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Review

Current and emerging pharmacotherapy for emergency management of preeclampsia

, , & ORCID Icon
Pages 701-712 | Received 19 Sep 2018, Accepted 11 Jan 2019, Published online: 01 Feb 2019

References

  • Roberts JM, Lain KY. Recent insights into the pathogenesis of pre-eclampsia. Placenta. 2002;23(5):359–372.
  • Kweider N, Wruck CJ, Rath W. New insights into the pathogenesis of preeclampsia - the role of nrf2 activators and their potential therapeutic impact. Geburtshilfe Frauenheilkd. 2013;73(12):1236–1240.
  • Mol BBWJ, Roberts CT, Thangaratinam S, et al. Pre-eclampsia. Lancet. 2016;387(10022):999–1011.
  • Lowe SA, Bowyer L, Lust K, et al. The SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014. Aust N Z J Obstet Gynaecol. 2015; 55(5):e1–29.
  • World Health Organization. WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia. Geneva: Author; 2011.
  • Tranquilli AL, Dekker G, Magee L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens. 2014;4(2):97–104.
  • Magee LA, Von Dadelszen P, Singer J, et al. Can adverse maternal and perinatal outcomes be predicted when blood pressure becomes elevated? Secondary analyses from the CHIPS (Control of hypertension in pregnancy study) randomized controlled trial. Acta Obstet Gynecol Scand. 2016;95(7):763–776.
  • Magee LA, Von Dadelszen P, Singer J, et al. The CHIPS randomized controlled trial (control of hypertension in pregnancy study). Hypertension. 2016;68(5):1153–1159.
  • Fenton C, Hobson SR, Wallace EM, et al. Future therapies for pre-eclampsia: beyond treading water. Aust N Z J Obstet Gynaecol. 2014;54(1):3–8.
  • Rolnik DL, Wright D, Poon LCY, et al. ASPRE trial: performance of screening for preterm pre-eclampsia. Ultrasound Obstet Gynecol. 2017;50(4):492–495.
  • Rolnik DL, Wright D, Poon LC, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017;377:613–622.
  • Hofmeyr GJ, Lawrie TA, Án A, et al. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2014;24(6):CD001059.
  • Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The eighth report of the confidential enquiries into maternal deaths in the United Kingdom. BJOG. 2011;118:1.
  • Martin JN, Thigpen BD, Moore RC, et al. Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on systolic blood pressure. Obstet Gynecol. 2005;105(2):246–254.
  • Rey E, LeLorier J, Burgess E, et al. Report of the Canadian hypertension society consensus conference: 3. pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ. 1997;157(9):1245–1254.
  • Redman CWG. Hypertension in pregnancy: the NICE guidelines. Heart. 2011;97(23):1967–1969.
  • Easterling TR. Pharmacological management of hypertension in pregnancy. Semin Perinatol. 2014;38(8):487–495.
  • Redman CW, Beilin LJ, Bonnar J. Treatment of hypertension in pregnancy with methyldopa: blood pressure control and side effects. Br J Obstet Gynaecol. 1977;84(6):419–426.
  • DeMuth GW, Ackerman SH. Alpha-methyldopa and depression: a clinical study and review of the literature. Am J Psychiatry. 1983;140(5):534–538.
  • Redman CW. Fetal outcome in trial of antihypertensive treatment in pregnancy. Lancet. 1976;2(7989):753–756.
  • Weitz C, Khouzami V, Maxwell K, et al. Treatment of hypertension in pregnancy with methyldopa: a randomized double blind study. Int J Gynaecol Obstet. 1987;25(1):35–40.
  • Redman CW, Ounsted MK. Safety for the child of drug treatment for hypertension in pregnancy. Lancet. 1982;1(8283):1237.
  • Xie RH, Guo Y, Krewski D, et al. Trends in using beta-blockers and methyldopa for hypertensive disorders during pregnancy in a Canadian population. Eur J Obstet Gynecol Reprod Biol. 2013;171(2):281–285.
  • El-Qarmalawi AM, Morsy AH, Al-Fadly A, et al. Labetalol vs. Int J Gynecol Obstet. 1995;49(2):125–130.
  • Magee LA, von Dadelszen P, Singer J, et al. Control of hypertension in pregnancy study randomised controlled trial—are the results dependent on the choice of labetalol or methyldopa? BJOG. 2016;123(7):1135–1141.
