Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1). Issue 6 (28th April 2022)

• Record Type: Journal Article
• Authors: Neuman, Rugina I.; Baars, Milan D.; Saleh, Langeza; Broekhuizen, Michelle; Nieboer, Daan; Cornette, Jérôme; Schoenmakers, Sam; Verhoeven, Michel; Koch, Birgit C.P.; Russcher, Henk; van den Berg, Sjoerd A.A.; van den Meiracker, Anton H.; Visser, Willy; Danser, A.H. Jan
• Is Part Of: Hypertension. Volume 79:Issue 6(2022)
• Page Start: 1297
• Page End: 1307
• Publication Date: 2022-04-28
• Subjects: adult -- endothelin-1 -- maternal age -- perfusion -- placenta; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.122.19070
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : Background: Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors. Methods: Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT-proET-1 after 4 days of omeprazole versus 20 preeclamptic women not receiving omeprazole. Results: Mean maternal age was 30 years, and median gestational age was 30 +3 weeks. Baseline sFlt-1 levels were identical in both groups, and the same was true for PlGF or CT-proET-1. After 4 days, sFlt-1 levels remained similar in women not receiving omeprazole compared with women receiving omeprazole, while the levels of PlGF and CT-proET-1 also did not differ between groups. Women receiving omeprazole had a similar prolongation of pregnancy after inclusion compared with those in the nonomeprazole group (median 15 versus 14 days). Except for a higher neonatal intubation rate in the nonomeprazole group (31% versus 4%, P =0.02), there were no differences in maternal/perinatal complications. Finally, making use of the placenta perfusion model, we established that both omeprazole and its S-isomer, esomeprazole, when maternally applied, reached the fetal compartment (fetal-to-maternal ratio's 0.43–0.59), while only esomeprazole inhibited placental sFlt-1 release. Conclusions: Administration of omeprazole to women with confirmed preeclampsia does not alter their circulating levels of sFlt-1, PlGF, or ET-1, arguing against a role of this drug as a treatment for this syndrome.