The impact of inflammatory and metabolic breast milk profiles associated with maternal HIV on infant growth and development
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University of Pretoria
Abstract
As of 2022, approximately 39 million (33.1–45.7 million) people were living with human immunodeficiency virus (HIV), with approximately 8.45 million of these infections being accounted for in the South African population. The introduction of combination antiretroviral therapy (ART) has led to a considerable decrease in HIV-1-linked morbidity and mortality globally, including in the South African setting, and HIV-1 has been reduced from a fatal disease to a controllable chronic condition. In addition, availability of ART to pregnant woman has dramatically reduced the number of HIV infections passed vertically from mother-to-child since 2000; however, as more women living with HIV (WLWH) gain access to ART, the number of HIV-exposed-uninfected (HEU) infants being born is increasing in resource-limited settings. The term HEU is commonly associated with children born to mothers living with HIV (MLWH) and, as such, have been exposed to HIV in utero and postpartum, however, these infants are born HIV-negative. It is, however, becoming ever evident that these children have complications that may be related to the inefficient transfer of immunological factors from mother to infant during pregnancy and lactation, and/or exposure to HIV/ART in utero. These complications include suboptimal growth, and increased susceptibility to opportunistic infections that cause diarrhoea and pneumonia. Globally in 2022, 16 million HEU children (0–14 years) were born to MLWH and consequently at risk of diminished health outcomes. South Africa has reported a 29% public sector antenatal HIV prevalence since 2009, with 25% of all children being HEU, and it is also home to 25% of the global HEU population. Indeed, South Africa has the world’s highest recorded number of HEU infants with an estimated 3.5 million HEU infants.
Despite the increased possibility of vertical transmission of HIV from mother-to-child through breastfeeding, the World Health Organisation (WHO) has suggested that MLWH exclusively breastfeed their infants until they are six months of age and should continue breastfeeding for at least 12 months and up to 24 months (in line with the general population) while fully supported to adhere to ART. The present study, therefore, aimed to build on the knowledge base of HEU infants, compared to HIV-unexposed-uninfected (HUU) infants. The current study determined whether inflammatory cytokines [interleukin (IL)-2, IL-6, IL-8, and tumour necrosis factor-alpha (TNF-α)], and antimicrobial peptides [beta-defensin-2, lactoferrin (LTF), lysozyme (LZM), and tenascin C (TNC)], as well as the metabolic profile (2-oxoglutaric acid, butyric acid, caproic acid, 6`-sialyllactose, lacto-n-neooctaose, myo-inositol, isoleucine, leucine, tryptophan, phenylalanine, tyrosine, and uridine) found in breast milk at the time of birth (colostrum), during exclusive breastfeeding (6 ± 4 weeks postpartum), and following the introduction of solids into the infants diet (6 ± 3 months postpartum) are associated with suboptimal infant growth.
A total of 24 mothers were selected to participate in the current study. These mothers were divided into two groups: 15 HIV-uninfected mothers and nine MLWH. All of the participants were of African descent with similar socioeconomic backgrounds attending follow-up clinics at Kalafong Tertiary Hospital in Southwest Tshwane, South Africa. The MLWH recruited for the present study were on a fixed dose of combination ART comprising tenofovir disoproxil fumarate, emtricitabine, and efavirenz. The infant anthropometric characteristics were analysed at birth, 6- or 10-weeks, and 6- or 9-months postpartum. For the analysis of the inflammatory immune factors, antimicrobial peptides and metabolomic profile, breast milk samples were analysed using suspension bead array technology, manual enzyme-linked immunosorbent assays, and untargeted nuclear magnetic resonance, respectively.
Human immunodeficiency virus-exposed-uninfected infants in the current study exhibited moderately poorer growth compared to the HUU cohort from the same socioeconomic background; these differences were, however, not significant. All the inflammatory markers (except for IL-6), as well as the antimicrobial peptides LZM and TNC, were markedly higher in the colostrum of HIV-uninfected mothers compared to MLWH. Moreover, breast milk metabolites, which are important for infant growth and immunity, detected in the current study were lower in the breast milk from MLWH when compared to that of HIV-uninfected mothers. The findings from the current study provide further insight into the immune, antimicrobial peptide, and metabolic profiles present in the breast milk of HIV-uninfected mothers compared to that of MLWH, and the extent to which these profiles differ. The results from the present study may lead to a better understanding of the maternal immunological and metabolite environment that may adversely affect HEU children’s health. These results underscore the importance of monitoring this vulnerable group of infants for possible infections from opportunistic microorganisms. Supplementing the diet of MLWH, and their HEU infants, to overcome the deficiencies in metabolites observed in the breast milk of MLWH compared to that of HIV-uninfected mothers, is highlighted.
Description
Dissertation (MSc (Medical Immunology))--University of Pretoria, 2024.
Keywords
UCTD, Sustainable Development Goals (SDGs), Cytokines, Antimicrobial peptides, Metabolites, Infant growth, Breast milk
Sustainable Development Goals
SDG-03: Good health and well-being
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