Predictive value of serum biomarkers for first trimester prediction of preterm prelabour rupture of membranes (PPROM): a systematic review and meta-analysis

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INTRODUCTION: The identification of early biomarkers is a critical prerequisite for the development and optimization of preventive strategies targeting preterm prelabour rupture of membranes (pPROM). The aim of this systematic review was to evaluate first trimester serum biomarkers for predicting the occurrence of pPROM. CONTENT: This is a systematic review of the literature made according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. Articles were extracted from the Medline, Embase, and Web of Science databases using the keywords "first trimester" and "prelabour rupture of membranes". Two investigators used a systematic strategy to select eligible publications. SUMMARY: We selected 28 studies of interest representing 7,928 cases of pPROM. A significant association was found between pPROM and thirteen biomarkers. None of them predicted pPROM accurately when assessed by single-biomarker approaches. Results were pooled to evaluate PAPP-A, AGE, CX3CL1 and platelet count and volume, representing respectively 330, 91, 204 and 378 cases of pPROM. Other biomarkers had not been studied in enough trials for data to be combined. PAPP-A was the most widely studied biomarker, offering the best confidence and the largest effect (-0.84 [-1.33; -0.35]). The best sensitivity was found for CX3CL1, with a small to moderate effect size (0.34 [0.16-0.52]). Platelet volume exhibited a moderate effect size (-0.62 [-0.97; -0.26]). OUTLOOK: Our review highlights the urgent need for well-designed studies to identify biomarkers for early prediction of pPROM, including combined approaches.

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