Abstract 040: Low Soluble Fms-like Tyrosine Kinase-1, Endoglin, and Endothelin-1 Levels in Women With Confirmed or Suspected Preeclampsia Using Proton Pump Inhibitors

Abstract

Preeclamptic patients display elevated placenta-derived soluble Fms-like tyrosine kinase-1 (sFlt-1) and endoglin levels, and decreased placental growth factor (PlGF) levels. Proton pump inhibitors (PPIs) decrease trophoblast sFlt-1 and endoglin secretion in vitro. PPIs are used during pregnancy, to combat reflux disease. Here we investigated whether PPIs affect sFlt-1 in women with confirmed/suspected preeclampsia, making use of a prospective cohort study involving 430 women. Of these women, 40 took PPIs (6 esomeprazole, 32 omeprazole and 2 pantoprazole) for 8-45 (median 29) days before sFlt-1 measurement. Measurements were only made once, at study entry between weeks 20-41 (median 33 weeks). PPI use associated with lower sFlt-1 levels, with no change in PlGF levels, both when compared to all non-PPI users, and to 80 gestational age-matched controls selected from the non-PPI users. No sFlt-1/PlGF alterations were observed in women using ferrous fumarate or macrogol, while, as expected, women using antihypertensive medication displayed higher sFlt-1 levels and/or lower PlGF levels. The PPI use-associated decrease in sFlt-1 was independent of the application of antihypertensive drugs and also occurred when restricting our analysis to patients with hypertensive disease of pregnancy at study entry. PPI users displayed more cases with preexisting proteinuria, less gestational hypertension, and a lower number of neonatal sepsis cases. Finally, their plasma endoglin and endothelin-1 levels were lower, while sFlt-1 levels correlated positively with both. In conclusion, PPI use associates with low sFlt-1, endoglin, and endothelin-1 levels, warranting prospective trials to investigate the therapeutic potential of PPIs in preeclampsia.