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Prediction of Preeclampsia-Bench to Bedside

  • Preeclampsia (VD Garovic, Section Editor)
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Abstract

Hypertensive disorders of pregnancy (HDP) constitute the most common medical condition seen during gestation, effecting 1 in 10 pregnancies in the USA. Traditionally, preeclampsia (PE) is defined as a new onset of hypertension and either proteinuria or end-organ dysfunction after 20 weeks of gestation in a previously normotensive woman. Preeclampsia is a potentially life-threatening condition with widespread underlying endothelial dysfunction, and accompanying inflammation, vasoconstriction, and platelet activation. Women with preeclampsia are at an increased risk for life-threatening complications and progression to eclampsia. Worldwide, 10 to 15 % of maternal deaths are from preeclampsia and related complications. Traditionally, diagnosis of preeclampsia is made based upon presence of risk factors and clinical criteria. Diagnosis is challenging in asymptomatic women early in pregnancy as well as in nulliparous women as they lack obstetric history; however, it is well known that women with previous preeclampsia have a 14.7 % risk of the condition in the second pregnancy. Prediction of those at risk and early diagnosis is crucial to enable close surveillance of high-risk women in order to improve maternal and fetal outcomes. There has been much advance in our understanding of the pathogenesis of PE and in the field of angiogenic markers. However, no one test meets the criteria for a good biomarker. A multiparametric approach appears to be optimal as we await newer systems biology approaches to give  us better insight into the pathogenesis of the disease.

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References

  1. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1,122–31. doi:10.1097/01.aog.0000437382.03963.88.

  2. Cunningham FG, Lindheimer MD. Hypertension in pregnancy. N Engl J Med. 1992;326(14):927–32. doi:10.1056/nejm199204023261405.

    PubMed  CAS  Google Scholar 

  3. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130–7. doi:10.1053/j.semperi.2009.02.010.

    PubMed  Google Scholar 

  4. Chang J, Elam-Evans LD, Berg CJ, Herndon J, Flowers L, Seed KA, et al. Pregnancy-related mortality surveillance—United States, 1991–1999. MMWR Surveill Summ. 2003;52(2):1–8.

    PubMed  Google Scholar 

  5. Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obstet Gynecol. 2013;209(6):544.el–e12.

    Google Scholar 

  6. Wright A, Zhou Y, Weier JF, Caceres E, Kapidzic M, Tabata T, et al. Trisomy 21 is associated with variable defects in cytotrophoblast differentiation along the invasive pathway. Am J Med Genet A. 2004;130a(4):354–64. doi:10.1002/ajmg.a.30254.

    PubMed  Google Scholar 

  7. Verghese L, Alam S, Beski S, Thuraisingham R, Barnes I, MacCallum P. Antenatal screening for pre-eclampsia: evaluation of the NICE and pre-eclampsia community guidelines. J Obstet Gynaecol. 2012;32(2):128–31. doi:10.3109/01443615.2011.635224.

    PubMed  CAS  Google Scholar 

  8. North RA, McCowan LM, Dekker GA, Poston L, Chan EH, Stewart AW, et al. Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort. BMJ. 2011;342:d1875. doi:10.1136/bmj.d1875.

    PubMed  PubMed Central  Google Scholar 

  9. Kane SC, Da Silva CF, Brennecke SP. New directions in the prediction of pre-eclampsia. Aust N Z J Obstet Gynaecol. 2014;54(2):101–7. doi:10.1111/ajo.12151.

    PubMed  Google Scholar 

  10. Freitag N, Tirado-Gonzalez I, Barrientos G, Herse F, Thijssen VL, Weedon-Fekjaer SM, et al. Interfering with Gal-1-mediated angiogenesis contributes to the pathogenesis of preeclampsia. Proc Natl Acad Sci U S A. 2013;110(28):11451–6. doi:10.1073/pnas.1303707110.

    PubMed  CAS  PubMed Central  Google Scholar 

  11. Horgan RP, Kenny LC. ‘Omic’ technologies: genomics, transcriptomics, proteomics and metabolomics. Obstet Gynaecol. 2011;13(3):189–95. doi:10.1576/toag.13.3.189.27672.

    Google Scholar 

  12. Myers JE, Tuytten R, Thomas G, Laroy W, Kas K, Vanpoucke G, et al. Integrated proteomics pipeline yields novel biomarkers for predicting preeclampsia. Hypertension. 2013;61(6):1281–8. doi:10.1161/hypertensionaha.113.01168.

    PubMed  CAS  Google Scholar 

  13. Theodorescu D, Mischak H. Mass spectrometry based proteomics in urine biomarker discovery. World J Urol. 2007;25(5):435–43. doi:10.1007/s00345-007-0206-3.

    PubMed  CAS  Google Scholar 

  14. Vlahou A, Fountoulakis M. Proteomic approaches in the search for disease biomarkers. J Chromatogr B Anal Technol Biomed Life Sci. 2005;814(1):11–9. doi:10.1016/j.jchromb.2004.10.024.