  • Vermillion ST, Scardo JA, Newman RB, et al. A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy. Am J Obstet Gynecol. 1999;181(4):858–861.
  • Walker JJ, Greer I, Calder AA. Treatment of acute pregnancy-related hypertension: labetalol and hydralazine compared. Postgr Med J. 1983;59:168–170.
  • Mabie WC, Gonzalez AR, Sibai BM, et al. A comparative trial of labetalol and hydralazine in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol. 1987;70:328–333.
  • Klarr J, Bhatt-Mehta V, Donn S. Neonatal adrenergic blockade following single dose maternal labetalol administration. Am J Perinatol. 1994;11(2):91–93.
  • Moore MP, Redman CWG. The treatment of hypertension in pregnancy. Curr Med Res Opin. 1982;90(2):1499–1504.
  • Petersen KM, Jimenez-Solem E, Andersen JT, et al. β-Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study. BMJ Open. 2012;2(4):e001185.
  • Bulpitt CJ, Lewis PJ, Swiet MD. How obstetricians manage hypertension in pregnancy. Br Med J. 1978;1(6113):626–629.
  • Pickles CJ, Symonds EM, Broughton Pipkin F. The fetal outcome in a randomized double-blind controlled trial of labetalol versus placebo in pregnancy-induced hypertension. Br J Obstet Gynaecol. 1989;96(1):38–43.
  • Pickles CJ, Broughton Pipkin F, Symonds EM. A randomised placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension. Br J Obstet Gynaecol. 1992;99(12):964–968.
  • Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2014;6(2):CD002252.
  • Xie RH, Guo Y, Krewski D, et al. Beta-Blockers increase the risk of being born small for gestational age or of being institutionalised during infancy. BJOG. 2014;121(9):1090–1096.
  • Bateman BT, Hernandez-Diaz S, Huybrechts KF, et al. Patterns of outpatient antihypertensive medication use during pregnancy in a medicaid population. Hypertension. 2012;60(4):913–920.
  • Cruickshank DJ, Robertson AA, Campbell DM, et al. Does labetalol influence the development of proteinuria in pregnancy hypertension? A randomised controlled study. Eur J Obstet Gynecol Reprod Biol. 1992;45(1):47–51.
  • Ismail AAA, Medhat I, Tawfic TAS, et al. Evaluation of calcium-antagonist (Nifedipine) in the treatment of pre-eclampsia. Int J Gynecol Obstet. 1993;40(1):39–43.
  • Katz AM. Pharmacology and mechanisms of action of calcium-channel blockers. J Clin Hypertens. 1986;2(3):28–37.
  • Jayawardana J, Lekamge N. A comparison of nifedipine with methyldopa in pregnancy induced hypertension. Ceylon Med J. 1994;39(2):87–90.
  • Firoz T, Magee LA, MacDonell K, et al. Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review. BJOG. 2014;1(1):1210–1218.
  • Melchiorre K, Sutherland GR, Watt-Coote I, et al. Severe myocardial impairment and chamber dysfunction in preterm preeclampsia. Hypertens Pregnancy. 2012;31(4):454–471.
  • Cong J, Fan T, Yang X, et al. Maternal cardiac remodeling and dysfunction in preeclampsia: a three-dimensional speckle-tracking echocardiography study. Int J Cardiovasc Imaging. 2015;31(7):1361–1368.
  • Melchiorre K, Thilaganathan B. Maternal cardiac function in preeclampsia. Curr Opin Obstet Gynecol. 2011;23(6):440–447.
  • Bhorat I, Naidoo DP, Moodley J. Maternal cardiac haemodynamics in severe pre-eclampsia complicated by acute pulmonary oedema. J Matern Fetal Neonatal Med. 2017;30(23):2769–2777.
  • Shi DD, Yang FZ, Zhou L, et al. Oral nifedipine vs. J Clin Pharm Ther. 2016;41(6):657–661.
  • Brown MA, McCowan LM, North RA, et al. Withdrawal of nifedipine capsules: jeopardizing the treatment of acute severe hypertension in pregnancy? Australasian society for the study of hypertension in pregnancy. Med J Aust. 1997;166(12):640–643.
  • Webster LM, Myers JE, Nelson-Piercy C, et al. Labetalol versus nifedipine as antihypertensive treatment for chronic hypertension in pregnancy: a randomized controlled trial. Hypertension. 2017;70(5):915–922.
