Related Experiment Video
Updated: Jul 31, 2025
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Biomarkers of Growth Faltering and Neurodevelopmental Delay in Children who are HIV-Exposed but Uninfected: A
Reshma Sirajee1, Jason Brophy2, Andrea L Conroy3
1Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Insights
Biomarkers like C-reactive protein and various interleukins are linked to growth faltering and neurodevelopmental delays in HIV-exposed, uninfected children. These inflammation markers may indicate pathways of injury in this vulnerable population.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Neurodevelopmental Biology
Background:
- Children who are HIV-exposed but uninfected (CHEU) face risks of linear growth faltering and neurodevelopmental delay.
- Identifying circulating biomarkers can elucidate injury pathways and inform interventions for CHEU.
Approach:
- A systematic review was conducted across major electronic databases (MEDLINE, EMBASE, Scopus, PubMed) following PRISMA guidelines.
- Studies associating biomarker abnormalities with growth and neurodevelopmental outcomes in CHEU were identified and analyzed.
Key Points:
- Seven studies linked biomarker abnormalities to growth outcomes, identifying C-reactive protein (CRP), tumor necrosis factor (TNF), and various interleukins (ILs) as significant.
- Two studies associated biomarker abnormalities with neurodevelopmental delay, highlighting CRP, interferon-gamma (IFN-γ), and multiple ILs.
- Specific biomarkers like insulin-like growth factor-1 (IGF-1) and neutrophil gelatinase-associated lipocalin (NGAL) were also implicated.
Conclusions:
- Elevated inflammation markers, including acute phase reactants and pro-inflammatory cytokines, are associated with growth faltering in CHEU.
- These inflammatory markers are also linked to adverse neurodevelopmental outcomes in this population.
- Intestinal microbial translocation is another factor associated with growth faltering in CHEU.
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.