    CAS  Google Scholar 

  15. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728):1592–4. doi:10.1126/science.1111726.

    PubMed  CAS  Google Scholar 

  16. Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649–58. doi:10.1172/jci17189.

    PubMed  CAS  PubMed Central  Google Scholar 

  17. Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005. doi:10.1056/NEJMoa055352.

    PubMed  CAS  Google Scholar 

  18. Chaiworapongsa T, Romero R, Kim YM, Kim GJ, Kim MR, Espinoza J, et al. Plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated prior to the clinical diagnosis of pre-eclampsia. J Matern Fetal Neonatal Med. 2005;17(1):3–18. doi:10.1080/14767050400028816.

    PubMed  CAS  Google Scholar 

  19. Hertig A, Berkane N, Lefevre G, Toumi K, Marti HP, Capeau J, et al. Maternal serum sFlt1 concentration is an early and reliable predictive marker of preeclampsia. Clin Chem. 2004;50(9):1702–3. doi:10.1373/clinchem.2004.036715.

    PubMed  CAS  Google Scholar 

  20. Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med. 2008;21(1):9–23. doi:10.1080/14767050701830480.

    PubMed  CAS  PubMed Central  Google Scholar 

  21. Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda, Md). 2009;24:147–58. doi:10.1152/physiol.00043.2008.

    Google Scholar 

  22. Polliotti BM, Fry AG, Saller DN, Mooney RA, Cox C, Miller RK. Second-trimester maternal serum placental growth factor and vascular endothelial growth factor for predicting severe, early-onset preeclampsia. Obstet Gynecol. 2003;101(6):1266–74.

    PubMed  CAS  Google Scholar 

  23. Thadhani R, Mutter WP, Wolf M, Levine RJ, Taylor RN, Sukhatme VP, et al. First trimester placental growth factor and soluble fms-like tyrosine kinase 1 and risk for preeclampsia. J Clin Endocrinol Metab. 2004;89(2):770–5. doi:10.1210/jc.2003-031244.

    PubMed  CAS  Google Scholar 

  24. Park JE, Chen HH, Winer J, Houck KA, Ferrara N. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem. 1994;269(41):25646–54.

    PubMed  CAS  Google Scholar 

  25. Knudsen UB, Kronborg CS, von Dadelszen P, Kupfer K, Lee S-W, Vittinghus E, et al. A single rapid point-of-care placental growth factor determination as an aid in the diagnosis of preeclampsia. Pregnancy Hypertens: Int J Women’s Cardiovasc Health. 2012;2(1):8–15.

    Google Scholar 

  26. Poon LC, Kametas NA, Maiz N, Akolekar R, Nicolaides KH. First-trimester prediction of hypertensive disorders in pregnancy. Hypertension. 2009;53(5):812–8. doi:10.1161/hypertensionaha.108.127977.

    PubMed  CAS  Google Scholar 

  27. Myers JE, Kenny LC, McCowan LM, Chan EH, Dekker GA, Poston L, et al. Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study. BJOG. 2013;120(10):1215–23. doi:10.1111/1471-0528.12195.

    PubMed  CAS  Google Scholar 

  28. Li H, Gu B, Zhang Y, Lewis DF, Wang Y. Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta. Placenta. 2005;26(2–3):210–7. doi:10.1016/j.placenta.2004.05.004.

    PubMed  CAS  Google Scholar 

  29. Clark DE, Smith SK, He Y, Day KA, Licence DR, Corps AN, et al. A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation. Biol Reprod. 1998;59(6):1540–8.

    PubMed  CAS  Google Scholar 

  30. Munaut C, Lorquet S, Pequeux C, Blacher S, Berndt S, Frankenne F, et al. Hypoxia is responsible for soluble vascular endothelial growth factor receptor-1 (VEGFR-1) but not for soluble endoglin induction in villous trophoblast. Hum Reprod. 2008;23(6):1407–15. doi:10.1093/humrep/den114.

    PubMed  CAS  Google Scholar 

  31. Redman CW, Sargent IL. Placental stress and pre-eclampsia: a revised view. Placenta. 2009;30 Suppl A:S38–42. doi:10.1016/j.placenta.2008.11.021.

    PubMed  CAS  Google Scholar 

  32. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–83. doi:10.1056/NEJMoa031884.

    PubMed  CAS  Google Scholar 

  33. Myatt L, Clifton RG, Roberts JM, Spong CY, Wapner RJ, Thorp Jr JM, et al. Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population? BJOG. 2013;120(10):1183–91. doi:10.1111/1471-0528.12128.

    PubMed  CAS  PubMed Central  Google Scholar 

  34. Powers RW, Roberts JM, Cooper KM, Gallaher MJ, Frank MP, Harger GF, et al. Maternal serum soluble fms-like tyrosine kinase 1 concentrations are not increased in early pregnancy and decrease more slowly postpartum in women who develop preeclampsia. Am J Obstet Gynecol. 2005;193(1):185–91. doi:10.1016/j.ajog.2004.11.038.

    PubMed  CAS  Google Scholar 

  35. Hassan MF, Rund NM, Salama AH. An elevated maternal plasma soluble fms-like tyrosine kinase-1 to placental growth factor ratio at midtrimester is a useful predictor for preeclampsia. Obstet Gynecol Int. 2013;2013:202346. doi:10.1155/2013/202346.

    PubMed  PubMed Central  Google Scholar 

  36. De Vivo A, Baviera G, Giordano D, Todarello G, Corrado F, D’Anna R. Endoglin, PlGF and sFlt-1 as markers for predicting pre-eclampsia. Acta Obstet Gynecol Scand. 2008;87(8):837–42. doi:10.1080/00016340802253759.

    PubMed  Google Scholar 

  37. Schoofs K, Grittner U, Engels T, Pape J, Denk B, Henrich W, et al. The importance of repeated measurements of the sFlt-1/PlGF ratio for the prediction of preeclampsia and intrauterine growth restriction. J Perinat Med. 2014;42(1):61–8. doi:10.1515/jpm-2013-0074.

    PubMed  CAS  Google Scholar 

  38. Levine RJ, Thadhani R, Qian C, Lam C, Lim KH, Yu KF, et al. Urinary placental growth factor and risk of preeclampsia. JAMA. 2005;293(1):77–85. doi:10.1001/jama.293.1.77.

    PubMed  CAS  Google Scholar 

  39. Savvidou MD, Akolekar R, Zaragoza E, Poon LC, Nicolaides KH. First trimester urinary placental growth factor and development of pre-eclampsia. BJOG. 2009;116(5):643–7. doi:10.1111/j.1471-0528.2008.02074.x.

    PubMed  CAS  Google Scholar 

  40. Campbell N, Ogle R, Thornton C, Hennessy A, Abbott J. Urinary placental growth factor differentiates the hypertensive disorders of pregnancy. Aust N Z J Obstet Gynaecol. 2011;51(6):523–6. doi:10.1111/j.1479-828X.2011.01349.x.

    PubMed  Google Scholar 

  41. Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642–9. doi:10.1038/nm1429.

    PubMed  CAS  Google Scholar 

  42. Toporsian M, Gros R, Kabir MG, Vera S, Govindaraju K, Eidelman DH, et al. A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res. 2005;96(6):684–92. doi:10.1161/01.res.0000159936.38601.22.

    PubMed  CAS  Google Scholar 

  43. Rana S, Karumanchi SA, Levine RJ, Venkatesha S, Rauh-Hain JA, Tamez H, et al. Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia. Hypertension. 2007;50(1):137–42. doi:10.1161/hypertensionaha.107.087700.

    PubMed  CAS  Google Scholar 

  44. Masuyama H, Nakatsukasa H, Takamoto N, Hiramatsu Y. Correlation between soluble endoglin, vascular endothelial growth factor receptor-1, and adipocytokines in preeclampsia. J Clin Endocrinol Metab. 2007;92(7):2672–9. doi:10.1210/jc.2006-2349.

    PubMed  CAS  Google Scholar 

  45. Kanasaki K, Palmsten K, Sugimoto H, Ahmad S, Hamano Y, Xie L, et al. Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia. Nature. 2008;453(7198):1117–21. doi:10.1038/nature06951.

    PubMed  CAS  Google Scholar 

  46. Pollheimer J, Fock V, Knofler M. Review: the ADAM metalloproteinases—novel regulators of trophoblast invasion? Placenta. 2014;35(Suppl):S57–63. doi:10.1016/j.placenta.2013.10.012.

    PubMed  CAS  Google Scholar 

  47. Redman CW, Sargent IL, Staff AC. IFPA Senior Award Lecture: making sense of pre-eclampsia—two placental causes of preeclampsia? Placenta. 2014;35(Suppl):S20–5. doi:10.1016/j.placenta.2013.12.008.

    PubMed  Google Scholar 

  48. Tirado-Gonzalez I, Freitag N, Barrientos G, Shaikly V, Nagaeva O, Strand M, et al. Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy. Mol Hum Reprod. 2013;19(1):43–53. doi:10.1093/molehr/gas043.

    PubMed  CAS  Google Scholar 

  49. Fischer I, Redel S, Hofmann S, Kuhn C, Friese K, Walzel H, et al. Stimulation of syncytium formation in vitro in human trophoblast cells by galectin-1. Placenta. 2010;31(9):825–32. doi:10.1016/j.placenta.2010.06.016.

    PubMed  CAS  Google Scholar 

  50. Kolundzic N, Bojic-Trbojevic Z, Kovacevic T, Stefanoska I, Kadoya T, Vicovac L. Galectin-1 is part of human trophoblast invasion machinery—a functional study in vitro. PLoS ONE. 2011;6(12):e28514. doi:10.1371/journal.pone.0028514.

    PubMed  CAS  PubMed Central  Google Scholar 

  51. Hsieh SH, Ying NW, Wu MH, Chiang WF, Hsu CL, Wong TY, et al. Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. Oncogene. 2008;27(26):3746–53. doi:10.1038/sj.onc.1211029.

    PubMed  CAS  Google Scholar 

  52. Graham CH, McCrae KR. Altered expression of gelatinase and surface-associated plasminogen activator activity by trophoblast cells isolated from placentas of preeclamptic patients. Am J Obstet Gynecol. 1996;175(3 Pt 1):555–62.

    PubMed  CAS  Google Scholar 

  53. Librach CL, Werb Z, Fitzgerald ML, Chiu K, Corwin NM, Esteves RA, et al. 92-kD type IV collagenase mediates invasion of human cytotrophoblasts. J Cell Biol. 1991;113(2):437–49.

    PubMed  CAS  Google Scholar 

  54. Kolben M, Lopens A, Blaser J, Ulm K, Schmitt M, Schneider KT, et al. Proteases and their inhibitors are indicative in gestational disease. Eur J Obstet Gynecol Reprod Biol. 1996;68(1–2):59–65.

    PubMed  CAS  Google Scholar 

  55. Rahimi Z, Rahimi Z, Shahsavandi MO, Bidoki K, Rezaei M. MMP-9 (−1562 C:T) polymorphism as a biomarker of susceptibility to severe pre-eclampsia. Biomark Med. 2013;7(1):93–8. doi:10.2217/bmm.12.95.

    PubMed  CAS  Google Scholar 

  56. Varanou A, Withington SL, Lakasing L, Williamson C, Burton GJ, Hemberger M. The importance of cysteine cathepsin proteases for placental development. J Mol Med (Berl). 2006;84(4):305–17. doi:10.1007/s00109-005-0032-2.

    CAS  Google Scholar 

  57. Zhou Y, Gormley MJ, Hunkapiller NM, Kapidzic M, Stolyarov Y, Feng V, et al. Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia. J Clin Invest. 2013;123(7):2862–72. doi:10.1172/jci66966.

    PubMed  CAS  PubMed Central  Google Scholar 

  58. Davidge ST. Oxidative stress and altered endothelial cell function in preeclampsia. Semin Reprod Endocrinol. 1998;16(1):65–73. doi:10.1055/s-2007-1016254.

    PubMed  CAS  Google Scholar 

  59. Lockwood CJ, Peters JH. Increased plasma levels of ED1+ cellular fibronectin precede the clinical signs of preeclampsia. Am J Obstet Gynecol. 1990;162(2):358–62.

    PubMed  CAS  Google Scholar 

  60. Nova A, Sibai BM, Barton JR, Mercer BM, Mitchell MD. Maternal plasma level of endothelin is increased in preeclampsia. Am J Obstet Gynecol. 1991;165(3):724–7.

    PubMed  CAS  Google Scholar 

  61. Gonzalez-Quintero VH, Jimenez JJ, Jy W, Mauro LM, Hortman L, O’Sullivan MJ, et al. Elevated plasma endothelial microparticles in preeclampsia. Am J Obstet Gynecol. 2003;189(2):589–93.

    PubMed  Google Scholar 

  62. Gonzalez-Quintero VH, Smarkusky LP, Jimenez JJ, Mauro LM, Jy W, Hortsman LL, et al. Elevated plasma endothelial microparticles: preeclampsia versus gestational hypertension. Am J Obstet Gynecol. 2004;191(4):1418–24. doi:10.1016/j.ajog.2004.06.044.

    PubMed  CAS  Google Scholar 

  63. Petrozella L, Mahendroo M, Timmons B, Roberts S, McIntire D, Alexander JM. Endothelial microparticles and the antiangiogenic state in preeclampsia and the postpartum period. Am J Obstet Gynecol. 2012;207(2):140.e20–6. doi:10.1016/j.ajog.2012.06.011.

    CAS  Google Scholar 

  64. Reyna-Villasmil E, Mejia-Montilla J, Reyna-Villasmil N, Torres-Cepeda D, Pena-Paredes E, Santos-Bolivar J, et al. [Endothelial microparticles in preeclampsia and eclampsia]. Med Clin (Barc). 2011;136(12):522–6. doi:10.1016/j.medcli.2010.07.026.

    Google Scholar 

  65. Jimenez JJ, Jy W, Mauro LM, Soderland C, Horstman LL, Ahn YS. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res. 2003;109(4):175–80.

    PubMed  CAS  Google Scholar 

  66. Record M. Intercellular communication by exosomes in placenta: a possible role in cell fusion? Placenta. 2014;35(5):297–302. doi:10.1016/j.placenta.2014.02.009.

    PubMed  CAS  Google Scholar 

  67. Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983;97(2):329–39.

    PubMed  CAS  Google Scholar 

  68. Atay S, Gercel-Taylor C, Suttles J, Mor G, Taylor DD. Trophoblast-derived exosomes mediate monocyte recruitment and differentiation. Am J Reprod Immunol. 2011;65(1):65–77. doi:10.1111/j.1600-0897.2010.00880.x.

