Dataset Information

Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort.

ABSTRACT: 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-? (IFN-?), interleukin IL-1?, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-? (TNF-?), 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?

SUBMITTER: Sevenoaks T

PROVIDER: S-EPMC7772888 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort.

Sevenoaks Tatum T Wedderburn Catherine J CJ Donald Kirsten A KA Barnett Whitney W Zar Heather J HJ Stein Dan J DJ Naudé Petrus J W PJW

Brain, behavior, and immunity 20200826

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 n ...[more]

PMID: 32860940

Similar Datasets

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:IntroductionExposure to maternal HIV in pregnancy may be a risk factor for impaired child neurodevelopment during the first years of life. Altered neurometabolites have been associated with HIV exposure in older children and may help explain the mechanisms underlying this risk. For the first time, we explored neurometabolic profiles of children who are HIV-exposed and uninfected (CHEU) compared to children who are HIV-unexposed (CHU) at 2-3 years of age.MethodsThe South African Drakenstein Child Health Study enrolled women during pregnancy and is following mother-child pairs through childhood. MRI scans were acquired on a sub-group of children at 2-3 years. We used single voxel magnetic resonance spectroscopy to measure brain metabolite ratios to total creatine in the parietal grey matter, and left and right parietal white matter of 83 children (36 CHEU; 47 CHU). Using factor analysis, we explored brain metabolite patterns in predefined parietal voxels in these groups using logistic regression models. Differences in relative concentrations of individual metabolites (n-acetyl-aspartate, myo-inositol, total choline, and glutamate) to total creatine between CHEU and CHU groups were also examined.ResultsFactor analysis revealed four different metabolite patterns, each one characterized by covarying ratios of a single metabolite in parietal grey and white matter. The cross-regional pattern dominated by myo-inositol, a marker for glial reactivity and inflammation, was associated with HIV exposure status (OR 1.63; 95% CI 1.11-2.50) which held after adjusting for child age, sex, and maternal alcohol use during pregnancy (OR 1.59; 95% CI 1.07 -2.47). Additionally, higher relative concentrations of myo-inositol to total creatine were found in left and right parietal white matter of CHEU compared to CHU (p=0.025 and p=0.001 respectively).DiscussionIncreased ratios of myo-inositol to total creatine in parietal brain regions at age 2-3 years in CHEU are suggestive of early and ongoing neuroinflammatory processes. Altered relative concentrations of neurometabolites were found predominantly in the white matter, which is sensitive to neuroinflammation, and may contribute to developmental risk in this population. Future work on the trajectory of myo-inositol over time in CHEU, alongside markers of neurocognitive development, and the potential for specific neurodevelopmental interventions will be useful.

Project description:IntroductionThere are approximately 16 million children who are HIV-exposed and uninfected (CHEU) worldwide. Studies suggest that CHEU are at risk for developmental impairment in infancy, particularly in language domains. However, there is limited research examining neurocognitive function in CHEU older than 2 years, including important pre-school years. This study aimed to investigate associations between HIV exposure without infection and neurocognitive outcomes and to determine risk factors for neurodevelopment in CHEU at age 3-4 years.MethodsThe Drakenstein Child Health Study is a South African population-based birth cohort which enrolled women in pregnancy with ongoing follow up. Neurocognitive outcomes were assessed in children at 3.5 years by trained assessors blinded to HIV status including general cognitive function, language, and memory, measured using the Kaufmann Assessment Battery for Children, Second Edition (KABC-II). Data were compared between CHEU and children who were HIV-unexposed uninfected (CHUU) using multivariable logistic and linear regression, including testing for effect modification; sex-stratified risk factor analyses were performed.ResultsA total of 497 children were included (97 [20%] CHEU; 400 [80%] CHUU; 50% male), with a mean age of 3.5 years (range 3.4-3.6). Groups had similar birth and household characteristics, although mothers of CHEU were older, on average. Overall, CHEU had lower expressive language scores compared to CHUU on unadjusted and adjusted analyses (effect size: -0.23 [95% CI -0.45, -0.01]). There were no group differences in general cognitive or memory function (p>0.05). On sex-stratified analyses, male CHEU were found to have higher odds of suboptimal cognitive development compared to male CHUU (aOR 2.28 [95% CI 1.06, 4.87], p = 0.034). Several other factors including birthweight, maternal education, maternal ART duration and HIV viral load during pregnancy were associated with cognition, memory, or expressive language outcomes in CHEU, dependent on child sex.InterpretationThe findings suggest that perinatal HIV exposure continues to be associated with impaired language development across the preschool years, highlighting the importance of targeting early interventions to optimise language outcomes. Further, the results suggest the importance of demographic, biological and HIV-related variables influencing developmental outcomes in CHEU. The greater risk of suboptimal cognitive development in male CHEU requires investigation around sex-specific mechanisms.

Dataset Information

Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort.

Publications

Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets