P 48 Low soluble Fms-like tyrosine kinase-1, endothelin-1 and endoglin levels in women with suspected or confirmed preeclampsia, using proton pump inhibitors

Abstract

Preeclamptic patients display elevated placenta-derived soluble Fms-like tyrosine kinase-1 (sFlt-1), endoglin and endothelin-1 levels and decreased placental growth factor (PlGF) levels. Proton pump inhibitors (PPIs) have been reported to decrease trophoblast sFlt-1 secretion in vitro. PPIs are widely used during pregnancy, to combat reflux disease. To investigate whether PPIs affect sFlt-1, endoglin, endothelin-1 and PlGF in women with (suspected) preeclampsia. This is a secondary analysis of a prospective cohort study involving 430 singleton pregnant women with suspicion or with confirmed preeclampsia from 20 weeks gestation. As a comparator of the PPIs, the effects of other drugs commonly used in women with suspected or confirmed preeclampsia, i.e., antihypertensive drugs (α-methyldopa, nifedipine), corticosteroids, ferrous fumarate and macrogol, is simultaneously assessed. 40 (9%) out of the 430 patients were treated with PPIs (6 esomeprazol, 32 omeprazol and 2 pantoprazol) for 8–45 (mean 29) days before blood sampling. PPI use was 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 or 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. Furthermore, their plasma endoglin levels were lower along with their plasma endothelin-1 levels, while sFlt-1 levels correlated positively with endothelin-1 levels. PPI use associates with low sFlt-1, endothelin-1 and endoglin levels, warranting prospective trials to investigate the therapeutic potential of PPIs in preeclampsia.