    PubMed  CAS  Google Scholar 

  69. Tolosa JM, Schjenken JE, Clifton VL, Vargas A, Barbeau B, Lowry P, et al. The endogenous retroviral envelope protein syncytin-1 inhibits LPS/PHA-stimulated cytokine responses in human blood and is sorted into placental exosomes. Placenta. 2012;33(11):933–41. doi:10.1016/j.placenta.2012.08.004.

    PubMed  CAS  Google Scholar 

  70. Gross JC, Chaudhary V, Bartscherer K, Boutros M. Active Wnt proteins are secreted on exosomes. Nat Cell Biol. 2012;14(10):1036–45. doi:10.1038/ncb2574.

    PubMed  CAS  Google Scholar 

  71. Matsuura K, Jigami T, Taniue K, Morishita Y, Adachi S, Senda T, et al. Identification of a link between Wnt/beta-catenin signalling and the cell fusion pathway. Nat Commun. 2011;2:548. doi:10.1038/ncomms1551.

    PubMed  Google Scholar 

  72. Bullerdiek J, Flor I. Exosome-delivered microRNAs of “chromosome 19 microRNA cluster” as immunomodulators in pregnancy and tumorigenesis. Mol Cytogenet. 2012;5(1):27. doi:10.1186/1755-8166-5-27.

    PubMed  CAS  PubMed Central  Google Scholar 

  73. Redman CW, Sargent IL. Pre-eclampsia, the placenta and the maternal systemic inflammatory response—a review. Placenta. 2003;24 Suppl A:S21–7.

    PubMed  CAS  Google Scholar 

  74. VanWijk MJ, Nieuwland R, Boer K, van der Post JA, VanBavel E, Sturk A. Microparticle subpopulations are increased in preeclampsia: possible involvement in vascular dysfunction? Am J Obstet Gynecol. 2002;187(2):450–6.

    PubMed  Google Scholar 

  75. Blumenstein M, McMaster MT, Black MA, Wu S, Prakash R, Cooney J, et al. A proteomic approach identifies early pregnancy biomarkers for preeclampsia: novel linkages between a predisposition to preeclampsia and cardiovascular disease. Proteomics. 2009;9(11):2929–45. doi:10.1002/pmic.200800625.

    PubMed  CAS  Google Scholar 

  76. Liu C, Zhang N, Yu H, Chen Y, Liang Y, Deng H, et al. Proteomic analysis of human serum for finding pathogenic factors and potential biomarkers in preeclampsia. Placenta. 2011;32(2):168–74. doi:10.1016/j.placenta.2010.11.007.

    PubMed  CAS  PubMed Central  Google Scholar 

  77. Baig S, Lim JY, Fernandis AZ, Wenk MR, Kale A, Su LL, et al. Lipidomic analysis of human placental syncytiotrophoblast microvesicles in adverse pregnancy outcomes. Placenta. 2013;34(5):436–42. doi:10.1016/j.placenta.2013.02.004.

    PubMed  CAS  Google Scholar 

  78. Lahiri S, Futerman AH. The metabolism and function of sphingolipids and glycosphingolipids. Cell Mol Life Sci. 2007;64(17):2270–84. doi:10.1007/s00018-007-7076-0.

    PubMed  CAS  Google Scholar 

  79. Leventis PA, Grinstein S. The distribution and function of phosphatidylserine in cellular membranes. Annu Rev Biophys. 2010;39:407–27. doi:10.1146/annurev.biophys.093008.131234.

    PubMed  CAS  Google Scholar 

  80. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007;447(7143):425–32. doi:10.1038/nature05918.

    PubMed  CAS  Google Scholar 

  81. Waterland RA, Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition. 2004;20(1):63–8.

    PubMed  CAS  Google Scholar 

  82. Haluskova J. Epigenetic studies in human diseases. Folia Biol (Praha). 2010;56(3):83–96.

    CAS  Google Scholar 

  83. Szyf M. Epigenetics, DNA methylation, and chromatin modifying drugs. Annu Rev Pharmacol Toxicol. 2009;49:243–63. doi:10.1146/annurev-pharmtox-061008-103102.

    PubMed  CAS  Google Scholar 

  84. Chelbi ST, Vaiman D. Genetic and epigenetic factors contribute to the onset of preeclampsia. Mol Cell Endocrinol. 2008;282(1–2):120–9. doi:10.1016/j.mce.2007.11.022.

    PubMed  CAS  Google Scholar 

  85. Silverman GA, Bird PI, Carrell RW, Church FC, Coughlin PB, Gettins PG, et al. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem. 2001;276(36):33293–6.

    PubMed  CAS  Google Scholar 

  86. Ness RB, Sibai BM. Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia. Am J Obstet Gynecol. 2006;195(1):40–9. doi:10.1016/j.ajog.2005.07.049.

    PubMed  Google Scholar 

  87. Chelbi ST, Mondon F, Jammes H, Buffat C, Mignot TM, Tost J, et al. Expressional and epigenetic alterations of placental serine protease inhibitors: SERPINA3 is a potential marker of preeclampsia. Hypertension. 2007;49(1):76–83. doi:10.1161/01.HYP.0000250831.52876.cb.

