<scp>sFlt</scp> ‐1/ <scp>PlGF</scp> ratio thresholds for diagnosing pre‐eclampsia in pregnant women with high blood pressure

Abstract

OBJECTIVE: An imbalance between soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) is characteristic of the progression of hypertensive disorder of pregnancy (HDP) to pre-eclampsia (PE). Monitoring the sFlt-1/PlGF ratio to determine whether HDP progresses to PE can aid clinical management and decision-making. This study aimed to determine the diagnostic thresholds of the sFlt-1/PlGF ratio for early-onset and late-onset PE in pregnant Chinese women with high blood pressure. METHODS: This single-center, prospective, observational cohort study was conducted among pregnant women with high blood pressure (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg) at a tertiary hospital in Southern China, from January 2020 to December 2023. Women with a singleton pregnancy and complete follow-up records were assigned to the derivation cohort or the validation cohort depending on their date of enrolment. Initial cut-offs of the sFlt-1/PlGF ratio to predict the development of early-onset or late-onset PE within 1 week after biomarker measurement were determined using receiver-operating-characteristics-curve analysis in the derivation cohort. This analysis was performed separately for pregnancies with gestational age (GA) < 34 weeks and those with GA ≥ 34 weeks at the time of biomarker measurement. Subsequently, the derived cut-offs were validated in the validation cohort. The rate of adverse maternal and perinatal outcomes was compared according to whether the sFlt-1/PlGF ratio was above or below the validated cut-off, stratified by GA at biomarker measurement, in both the derivation and validation cohorts. RESULTS: A total of 1329 women with a singleton pregnancy complicated by high blood pressure, presenting between 24 + 0 and 38 + 6 weeks' gestation, were recruited during the study period. Participants were stratified into the derivation (n = 814 (61.2%)) and validation (n = 515 (38.8%)) cohorts, which had comparable PE incidence within 1 week after sFlt-1/PlGF measurement (35.5% vs 38.6%, respectively; P = 0.267). In the derivation cohort, the optimal sFlt-1/PlGF ratio cut-offs were determined to be 74 for predicting early-onset PE (diagnosis < 34 weeks) and 95 for predicting late-onset PE (diagnosis ≥ 34 weeks). In the validation cohort, the predetermined sFlt-1/PlGF ratio cut-off of ≥ 74 showed a sensitivity of 87.7% (95% CI, 77.9-94.2%) and a specificity of 97.0% (95% CI, 91.6-99.4%) for predicting early-onset PE within 1 week after biomarker measurement, while a sFlt-1/PlGF ratio of ≥ 95 demonstrated a sensitivity of 36.5% (95% CI, 28.1-45.6%) and a specificity of 95.0% (95% CI, 91.0-97.4%) for the prediction of late-onset PE within 1 week. Additionally, these ratios (≥ 74 for GA < 34 weeks and ≥ 95 for GA ≥ 34 weeks at biomarker measurement) significantly predicted adverse maternal and perinatal outcomes in both cohorts. CONCLUSIONS: In pregnant women with high blood pressure presenting between 24 + 0 and 38 + 6 weeks' gestation, the validated sFlt-1/PlGF ratio cut-offs for predicting early-onset PE and late-onset PE diagnosis within 1 week after biomarker measurement were 74 and 95, respectively. Furthermore, sFlt-1/PlGF ratios ≥ 74 and ≥ 95 were associated with increased risks of adverse maternal and perinatal outcomes, suggesting clinical utility for these cut-offs for risk stratification in Chinese women with a singleton pregnancy and high blood pressure. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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