understand developmental outcomes of HIV-exposed uninfected children, especially in regions such as sub-Saharan Africa that have a high prevalence of HIV exposure among children.

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Section: Discussionmentioning

confidence: 99%

Neurodevelopment of HIV-exposed uninfected children in South Africa: outcomes from an observational birth cohort study

Wedderburn

Yeung

Rehman

et al. 2019

The Lancet Child & Adolescent Health

129

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“…30 Additionally, neurodevelopmental outcomes of HEU children perinatally exposed to 3-drug ART were similar to those exposed to zidovudine monotherapy. 31…”

Section: Discussionmentioning

confidence: 99%

Pediatric Neurodevelopmental Functioning After In Utero Exposure to Triple-NRTI vs. Dual-NRTI + PI ART in a Randomized Trial, Botswana

Kacanek

Williams

Mayondi

et al. 2018

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Studies included in the present review also considered the relationships between child development and malaria or HIV (five studies on malaria and 11 studies on HIV). Malaria studies focused primarily on cognitive development ( 44‐47 ) , whereas HIV studies incorporated both cognitive and motor development ( 29,42‐52 ) .…”

Section: Resultsmentioning

confidence: 99%

Nutrition, growth, and other factors associated with early cognitive and motor development in Sub‐Saharan Africa: a scoping review

French

Outhwaite

Langley‐Evans

et al. 2020

J Human Nutrition Diet

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Background: Food insecurity, poverty and exposure to infectious disease are well-established drivers of malnutrition in children in Sub-Saharan Africa. Early development of cognitive and motor skillsthe foundations for learningmay also be compromised by the same or additional factors that restrict physical growth. However, little is known about factors associated with early child development in this region, which limits the scope to intervene effectively. To address this knowledge gap, we compared studies that have examined factors associated with early cognitive and/or motor development within this population. Methods: Predetermined criteria were used to examine four publication databases (PsycInfo, Embase, Web of Science and Medline) and identify studies considering the determinants of cognitive and motor development in children aged 0-8 years in Sub-Saharan Africa. Results: In total, 51 quantitative studies met the inclusion criteria, reporting on 30% of countries across the region. Within these papers, factors associated with early child development were grouped into five themes: Nutrition, Growth and Anthropometry, Maternal Health, Malaria and HIV, and Household. Food security and dietary diversity were associated with positive developmental outcomes, whereas exposure to HIV, malaria, poor maternal mental health, poor sanitation, maternal alcohol abuse and stunting were indicators of poor cognitive and motor development. Discussion: In this synthesis of research findings obtained across Sub-Saharan Africa, factors that restrict physical growth are also shown to hinder the development of early cognitive and motor skills, although additional factors also influence early developmental outcomes. The study also reviews the methodological limitations of conducting research using Western methods in sub-Saharan Africa.

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In-utero exposure to antiretrovirals and neurodevelopment among HIV-exposed-uninfected children in Botswana

Abstract: Neurodevelopmental outcomes at 24 months of age were similar in ART-exposed vs. ZDV-exposed HEU children. Maternal ART with breastfeeding does not appear to have an adverse effect on neurodevelopment.

Cited by 20 publications

References 33 publications

Neurodevelopment of HIV-exposed uninfected children in South Africa: outcomes from an observational birth cohort study

Neurodevelopment of HIV-exposed uninfected children in South Africa: outcomes from an observational birth cohort study

Pediatric Neurodevelopmental Functioning After In Utero Exposure to Triple-NRTI vs. Dual-NRTI + PI ART in a Randomized Trial, Botswana

Nutrition, growth, and other factors associated with early cognitive and motor development in Sub‐Saharan Africa: a scoping review

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