Strengths and limitations
The only current validated use of sFlt-1/PlGF ratio in pre-eclampsia prognosis is the first measurement for each pregnancy (PROGNOSIS study). Subsequent measurements in the same woman are of unknown value.
This prognostic prediction tool, after proper external validation, will only be able to identify a portion of high-risk pregnancies between those with an sFlt-1/PlGF ratio above 38 (detection rate= 59.6%). However, it is the first step towards the reduction of the sFlt-1/PlGF ratio 38 cut-off criteria false positive rate. It has also been shown as superior to the use of a higher sFlt-1/PlGF ratio cut-off level, considering repeated determinations.
Despite MoM transformation of sFlt-1 not yet being usual practice, it should be considered when assessing pre-eclampsia prognosis prediction. sFlt-1 also depends on maternal weight. However, as multiple testing was allowed, markers should be adjusted for maternal weight at determination, which varies substantially during pregnancy. Unfortunately, this information was not available in the present study.
Despite the study duration (nearly four years), sample size may have reduced the accuracy of predictions; on the other hand, it has been sufficient to prove the superiority of adding NT-proBNP to the model and showed the risks of using sFlt-1/PlGF ratio raw values after selecting pregnancies with an sFlt-1/PlGF ratio above 38.
We did not consider maternal characteristics to assess the prior risk. One possible alternative approach would have been to combine the information obtained from first trimester pre-eclampsia screening to assess pregnancy’s prior risk particularly when first trimester pre-eclampsia screening since the inclusion of PlGF has shown adequate test performances predicting early-onset pre-eclampsia (18-19). Despite the ASPRE study not showing the preventive role of low dose aspirin intake from 16 weeks of pregnancy in early-onset pre-eclampsia (20), future studies may offer further information of prior risk adjustment.