The Use of Proton Pump Inhibitors in Managing Preeclampsia: A Systematic Review
DOI:
https://doi.org/10.19166/med.v14i2.9551Keywords:
Proton pump, Inhibitors, Preeclampsia, Review, LiteratureAbstract
Background: Maternal mortality remains a major global challenge, with preeclampsia (PE) as a leading cause after hemorrhage and infection. PE, a hypertensive disorder after 20 weeks of gestation, affects over. 4 million pregnancies annually, causing 50,000–70,000 maternal deaths. If untreated, it can lead to severe complications like eclampsia, HELLP syndrome, organ failure, and death. It also increases risks for the fetus, including low birth weight, preterm birth, and perinatal mortality. Early and effective management is crucial. Research suggests proton pump inhibitors (PPIs) may help by reducing sFlt-1 secretion, offering potential treatment options.
Methods: A literature search was conducted in PubMed, ScienceDirect, Directory of Open Access Journals, and Cochrane Library, yielding 354 studies. Two studies meeting inclusion and exclusion criteria were included in this review.
Result: Omeprazole and esomeprazole reduced sFlt-1 levels and increased PlGF levels in PE pregnancies, although the changes were not statistically significant. Esomeprazole increased sFlt-1 levels specifically in placental tissue. No adverse effects were reported with PPI use in the included studies.
Conclusions: PPIs (omeprazole or esomeprazole 40 mg) show potential as safe therapies for managing preeclampsia, with minimal side effects, by reducing sFlt-1 levels and increasing PlGF levels. Further research is needed to confirm these findings.
References
1. World Health Organization. World Health Organization Fact Sheets. 2023 [Internet]. Maternal mortality. Available from: https://www.who.int/news-room/fact-sheets/detail/maternal-mortality
2. Kementrian Kesehatan Republik Indonesia. Keputusan Menteri Kesehatan Republik Indonesia Nomor Hk.01.07/Menkes/91/2017 Tentang Pedoman Nasional Pelayanan Kedokteran Tata Laksana Komplikasi Kehamilan. Available from: https://yankes.kemkes.go.id/unduhan/fileunduhan_1610340147_342181.pdf
3. Anggasari Y, Anggraini F. Pengaruh Status Gizi Dengan Kejadian Preeklampsia Ibu Hamil Trimester Iii Di Puskesmas Sidotopo Wetan. The Indonesian Journal of Health Science. 2018; 10(2):93-100. https://doi.org/10.32528/ijhs.v10i2.1861
4. Karrar SA, Martingano DJ, Hong PL. Preeclampsia. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Jan 8]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK570611/
5. Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circulation Research. 2019 Mar 29;124(7):1094–112. https://doi.org/10.1161/circresaha.118.313276
6. Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019 May;15(5):275–89. https://doi.org/10.1038/s41581-019-0119-6
7. Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, et al. The etiology of preeclampsia. American Journal of Obstetrics and Gynecology. 2022 Feb;226(2):S844–66. https://doi.org/10.1016/j.ajog.2021.11.1356
8. Onda K, Tong S, Beard S, Binder N, Muto M, Senadheera SN, et al. Proton Pump Inhibitors Decrease Soluble fms-Like Tyrosine Kinase-1 and Soluble Endoglin Secretion, Decrease Hypertension, and Rescue Endothelial Dysfunction. Hypertension. 2017 Mar;69(3):457–68. https://doi.org/10.1161/hypertensionaha.116.08408
9. Hussain S, Singh A, Antony B, Klugarová J, Murad MH, Jayraj AS, et al. Proton Pump Inhibitors Use and Risk of Preeclampsia: A Meta-Analysis. J Clin Med. 2022 Aug 10;11(16):4675. https://doi.org/10.3390/jcm11164675
10. Choi A, Noh Y, Park SH, Choe SA, Shin JY. Exploration of Proton Pump Inhibitors Use During Pregnancy and Preeclampsia. JAMA Netw Open. 2021 Sep 1;4(9):e2124339. https://doi.org/10.1001/jamanetworkopen.2021.24339
11. Hastie R, Bergman L, Cluver CA, Wikman A, Hannan NJ, Walker SP, et al. Proton Pump Inhibitors and Preeclampsia Risk Among 157 720 Women. Hypertension. 2019 May;73(5):1097–103. https://doi.org/10.1161/hypertensionaha.118.12547
12. Neuman RI, Baars MD, Saleh L, Broekhuizen M, Nieboer D, Cornette J, et al. 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). Hypertension. 2022 Jun;79(6):1297–307. https://doi.org/10.1161/HYPERTENSIONAHA.122.19070
13. Cluver CA, Hannan NJ, van Papendorp E, Hiscock R, Beard S, Mol BW, et al. Esomeprazole to treat women with preterm preeclampsia: a randomized placebo controlled trial. Am J Obstet Gynecol. 2018 Oct;219(4):388.e1-388.e17. https://doi.org/10.1016/j.ajog.2018.07.019
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Taura Avensia, Dinda Tsania Bahardiani
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (CC-BY-SA 4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website). The final published PDF should be used and bibliographic details that credit the publication in this journal should be included.
