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Determinants of growth in HIV-exposed and HIV-uninfected infants in the Kabeho Study.

ABSTRACT: HIV-exposed and HIV-uninfected (HEU) infants may be at increased risk of poor health and growth outcomes. We characterized infant growth trajectories in a cohort of HEU infants to identify factors associated with healthy growth. HIV-positive women participating in prevention of mother-to-child HIV transmission programmes in Kigali, Rwanda, were followed until their infants were 2 years old. Infant anthropometrics were regularly collected. Latent class analysis was used to categorize infant growth trajectories. Multiple logistic regression was used to estimate the odds of infants belonging to each growth trajectory class. On average, this population of HEU infants had moderate linear growth faltering, but only modest faltering in weight, resulting in mean weight-for-length z-score (WLZ) above the World Health Organization (WHO) median. Mean WLZ was 0.53, and mean length-for-age z-score (LAZ) was -1.14 over the first 2 years of life. We identified four unique WLZ trajectories and seven trajectories in LAZ. Low neonatal weight-for-age and a high rate of illness increased the likelihood that infants were in the lightest WLZ class. Shorter mothers were more likely to have infants with linear growth faltering. Female infants who were older at the end of exclusive breastfeeding were more likely to be in the second tallest LAZ class. In conclusion, the current WHO recommendations of Option B+ and extended breastfeeding may induce higher WLZ and lower LAZ early in infancy. However, there is considerable heterogeneity in growth patterns that is obscured by simply analysing average growth trends, necessitating the analysis of growth in subpopulations.

SUBMITTER: Lane CE

PROVIDER: S-EPMC6667835 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Determinants of growth in HIV-exposed and HIV-uninfected infants in the Kabeho Study.

Lane Charlotte E CE Bobrow Emily A EA Ndatimana Diuedonne D Ndayisaba Gilles F GF Adair Linda S LS

Maternal & child nutrition 20190129 3

HIV-exposed and HIV-uninfected (HEU) infants may be at increased risk of poor health and growth outcomes. We characterized infant growth trajectories in a cohort of HEU infants to identify factors associated with healthy growth. HIV-positive women participating in prevention of mother-to-child HIV transmission programmes in Kigali, Rwanda, were followed until their infants were 2 years old. Infant anthropometrics were regularly collected. Latent class analysis was used to categorize infant growt ...[more]

PMID: 30609287

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Project description:ObjectivesHIV-exposed uninfected (HEU) infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU) infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK) cell activity might occur in HEU infants and predispose them to severe infections.DesignCase-control study using cryopreserved peripheral blood mononuclear cells (PBMCs) at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001) and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005). At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001) and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047), but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFN)γ at birth (0.77 vs. 2.64%, p = 0.008) and at 6 months (4.12 vs. 8.39%, p = 0.001), and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008). Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL)-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory cell function may contribute to the increased susceptibility to infection in HEU infants.

Dataset Information

Determinants of growth in HIV-exposed and HIV-uninfected infants in the Kabeho Study.

Publications

Determinants of growth in HIV-exposed and HIV-uninfected infants in the Kabeho Study.

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