Quantitating soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) biomarker levels along with sFlt-1/PlGF ratio in patients with extragenital diseases for diagnostics of early- and late-onset preeclampsia

Introduction. Preeclampsia (PE) remains one of the most pressing issues in modern obstetrics being a leading cause of maternal and perinatal morbidity and mortality. PE is a multisystem disorder that manifests after 20 weeks of gestational age, which is characterized by arterial hypertension accompanied by proteinuria and/or multiorgan dysfunction.

Aim: to quantitate the levels of biomarkers – soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) as well as sFlt-1/PlGF ratio – in patients with pre-existing extragenital diseases for diagnostics of early- and late-onset PE.

Materials and Methods. This prospective study enrolled 439 patients with pre-existing extragenital diseases (type 1 and type 2 diabetes mellitus, chronic arterial hypertension, chronic pyelonephritis, chronic glomerulonephritis), divided into subgroup with PE (n = 94) and subgroup without PE (n = 345). Patients were monitored throughout pregnancy, starting from 12 weeks of gestational age. Serum PlGF and sFlt-1 levels were measured using electrochemiluminescent diagnostic tests on automated analyzers followed by calculating sFlt-1/PlGF ratio for each serum sample. In order to determine the prognostic value of sFlt1/PlGF ratio for diagnosing PE, ROC curves were created for subsequent assessing the quality of the prognosis.

Results. The timing for manifestation of early- and late-onset PE showed distinct dynamics of angiogenic biomarker changes. In early-onset PE, a statistically significant increase in sFlt-1 levels (p = 0.001) and sFlt-1/PlGF ratio (p = 0.003) was observed as early as 22–24 weeks of gestational age. In late-onset PE, the changes were less pronounced and reached statistical significance only sporadically at 25–27 weeks of gestational age (p = 0.027). While assessing PE development, alterations in the examined biomarker levels served as early predictors, preceding delivery by up to 6 weeks. For patients with pre-existing extragenital diseases, a lower cut-off value for sFlt-1/PlGF ratio was established at 11.8.

Conclusion. It may be concluded that assessing angiogenic biomarker levels provide high diagnostic value in patients with pre-existing extragenital diseases from late second to early third trimester of gestation (28–33 weeks). Examining the biomarkers' diagnostic value based on ROC-analysis revealed the following hierarchy of predictive efficacy: sFlt-1/PlGF ratio demonstrated the highest predictive value, outperforming separately quantitated either sFlt-1 or PlGF. Key metrics (sensitivity, specificity, and the area under the ROC curve – AUC) confirm that sFlt-1/PlGF ratio is the most effective predictor for diagnosing PE in the patient cohort compared with isolated measurement of sFlt-1 and PlGF magnitude. The optimal cut-off value for sFlt-1/PlGF ratio is identified at level of 11.8. It was established that the maximum predictive window for assessing risk of developing PE using this criterion is 6 weeks underscoring its high clinical value for timely identifying at-risk groups and initiating preventive measures.

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