Alternative methods in the management of preeclampsia. Analytical inspection

Authors

DOI:

https://doi.org/10.15574/PP.2021.87.56

Keywords:

preeclampsia, pregnancy, pravastatin, metformin, sulfalazine

Abstract

There are many alternative drugs for the prevention and treatment of preeclampsia in the new research. This drugs can effect on the underlying pathophysiology of the disease: oxidative stress, antiangiogenic factors, as well as angiotensin, nitric oxide and various parts of the inflammatory process. Thus, they affect the disease of the placenta or endothelium. The proposed treatments are currently undergoing preclinical and clinical trials. Pravastatin was of the greatest interest among all the proposed therapeutic agents. It has pleiotropic effect, i.e. affects multiple molecular targets against preeclampsia. Proton pump inhibitors, metformin, and sulfasalazine are other drugs that have preclinical evidence of multiple molecular actions that may address the pathophysiology of preeclampsia. Currently, these molecules are also in clinical trials. Many natural compounds for the treatment of preeclampsia, such as plant extracts and trace elements, are being researched to identify the potential in anti-inflammatory or antioxidant activity. Monoclonal antibodies are another direction is new molecular-oriented strategies. They are targeting tumor necrosis factor alpha, placental growth factor and short interfering RNA technology to inhibit the expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, and immunogenic digoxin antigen and melatonin are other treatment approaches that have been tested in humans (ranging from single-group studies to phase III trials that have been completed or are ongoing). The series of cases demonstrated that removal of circulating soluble fms-like tyrosine kinase-1 can help stabilize the disease and prolong pregnancy. Monoclonal antibodies such as eculizumab (a complement inhibitor) may have therapeutic potential. Thus, the identified alternative drugs in the treatment and prevention of preeclampsia create the potential to improve maternal health and pregnancy.

No conflict of interests was declared by the author.

References

Abalos E, Cuesta C, Grosso AL et al. (2013). Global and regional estimates of preeclampsia and eclampsia: a systematic review. European journal of obstetrics, gynecology, and reproductive biology. 170: 1-7. https://doi.org/10.1016/j.ejogrb.2013.05.005; PMid:23746796

Ahmed A, Williams DJ, Cheed V et al. (2020). Pravastatin for early-onset pre-eclampsia: a randomised, blinded, placebo-controlled trial. BJOG: 127: 478-488. https://doi.org/10.1111/1471-0528.16240; PMid:32372433

Alqudah A, McKinley MC, McNally R et al. (2018). Risk of pre-eclampsia in women taking metformin: a systematic review and meta-analysis. Diabet Med. 35: 160-172. https://doi.org/10.1111/dme.13523; PMid:29044702

Ananth CV, Keye S KM, Wapner RJ. (2013). Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ. 347: f6564. Antioxid Redox Signal: (Epub ahead of print). https://doi.org/10.1136/bmj.f6564; PMid:24201165 PMCid:PMC3898425

Brownfoot FC, Hannan NJ, Cannon P et al. (2019). Sulfasalazine reduces placental secretion of antiangiogenic factors, up-regulates the secretion of placental growth factor and rescues endothelial dysfunction. EBioMedicine. 41: 636-648. https://doi.org/10.1016/j.ebiom.2019.02.013; PMid:30824385 PMCid:PMC6442229

Carson RA, Rudine AC, Tally SJ et al. (2018). Statins impact primary embryonic mouse neural stem cell survival, cell death, and fate through distinct mechanisms. PLoS One: 13e0196387. https://doi.org/10.1371/journal.pone.0196387; PMid:29738536 PMCid:PMC5940229

Cluver CA, Hannan NJ, van Papendorp E et al. (2018). Esomeprazole to treat women with preterm preeclampsia: a randomized placebo controlled trial. Am J Obstet Gynecol. 219: 388.e1-388.e17. https://doi.org/10.1016/j.ajog.2018.07.019; PMid:30055127

Costantine MM, Cleary K, Hebert MF et al. (2016). Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial. Am J Obstet Gynecol. 214: 720.e1-720.e17. https://doi.org/10.1016/j.ajog.2015.12.038; PMid:26723196 PMCid:PMC4884459

De Alwis N, Beard S, Mangwiro YT et al. (2020). Pravastatin as the statin of choice for reducing pre-eclampsia-associated endothelial dysfunction. Pregnancy Hypertens: 20: 83-91. https://doi.org/10.1016/j.preghy.2020.03.004; PMid:32199147

Eddy AC, Howell JA, Chapman H et al. (2020). Biopolymer-delivered, maternally sequestered NF-κB (nuclear factor-κB) inhibitory peptide for treatment of preeclampsia. Hypertension. 75: 193-201. https://doi.org/10.1161/HYPERTENSIONAHA.119.13368; PMid:31786977 PMCid:PMC7008946

