sFlt1/PlGF among patients with suspected preeclampsia when considering hypertensive status

In high-resource settings, biomarkers of angiogenic balance, such as the soluble fms-like tyrosine kinase-1 (sFlt1)/placental growth factor (PlGF) ratio, have been studied extensively to aid in evaluation of patients with suspected preeclampsia (PE), and have been incorporated into the 2021 International Society for the Study of Hypertension in Pregnancy definition of PE. The utility in under-resourced settings has not been as well characterized.

This analysis sought to identify the role of the sFlt1/PlGF ratio in the evaluation of patients with or without hypertension who are suspected of having PE without other diagnostic information.

This is a secondary analysis of a prior prospective study of patients who were presented with suspected PE at ≥20+0 weeks' gestation at a single academic tertiary care center. Patients were recruited in the parent study from July 2009 to June 2012. In the original study, clinicians were masked to biomarker results, and patients were followed by chart review. In this analysis, the performance of the sFlt1/PlGF ratio (≤38, >38, or >85) was assessed alone in identifying both hypertensive and non-hypertensive patients at risk of evolving into PE with severe features (PE-SF; American College of Obstetricians and Gynecologists' definition) within two weeks of the triage visit (PE-SF₂). Hypertension was defined as a blood pressure (BP)≥140/90 mmHg.

There were 1043 patients included in the analysis; of whom, 579 (55.5%) and 464 (44.5%) presented with or without hypertension, respectively. In triage, 332 (75.4%) of hypertensive patients presented due to BP concerns, and the remainder were evaluated due to other features (new-onset headache, proteinuria, or edema). On triage evaluation, 66.8% of all patients had a normal sFlt1/PlGF ratio ≤38, and 17.0% had an elevated ratio >85. Among hypertensive patients, a sFlt1/PlGF ratio ≤38 was a good rule-out test for PE-SF₂ (negative likelihood ratio [LR-] of 0.15), and a ratio >85 was a good rule-in test (positive likelihood ratio [LR+] of 5.75). Among normotensive patients, sFlt1/PlGF was useful as a rule-in test for ratio >38 (LR+ 5.13) and >85 (LR+ 12.80). Stratified by gestational age, sFlt1/PlGF continued to be a good rule in and good rule out test at <35 weeks among those with hypertension but did not have good test performance ≥35 weeks. sFlt1/PlGF had a good test performance as a rule in test for >85 regardless of gestational age. In triage, 4.3% (30/693) of patients with sFlt1/PlGF ratio <38 had concurrent laboratory evidence of PE, compared with 15.9% (28/176) patients with ratio >85.

These findings support the potential for the use of sFlt1/PlGF and BP measurement alone in resource-limited settings where other laboratory tests or clinical expertise are unavailable for risk stratification. Performance of the biomarker varied by the presence of hypertension and gestational age.