Potential effect of proton-pump inhibitor on angiogenic markers in preeclampsia

Rationale: Preeclampsia (PE) is a devastating complication of pregnancy. The pathogenesis of PE is unknown. Recent data suggest an angiogenic imbalance characterized by elevated placenta-derived soluble Fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF) levels in the maternal circulation. As a consequence, novel therapies now focus on sFlt-1 removal or PlGF supplementation. Given the fact that heme-oxygenase-1 negatively regulates sFlt-1 secretion, a role for proton pump inhibitors (PPIs) that upregulate heme oxygenase-1, has been suggested as potential treatment for preeclampsia. Indeed, Onda et al. observed that PPIs decreased sFlt-1 secretion from trophoblasts and reduced blood pressure in a transgenic PE mouse model with placental sFlt-1 overexpression. Recently, we reported that women with suspected/confirmed PE using PPIs, displayed lower levels of sFlt-1 in comparison to women not using PPIs.
In this study, our aim is to evaluate the potential effect of PPI administration in women with confirmed preeclampsia on sFlt-1 levels until delivery. Study design will be a single-centre, randomized, intervention proof-of-concept study performed at the Erasmus MC Rotterdam. Study population will consist of women with confirmed PE with a gestational age ≥ 20 weeks and <35 weeks who did not use PPIs at study entrance.
The intervention group will receive omeprazole, 40mg, once daily while the control group will receive no medication. In both groups, blood will be drawn at several time points, until delivery.

PPI administration to women with confirmed PE lowers sFlt-1 levels and which may lead to less complications or progression of disease.

Measurements of sFlt-1 will be performed on day 0 (before PPI use), 1, 2, 4, 8 and thereafter twice weekly until delivery

Omeprazole 40mg once daily