The association between serum soluble fms-like tyrosine kinase-1, placental growth factor, and soluble fms-like tyrosine kinase-1/placental growth factor ratio in singleton pregnancy and placental abruption: a systematic review and meta-analysis

Abstract

Objective: The study aimed to evaluate whether women with singleton pregnancies who experienced subsequent placental abruption had lower serum placental growth factor concentrations, higher serum soluble fms-like tyrosine kinase-1 concentrations, and a higher soluble fms-like tyrosine kinase-1/placental growth factor ratio compared to women with singleton pregnancies without placental abruption.

Data sources: PubMed/MEDLINE, Scopus, and the Web of Science and ClinicalTrials.gov databases had been searched electronically until March 2025, using combinations of relevant medical subject heading terms, keywords, and word variants considered suitable for the topic.

Study eligibility criteria: Prospective and retrospective comparative cohort studies and case-control studies were included. Case reports, editorials, letters to the editor, and conference abstracts were excluded from the systematic review.

Study appraisal and synthesis methods: The outcome of the study included differences in placental growth factor, soluble fms-like tyrosine kinase-1 concentrations, or the soluble fms-like tyrosine kinase-1/placental growth factor ratio between placental abruption cases and a group without placental abruption. The quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Continuous data were expressed as the mean difference with a 95% confidence interval when the units of measurement for the outcome variable were the same. When conducting the meta-analysis, a random effects model was consistently employed.

Results: The main findings of this systematic review and meta-analysis are as follows: 1) maternal serum placental growth factor concentration did not differ between women with and without placental abruption; 2) maternal serum soluble fms-like tyrosine kinase-1 concentration was higher in women with placental abruption, especially when assessed in the second half of gestation; and 3) maternal serum soluble fms-like tyrosine kinase-1/placental growth factor ratio was higher in women with placental abruption, both in the first and second half of pregnancy, with the difference being no longer significant in women with the diagnosis or symptoms of preeclampsia.

Conclusion: The results presented in this systematic review may improve the risk stratification for placental abruption. Understanding the changes of the above markers in placental abruption may support clinical guideline development with regard to prediction models of the above complication.

Keywords: maternal angiogenic biomarkers; meta-analysis; placental abruption; placental dysfunction; placental growth factor (PlGF); sFlt-1/PlGF ratio; soluble fms-like tyrosine kinase-1 (sFlt-1); systematic review.