  • Koontz SL, Friedman SA, Schwartz ML. Symptomatic hypocalcemia after tocolytic therapy with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 2004;190(6):1773–1776.
  • Hodges R, Barkehall-Thomas A, Tippett C. Maternal hypoxia associated with nifedipine for threatened preterm labour. BJOG. 2004;111(4):380–381.
  • Ben Ami M, Giladi Y, Shalev E. The combination of magnesium sulphate and nifedipine: a cause of neuromuscular blockade. BJOG. 1994;101(3):262–263.
  • Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 1989;161(1):35–36.
  • Magee LA, Miremadi S, Li J, et al. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with preeclampsia. Am J Obstet Gynecol. 2005;193(1):153–163.
  • Magee LA, Cham C, Waterman EJ, et al. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003;327(7421):955–960.
  • NICE. Hypertension in pregnancy: diagnosis and management, 2010. Available from: https://www.nice.org.uk/guidance/cg107 [Accessed 22 January 2019].
  • Crozier TM, Wallace EM, Parkin WG. Haemodynamic assessment in pregnancy and pre-eclampsia: a Guytonian approach. Pregnancy Hypertens. 2015;5(2):177–181.
  • Walker JJ. Severe pre-eclampsia and eclampsia. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14(1):57–71.
  • Rezaei Z, Sharbaf FR, Pourmojieb M, et al. Comparison of the efficacy of nifedipine and hydralazine in hypertensive crisis in pregnancy. Acta Med Iran. 2011;49(11):701–706.
  • Aali BS, Nejad SS. Nifedipine or hydralazine as a first-line agent to control hypertension in severe preeclampsia. Acta Obstet Gynecol Scand. 2002;81(1):25–30.
  • Walss Rodriguez RJ, Flores Padilla LM. Management of severe pre-eclampsia/eclampsia. Comparison between nifedipine and hydralazine as antihypertensive agents. Ginecol Obs Mex. 1993;61:76–79.
  • Voto LS, Zin C, Neira J, et al. Ketanserin versus alpha-methyldopa in the treatment of hypertension during pregnancy: a preliminary report. J Cardiovasc Pharmacol. 1987;10(3):101–103.
  • Weiner CP, Socol ML, Vaisrub N. Control of preeclamptic hypertension by ketanserin, a new serotonin receptor antagonist. Am J Obstet Gynecol. 1984;149(5):496–500.
  • Rossouw HJ, Howarth G, Odendaal HJ. Ketanserin and hydralazine in hypertension in pregnancy - A randomised double-blind trial. S Afr Med J. 1995;85(6):525–528.
  • Bijvank SWN, Visser W, Duvekot JJ, et al. Ketanserin versus dihydralazine for the treatment of severe hypertension in early-onset preeclampsia: a double blind randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2015;1889:106–111.
  • Hennessy A, Thornton CE, Makris A, et al. A randomised comparison of hydralazine and mini-bolus diazoxide for hypertensive emergencies in pregnancy: the PIVOT trial. Aust N Z J Obstet Gynaecol. 2007;47(4):279–285.
  • Michael CA. Intravenous labetalol and intravenous diazoxide in severe hypertension complicating pregnancy. ANZ J Obstet Gynaecol. 1986;26(1):26–29.
  • Hall DR, Odendaal HJ, Steyn DW, et al. Nifedipine or prazosin as a second agent to control early severe hypertension in pregnancy: a randomised controlled trial. BJOG. 2000;107(6):759–765.
  • Diemunsch P, Garcia V, Lyons G, et al. Urapidil versus nicardipine in preeclamptic toxaemia: a randomised feasibility study. Eur J Anaesthesiol. 2015;32(11):822–823.
  • Jannet D, Carbonne B, Sebban E, et al. Nicardipine versus metoprolol in the treatment of hypertension during pregnancy: a randomized comparative trial. Obstet Gynecol. 1994;84(3):354–359.
  • Montan S, Anandakumar C, Arulkumaran S, et al. Randomised controlled trial of methyldopa and isradipine in preeclampsia - effects on uteroplacental and fetal hemodynamics. J Perinat Med. 1996;24(2):177–184.
  • Fletcher H, Roberts G, Mullings A, et al. An open trial comparing isradipine with hydralazine and methyldopa in the treatment of patients with severe pre-eclampsia. J Obstet Gynaecol (Lahore). 1999;19(3):235–238.
