Skip to main content Accessibility help




Endothelial cell proliferation and survival require continuous low levels of vascular endothelial growth factor (VEGF). The bioavailability of this angiogenic factor appears to be regulated by anti-angiogenic factors, including the soluble form of VEGF receptor 1 (sFlt-1) in the non-pregnant and pregnant states. During pregnancy a VEGF antagonist (sFlt-1) and other anti-angiogenic factors, including soluble endoglin (s-Eng), are produced by the human placenta and released into the maternal circulation; an excess of these anti-angiogenic factors can lead into angiogenic imbalances and pregnancy complications. This is important because regulation of VEGF action on angiogenic balances appears to be essential for a successful pregnancy.


Corresponding author

Dr Jimmy Espinoza, MD, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and TCH Pavilion for Women, 6651 Main Street, Suite 1020, Houston TX 77030. Email:


Hide All
1.Luttun, A, Carmeliet, P. Soluble VEGF receptor Flt1: the elusive preeclampsia factor discovered? J Clin Invest 2003; 111 (5): 600–2.
2.Barleon, B, Reusch, P, Totzke, F, Herzog, C, Keck, C, Martiny-Baron, G, et al.Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors. Angiogenesis 2001; 4 (2): 143–54.
3.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): 1540–48.
4.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.
5.Levine, RJ, Karumanchi, SA. Circulating angiogenic factors in preeclampsia. Clin Obstet Gynecol 2005; 48 (2): 372–86.
6.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.
7.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.
8.Ferrara, N, Gerber, HP, LeCouter, J. The biology of VEGF and its receptors. Nat Med 2003; 9 (6): 669–76.
9.Ferrara, N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004; 25 (4): 581611.
10.Torry, DS, Wang, HS, Wang, TH, Caudle, MR, Torry, RJ. Preeclampsia is associated with reduced serum levels of placenta growth factor. Am J Obstet Gynecol 1998; 179 (6, Pt 1): 1539–44.
11.Koga, K, Osuga, Y, Yoshino, O, Hirota, Y, Ruimeng, X, Hirata, T, et al.Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia. J Clin Endocrinol Metab 2003; 88 (5): 2348–51.
12.Krauss, T, Pauer, HU, Augustin, HG. Prospective analysis of placenta growth factor (PlGF) concentrations in the plasma of women with normal pregnancy and pregnancies complicated by preeclampsia. Hypertens Pregnancy 2004; 23 (1): 101–11.
13.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): 318.
14.Redman, CW, Sargent, IL. Latest advances in understanding preeclampsia. Science 2005; 308 (5728): 1592–94.
15.Bdolah, Y, Karumanchi, SA, Sachs, BP. Recent advances in understanding of preeclampsia. Croat Med J 2005; 46 (5): 728–36.
16.Robinson, CJ, Johnson, DD, Chang, EY, Armstrong, DM, Wang, W. Evaluation of placenta growth factor and soluble FMS-like tyrosine kinase 1 receptor levels in mild and severe preeclampsia. Am J Obstet Gynecol 2006; 195 (1): 255–9.
17.Crispi, F, Dominguez, C, Llurba, E, Martin-Gallan, P, Cabero, L, Gratacos, E. Placental angiogenic growth factors and uterine artery Doppler findings for characterization of different subsets in preeclampsia and in isolated intrauterine growth restriction. Am J Obstet Gynecol 2006; 195 (1): 201–7.
18.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): 9921005.
19.Boutsikou, T, Malamitsi-Puchner, A, Economou, E, Boutsikou, M, Puchner, KP, Hassiakos, D. Soluble vascular endothelial growth factor receptor-1 in intrauterine growth restricted fetuses and neonates. Early Hum Dev 2006; 82 (4): 235–9.
20.Wallner, W, Sengenberger, R, Strick, R, Strissel, PL, Meurer, B, Beckmann, MW, et al.Angiogenic growth factors in maternal and fetal serum in pregnancies complicated by intrauterine growth restriction. Clin Sci (Lond) 2007; 112 (1): 51–7.
21.Espinoza, J, Romero, R, Nien, JK, Kusanovic, JP, Richani, K, Gomez, R, et al.A role of the anti-angiogenic factor sVEGFR-1 in the “mirror syndrome” (Ballantyne's syndrome). J Matern Fetal Neonatal Med 2006; 19 (10): 607–13.
