Doctoral defence: Kaspar Ratnik "Development of predictive multimarker test for preeclampsia in early and late pregnancy”

On 22 June at 10:00 Kaspar Ratnik will defend his doctoral thesis "Development of predictive multimarker test for preeclampsia in early and late pregnancy".

Supervisors:
Professor Maris Laan, University of Tartu
Professor Kalle Kisand, University of Tartu

Opponent: 
Professor Stefan Hansson, Lund University (Sweden)

Summary
Preeclampsia (PE) affects in total close 3-5% pregnancies worldwide, depending on the access and level of local healthcare. PE is defined as mother`s new hypertension after 20 weeks of gestation with most common additional symptom being proteinuria. It can also cause maternal organ dysfunction (hepatic, renal, haematological) and in worst case mother`s/baby`s death. One of the core causes of PE is uteroplacental pathology, leaded by inadequate spiral artery modification and poor villous development. PE is divided based on its symptomatic presence to be early- (before 34th gestational week) or late-onset (from 34th gestational week). Modern practice for PE management holds two concepts - early phase prediction for prophylaxis with aspirin or late pregnancy PE rule-out in-case of PE suspicion. First, general today to assess PE prediction based on FMF model (screening on gestational weeks 11-14) and assessing maternal characteristics and measuring preferably UtA-PI, PAPP-A or PlGF reaches to correct prognosis in 90% of cases with early-onset PE but moderate 40% with late-onset. PE rule-out method, in case of developed symptoms, by assessing sFlt-1/PLGF ratio only works effectively for early-onset situation. Use in case of late-onset increases false-positive PE predictions sharply.

The aim of this thesis was to explore the dynamics and value of proposed serum biomarkers of PE in predicting the risk for the disease, and to combine informative biomarkers and clinical data to develop novel PE prediction models applicable either in early or late pregnancy:

1. The novel Luminex® based 6PLEX assay detects six PE related biomarkers ADAM12, PlGF, sENG, sFlt1, PTX3 and leptin in multiplex format with high precision and low intra- and interassay variation.
2. 6PLEX assay based multicomponent modelling enables superior PE prediction in III trimester (samples collected after 179th gestational day) with 96.5% accuracy.
3. Applying the 6PLEX assay on I trimester, specifically between 10-14 gestational weeks, allows 88.2% precise PE prediction without any false negative cases and 80% specificity. Incorporation of fetal FLT1 rs4769613 data even improves the prediction performance to 93.5%, raising the precificity metrics.