INTRODUCTION
Pre-eclampsia is a pregnancy-related disorder and is a leading cause of maternal and perinatal complications (1). Early-onset pre-eclampsia is a rare and severe subtype of pre-eclampsia (0.2-0.5% of pregnancies) that presents before 34 weeks of gestation (2).
The main biochemical achievement in predicting pre-eclampsia has been defining a cut-off point for the soluble FMS-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio of 38 or below to rule-out pre-eclampsia in one week with a negative predictive value of 99.3%, in the PROGNOSIS study (3). On the other hand, the sFlt-1/PlGF ratio rises in cases of other pathologies (4) and has an elevated false positive rate, such as 21.7% in the PROGNOSIS study and 32.5% in our previous study (5). Therefore, no treatment can be indicated to test positive pregnancies.
Apart from placental dysfunction, women with pre-eclampsia experience cardiovascular abnormalities such as increased blood pressure and peripheral vascular resistance, vasoconstriction or reduced plasma volume (6). The heart responds by producing N-terminal pro-B-type natriuretic peptide (NT-proBNP), which shows higher concentrations in women presenting with severe pre-eclampsia and may predict cardiovascular complications (7-9). Additionally, NT-proBNP levels do not change during pregnancy in healthy women (10), and their transplacental transfer seems negligible (11).
There is a considerable rate of repeated consultations when pre-eclampsia is clinically suspected. In our previous study (12), 42.6% of women with an sFlt-1/PlGF ratio above 38 had repeated measurements, even though only one determination per gestational week was permitted.
In this study, we focus on early-onset pre-eclampsia and only consider samples obtained between 27 and 34 weeks of gestation, with repeated testing permitted. The aim of the study is two-fold: to develop an online prognostic prediction tool to predict delivery due to early-onset pre-eclampsia within seven days of determination, in pregnancies with an sFlt-1/PlGF ratio above 38 and to compare it (i) with sFlt-1/PlGF ratio model and (ii) with the sFlt-1/PlGF ratio 655 cut-off. When constructing the prognostic prediction tool, we assessed the addition of NT-proBNP and the adequacy of using sFlt-1/PlGF ratio raw values or whether these two markers should be gestational age adjusted and considered individually.