22.Rana, S, Venkatesha, S, DePaepe, M, Chien, EK, Paglia, M, Karumanchi, SA. Cytomegalovirus-induced mirror syndrome associated with elevated levels of circulating antiangiogenic factors. Obstet Gynecol 2007; 109 (2, Pt2): 549–52.
23.Kusanovic, JP, Romero, R, Espinoza, J, Nien, JK, Kim, CJ, Mittal, P, et al.Twin-to-twin transfusion syndrome: an antiangiogenic state? Am J Obstet Gynecol 2008; 198 (4): 382–8.
24.Espinoza, J, Chaiworapongsa, T, Romero, R, Kim, YM, Kim, GJ, Nien, JK, et al.Unexplained fetal death: another anti-angiogenic state. J Matern Fetal Neonatal Med 2007; 20 (7): 495507.
25.Espinoza, J, Uckele, JE, Starr, RA, Lorenz, RP, Bronsteen, RA, Berry, SM. Insights into angiogenic imbalances during pregnancy. Obstet Gynecol 2009; 114: 437440.
26.Zhou, Y, McMaster, M, Woo, K, Janatpour, M, Perry, J, Karpanen, T, et al.Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol 2002; 160 (4): 1405–23.
27.Tsatsaris, V, Goffin, F, Munaut, C, Brichant, JF, Pignon, MR, Noel, A, et al.Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab 2003; 88 (11): 5555–63.
28.Aggarwal, PK, Jain, V, Sakhuja, V, Karumanchi, SA, Jha, V. Low urinary placental growth factor is a marker of pre-eclampsia. Kidney Int 2006; 69 (3): 621–4.
29.Signore, C, Mills, JL, Qian, C, Yu, K, Lam, C, Epstein, FH, et al.Circulating angiogenic factors and placental abruption. Obstet Gynecol 2006; 108 (2): 338–44.
30.Stepan, H, Faber, R. Elevated sFlt1 level and preeclampsia with parvovirus-induced hydrops. N Engl J Med 2006; 354 (17): 1857–58.
31.Kallen, B. Maternal morbidity and mortality in in-vitro fertilization. Best Pract Res Clin Obstet Gynaecol 2008; 22 (3): 549–58.
32.Kallen, B, Finnstrom, O, Nygren, KG, Otterblad, OP, Wennerholm, UB. In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality. BJOG 2005; 112 (11): 1529–35.
33.Gilbert, JS, Babcock, SA, Granger, JP. Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble FMS-like tyrosine kinase-1 expression. Hypertension 2007; 50 (6): 1142–47.
34.Lyall, F, Greer, IA, Boswell, F, Fleming, R. Suppression of serum vascular endothelial growth factor immunoreactivity in normal pregnancy and in pre-eclampsia. Br J Obstet Gynaecol 1997; 104 (2): 223228.
35.Kupferminc, MJ, Daniel, Y, Englender, T, Baram, A, Many, A, Jaffa, AJ, et al.Vascular endothelial growth factor is increased in patients with preeclampsia. Am J Reprod Immunol 1997; 38 (4): 302306.
36.McKeeman, GC, Ardill, JE, Caldwell, CM, Hunter, AJ, McClure, N. Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop. Am J Obstet Gynecol 2004; 191 (4): 12401246.
37.Chaiworapongsa, T, Romero, R, Espinoza, J, Bujold, E, Mee, KY, Goncalves, LF, et al.Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia. Young investigator award. Am J Obstet Gynecol 2004; 190 (6): 1541–47.
38.Maynard, SE, Venkatesha, S, Thadhani, R, Karumanchi, SA. Soluble FMS-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia. Pediatr Res 2005; 57 (5, Pt 2): 1R7R.
39.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): 7785.
40.Rajakumar, A, Michael, HM, Rajakumar, PA, Shibata, E, Hubel, CA, Karumanchi, SA, et al.Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1) by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women. Placenta 2005; 26 (7): 563–73.
41.Shibata, E, Rajakumar, A, Powers, RW, Larkin, RW, Gilmour, C, Bodnar, LM, et al.Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor. J Clin Endocrinol Metab 2005; 90 (8): 48954903.
42.Staff, AC, Braekke, K, Harsem, NK, Lyberg, T, Holthe, MR. Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 2005; 122 (1): 33–9.
43.Steegers, EA, von Dadelszen, P, Duvekot, JJ, Pijnenborg, R. Pre-eclampsia. Lancet 2010; 376 (9741): 631–44.
44.von Dadelszen, P, Magee, LA, Roberts, JM. Subclassification of preeclampsia. Hypertens Pregnancy 2003; 22 (2): 143–8.