  • Vargas-Ayala G, Salmeron Perez G, Sanchez Garcia AR, et al. Efficancy of isosorbide in aerosol in the management of hypertensive crisis of severe preeclampsia. Ginecol Obstet Mex. 1998;66:316–319.
  • Manzur-Verástegui S, Mandeville PB, Gordillo-Moscoso A, et al. Efficacy of nitroglycerine infusion versus sublingual nifedipine in severe pre-eclampsia: a randomized, triple-blind, controlled trial. Clin Exp Pharmacol Physiol. 2008;35(5–6):580–585.
  • Tabacova S, Little R, Tsong Y, et al. Adverse pregnancy outcomes associated with maternal enalapril antihypertensive treatment. Pharmacoepidemiol Drug Saf. 2003;12(8):633–646.
  • Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. Obstet Gynecol. 1992;80(3):429–432.
  • Lip GYH, Churchill D, Beevers M, et al. Angiotensin-converting-enzyme inhibitors in early pregnancy. Lancet. 1997;350(9089):1446–1447.
  • Velázquez-Armenta EY, Han JY, Choi JS, et al. Angiotensin II receptor blockers in pregnancy: a case report and systematic review of the literature. Hypertens Pregnancy. 2007;26(1):51–66.
  • Gallery EDM, Saunders DM, Hunyor SN, et al. Randomised comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy. Br Med J. 1979;1(6178):1591–1594.
  • Gallery ED, Ross MR, Gyory AZ, et al. Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa. Br Med J (Clin Res Ed). 1985;291(6495):563–566.
  • Livingstone I, Craswell PW, Bevan EB, et al. Propranolol in pregnancy three year prospective study. Hypertens Pregnancy. 1983;2(2):341–350.
  • Oumachigui A, Verghese M, Balachander J. A comparative evaluation of metoprolol and methyldopa in the management of pregnancy induced hypertension. Indian Heart J. 1992;44(1):39–41.
  • Wichman K, Ryden G, Karlberg BE. A placebo controlled trial of metoprolol in the treatment of hypertension in pregnancy. Scand J Clin Lab Invest. 1984;44(169):90–95.
  • Lydakis C, Lip GYH, Beevers M, et al. Atenolol and fetal growth in pregnancies complicated by hypertension. Am J Hypertens. 1999;12(6):541–547.
  • Ellenbogen A, Jaschevatzky O, Davidson A, et al. Management of pregnancy-induced hypertension with pindolol-comparative study with methyldopa. Int J Gynecol Obstet. 1986;24(1):3–7.
  • Paran E, Holzberg G, Mazor M, et al. Beta-adrenergic blocking agents in the treatment of pregnancy-induced hypertension. Int J Clin Pharmacol Ther. 1995;33(2):119–123.
  • The Magpie Trial Collaborative Group. Do women with preeclampsia, and their babies, benefit from magnesium sulphate? The magpie trial: a randomised placebo-controlled trial. Lancet 2002;369:1877–1890
  • Simon J, Gray A, Duley L. Cost-effectiveness of prophylactic magnesium sulphate for 9996 women with pre-eclampsia from 33 countries: economic evaluation of the Magpie Trial. BJOG. 2006;113(2):144–151.
  • Hutton JD, James DK, Stirrat GM, et al. Management of severe pre‐eclampsia and eclampsia by UK consultants. BJOG. 2018;99(7):554–556. 25.
  • ACOG guidelines: hypertension in pregnancy. American college of obstetricians and gynecologists. Task Force on Hypertension in Pregnancy. 2013.
  • Magee LA, Bc V, Helewa M, et al. SOGC clinical practice guidelines diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary. J Obs Gynaecol Can. 2014;36(5):416–438
  • Duley L, Gülmezoglu AM, Henderson-Smart DJ, et al. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010;10(11):CD000025.
  • Smyth RMD, Spark P, Armstrong N, et al. Magpie trial in the UK: methods and additional data for women and children at 2 years following pregnancy complicated by pre-eclampsia. BMC Pregnancy Childbirth. 2009;14(9):5.
  • Duley L, Farrell B, Armstrong N, et al. The magpie trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for women at 2 years. BJOG. 2007;114(3):300–309.
  • Duley L, Farrell B, Armstrong N, et al. The magpie trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BJOG. 2007;114(3):289–299.
