Preeclampsia 2012

Elosha Eiland, Chike Nzerue, Marquetta Faulkner, Elosha Eiland, Chike Nzerue, Marquetta Faulkner

Abstract

Preeclampsia is a common complication of pregnancy associated with high maternal morbidity and mortality and intrauterine fetal growth restriction. There is extensive evidence that the reduction of uteroplacental blood flow in this syndrome results from the toxic combination of hypoxia, imbalance of angiogenic and antiangiogenic factors, inflammation, and deranged immunity. Women treated for preeclampsia also have an increased risk for cardiovascular and renal disease. At present it is unclear if the increased cardiovascular and renal disease risks are due to residual and or progressive effects of endothelial damage from the preeclampsia or from shared risk factors between preeclampsia and cardiac disease. Moreover, it appears that endothelin-1 signaling may play a central role in the hypertension associated with preeclampsia. In this paper, we discuss emerging data on the pathogenesis of preeclampsia and review therapeutic options.

Figures

Figure 1
Figure 1
Showing unified hypothesis on pathogenesis of endothelial dysfunction, hypertension, and edema with preeclampsia.

References

    1. Ghulmiyyah L, Sibai B. Maternal mortality from preeclampsia/eclampsia. Seminars in Perinatology. 2012;36(1):56–59.
    1. Moodley J. Maternal deaths associated with hypertensive disorders of pregnancy: a population-based study. Hypertension in Pregnancy. 2004;23(3):247–256.
    1. Duley L. The global impact of pre-eclampsia and eclampsia. Seminars in Perinatology. 2009;33(3):130–137.
    1. WHO Recommendations for Prevention and Treatment of Preeclampsia and Eclampsia. Geneva, Switzerland: WHO Department of Maternal and Child Health; 2011.
    1. Osungbade OK, Ige OK. Public heath perspectives of preeclampsia in developing countries: implication for health system strenghtening. Journal of Pregnancy. 2011;2011481095
    1. Rao AK, Daniels K, El-Sayed YY, Moshesh MK, Caughey AB. Perinatal outcomes among Asian American and Pacific Islander women. American Journal of Obstetrics and Gynecology. 2006;195(3):834–838.
    1. Steinberg G, Khankin EV, Karumanchi SA. Angiogenic factors and preeclampsia. Thrombosis Research. 2009;123:S93–S99.
    1. Aggarwal PK, Chandel N, Jain V, Jha V. The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia. Journal of Human Hypertension. 2011;26:236–241.
    1. Hui D, Okun N, Murphy K, Kingdom J, Uleryk E, Shah PS. Combinations of maternal serum markers to predict preeclampsia, small for gestational age, and stillbirth: a systematic review. Journal of Obstetrics and Gynaecology Canada. 2012;34(2):142–153.
    1. Venkatesha S, Toporsian M, Lam C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nature Medicine. 2006;12(6):642–649.
    1. Ramma W, Ahmed A. Is inflammation the cause of pre-eclampsia? Biochemical Society Transactions. 2011;39(6):1619–1627.
    1. Clifton VL, Stark MJ, Osei-Kumah A, Hodyl NA. Review: the feto-placental unit, pregnancy pathology and impact on long term maternal health. Placenta. 2012;33:S37–S41.
    1. Powe CE, Levine RJ, Karumanchi SA. Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation. 2011;123(24):2856–2869.
    1. Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. New England Journal of Medicine. 2006;355(10):992–1005.
    1. Izzedine H, Massard C, Spano JP, Goldwasser F, Khayat D, Soria JC. VEGF signalling inhibition-induced proteinuria: mechanisms, significance and management. European Journal of Cancer. 2010;46(2):439–448.
    1. Gélinas DS, Bernatchez PN, Rollin S, Bazan NG, Sirois MG. Immediate and delayed VEGF-mediated NO synthesis in endothelial cells: role of PI3K, PKC and PLC pathways. British Journal of Pharmacology. 2002;137(7):1021–1030.
    1. McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. American Heart Journal. 2008;156(5):918–930.
    1. Smith GCS, Pell JP, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129 290 births. The Lancet. 2001;357(9273):2002–2006.
