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

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.