    PubMed  CAS  Google Scholar 

  88. Wenger RH, Kvietikova I, Rolfs A, Camenisch G, Gassmann M. Oxygen-regulated erythropoietin gene expression is dependent on a CpG methylation-free hypoxia-inducible factor-1 DNA-binding site. Eur J Biochem. 1998;253(3):771–7.

    PubMed  CAS  Google Scholar 

  89. Yuen RK, Penaherrera MS, von Dadelszen P, McFadden DE, Robinson WP. DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia. Eur J Hum Genet. 2010;18(9):1006–12. doi:10.1038/ejhg.2010.63.

    PubMed  CAS  PubMed Central  Google Scholar 

  90. Higuchi T, Kanzaki H, Nakayama H, Fujimoto M, Hatayama H, Kojima K, et al. Induction of tissue inhibitor of metalloproteinase 3 gene expression during in vitro decidualization of human endometrial stromal cells. Endocrinology. 1995;136(11):4973–81. doi:10.1210/endo.136.11.7588231.

    PubMed  CAS  Google Scholar 

  91. Kulkarni A, Chavan-Gautam P, Mehendale S, Yadav H, Joshi S. Global DNA methylation patterns in placenta and its association with maternal hypertension in pre-eclampsia. DNA Cell Biol. 2011;30(2):79–84. doi:10.1089/dna.2010.1084.

    PubMed  CAS  Google Scholar 

  92. Tadesse S, Kidane D, Guller S, Luo T, Norwitz NG, Arcuri F, et al. In vivo and in vitro evidence for placental DNA damage in preeclampsia. PLoS ONE. 2014;9(1):e86791. doi:10.1371/journal.pone.0086791.

    PubMed  PubMed Central  Google Scholar 

  93. Mousa AA, Archer KJ, Cappello R, Estrada-Gutierrez G, Isaacs CR, Strauss 3rd JF, et al. DNA methylation is altered in maternal blood vessels of women with preeclampsia. Reprod Sci. 2012;19(12):1332–42. doi:10.1177/1933719112450336.

    PubMed  PubMed Central  Google Scholar 

  94. Mousa AA, Cappello RE, Estrada-Gutierrez G, Shukla J, Romero R, Strauss 3rd JF, et al. Preeclampsia is associated with alterations in DNA methylation of genes involved in collagen metabolism. Am J Pathol. 2012;181(4):1455–63. doi:10.1016/j.ajpath.2012.06.019.

    PubMed  CAS  PubMed Central  Google Scholar 

  95. Auer J, Camoin L, Guillonneau F, Rigourd V, Chelbi ST, Leduc M, et al. Serum profile in preeclampsia and intra-uterine growth restriction revealed by iTRAQ technology. J Proteome. 2010;73(5):1004–17. doi:10.1016/j.jprot.2009.12.014.

    CAS  Google Scholar 

  96. Wen SW, Chen XK, Rodger M, White RR, Yang Q, Smith GN, et al. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol. 2008;198(1):45.e1–7. doi:10.1016/j.ajog.2007.06.067.

    Google Scholar 

  97. Tong YK, Lo YM. Plasma epigenetic markers for cancer detection and prenatal diagnosis. Front Biosci. 2006;11:2647–56.

    PubMed  CAS  Google Scholar 

  98. Zhu XM, Han T, Sargent IL, Yin GW, Yao YQ. Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs normal pregnancies. Am J Obstet Gynecol. 2009;200(6):661.e1–7. doi:10.1016/j.ajog.2008.12.045.

    CAS  Google Scholar 

  99. Zhang Y, Fei M, Xue G, Zhou Q, Jia Y, Li L, et al. Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease. J Cell Mol Med. 2012;16(2):249–59. doi:10.1111/j.1582-4934.2011.01291.x.

    PubMed  CAS  Google Scholar 

  100. Mayor-Lynn K, Toloubeydokhti T, Cruz AC, Chegini N. Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor. Reprod Sci. 2011;18(1):46–56. doi:10.1177/1933719110374115.

    PubMed  CAS  PubMed Central  Google Scholar 

  101. Dai Y, Diao Z, Sun H, Li R, Qiu Z, Hu Y. MicroRNA-155 is involved in the remodelling of human-trophoblast-derived HTR-8/SVneo cells induced by lipopolysaccharides. Hum Reprod. 2011;26(7):1882–91. doi:10.1093/humrep/der118.

    PubMed  CAS  Google Scholar 

  102. Zhang Y, Diao Z, Su L, Sun H, Li R, Cui H, et al. MicroRNA-155 contributes to preeclampsia by down-regulating CYR61. Am J Obstet Gynecol. 2010;202(5):466.e1–7. doi:10.1016/j.ajog.2010.01.057.

    Google Scholar 

  103. Doridot L, Houry D, Gaillard H, Chelbi ST, Barbaux S, Vaiman D. miR-34a expression, epigenetic regulation, and function in human placental diseases. Epigenetics : Off J DNA Methylation Soc. 2014;9(1):142–51. doi:10.4161/epi.26196.