45.Dekker, GA, Sibai, BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998; 179 (5): 1359–75.
46.Austgulen, R, Isaksen, CV, Chedwick, L, Romundstad, P, Vatten, L, Craven, C. Pre-eclampsia: associated with increased syncytial apoptosis when the infant is small-for-gestational-age. J Reprod Immunol 2004; 61 (1): 3950.
47.Crocker, IP, Cooper, S, Ong, SC, Baker, PN. Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. Am J Pathol 2003; 162 (2): 637–43.
48.Leung, DN, Smith, SC, To, KF, Sahota, DS, Baker, PN. Increased placental apoptosis in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 2001; 184 (6): 1249–50.
49.Sargent, IL, Germain, SJ, Sacks, GP, Kumar, S, Redman, CW. Trophoblast deportation and the maternal inflammatory response in pre-eclampsia. J Reprod Immunol 2003; 59 (2): 153–60.
50.Johansen, M, Redman, CW, Wilkins, T, Sargent, IL. Trophoblast deportation in human pregnancy – its relevance for pre-eclampsia. Placenta 1999; 20 (7): 531–9.
51.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.
52.Chua, S, Wilkins, T, Sargent, I, Redman, C. Trophoblast deportation in pre-eclamptic pregnancy. Br J Obstet Gynaecol 1991; 98 (10): 973–9.
53.Makris, A, Thornton, C, Thompson, J, Thomson, S, Martin, R, Ogle, R, et al.Uteroplacental ischemia results in proteinuric hypertension and elevated sFLT-1. Kidney Int 2007; 71 (10): 977–84.
54.Nagamatsu, T, Fujii, T, Kusumi, M, Zou, L, Yamashita, T, Osuga, Y, et al.Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia. Endocrinology 2004; 145 (11): 4838–45.
55.Nevo, O, Soleymanlou, N, Wu, Y, Xu, J, Kingdom, J, Many, A, et al.Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol 2006; 291 (4): R1085–R93.
56.Chaiworapongsa, T, Espinoza, J, Gotsch, F, Kim, YM, Kim, GJ, Goncalves, LF, et al.The maternal plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated in SGA and the magnitude of the increase relates to Doppler abnormalities in the maternal and fetal circulation. J Matern Fetal Neonatal Med 2008; 21 (1): 2540.
57.Soto, E, Romero, R, Kusanovic, JP, Ogge, G, Hussein, Y, Yeo, L, et al.Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion. J Matern Fetal Neonatal Med 2011; 25: 498–507.
58.Espinoza, J, Uckele, JE, Starr, RA, Seubert, DE, Espinoza, AF, Berry, SM. Angiogenic imbalances: the obstetric perspective. Am J Obstet Gynecol 2010; 203 (1): 1718.
59.Rajakumar, A, Cerdeira, AS, Rana, S, Zsengeller, Z, Edmunds, L, Jeyabalan, A, et al.Transcriptionally active syncytial aggregates in the maternal circulation may contribute to circulating soluble fms-like tyrosine kinase 1 in preeclampsia. Hypertension 2012; 59 (2): 256–64.
60.Rana, S, Schnettler, WT, Powe, C, Wenger, J, Salahuddin, S, Cerdeira, AS, et al.Clinical characterization and outcomes of preeclampsia with normal angiogenic profile. Hypertens Pregnancy 2013; 32 (2): 189201.
61.Malamitsi-Puchner, A, Boutsikou, T, Economou, E, Sarandakou, A, Makrakis, E, Hassiakos, D, et al.Vascular endothelial growth factor and placenta growth factor in intrauterine growth-restricted fetuses and neonates. Mediators Inflamm 2005; 2005 (5): 293–7.
62.Girardi, G, Yarilin, D, Thurman, JM, Holers, VM, Salmon, JE. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med 2006; 203 (9): 2165–75.
63.Padavala, S, Pope, N, Baker, P, Crocker, I. An imbalance between vascular endothelial growth factor and its soluble receptor in placental villous explants of intrauterine growth-restricted pregnancies. J Soc Gynecol Investig 2006; 13 (1): 40–7.
64.Sandrim, VC, Palei, AC, Cavalli, RC, Araujo, FM, Ramos, ES, Duarte, G, et al.Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension. Mol Hum Reprod 2009; 15 (2): 115–20.
65.Tjoa, ML, van Vugt, JM, Mulders, MA, Schutgens, RB, Oudejans, CB, van Wijk, IJ. Plasma placenta growth factor levels in midtrimester pregnancies. Obstet Gynecol 2001; 98 (4): 600–7.