    1. Vikse BE, Irgens LM, Leivestad T, Skjærven R, Iversen BM. Preeclampsia and the risk of end-stage renal disease. New England Journal of Medicine. 2008;359(8):800–809.
    1. McDonald SD, Han Z, Walsh MW, Gerstein HC, Devereaux PJ. Kidney disease after preeclampsia: a systematic review and meta-analysis. American Journal of Kidney Diseases. 2010;55(6):1026–1039.
    1. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. British Medical Journal. 2007;335(7627):974–977.
    1. Ray JG, Vermeulen MJ, Schull MJ, Redelmeier DA. Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study. The Lancet. 2005;366(9499):1797–1803.
    1. Lawlor DA, MacDonald-Wallis C, Fraser A, et al. Cardiovascular biomarkers and vascular function during childhood in the offspring of mothers with hypertensive disorders of pregnancy: findings from the Avon Longitudinal Study of Parents and Children. European Heart Journal. 2012;33(3):335–345.
    1. Palti H, Rothschild E. Blood pressure and growth at 6 years of age among offsprings of mothers with hypertension of pregnancy. Early Human Development. 1989;19(4):263–269.
    1. Williams D . Long-term complications of preeclampsia. Seminars in Nephrology. 2011;31(1):111–122.
    1. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunology Today. 1993;14(7):353–356.
    1. Redman CWG, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. American Journal of Obstetrics and Gynecology. 1999;180(2 I):499–506.
    1. Shamshirsaz AA, Paidas M, Krikun G. Preeclampsia, hypoxia, and inflammation. Journal of Pregnancy. 2012;2012:6 pages.374047
    1. Szarka A, Rigó J, Lázár L, Beko G, Molvarec A. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunology. 2010;11, article 59
    1. Sharma A, Satyam A, Sharma JB. Leptin, IL-10 and inflammatory markers (TNF-α, IL-6 and IL-8) in pre-eclamptic, normotensive pregnant and healthy non-pregnant women. American Journal of Reproductive Immunology. 2007;58(1):21–30.
    1. Lynch AM, Murphy JR, Gibbs RS, et al. The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia. British Journal of Obstetrics and Gynaecology. 2010;117(4):456–462.
    1. Djurovic S, Clausen T, Wergeland R, Brosstad F, Berg K, Henriksen T. Absence of enhanced systemic inflammatory response at 18 weeks of gestation in women with subsequent pre-eclampsia. British Journal of Obstetrics and Gynaecology. 2002;109(7):759–764.
    1. Kronborg CS, Gjedsted J, Vittinghus E, Hansen TK, Allen J, Knudsen UB. Longitudinal measurement of cytokines in pre-eclamptic and normotensive pregnancies. Acta Obstetricia et Gynecologica Scandinavica. 2011;90(7):791–796.
    1. George EM, Granger JP. Endothelin: key mediator of hypertension in preeclampsia. American Journal of Hypertension. 2011;24:964–969.
    1. Chen Q, Chen L, Liu B, et al. The role of autocrine TGFβ1 in endothelial cell activation induced by phagocytosis of necrotic trophoblasts: a possible role in the pathogenesis of pre-eclampsia. Journal of Pathology. 2010;221(1):87–95.
    1. Sandrim VC, Palei ACT, Metzger IF, Gomes VA, Cavalli RC, Tanus-Santos JE. Nitric oxide formation is inversely related to serum levels of antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluble endogline in preeclampsia. Hypertension. 2008;52(2):402–407.
    1. Duplain H, Burcelin Ŕ, Sartori C, et al. Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation. 2001;104(3):342–345.
    1. Niu W, Qi Y. An updated meta-analysis of endothelial nitric oxide synthase gene: three well-characterized polymorphisms with hypertension. PLoS ONE. 2011;6(9)e24266
    1. Serrano NC, Casas JP, Díaz LA, et al. Endothelial NO synthase genotype and risk of preeclampsia: a multicenter case-control study. Hypertension. 2004;44(5):702–707.
    1. Fatini C, Sticchi E, Gensini F, et al. Endothelial nitric oxide synthase gene influences the risk of pre-eclampsia, the recurrence of negative pregnancy events, and the maternal-fetal flow. Journal of Hypertension. 2006;24(9):1823–1829.
