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

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.