    CAS  Google Scholar 

  104. Kanayama N, Takahashi K, Matsuura T, Sugimura M, Kobayashi T, Moniwa N, et al. Deficiency in p57Kip2 expression induces preeclampsia-like symptoms in mice. Mol Hum Reprod. 2002;8(12):1129–35.

    PubMed  CAS  Google Scholar 

  105. Yu L, Chen M, Zhao D, Yi P, Lu L, Han J, et al. The H19 gene imprinting in normal pregnancy and pre-eclampsia. Placenta. 2009;30(5):443–7. doi:10.1016/j.placenta.2009.02.011.

    PubMed  CAS  Google Scholar 

  106. Lapaire O, Holzgreve W, Oosterwijk JC, Brinkhaus R, Bianchi DW. Georg Schmorl on trophoblasts in the maternal circulation. Placenta. 2007;28(1):1–5. doi:10.1016/j.placenta.2006.02.004.

    PubMed  CAS  Google Scholar 

  107. Lo YM, Leung TN, Tein MS, Sargent IL, Zhang J, Lau TK, et al. Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia. Clin Chem. 1999;45(2):184–8.

    PubMed  CAS  Google Scholar 

  108. Leung TN, Zhang J, Lau TK, Chan LY, Lo YM. Increased maternal plasma fetal DNA concentrations in women who eventually develop preeclampsia. Clin Chem. 2001;47(1):137–9.

    PubMed  CAS  Google Scholar 

  109. Zhong XY, Holzgreve W, Hahn S. The levels of circulatory cell free fetal DNA in maternal plasma are elevated prior to the onset of preeclampsia. Hypertens Pregnancy. 2002;21(1):77–83. doi:10.1081/prg-120002911.

    PubMed  CAS  Google Scholar 

  110. Huppertz B, Kingdom J, Caniggia I, Desoye G, Black S, Korr H, et al. Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation. Placenta. 2003;24(2–3):181–90.

    PubMed  CAS  Google Scholar 

  111. Knight M, Redman CW, Linton EA, Sargent IL. Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br J Obstet Gynaecol. 1998;105(6):632–40.

    PubMed  CAS  Google Scholar 

  112. Zimmermann BG, Holzgreve W, Avent N, Hahn S. Optimized real-time quantitative PCR measurement of male fetal DNA in maternal plasma. Ann N Y Acad Sci. 2006;1075:347–9. doi:10.1196/annals.1368.047.

    PubMed  CAS  Google Scholar 

  113. Chim SS, Tong YK, Chiu RW, Lau TK, Leung TN, Chan LY, et al. Detection of the placental epigenetic signature of the maspin gene in maternal plasma. Proc Natl Acad Sci U S A. 2005;102(41):14753–8. doi:10.1073/pnas.0503335102.

    PubMed  CAS  PubMed Central  Google Scholar 

  114. Chan KC, Ding C, Gerovassili A, Yeung SW, Chiu RW, Leung TN, et al. Hypermethylated RASSF1A in maternal plasma: a universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis. Clin Chem. 2006;52(12):2211–8. doi:10.1373/clinchem.2006.074997.

    PubMed  CAS  Google Scholar 

  115. Wang J, Yang J, Wu X, Mu Y, Li S, Cui K, et al. [Predictive value of placenta-derived RASSF1A sequence expression in maternal plasma for pre-eclampsia]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2014;31(1):25–8. doi:10.3760/cma.j.issn.1003-9406.2014.01.006.

    PubMed  CAS  Google Scholar 

  116. Henao DE, Mathieson PW, Saleem MA, Bueno JC, Cadavid A. A novel renal perspective of preeclampsia: a look from the podocyte. Nephrol Dial Transplant. 2007;22(5):1477. doi:10.1093/ndt/gfl804.

    PubMed  CAS  Google Scholar 

  117. Garovic VD, Wagner SJ, Petrovic LM, Gray CE, Hall P, Sugimoto H, et al. Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia. Nephrol Dial Transplant. 2007;22(4):1136–43. doi:10.1093/ndt/gfl711.

    PubMed  CAS  Google Scholar 

  118. Henao DE, Arias LF, Mathieson PW, Ni L, Welsh GI, Bueno JC, et al. Preeclamptic sera directly induce slit-diaphragm protein redistribution and alter podocyte barrier-forming capacity. Nephron Exp Nephrol. 2008;110(3):e73–81. doi:10.1159/000166993.

    PubMed  CAS  Google Scholar 

  119. Maharaj AS, Saint-Geniez M, Maldonado AE, D’Amore PA. Vascular endothelial growth factor localization in the adult. Am J Pathol. 2006;168(2):639–48. doi:10.2353/ajpath.2006.050834.

    PubMed  CAS  PubMed Central  Google Scholar 

  120. Harper SJ, Xing CY, Whittle C, Parry R, Gillatt D, Peat D, et al. Expression of neuropilin-1 by human glomerular epithelial cells in vitro and in vivo. Clin Sci (Lond). 2001;101(4):439–46.