66.Tidwell, SC, Ho, HN, Chiu, WH, Torry, RJ, Torry, DS. Low maternal serum levels of placenta growth factor as an antecedent of clinical preeclampsia. Am J Obstet Gynecol 2001; 184 (6): 1267–72.
67.Chappell, LC, Seed, PT, Briley, A, Kelly, FJ, Hunt, BJ, Charnock-Jones, DS, et al.A longitudinal study of biochemical variables in women at risk of preeclampsia. Am J Obstet Gynecol 2002; 187 (1): 127–36.
68.Taylor, RN, Grimwood, J, Taylor, RS, McMaster, MT, Fisher, SJ, North, RA. Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol 2003; 188 (1): 177–82.
69.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.
70.Parra, M, Rodrigo, R, Barja, P, Bosco, C, Fernandez, V, Munoz, H, et al.Screening test for preeclampsia through assessment of uteroplacental blood flow and biochemical markers of oxidative stress and endothelial dysfunction. Am J Obstet Gynecol 2005; 193 (4): 1486–91.
71.Moore Simas, TA, Crawford, SL, Solitro, MJ, Frost, SC, Meyer, BA, Maynard, SE. Angiogenic factors for the prediction of preeclampsia in high-risk women. Am J Obstet Gynecol 2007; 197 (3): 244–8.
72.Ohkuchi, A, Hirashima, C, Matsubara, S, Suzuki, H, Takahashi, K, Arai, F, et al.Alterations in placental growth factor levels before and after the onset of preeclampsia are more pronounced in women with early onset severe preeclampsia. Hypertens Res 2007; 30 (2): 151–9.
73.Poon, LC, Zaragoza, E, Akolekar, R, Anagnostopoulos, E, Nicolaides, KH. Maternal serum placental growth factor (PlGF) in small for gestational age pregnancy at 11(+0) to 13(+6) weeks of gestation. Prenat Diagn 2008; 28 (12): 1110–15.
74.Erez, O, Romero, R, Espinoza, J, Fu, W, Todem, D, Kusanovic, JP, et al.The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age. J Matern Fetal Neonatal Med 2008; 21 (5): 279–87.
75.Poon, LC, Kametas, NA, Maiz, N, Akolekar, R, Nicolaides, KH. First-trimester prediction of hypertensive disorders in pregnancy. Hypertension 2009; 53 (5): 812–18.
76.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.
77.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.
78.Baumann, MU, Bersinger, NA, Mohaupt, MG, Raio, L, Gerber, S, Surbek, DV. First-trimester serum levels of soluble endoglin and soluble fms-like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia. Am J Obstet Gynecol 2008; 199 (3): 266.
79.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): 923.
80.Schmidt, M, Dogan, C, Birdir, C, Kuhn, U, Gellhaus, A, Kimmig, R, et al.Placental growth factor: a predictive marker for preeclampsia? Gynakol Geburtshilfliche Rundsch 2009; 49 (2): 9499.
81.Espinoza, J, Romero, R, Nien, JK, Gomez, R, Kusanovic, JP, Goncalves, LF. 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.
82.Espinoza, J. Recent biomarkers for the identification of patients at risk for preeclampsia: the role of uteroplacental ischemia. Expert Opin Med Diagn 2012; 6 (2): 109–20.
83.Rasmussen, S, Irgens, LM. Fetal growth and body proportion in preeclampsia. Obstet Gynecol 2003; 101 (3): 575–83.
84.Aardema, MW, Saro, MC, Lander, M, De Wolf, BT, Oosterhof, H, Aarnoudse, JG. Second trimester Doppler ultrasound screening of the uterine arteries differentiates between subsequent normal and poor outcomes of hypertensive pregnancy: two different pathophysiological entities? Clin Sci (Lond) 2004; 106 (4): 377–82.
85.Harrington, K, Cooper, D, Lees, C, Hecher, K, Campbell, S. Doppler ultrasound of the uterine arteries: the importance of bilateral notching in the prediction of pre-eclampsia, placental abruption or delivery of a small-for-gestational-age baby. Ultrasound Obstet Gynecol 1996; 7 (3): 182–88.
86.Albaiges, G, Missfelder-Lobos, H, Lees, C, Parra, M, Nicolaides, KH. One-stage screening for pregnancy complications by color Doppler assessment of the uterine arteries at 23 weeks’ gestation. Obstet Gynecol 2000; 96 (4): 559–64.
