The sFlt-1/PlGF ratio of high-risk pregnant women for preeclampsia compared in singleton, twin, and triplet pregnancies

Taiwan J Obstet Gynecol. 2025 Nov;64(6):996-1003. doi: 10.1016/j.tjog.2025.07.023.

Abstract

Objective: To evaluate the predictive performance of the soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio for preeclampsia across singleton, twin, and triplet pregnancies.

Materials and methods: A retrospective cohort study was performed in pregnant women who had sFlt-1/PlGF testing and delivered at Seoul National University Bundang Hospital from March 2019 to December 2023. Maternal characteristics and obstetric outcomes were reviewed, and patients were classified into singleton, twin, and triplet pregnancies. The predictive performance of the sFlt-1/PlGF ratio was assessed using logistic regression and receiver operating characteristic (ROC) curve analysis. Clinically validated cut-off values from the NICE guideline were applied.

Results: Among 773 patients (288 singletons, 469 twins, and 16 triplets), preeclampsia was diagnosed in 55.9 %, 29.4 %, and 62.5 % of cases, respectively. In singleton pregnancies, 81.4 % of preeclampsia cases had an sFlt-1/PlGF ratio >38, and 73.3 % had a ratio >85, compared to 68.1 % and 32.6 % in twins. For preeclampsia before 34 weeks, the sFlt-1/PlGF ratio was significantly lower in twin and triplet pregnancies than in singletons (both p < 0.05). The predictive value of the sFlt-1/PlGF ratio was highest in singleton pregnancies, with an area under the curve (AUC) of 0.870 [95 % Confidence interval (CI) = 0.826-0.914] for preeclampsia before 34 weeks, compared to 0.789 [95 % CI = 0.717-0.862] in twins and 0.813 [95 % CI = 0.592-1.033] in triplets. At the predefined cut-off of 85, logistic regression confirmed that an sFlt-1/PlGF ratio >85 was significantly associated with preeclampsia before 34 weeks in singletons (OR = 16.06, 95 % CI = 8.75-29.49, p < 0.001) and still significant in twins (OR = 3.66, 95 % CI = 1.74-7.69, p = 0.001), but not in triplets.

Conclusions: While the sFlt-1/PlGF ratio remains a valuable biomarker for preeclampsia prediction in singleton and twin pregnancies, its clinical utility in triplet pregnancies is limited. Further large-scale studies are needed to establish optimal cut-off values for multifetal pregnancies, particularly in triplets, to enhance risk stratification and clinical application.

Keywords: Angiogenic factor; Multifetal pregnancy; Preeclampsia; Triplet; Twin; sFlt-1/PlGF ratio.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Female
  • Humans
  • Placenta Growth Factor* / blood
  • Pre-Eclampsia* / blood
  • Pre-Eclampsia* / diagnosis
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy, High-Risk* / blood
  • Pregnancy, Triplet* / blood
  • Pregnancy, Twin* / blood
  • ROC Curve
  • Retrospective Studies
  • Vascular Endothelial Growth Factor Receptor-1* / blood

Substances

  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1
  • Biomarkers
  • FLT1 protein, human
  • PGF protein, human