Protocol: Multi-Centre Study for Biomarker Identification in Healthy Controls for Comparison to

08 Apr 20264 min read0 viewsJournal Feed

GIST

by Carina C. Babbo, Jeanne van Rensburg, Juanita Mellet, Sithembiso C.

Velaphi, Firdose L. Nakwa, Mogomane Y.K.

Masemola, Gugulabatembunamahlubi T.J. Kali, Caroline J.

Foden, Solize Oosthuizen-Vosloo, Vedarsha Chellan, Odireleng Mosuwe, Priyal Mistry, Ariel R.M. Buyens, Fatima Barmania, Shakti Pillay, Daynia E.

Ballot, Melantha Coetzee, Alan R. Horn, Colleen Wright, Pawel T.

Schubertand, Michael S. Pepper Neonatal encephalopathy suspected to be hypoxic-ischaemic encephalopathy (NESHIE) remains a leading cause of neonatal mortality and long-term neurodevelopmental impairment, particularly in low- and middle-income countries.

While therapeutic hypothermia reduces mortality in moderate to severe cases, a significant proportion of affected infants continue to experience adverse neurological outcomes. This multi-centre observational study aims to elucidate the clinical and biological mechanisms underlying NESHIE by conducting a comprehensive comparative analysis of neonates with moderate to severe NESHIE and healthy term controls.

Participants with NESHIE were previously recruited under an existing approved protocol (University of Pretoria ethics reference: 481/2017), and healthy neonates will be newly enrolled.

Clinical Editorial

Study purpose and design

This is a multi-centre observational project conducted in South Africa, focusing on moderate to severe neonatal encephalopathy suspected to be hypoxic-ischaemic (NESHIE) and comparing these cases with healthy term newborns.
NESHIE participants were previously enrolled under an existing ethics protocol; healthy controls are being enrolled anew to enable a broad, integrative analysis.
The initiative aims to link clinical information with a wide array of molecular data to uncover factors associated with NESHIE and to map its underlying biology.

Comprehensive, multi-omics investigators

Genetic and epigenetic profiling: whole genome sequencing to identify relevant variants and DNA methylation patterns assessed by bisulfite sequencing.
Transcriptomics: both bulk and single-cell RNA sequencing to evaluate gene expression profiles.
Proteomics and metabolomics: liquid chromatography–mass spectrometry applied to dried blood spot samples to delineate protein and metabolite landscapes.
Microbiome and placental analysis: evaluation of the placental microbiome and detailed placental histopathology to characterize differences between NESHIE cases and controls.
Clinical integration: collection and synthesis of clinical data alongside molecular results to identify risk factors and mechanistic clues.

Intended outcomes and potential impact

Identification of clinical risk factors linked to NESHIE within a South African context.
Discovery of molecular signatures that could serve as early diagnostic biomarkers and improve risk stratification for affected neonates.
Generation of foundational knowledge that may guide development of new therapeutic approaches by clarifying disease pathways and placental/microbial contributions.

Operational and ethical context

The study carries National Health Research Database registrations in Gauteng and the Western Cape, and has ethics approvals from the University of Pretoria, University of the Witwatersrand, and Stellenbosch University, along with associated tertiary hospitals.
By leveraging a multi-center design and diverse data types, the project seeks to create a holistic view of NESHIE etiology, encompassing genetic, epigenetic, transcriptomic, proteomic, metabolomic, placental, and microbiome dimensions.

Limitations and scope

The summary notes that healthy controls are newly enrolled, while NESHIE cases come from an existing protocol, which may influence baseline comparability.
As a protocol-focused report, explicit results or quantitative findings are not provided; the emphasis is on planned methods, data types, and intended analyses to advance biomarker discovery and pathophysiological understanding.