First-trimester urinary glycolic acid and methylsuccinic acid measurement for preeclampsia prediction: A Systematic review protocol.

INTRODUCTION: Preeclampsia is an important cause of maternal and neonatal morbidity and mortality around the world, with hypertension on the rise in sub-Saharan Africa. First-trimester screening for preeclampsia is vital for guiding preventative therapies like low dose aspirin. Traditional biomarkers face accessibility barriers in low-resource settings. Urinary glycolic acid (GA) and methylsuccinic acid (MSA) have emerged as stable, cost-effective, non-invasive metabolic candidates. However, their prognostic value has not been systematically evaluated. This systematic review aims to evaluate the prognostic value of first trimester urinary glycolic acid and methylsuccinic acid for development of preeclampsia. METHODS: This systematic review will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis - Protocols (PRISMA-P) checklist and has been registered with PROSPERO (CRD420251057596). The following databases will be searched: Cochrane Library, Embase, PubMed/MEDLINE, Scopus, Web of Science, grey literature and trial registries from 2008 to August 2026. Eligible studies will include pregnant women in the first trimester (<14 weeks) with urinary GA and/or MSA measured, comparing those who develop preeclampsia to normotensive controls. Two independent reviewers will screen titles/abstracts and full texts, with conflicts resolved by a third reviewer. Risk of bias will be assessed using the Quality in Prognosis Studies (QUIPS) tool. Data will be synthesized narratively: if more than 3 studies report comparable metrics, a meta-analysis using a random effects model will be performed. ETHICS AND DISSEMINATION: As a secondary analysis of peer reviewed articles, this review does not require ethical approval. Findings from the review will be disseminated through conference presentations and peer-reviewed publication.