Assessment of a salivary cfRNA biomarker panel to predict preeclampsia

Placental proteins, including placental alkaline phosphatase (PLAP), soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF), are quantifiable in maternal saliva and show promise as predictive biomarkers for the development of pregnancy complications including preeclampsia. We aimed to develop a more comprehensive cell-free RNA saliva based placental biomarker panel with the addition of vascular endothelial growth factor A (VEGFA), soluble endoglin (sENG), pregnancy-associated plasma protein A (PAPPA), and sFLT-1:PlGF to predict preeclampsia prior to the onset of symptoms.

In this prospective, observational study, 127 asymptomatic, pregnant women provided whole saliva samples in either the second (n = 55) or third (n = 72) trimesters. Saliva samples underwent RNA extraction and droplet digital PCR quantification for the six biomarkers. Clinical outcomes were correlated to salivary profiles.

Nine participants (7 %) were diagnosed with preeclampsia. All genes in the biomarker panel were detected. The sFLT-1:PlGF ratio was significantly higher (Mann-Whitney U test, p = 0.032) in women assessed in the third trimester who developed preeclampsia compared to women who did not. Area under the receiver operating curve for all 6 quantified placental markers had a predictive value of 68.4 % for the future onset of preeclampsia. Mean latency from sampling to diagnosis was 10.7 weeks.

A cell-free RNA saliva-based gene panel may predict preeclampsia in asymptomatic women. Specifically, elevated salivary sFLT-1:PlGF in the third trimester is predictive of impending disease onset. This represents an important opportunity to leverage non-invasive saliva screening to better identify women at risk for developing preeclampsia.