  • Maternal deaths in Australia 2008–2012 [Internet]. 2012. Available from: https://www.aihw.gov.au/reports/mothers-babies/maternal-deaths-in-australia-2008-2012/contents/table-of-contents [Accessed 22 January 2019].
  • Crowther CA, Middleton PF, Voysey M, et al. Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: an individual participant data meta-analysis. PLoS Med. 2017; 14(10):e1002398
  • Jacquemyn Y, Zecic A, Van Laere D, et al. The use of intravenous magnesium in non-preeclamptic pregnant women: fetal/neonatal neuroprotection. Arch Gynecol Obstet. 2015;291(5):969–975.
  • Sibai BM, Mercer BM, Schiff E, et al. Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks’ gestation: a randomized controlled trial. Am J Obstet Gynecol. 1994;171(3):818–822.
  • Oláh KS, Redman CWG, Gee H. Management of severe, early pre-eclampsia: is conservative management justified? Eur J Obstet Gynecol Reprod Biol. 1993;51(3):175–180.
  • Sarsam DS, Shamden M, Al Wazan R, et al. Expectant versus aggressive management in severe preeclampsia remote from term. Singapore Med J. 2008;49(9):698–703.
  • Schwartz RB, Feske SK, Polak JF, et al. Preeclampsia-Eclampsia: clinical and neuroradiographic correlates and insights into the pathogenesis of hypertensive encephalopathy. Radiology. 2000;217(2):371–376.
  • Teela KC, Ferguson RM, Donnay FA, et al. The PIERS trial: hope for averting deaths from pre-eclampsia. Lancet. 2011;9761(377):185–186.
  • Ukah UV, Payne B, Karjalainen H, et al. Temporal and external validation of the fullPIERS model for the rpediction of adverse maternal outcomes in women with preeclampsia. Pregnancy Hypertens. 2019;15:42–50.
  • Hobson SR, Gurusinghe S, Lim R, et al. Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia. J Pineal Res. 2018;65(3):e12508.
  • Ray JG, Vermeulen MJ, Schull MJ, et al. Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study. Lancet. 2005;366(9499):1797–1803.
  • Nisell H, Lintu H, Lunell NO, et al. Blood pressure and renal function seven years after pregnancy complicated by hypertension. Br J Obstet Gynaecol. 1995;102(11):876–881.
  • Bellamy L, Casas J-P, Hingorani AD, et al. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335(7627):974.
  • Agatisa PK. Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk. AJP Hear Circ Physiol. 2003;286(4):1389–1393.
  • Craici I, Wagner S, Garovic VD. Preeclampsia and future cardiovascular risk: formal risk factor or failed stress test? Ther Adv Cardiovasc Dis. 2008;2(4):249–259.
  • Cain MA, Salemi JL, Tanner JP, et al. Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes. Am J Obstet Gynecol. 2016;215(4):484.
  • Roberts JM, Hubel CA. Is oxidative stress the link in the two-stage model of pre-eclampsia? Lancet. 1999;354(9181):788–789.
  • Trapani A, Gonçalves LF, Trapani TF, et al. Perinatal and hemodynamic evaluation of sildenafil citrate for preeclampsia treatment. Obstet Gynecol. 2016;128(2):253–259.
  • Trapani A, Gonçalves LF, Trapani TF. Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices. Ultrasound Obstet Gynecol. 2016;48(1):61–65.
  • Samangaya RA, Mires G, Shennan A, et al. A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia. Hypertens Pregnancy. 2009;28(4):369–382.
  • Sharp A, Cornforth C, Jackson R, et al. Maternal sildenafil for severe fetal growth restriction (STRIDER): a multicentre, randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Heal. 2018;2(2):93–102.
  • Groom KM, Ganzevoort W, Alfirevic Z, et al. Clinicians should stop prescribing sildenafil for fetal growth restriction (FGR): comment from the STRIDER Consortium. Ultrasound Obstet Gynecol. 2018;52(3):295–296.
  • Miller SL, Loose JM, Jenkin G, et al. The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus. Am J Obstet Gynecol. 2009;200(1):102–107.
  • Facchinetti F, Longo M, Piccinini F, et al. L-arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release. J Soc Gynecol Investig. 1999;6(4):202–207.
  • Staff AC, Berge L, Haugen G, et al. Dietary supplementation with L-arginine or placebo in women with pre-eclampsia. Acta Obstet Gynecol Scand. 2004;83(1):103–107.
