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Pregnancy-associated plasma protein A (PAPP-A) as a first trimester serum biomarker for preeclampsia screening: a systematic review and meta-analysis

Ismini Tzanaki, Antonis Makrigiannakis, Charoula Lymperopoulou, Zeyad Al-Jazrawi, Aris P. Agouridis

2025The Journal of Maternal-Fetal & Neonatal Medicine11 citationsDOIOpen Access PDF

Abstract

Objective The aim of this study is to systematically examine the role of the pregnancy-associated plasma protein A (PAPP-A) serum biomarker in the first trimester screening of preeclampsia (PE).Materials and methods A systematic search of the literature was conducted on PubMed via Medline, and Cochrane Library up to 8 November 2022, for prospective studies evaluating PAPP-A serum levels in first trimester pregnant women as a screening biomarker for PE. Eligible were all prospectively designed case-control or cohort studies, published in English. Two investigators independently examined the studies and the studies’ characteristics were extracted. Newcastle-Ottawa Scale (NOS) for case-control and cohort studies were applied to assess the risk of bias. For the quantitative analysis of the studies, a meta-analysis was also performed.Results A total of 22 studies including 33,651 pregnant women were assessed, of whom, 2001 were diagnosed with PE. A meta-analysis was performed, showing that PAPP-A levels in the first trimester were significantly lower in early onset preeclamptic women (MD: −0.24, 95% CI: −0.37, −0.11, p = .0002), late onset (MD: −0.15, 95% CI: −0.25, −0.05, p = .03), and total preeclamptic cases (MD = −0.17, 95% CI = −0.23, −0.11, p < .00001) when compared with controls.Conclusions Our results suggest that PAPP-A can be a promising predictor in early screening for PE; hence, women at risk can be diagnosed early in their pregnancy stage and benefit from individualized PE treatment before it progresses.

Topics & Concepts

PreeclampsiaBiomarkerPregnancy-associated plasma protein APregnancyMeta-analysisMedicineObstetricsFirst trimesterInternal medicineBiologyGestationBiochemistryGeneticsPregnancy and preeclampsia studiesMaternal and fetal healthcareGestational Diabetes Research and Management