    1. Li F, Hagaman JR, Kim H-S, et al. eNOS deficiency acts through endothelin to aggravate sFlt-1-induced pre-eclampsia-like phenotype. Journal of the American Society of Nephrology. 2012;23(4):652–660.
    1. Conrad KP. Maternal vasodilation in pregnancy: the emerging role of relaxin. American Journal of Physiology. 2011;301(2):R267–R275.
    1. Conrad KP. Emerging role of relaxine in the maternal adaptation to normal pregnancy:implications for preeclampsia. Seminars in Nephrology. 2011;31(1):15–32.
    1. Unemori E, Sibai B, Teichmana SL. Scientific rationale and design of a phase I safety study of relaxin inwomen with severe preeclampsia. Annals of the New York Academy of Sciences. 2009;1160:381–384.
    1. Lafayette RA, Hladunewich MA, Derby G, Blouch K, Druzin ML, Myers BD. Serum relaxin levels and kidney function in late pregnancy with or without preeclampsia. Clinical Nephrology. 2011;75(3):226–232.
    1. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728):1592–1594.
    1. Stillman IE, Karumanchi SA. The glomerular injury of preeclampsia. Journal of the American Society of Nephrology. 2007;18(8):2281–2284.
    1. Wang Y, Zhao S, Loyd S, Groome LJ. Increased urinary excretion of nephrin, podocalyxin, and βig-h3 in women with preeclampsia. American Journal of Physiology. 2012;302(9):F1084–F1089.
    1. Dasgupta S, Ghosh D, Seal SL, Kamilya G, Karmakar M, Saha D. Randomized controlled study comparing effect of magnesium sulfate with placebo on fetal umbilical artery and middle cerebral artery blood flow in mild preeclampsia at ≥34 weeks gestational age. Journal of Obstetrics and Gynaecology Research. 2012;38(5):763–771.
    1. Souza ASR, Amorim MMR, Santos RE, Neto CN, Porto AMF. Effect of magnesium sulfate on pulsatility index of uterine, umbilical and fetal middle cerebral arteries according to the persistence of bilateral diastolic notch of uterine arteries in patients with severe preeclampsia. Revista Brasileira de Ginecologia e Obstetricia. 2009;31(2):82–88.
    1. Vadnais MA, Rana S, Quant HS, et al. The impact of magnesium sulfate therapy on angiogenic factors in preeclampsia. Pregnancy Hypertension. 2012;2(1):16–21.
    1. la Marca B, Brewer J, Wallace K. IL-6-induced pathophysiology during pre-eclampsia: potential therapeutic role for magnesium sulfate? International Journal of Interferon, Cytokine and Mediator Research. 2011;3(1):59–64.
    1. Beaufils M, Donsimoni R, Uzan S, Colau JC. Prevention of pre-elcampsia by early antiplatelet therapy. The Lancet. 1985;1(8433):840–842.
    1. Schiff E, Peleg E, Goldenberg M, et al. The use of aspirin to prevent preeclampsia. New England Journal of Medicine. 1989;321(6):351–356.
    1. Hauth JC, Goldenberg RL, Parker R, et al. Low-dose aspirin therapy to prevent preeclampsia. American Journal of Obstetrics and Gynecology. 1993;168(4):1083–1093.
    1. Beroyz G, Casale R, Farreiros A, et al. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. The Lancet. 1994;343(8898):619–629.
    1. Caritis S, Sibai B, Hauth J, et al. Low-dose aspirin to prevent preeclampsia in women at high risk. New England Journal of Medicine. 1998;338(11):701–705.
    1. Roberts JM, Catov JM. Aspirin for pre-eclampsia: compelling data on benefit and risk. The Lancet. 2007;369(9575):1765–1766.
    1. Askie LM, Duley L, Henderson-Smart DJ, Stewart LA. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. The Lancet. 2007;369(9575):1791–1798.
    1. Verheugt FWA, Bolte AC. The role of aspirin in women's health. International Journal of Women's Health. 2011;3(1):151–166.
    1. Bucher HC, Guyatt GH, Cook RJ, et al. Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a peta-analysis of randomized controlled trials. Journal of the American Medical Association. 1996;275(14):1113–1117.
    1. Mert I, Oruc AS, Yuksel S, et al. Role of oxidative stress in preeclampsia and intrauterine growth restriction. Journal of Obstetrics and Gynaecology Research. 2012;38(4):658–664.
