Soluble endoglin concentration in maternal blood as a diagnostic biomarker of preeclampsia: A systematic review and meta-analysis

Objective: Preeclampsia is a main cause of maternal and fetal morbidity and mortality. Research about maternal circulating diagnostic biomarkers is continuously performed, often with conflicting results that necessitate quantitative synthesis. Objective of this meta-analysis is to examine the value of soluble endoglin as predictor of preeclampsia separately at each pregnancy trimester, therefore exploring its potential usage as diagnostic biomarker in preeclampsia.Study design: This systematic review and meta-analysis adhered to PRISMA and MOOSE guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and ClinicalTrials.gov were searched up to April 20, 2020. Included studies were those comparing soluble endoglin levels in maternal serum or plasma at any pregnancy trimester, between women who subsequently developed preeclampsia and normotensive pregnant women being low-risk for preeclampsia development. Primary outcome was development of preeclampsia, while soluble endoglin levels in 1 st, 2nd and 3rd trimester of pregnancy were examined as possible predictors of preeclampsia. Subgroup analysis was performed regarding time of preeclampsia onset (early, late). Methodological quality of included studies was assessed using Newcastle-Ottawa scale. Overall quality of evidence for primary and secondary outcomes was evaluated using GRADEpro GD tool.Results: There were overall 20 studies included in meta-analysis, enrolling 1146 preeclamptic and 1675 normotensive pregnant women. Soluble endoglin concentration (ng/mL) was significantly higher in preeclamptic women during 2nd (8 studies, MD:5.554, 95 %CI:2.671-8.436, P < .001, I-2 = 97 %) and 3rd trimester (12studies, MD:31.006, 95 %CI:24.734-37.278, P < .001, I-2 = 98 %). Levels were also higher during 1st trimester; however, the difference was marginally not significant (MD:1.105, 95 %CI: -0.071 to 2.282, P = .06, I-2= 64 %). Furthermore, levels were significantly higher both in early-onset and late-onset preeclamptic vs normotensive pregnancies, (4 studies, MD:51.611, 95 %CI: 2.250-100.972, P = .04,I-2 = 97 %), (5 studies, MD:12.426, 95 %CI:7.863-16.989, P < .001, I-2 = 98 %) respectively. However, when comparing directly early and late-onset preeclamptic women, no significant difference was detected (3 studies, MD:20.725, 95 %CI: -11.601 to 53.052, P = .209, I-2 = 93 %).Conclusions: Soluble endoglin levels were consistently higher in preeclamptic compared to normotensive pregnant women almost throughout pregnancy. Our results firmly indicate soluble endoglin's potential use as predictor of preeclampsia. Further studies are required to support the use of soluble endoglin as a diagnostic tool for preeclampsia in clinical settings. (C) 2021 Elsevier B.V. All rights reserved.