Serum cystatin-c as predictive factor of preeclampsia: A meta-analysis of 27 observational studies

Pregnancy Hypertens. 2019 Apr;16:97-104. doi: 10.1016/j.preghy.2019.03.006. Epub 2019 Mar 11.


Objective: Serum cystatin-c is a protein that is filtered freely through the glomerulus and reabsorbed and degraded by proximal tubular cells and can be used as a biomarker of renal function. Its levels rise during the third trimester and decrease in the postpartum period. The purpose of the present meta-analysis is to assess the performance of serum cystatin-c for the prediction of preeclampsia.

Design and methods: We used the Medline, Scopus,, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar. We selected all observational studies (both prospective and retrospective) that investigated the accuracy of cystatin-c in predicting preeclampsia. Statistical meta-analysis was performed with the RevMan 5.3 and Stata/IC 13.0 software, using hierarchical models to develop the SROC curve.

Results: The quantitative synthesis was based in 27 studies with a total number of 2,320 women. Serum cystatin-c levels were higher in preeclamptic women compared to healthy pregnant controls (MD: 0.40 mg/l, 95% CI [0.33, 0.46]). The pooled sensitivity of serum cystatin-c for the prediction of preeclampsia was 0.85 (95% CI [0.79-0.89]) and the pooled specificity 0.84 (95% CI [0.77-0.90]. Fagan's nomogram indicated that the post-test probability increased to 14% (positive test) and decreased to 1% (negative test), when the pre-test probability was set at 3%.

Conclusions: According to the findings of our study serum cystatin-c seems to be a promising biomarker for the detection of preeclampsia during the third trimester of pregnancy. Therefore, its implementation in future predictive models in the field is recommended.

Keywords: Cystatin-c; Hypertension; Meta-analysis; Preeclampsia; Pregnancy.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Biomarkers / blood
  • Cystatin C / blood*
  • Female
  • Humans
  • Observational Studies as Topic
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis*
  • Predictive Value of Tests
  • Pregnancy
  • Prenatal Diagnosis*


  • Biomarkers
  • Cystatin C