  • Vadillo-Ortega F, Perichart-Perera O, Espino S, et al. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. BMJ. 2011;342:d2901.
  • Walker JD. NICE guidance on diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Diabet Med. 2008;25(9):1025–1027.
  • Romero R, Erez O, Hüttemann M, et al. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. Am J Obstet Gynecol. 2017;217:3282–3302.
  • Alqudah A, McKinley MC, McNally R, et al. Risk of pre-eclampsia in women taking metformin: a systematic review and meta-analysis. Diabet Med. 2018;35(2):160–172.
  • Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222(3):222–235.
  • Livingston JC, Chin R, Haddad B. Reductions of vascular endothelial growth factor and placental growth factor concentrations in severe preeclampsia. Am J Obstet Gynecol. 2000;183(6):1554–1557.
  • Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet. 1999;354(9181):810–816.
  • Beazley D, Ahokas R, Livingston J, et al. Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial. Am J Obstet Gynecol. 2005;192(2):520–521.
  • Chappell LC, Seed PT, Kelly FJ, et al. Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function. Am J Obstet Gynecol. 2002;187(3):777–784.
  • McCance DR, Holmes VA, Maresh MJA, et al. Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial. Lancet. 2010;376(6736):259–266.
  • Kalpdev A, Saha SC, Dhawan V. Vitamin C and e supplementation does not reduce the risk of superimposed PE in pregnancy. Hypertens Pregnancy. 2011;30(4):447–456.
  • Rayman MP, Bath SC, Westaway J, et al. Selenium status in UK pregnant women and its relationship with hypertensive conditions of pregnancy. Br J Nutr. 2015;113(2):249–258.
  • Vanderlelie J, Venardos K, Perkins AV. Selenium deficiency as a model of experimental pre-eclampsia in rats. Reproduction. 2004;128(5):635–641.
  • Lymbury RS, Marino MJ, Perkins AV. Effect of dietary selenium on the progression of heart failure in the ageing spontaneously hypertensive rat. Mol Nutr Food Res. 2010;54(10):1436–1444.
  • Kiełczykowska M, Kocot J, Lewandowska A, et al. The protective influence of selenium on oxidant disturbances in brain of rats exposed to lithium. Physiol Res. 2015;64(5):739–746.
  • Rayman MP, Searle E, Kelly L, et al. Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial. Br J Nutr. 2014;112(1):99–111.
  • Ahmed A, Rezai H, Broadway-Stringer S. Evidence-based revised view of the pathophysiology of preeclampsia. Adv Exp Med Biol. 2017;956:355–374.
  • Tara F, Maamouri G, Rayman MP, et al. Selenium supplementation and the incidence of preeclampsia in pregnant Iranian women: a randomized, double-blind, placebo-controlled pilot trial. Taiwan J Obstet Gynecol. 2010;49(2):181–187.
  • Han L, Zhou S. Selenium supplement in the prevention of pregnancy induced hypertension. Chin Med J (Engl). 1994;107(11):870–871.
  • Oldfield JE. The two faces of selenium. J Nutr. 1987;117(12):2002–2008.
  • Vinceti M, Wei E, Malagoli C, et al. Adverse health effects of selenium in humans. Rev Environ Health. 2001;16:233.
  • Usami M, Ohno Y. Teratogenic effects of selenium compounds on cultured postimplantation rat embryos. Teratog Carcinog Mutagen. 1996;16(1):27–36.
  • Yang X, Yu X, Fu H, et al. Different levels of prenatal zinc and selenium had different effects on neonatal neurobehavioral development. Neurotoxicology. 2013;37:35–39.
  • Parrish RM, Martin NJ, Lamarca BB, et al. Randomized, placebo controlled, double blind trial evaluating early pregnancy phytonutrient supplementation in the prevention of preeclampsia. J Perinatol. 2013;33(8):593–599.
  • Ding J, Kang Y, Fan Y, et al. Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia. Endocr Connect. 2017;6(8):595–600.
  • Gurusinghe S, Cox AG, Rahman R, et al. Resveratrol mitigates trophoblast and endothelial dysfunction partly via activation of nuclear factor erythroid 2-related factor-2. Placenta. 2017;60:74–85.
  • Bouchlariotou S, Liakopoulos V, Giannopoulou M, et al. Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm. Ren Fail. 2014;36(7):1001–1007.
