We thank the authors for writing the letter to the editor underlining their important comments. Indeed, the study type of the INSPIRE trial was initially incorrectly presented in Table 1 in the inpress version of our manuscript. This has now been corrected.
The INSPIRE trial is adding prominently to the growing body of evidence that the soluble fms-like tyrosine kinase 1/placental growth factor (sFlt-1/PlGF) ratio can accurately predict preeclampsia in women presenting at high risk for the disease. The main result of INSPIRE, which is a negative predictive value of 100% (95% confidence interval, 97.1–100) to rule out the onset of the disease within 7 days at an sFlt-1/PlGF-ratio cutoff of 38 is a very important finding. In a single-center, prospective, interventional randomized trial, INSPIRE confirmed the results of the PROGNOSIS study, which was a prospective, observational, multicenter study, and thus strengthened the case for the sFlt-1/PlGF-ratio as a rule out test for preeclampsia. The host of publications to which INSPIRE contributed significantly led to an incorporation of the sFlt-1/PlGF-ratio into clinical best practice recommendations and guidelines.
We want to congratulate the authors for their recent publication of the post hoc analysis of the INSPIRE study in the American Journal of Obstetrics and Gynecology . The finding that the sFlt-1/PlGF-ratio at the cutoff of 85 predicts preeclampsia with a positive predictive value (PPV) of 71.5% confirms the predictive utility of this cutoff that had been initially described as an aid in diagnosis. This is another important step toward a more widespread implementation of the sFlt-1/PlGF-ratio into the standard clinical work-up for preeclampsia. We have recently shown that incorporating the sFlt-1/PlGF-ratio into a multimarker regression model to predict preeclampsia-related adverse outcomes in women at risk for the disease yielded a PPV of up to 88.6% as compared with an PPV of 64.1% of the sFlt-1/PlGF-ratio alone. In our retrospective, real-world cohort, we included patients who were at a high risk of the disease and in whom the sFlt-1/PlGF-ratio was measured in the clinical routine, as the sFtl-1/PlGF-ratio is part of the standard clinical work-up for preeclampsia at our institution.
The road clearly leads to a more prominent role for sFlt-1 and PlGF in the diagnostic process for preeclampsia. Lai et al have recently shown that a broad definition of preeclampsia that includes angiogenic biomarkers is superior in predicting preeclampsia-related adverse outcomes to definitions that do not include these. Therefore, including sFlt-1 and PlGF into the clinical work-up and ultimately into the definition of preeclampsia has the potential to reduce maternal and fetal morbidity and mortality.
S.V. received speaker fees from and participated in advisory boards at Roche Diagnostics, ThermoFisher, and Alexion. L.A.D. received speaker fees from Roche Diagnostics.