    CAS  Google Scholar 

  121. Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008;358(11):1129–36. doi:10.1056/NEJMoa0707330.

    PubMed  CAS  PubMed Central  Google Scholar 

  122. Henao DE, Cadavid AP, Saleem MA. Exogenous vascular endothelial growth factor supplementation can restore the podocyte barrier-forming capacity disrupted by sera of preeclamptic women. J Obstet Gynaecol Res. 2013;39(1):46–52. doi:10.1111/j.1447-0756.2012.01889.x.

    PubMed  Google Scholar 

  123. Garovic VD, Wagner SJ, Turner ST, Rosenthal DW, Watson WJ, Brost BC, et al. Urinary podocyte excretion as a marker for preeclampsia. Am J Obstet Gynecol. 2007;196(4):320.e1–7. doi:10.1016/j.ajog.2007.02.007.

    Google Scholar 

  124. Jim B, Jean-Louis P, Qipo A, Garry D, Mian S, Matos T, et al. Podocyturia as a diagnostic marker for preeclampsia amongst high-risk pregnant patients. J Pregnancy. 2012;2012:984630. doi:10.1155/2012/984630.

    PubMed  PubMed Central  Google Scholar 

  125. Wang Y, Zhao S, Loyd S, Groome LJ. Increased urinary excretion of nephrin, podocalyxin, and betaig-h3 in women with preeclampsia. Am J Physiol Ren Physiol. 2012;302(9):F1084–9. doi:10.1152/ajprenal.00597.2011.

    CAS  Google Scholar 

  126. Garovic VD, Craici IM, Wagner SJ, White WM, Brost BC, Rose CH, et al. Mass spectrometry as a novel method for detection of podocyturia in pre-eclampsia. Nephrol Dial Transplant. 2013;28(6):1555–61. doi:10.1093/ndt/gfs074.

    PubMed  CAS  PubMed Central  Google Scholar 

  127. McLeod L. How useful is uterine artery Doppler ultrasonography in predicting pre-eclampsia and intrauterine growth restriction? CMAJ. 2008;178(6):727–9. doi:10.1503/cmaj.080242.

    PubMed  PubMed Central  Google Scholar 

  128. Papageorghiou AT, Yu CK, Nicolaides KH. The role of uterine artery Doppler in predicting adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol. 2004;18(3):383–96. doi:10.1016/j.bpobgyn.2004.02.003.

    PubMed  Google Scholar 

  129. Papageorghiou AT, Yu CK, Bindra R, Pandis G, Nicolaides KH. Multicenter screening for pre-eclampsia and fetal growth restriction by transvaginal uterine artery Doppler at 23 weeks of gestation. Ultrasound Obstet Gynecol. 2001;18(5):441–9. doi:10.1046/j.0960-7692.2001.00572.x.

    PubMed  CAS  Google Scholar 

  130. Myatt L, Clifton RG, Roberts JM, Spong CY, Hauth JC, Varner MW, et al. The utility of uterine artery Doppler velocimetry in prediction of preeclampsia in a low-risk population. Obstet Gynecol. 2012;120(4):815–22. doi:10.1097/AOG.0b013e31826af7fb.

    PubMed  PubMed Central  Google Scholar 

  131. Cnossen JS, Morris RK, ter Riet G, Mol BW, van der Post JA, Coomarasamy A, et al. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis. CMAJ. 2008;178(6):701–11. doi:10.1503/cmaj.070430.

    PubMed  PubMed Central  Google Scholar 

  132. Scazzocchio E, Figueras F, Crispi F, Meler E, Masoller N, Mula R, et al. Performance of a first-trimester screening of preeclampsia in a routine care low-risk setting. Am J Obstet Gynecol. 2013;208(3):203.e1–e10. doi:10.1016/j.ajog.2012.12.016.

    Google Scholar 

  133. Espinoza J, Romero R, Nien JK, Gomez R, Kusanovic JP, Goncalves LF, et al. Identification of patients at risk for early onset and/or severe preeclampsia with the use of uterine artery Doppler velocimetry and placental growth factor. Am J Obstet Gynecol. 2007;196(4):326.e1–13. doi:10.1016/j.ajog.2006.11.002.

    Google Scholar 

  134. Stepan H, Unversucht A, Wessel N, Faber R. Predictive value of maternal angiogenic factors in second trimester pregnancies with abnormal uterine perfusion. Hypertension. 2007;49(4):818–24. doi:10.1161/01.HYP.0000258404.21552.a3.

    PubMed  CAS  Google Scholar 

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Anjali Acharya, Wunnie Brima, Shivakanth Burugu, and Tanvi Rege declare no conflict of interest.

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  1. Nephrology Division, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Anjali Acharya, Shivakanth Burugu & Tanvi Rege

  2. Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Wunnie Brima

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  1. Anjali Acharya
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Acharya, A., Brima, W., Burugu, S. et al. Prediction of Preeclampsia-Bench to Bedside. Curr Hypertens Rep 16, 491 (2014). https://doi.org/10.1007/s11906-014-0491-3

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