Fushima T, Sekimoto A, Oe Y et al. (2020). Nicotinamide ameliorates a preeclampsia-like condition in mice with reduced uterine perfusion pressure. Am J Physiol Renal Physiol. 312: F366-F372. https://doi.org/10.1152/ajprenal.00501.2016; PMid:27927652

Garrett N, Pombo J, Umpierrez M et al. (2018). Pravastatin therapy during preeclampsia prevents long-term adverse health effects in mice. JCI Insight: 3e120147. https://doi.org/10.1172/jci.insight.120147; PMid:29669946 PMCid:PMC5931129

Haase N, Foster DJ, Cunningham MW et al. (2020). RNA interference therapeutics targeting angiotensinogen ameliorate preeclamptic phenotype in rodent models. J Clin Invest. 130: 2928-2942. https://doi.org/10.1172/JCI99417; PMid:32338644 PMCid:PMC7260005

Hannan NJ, Brownfoot FC, Cannon P et al. (2017). Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction - implications as a preeclampsia treatment. Sci Rep. 7: 1819. https://doi.org/10.1038/s41598-017-01993-w; PMid:28500309 PMCid:PMC5431923

Hastie R, Bergman L, Cluver CA et al. (2019). Proton pump inhibitors and preeclampsia risk among 157 720 women. Hypertension. 73: 1097-1103. https://doi.org/10.1161/HYPERTENSIONAHA.118.12547; PMid:30827143

Hobson SR, Gurusinghe S, Lim R et al. (2018). Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia. J Pineal Res: 65e12508. https://doi.org/10.1111/jpi.12508; PMid:29766570

Huang J, Zheng L, Wang F et al. (2020). Mangiferin ameliorates placental oxidative stress and activates PI3K/Akt/mTOR pathway in mouse model of preeclampsia. Arch Pharm Res. 43: 233-241. Hypertension. 69: 457-468. https://doi.org/10.1007/s12272-020-01220-7; PMid:31989480

Kraker K, O'Driscoll JM, Schutte T et al. (2020). Statins reverse postpartum cardiovascular dysfunction in a rat model of preeclampsia. Hypertension. 75: 202-210. https://doi.org/10.1161/HYPERTENSIONAHA.119.13219; PMid:31786987

Lai T, Wu M, Liu J et al. (2018). Acid-suppressive drug use during pregnancy and the risk of childhood asthma: a meta-analysis. Pediatrics: 141e20170889. https://doi.org/10.1542/peds.2017-0889; PMid:29326337

Lam GK, Hopate-Sitake M, Adair D et al. (2013). Digoxin antibody fragment, antigen binding (Fab), treatment of preeclampsia in women with endogenous digitals-like factor: a secondary analysis of the DEEP Trial. Am J Obstet Gynecol. 209: 119.e1-119.e. https://doi.org/10.1016/j.ajog.2013.04.010; PMid:23583219

Landi SN, Radke S, Engel SM et al. (2019). Association of long-term child growth and developmental outcomes with metformin vs insulin treatment for gestational diabetes. JAMA Pediatr. 173: 160-168. https://doi.org/10.1001/jamapediatrics.2018.4214; PMid:30508164 PMCid:PMC6439608

Lefkou E, Mamopoulos A, Dagklis T et al. (2016). Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy. J Clin Invest. 126: 2933-2940. https://doi.org/10.1172/JCI86957; PMid:27454295 PMCid:PMC4966313

Leon LJ, McCarthy FP, Direk K et al. (2019). Preeclampsia and Cardiovascular Disease in a Large UK Pregnancy Cohort of Linked Electronic Health Records: A CALIBER Study. Circulation. 140: 1050-1060. https://doi.org/10.1161/CIRCULATIONAHA.118.038080; PMid:31545680

Li F, Fushima T, Oyanagi G et al. (2016). Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia. Proc Natl Acad Sci USA. 113: 13450-13455. https://doi.org/10.1073/pnas.1614947113; PMid:27821757 PMCid:PMC5127378

Lokki AI, Haapio M, Heikkinen-Eloranta J. (2020). Eculizumab treatment for postpartum HELLP syndrome and aHUS-case report. Front Immunol. 11: 548. https://doi.org/10.3389/fimmu.2020.00548; PMid:32308654 PMCid:PMC7145984

Matok I, Levy A, Wiznitzer A et al. (2012). The safety of fetal exposure to proton-pump inhibitors during pregnancy. Dig Dis Sci. 57: 699-705. https://doi.org/10.1007/s10620-011-1940-3; PMid:22038541

Mol BWJ, Roberts CT, Thangaratinam S et al. (2016). Preeclampsia. Lancet. 387: 999-1011. https://doi.org/10.1016/S0140-6736(15)00070-7

Onda K, Tong S, Beard S et al. (2017). Proton Pump Inhibitors Decrease Soluble fms-Like Tyrosine Kinase-1 and Soluble Endoglin Secretion, Decrease Hypertension, and Rescue Endothelial Dysfunction. Hypertension. 69: 457-468. https://doi.org/10.1161/HYPERTENSIONAHA.116.08408; PMid:28115513