    1. Roberts JM, Myatt L, Spong Y, et al. Vitamins C and E to prevent complications of pregnancy-associated hypertension. New England Journal of Medicine. 2010;362(14):1282–1291.
    1. Kassab S, Miller MT, Hester R, Novak J, Granger JP. Systemic hemodynamics and regional blood flow during chronic nitric oxide synthesis inhibition in pregnant rats. Hypertension. 1998;31(1):315–320.
    1. Sladek SM, Magness RR, Conrad KP. Nitric oxide and pregnancy. American Journal of Physiology. 1997;272(2):R441–R463.
    1. Rytlewski K, Olszanecki R, Korbut R, Zdebski Z. Effects of prolonged oral supplementation with L-arginine on blood pressure and nitric oxide synthesis in preeclampsia. European Journal of Clinical Investigation. 2005;35(1):32–37.
    1. Begum S, Yamasaki M, Mochizuki M. Urinary levels of nitric oxide metabolites in normal pregnancy and preeclampsia. Journal of Obstetrics and Gynaecology Research. 1996;22(6):551–559.
    1. Roberts JM, Davidge ST, Silver RK, Caplan MS. Plasma nitrites as an indicator of nitric oxide production: unchanged production or reduced renal clearance in preeclampsia? American Journal of Obstetrics and Gynecology. 1997;176(4):954–955.
    1. Carbonne B, Macé G, Cynober E, Milliez J, Cabane J. Successful pregnancy with the use of nitric oxide donors and heparin after recurrent severe preeclampsia in a woman with scleroderma. American Journal of Obstetrics and Gynecology. 2007;197(2):e6–e7.
    1. Giuggioli D, Colaci M, Sebastiani M, Ferri C. L-arginine in pregnant scleroderma patients. Clinical Rheumatology. 2010;29(8):937–939.
    1. Mistry HD, Williams PJ. The importance of antioxidant micronutrients in pregnancy. Oxidative Medicine and Cellular Longevity. 2011;2011:12 pages.841749
    1. Rossi AC, Mullin PM. Prevention of pre-eclampsia with low-dose aspirin or vitamins C and E in women at high or low risk: a systematic review with meta-analysis. European Journal of Obstetrics Gynecology and Reproductive Biology. 2011;158(1):9–16.
    1. Villar J, Purwar M, Merialdi M, et al. World Health Organisation multicentre randomised trial of supplementation with vitamins C and e among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries. British Journal of Obstetrics and Gynaecology. 2009;116(6):780–788.
    1. Salles AMR, Galvao TF, Silva MT, Motta LCD, Pereira MG. Antioxidants for preventing preeclampsia: a systematic review. The Scientific World Journal. 2012;2012:10 pages.243476
    1. Treinen KA, Louden C, Dennis MJ, Wier PJ. Developemental toxicity and toxicokinetics of 2 endothelial antagonists in rats and rabbits. Terratology. 1999;59(1):51–59.
    1. Clark SL, Hankins GDV. Preventing maternal death: 10 clinical diamonds. Obstetrics and Gynecology. 2012;119(2):360–364.
    1. Chhabra S, Tyagi S, Bhavani M, Gosawi M. Late postpartum eclampsia. Journal of Obstetrics and Gynaecology. 2012;32(3):264–266.
    1. Larsen WI, Strong JE, Farley JH. Risk factors for late postpartum preeclampsia. Journal of Reproductive Medicine for the Obstetrician and Gynecologist. 2012;57(1):35–38.
    1. Chames MC, Livingston JC, Ivester TS, Barton JR, Sibai BM. Late postpartum eclampsia: a preventable disease? American Journal of Obstetrics and Gynecology. 2002;186(6):1174–1177.
    1. Walsh SW. Preeclampsia: an imbalance in placental prostacyclin and thromboxane production. American Journal of Obstetrics and Gynecology. 1985;152(3):335–340.
    1. Chavarría ME, Lara-González L, González-Gleason A, García-Paleta Y, Vital-Reyes VS, Reyes A. Prostacyclin/thromboxane early changes in pregnancies that are complicated by preeclampsia. American Journal of Obstetrics and Gynecology. 2003;188(4):986–992.
    1. Mousa AA, Strauss III JF, Walsh SW. Reduced methylation of the thromboxane synthase gene is correlated with its increased vascular expression in preeclampsia. Hypertension. 2012;59(6):1249–1255.

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