Title:Biomarkers of Growth Faltering and Neurodevelopmental Delay in
Children who are HIV-Exposed but Uninfected: A Systematic Review
Volume: 21
Issue: 3
Author(s): Reshma Sirajee, Jason Brophy, Andrea L. Conroy, Sophie Namasopo, Robert O. Opoka, Urvi Rai, Sarah Forgie, Bukola O. Salami and Michael T. Hawkes*
Affiliation:
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
- Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton,
Canada
- School of Public Health, University of Alberta, Edmonton, Canada
- Stollery Science Lab, Women
and Children’s Health Research Institute, Edmonton, Canada
Keywords:
HIV, child, inflammation, growth, neurodevelopment, CHEU.
Abstract:
Introduction: Children who are HIV-exposed but uninfected (CHEU) are at risk of linear
growth faltering and neurodevelopmental delay. Circulating biomarkers associated with these adverse
outcomes may elucidate pathways of injury.
Objective: To identify biomarkers associated with growth faltering and neurodevelopmental delay
in CHEU.
Methods: We performed a systematic review of electronic databases MEDLINE (1946-April 2021),
EMBASE (1974-April 2021), Scopus (2004-April 2021), and PubMed (1985-April 2021), following
the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic
review was registered on the International Prospective Register of Systematic Reviews
(PROSPERO, registration number CRD42021238363).
Results: We found seven studies associating biomarker abnormalities and growth outcomes in
CHEUs and two studies on biomarker abnormalities and neurodevelopmental delay. Biomarker abnormalities
associated with growth restriction were: C-reactive protein (CRP), tumour necrosis factor
(TNF), interferon-gamma (IFN-γ), interleukin (IL)-12p70, IFN-γ-induced protein-10
(CXCL10/IP-10), lipopolysaccharide binding protein (LBP), insulin-like growth factor-1 (IGF-1),
and IGF-binding protein-1 (IGFBP-1). Biomarkers associated with motor, language, and cognitive
delay were CRP, IFN-γ, IL-1β, -2, -4, -6, -10, -12p70, neutrophil gelatinase-associated lipocalin
(NGAL), granulocyte-macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase-
9 (MMP-9).
Conclusion: Elevated markers of inflammation (acute phase reactants, pro-inflammatory cytokines,
chemokines) and intestinal microbial translocation are associated with growth faltering. Elevated
markers of inflammation are associated with adverse neurodevelopment.