Onda K, Tong S, Beard S et al. (2017). Proton pump inhibitors decrease soluble fms-like tyrosine kinase-1 and soluble endoglin secretion, decrease hypertension, and rescue endothelial dysfunction. https://doi.org/10.1161/HYPERTENSIONAHA.116.08408; PMid:28115513

Onda K, Tong S, Nakahara A et al. (2015). Sofalcone upregulates the nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 pathway, reduces soluble fms-like tyrosine kinase-1, and quenches endothelial dysfunction: potential therapeutic for preeclampsia. Hypertension. 65: 855-862. https://doi.org/10.1161/HYPERTENSIONAHA.114.04781; PMid:25667213

Paidas MJ, Tita ATN, Macones GA et al. (2020). Prospective, randomized, double-blind, placebo-controlled evaluation of the pharmacokinetics, safety and efficacy of recombinant antithrombin versus placebo in preterm preeclampsia. Am J Obstet Gynecol. (Epub ahead of print). https://doi.org/10.1016/j.ajog.2020.08.004; PMid:32780999

Polsani S, Phipps E, Jim B. (2020). Emerging new biomarkers of preeclampsia. Adv Chronic Kidney Dis. 20 (3): 271-279. https://doi.org/10.1053/j.ackd.2013.01.001; PMid:23928393

Regal JF, Burwick RM, Fleming SD. (2017). The complement system and preeclampsia. Curr Hypertens Rep. 19: 87. https://doi.org/10.1007/s11906-017-0784-4; PMid:29046976 PMCid:PMC5849056

Roberts JM, Myatt L, Spong CY et al. (2010). Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 362: 1282-1291. https://doi.org/10.1056/NEJMoa0908056; PMid:20375405 PMCid:PMC3039216

Saleh L, Samantar R, Garrelds IM et al. (2017). Low soluble fms-like tyrosine kinase-1, endoglin, and endothelin-1 levels in women with confirmed or suspected preeclampsia using proton pump inhibitors. Hypertension. 70: 594-600. https://doi.org/10.1161/HYPERTENSIONAHA.117.09741; PMid:28716993

Syngelaki A, Nicolaides KH, Balani J et al. (2016). Metformin versus placebo in obese pregnant women without diabetes mellitus. N Engl J Med. 374: 434-443. https://doi.org/10.1056/NEJMoa1509819; PMid:26840133

Thadhani R, Hagmann H, Schaarschmidt W et al. (2016). Removal of soluble fms-like tyrosine kinase-1 by dextran sulfate apheresis in preeclampsia. J Am Soc Nephrol. 27: 903-913. https://doi.org/10.1681/ASN.2015020157; PMid:26405111 PMCid:PMC4769204

Turanov AA, Lo A, Hassler MR et al. (2018). RNAi modulation of placental sFLT1 for the treatment of preeclampsia. Nat Biotechnol. (Epub ahead of print). https://doi.org/10.1038/nbt.4297; PMid:30451990 PMCid:PMC6526074

Warrington JP, Drummond HA, Granger JP, Ryan MJ. (2015). Placental ischemia-induced increases in brain water content and cerebrovascular permeability: role of TNF-α. Am J Physiol Regul Integr Comp Physiol. 309: R1425-R1431. https://doi.org/10.1152/ajpregu.00372.2015; PMid:26400187 PMCid:PMC4698405

Wen SW, White RR, Rybak N et al. (2018). Effect of high dose folic acid supplementation in pregnancy on preeclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial. BMJ. 362: k3478. https://doi.org/10.1136/bmj.k3478; PMid:30209050 PMCid:PMC6133042

Williamson RD, McCarthy FP, Manna S et al. (2020). L-(+)-ergothioneine significantly improves the clinical characteristics of preeclampsia in the reduced uterine perfusion pressure rat model. Hypertension. 75: 561-568. https://doi.org/10.1161/HYPERTENSIONAHA.119.13929; PMid:31865793

Wu P, Haththotuwa R, Kwok CS et al. (2017). Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis. Circ Cardiovasc Qual Outcomes: 10. https://doi.org/10.1161/CIRCOUTCOMES.116.003497; PMid:28228456

Yang Y, Xu P, Zhu F et al. (2020). The potent antioxidant MitoQ protects against preeclampsia during late gestation but increases the risk of preeclampsia when administered in early pregnancy. https://doi.org/10.1089/ars.2019.7891; PMid:32228063

Yebyo HG, Aschmann HE, Kaufmann M, Puhan MA. (2019). Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with. 94, 283 participants. Am Heart J. 210: 18-28. https://doi.org/10.1016/j.ahj.2018.12.007; PMid:30716508

Zeisler H, Llurba E, Chantraine F et al. (2016). Predictive value of the sFlt1: PlGF ratio in women with suspected preeclampsia. N Engl J Med. 374 (1): 13-22. https://doi.org/10.1056/NEJMoa1414838; PMid:26735990

Published

2021-09-29