  • Hobson SR, Mockler JC, Lim R, et al. Melatonin for treating pre-eclampsia. Cochrane Database Syst Rev. 2016.
  • Girouard H, Chulak C, Lejossec M, et al. Vasorelaxant effects of the chronic treatment with melatonin on mesenteric artery and aorta of spontaneously hypertensive rats. J Hypertens. 2001;19(8):1369–1377.
  • Hu ZP, Fang XL, Fang N, et al. Melatonin ameliorates vascular endothelial dysfunction, inflammation, and atherosclerosis by suppressing the TLR4/NF-κB system in high-fat-fed rabbits. J Pineal Res. 2013;55(4):388–398.
  • Huang L, Zhang C, Hou Y, et al. Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats. Eur Rev Med Pharmacol Sci. 2013;17(18):2449–2456.
  • Matok I, Levy A, Wiznitzer A, et al. The safety of fetal exposure to proton-pump inhibitors during pregnancy. Dig Dis Sci. 2012;57(3):699–705.
  • Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med. 2010;363(22):2114–2123.
  • Onda K, Tong S, Beard S, et al. Proton pump inhibitors decrease soluble fms-like tyrosine kinase-1 and soluble endoglin secretion, decrease hypertension, and rescue endothelial dysfunction. Hypertension. 2017;69(3):457–468.
  • Kuroda M, Yoshida N, Ichikawa H, et al. Lansoprazole, a proton pump inhibitor, reduces the severity of indomethacin-induced rat enteritis. Int J Mol Med. 2006;17(1):89–93.
  • Cluver CA, Walker SP, Mol BW, et al. Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol. BMJ Open. 2015;5(10):e008211.
  • Cluver CA, Hannan NJ, van Papendorp, E, et al. Esomeprazole to treat women with preterm preeclampsia: a randomised placebo controlled trial. Am J Obstet Gynecol. 2018;219(4):388–e1
  • Myers JE, Kenny LC, McCowan LM, et al. SCOPE consortium. Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study. BJOG. 2013;120:1215–1223.
  • Park FJ, Leung CH, Poon LC, et al. Clinical evaluation of a first trimester algorithm predicting the risk of hypertensive disease of pregnancy. Aust N Z J Obstet Gynaecol. 2013;53:532–539.
  • Saleh L, Verdonk K, Danser AHJ, et al. The sFlt-1/PlGF ration associated with prolongation and adverse outcome of pregnancy in women with (suspected) preeclampsia: analysis of a high-risk cohort. Eur J Obstet Gynecol. 2016;199:121–126.
  • Rana S, Salahuddin S, Mueller A, et al. Angiogenic biomarkers in triage and risk for preeclampsia with severe features. Pregnancy Hypertens. 2018;13:100–106.
  • Dragan I, Georgiou T, PRodan N, et al. Screening for preeclampsia using sFLt-1/PlGF ration cut-off of 38 at 30–37 weeks’ gestation. Ultrasound Obstetrics Gynecology. 2017;49::73–77.
  • Agrawal S, Cerdeira AS, Redman C, et al. Meta-analysis and systematic review to assess the role of soluble FMS-like tyrosine kinase-1 and placental growth factor ration in the prediction of preeclampsia. The SaPPPhirE study. Hypertens. 2018;71:306–331.
  • D’Antona D, Reis FM, Benedetto C, et al. Increased maternal serum activin A but not follistatin levels in pregnant women with hypertensive disorders. J Endocrinol. 2000.
  • Lim R, Acharya R, Delpachitra P, et al. Activin and NADPH-oxidase in preeclampsia: insights from in vitro and murine studies. Am J Obstet Gynecol. 2015;212(1):86e1–12.
  • Lim R, Adhikari S, Gurusinghe S, et al. Inhibition of activin A signaling in a mouse model of preeclampsia. Placenta. 2015;36:926–931.
  • Hobson SR, Acharya R, Lim R, et al. Role of activin A in the pathogenesis of endothelial cell dysfunction preeclampsia. Pregnancy Hypertens. 2016;6:130–133.
  • Chen B, Tuuli MG, Longtime MS, et al. Pomegranate juice and punicalagin attentuate oxidative stress and apoptosis in human placenta and in human placental trophoblast. Am J Physiol Endocrinol Metab. 2012;302:E1142–E1152.

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