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Neurodevelopment of breastfed HIV-exposed uninfected and HIV-unexposed children in South Africa.

ABSTRACT: OBJECTIVES:To assess neurodevelopment of breastfed HIV-exposed uninfected (HEU) and breastfed HIV-unexposed children in the context of universal maternal antiretroviral therapy (ART). DESIGN:Prospective study with antenatal enrolment and follow-up of breastfeeding HEU and HIV-unexposed mother-infant pairs through 12-18 months postpartum. SETTING:Peri-urban community, Cape Town, South Africa. PARTICIPANTS:HEU (n?=?215) and HIV-unexposed (n?=?306) children. MAIN OUTCOME MEASURES:Cognitive, motor and language development at median 13 (interquartile range 12-14) months of age: continuous and dichotomous Bayley Scales of Infant and Toddler Development Third Edition (delay defined as composite score <85). RESULTS:Incidence of preterm delivery (<37 weeks) was similar among HEU and HIV-unexposed children (11 vs. 9%, P?=?0.31; median gestation 39 weeks); 48% were boys. Median breastfeeding duration was shorter among HEU vs. HIV-unexposed children (6 vs. 10 months). All HIV-infected mothers initiated lifelong ART (tenofovir-emtricitabine-efavirenz) antenatally. HEU (vs. HIV-unexposed) children had higher odds of cognitive delay [odds ratio (OR) 2.28 (95% confidence interval (CI) 1.13-4.60)] and motor delay [OR 2.10 (95% CI 1.03-4.28)], but not language delay, in crude and adjusted analysis. Preterm delivery modified this relationship for motor development: compared with term HIV-unexposed children, term HEU children had similar odds of delay, preterm HIV-unexposed children had five-fold increased odds of delay (adjusted OR 4.73, 95% CI 1.32; 16.91) and preterm HEU children, 16-fold increased odds of delay (adjusted OR 16.35, 95% CI 5.19; 51.54). CONCLUSION:Young HEU children may be at increased risk for cognitive and motor delay despite universal maternal ART and breastfeeding; those born preterm may be particularly vulnerable.

SUBMITTER: le Roux SM

PROVIDER: S-EPMC6341164 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Neurodevelopment of breastfed HIV-exposed uninfected and HIV-unexposed children in South Africa.

le Roux Stanzi M SM Donald Kirsten A KA Brittain Kirsty K Phillips Tamsin K TK Zerbe Allison A Nguyen Kelly K KK Strandvik Andrea A Kroon Max M Abrams Elaine J EJ Myer Landon L

AIDS (London, England) 20180801 13

<h4>Objectives</h4>To assess neurodevelopment of breastfed HIV-exposed uninfected (HEU) and breastfed HIV-unexposed children in the context of universal maternal antiretroviral therapy (ART).<h4>Design</h4>Prospective study with antenatal enrolment and follow-up of breastfeeding HEU and HIV-unexposed mother-infant pairs through 12-18 months postpartum.<h4>Setting</h4>Peri-urban community, Cape Town, South Africa.<h4>Participants</h4>HEU (n = 215) and HIV-unexposed (n = 306) children.<h4>Main out ...[more]

PMID: 29794831

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Project description:BackgroundHIV 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.MethodsPregnant 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.Findings1225 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]).InterpretationUninfected 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.FundingBill & Melinda Gates Foundation, SA Medical Research Council, Wellcome Trust.

Project description:BackgroundHIV infection and its management confer a substantial health burden to affected individuals and have been associated with increased risk of oral and dental diseases. In this study, we sought to quantify HIV-associated differences in the prevalence and severity of dental caries in the primary and permanent dentition of 4-11-year-old Nigerian Children.MethodsWe used clinical, laboratory, demographic, and behavioral data obtained from an ongoing cohort study of age-matched HIV-infected (HI, n = 181), HIV-exposed-but-uninfected (HEU, n = 177), and HIV-unexposed-and-uninfected (HUU, n = 186) children. Measures of dental caries experience (i.e., prevalence and severity) were based on dmft/DMFT indices recorded by trained and calibrated clinical examiners. Differences in primary and permanent dentition caries experience between HI, HEU, and HUU were estimated using multivariable logistic and negative binomial regression modeling.ResultsHI children had significantly higher caries experience (33%) compared to HEU (15%) and HUU (22%) children. This difference persisted in fully adjusted analyses [odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.0-2.6], was most pronounced in the permanent dentition (OR = 3.4; 95% CI = 1.2-9.5), and mirrored differences in caries severity. While molars were predominantly affected in both primary and permanent dentitions, caries lesion patterns differed between dentitions. Caries severity was significantly associated with hypoplastic primary teeth, gingival inflammation, and lower CD4 counts.ConclusionsWe found that the higher prevalence and severity of dental caries among HI children was driven by increased burden of permanent dentition caries compared to their uninfected counterparts. The dentition-specific associations identified in this study highlight the need to design and implement age-specific caries prevention strategies. These may include intensified oral hygiene regimens aimed at mitigating the cariogenic impact of hyposalivation among HI children. Similarly, the long-lasting impacts of developmental defects of the enamel in the primary and permanent dentitions must not be ignored.

Project description:HIV-exposed uninfected (HEU) children may have altered immune regulation and poorer neurodevelopment outcomes compared to their HIV-unexposed (HU) counterparts. However, studies investigating the association of maternal and infant inflammation with neurodevelopment in HEU children are limited and longitudinal data are lacking. This study investigated serum inflammatory markers in women living with HIV vs. HIV-uninfected women during pregnancy and in their children, as well as associations with neurodevelopmental outcomes at two years of age in an African birth cohort study. A sub-group of mother-child dyads from the Drakenstein Child Health Study had serum inflammatory markers measured at ≈26 week's gestation (n = 77 HIV-infected mothers; n = 190 HIV-uninfected mothers), at 6-10 weeks (n = 63 HEU infants and n = 159 HU infants) and at 24-28 months (n = 77 HEU children and n = 190 HU children). Serum inflammatory markers [granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were analyzed with a multiplex bead array and ELISA assays. The Bayley Scales of Infant and Toddler Development, third edition, was used to assess neurodevelopment at 24-28 months. After correcting for multiple comparisons, HIV infection during pregnancy was associated with lower serum levels of inflammatory markers in mothers at 26 weeks gestation (GM-CSF and MMP-9, p < 0.05) and HEU children at 6-10 weeks (IFN-γ and IL-1β, p < 0.01), and at 24-28 months (IFN-γ, IL-1β, IL-2 and IL-4, p < 0.05) compared to HIV-uninfected mothers and HU children. In HEU infants at 6-10 weeks, inflammatory markers (GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1β, IL-2, IL-4, IL-6 and NGAL, all p < 0.05) were associated with poorer motor function at two years of age. This is the first study to evaluate the associations of follow-up immune markers in HEU children with neurodevelopment. These findings suggest that maternal HIV infection is associated with immune dysregulation in mothers and their children through two years of age. An altered immune system in HEU infants is associated with poorer follow-up motor neurodevelopment. These data highlight the important role of the immune system in early neurodevelopment and provide a foundation for future research.

Dataset Information

Neurodevelopment of breastfed HIV-exposed uninfected and HIV-unexposed children in South Africa.

Publications

Neurodevelopment of breastfed HIV-exposed uninfected and HIV-unexposed children in South Africa.

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