87.Papageorghiou, AT, Yu, CK, Cicero, S, Bower, S, Nicolaides, KH. Second-trimester uterine artery Doppler screening in unselected populations: a review. J Matern Fetal Neonatal Med 2002; 12 (2): 7888.
88.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): 441449.
89.Moldenhauer, JS, Stanek, J, Warshak, C, Khoury, J, Sibai, B. The frequency and severity of placental findings in women with preeclampsia are gestational age dependent. Am J Obstet Gynecol 2003; 189 (4): 11731177.
90.Ogge, G, Chaiworapongsa, T, Romero, R, Hussein, Y, Kusanovic, JP, Yeo, L, et al.Placental lesions associated with maternal underperfusion are more frequent in early-onset than in late-onset preeclampsia*. J Perinat Med 2011; 39 (6): 641–52.
91.Bolin, M, Wiberg-Itzel, E, Wikstrom, AK, Goop, M, Larsson, A, Olovsson, M, et al.Angiopoietin-1/angiopoietin-2 ratio for prediction of preeclampsia. Am J Hypertens 2009; 22 (8): 891895.
92.Kusanovic, JP, Romero, R, Chaiworapongsa, T, Erez, O, Mittal, P, Vaisbuch, E, et al.A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. J Matern Fetal Neonatal Med 2009; 22 (11): 1021–38.
93.Poon, LC, Maiz, N, Valencia, C, Plasencia, W, Nicolaides, KH. First-trimester maternal serum pregnancy-associated plasma protein-A and pre-eclampsia. Ultrasound Obstet Gynecol 2009; 33 (1): 2333.
94.Chaiworapongsa, T, Romero, R, Savasan, ZA, Kusanovic, JP, Ogge, G, Soto, E, et al.Maternal plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in patients presenting to the obstetrical triage area with the suspicion of preeclampsia. J Matern Fetal Neonatal Med 2011; 24 (10): 1187–207.
95.Stepan, H, Schaarschmidt, W, Jank, A, Verlohren, S, Kratzsch, J. Use of angiogenic factors (sFlt-1/PlGF ratio) to confirm the diagnosis of preeclampsia in clinical routine: first experience. Z Geburtshilfe Neonatol 2010; 214 (6): 234–38.
96.Rana, S, Powe, CE, Salahuddin, S, Verlohren, S, Perschel, FH, Levine, RJ, et al.Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation 2012; 125 (7): 911–9.
97.Verlohren, S, Herraiz, I, Lapaire, O, Schlembach, D, Zeisler, H, Calda, P, et al.New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension 2013; 63 (2): 346–52.
98.Lindheimer, MD, Kanter, D. Interpreting abnormal proteinuria in pregnancy: the need for a more pathophysiological approach. Obstet Gynecol 2010; 115 (2, Pt 1): 365–75.
99.Benton, SJ, Hu, Y, Xie, F, Kupfer, K, Lee, SW, Magee, LA, et al.Angiogenic factors as diagnostic tests for preeclampsia: a performance comparison between two commercial immunoassays. Am J Obstet Gynecol 2011; 205 (5): 469–8.
100.Sunderji, S, Gaziano, E, Wothe, D, Rogers, LC, Sibai, B, Karumanchi, SA, et al.Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstet Gynecol 2010; 202 (1): 40–7.
101.Verlohren, S, Herraiz, I, Lapaire, O, Schlembach, D, Moertl, M, Zeisler, H, et al.The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol 2012; 206 (1): 58.
102.Knudsen, UB, Kronborg, CS, von Dadelszen, P, Kupfer, K, Lee, S, Vittinghus, E, et al.A single rapid point-of-care placental growth factor determination as an aid in the diagnosis of preeclampsia. Pregnancy Hypertens 2012; 2: 815.
103.Chappell, LC, Duckworth, S, Seed, PT, Griffin, M, Myers, J, Mackillop, L, et al.Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation 2013; 128 (19): 2121–31.
104.Espinoza, J, Kusanovic, JP, Bahado-Singh, R, Gervasi, MT, Romero, R, Lee, W, et al.Should bilateral uterine artery notching be used in the risk assessment for preeclampsia, small-for-gestational-age, and gestational hypertension? J Ultrasound Med 2010; 29 (7): 1103–15.
105.O’driscoll, DT. A fluid retention syndrome associated with severe iso-immunization to the rhesus factor. J Obstet Gynaecol Br Emp 1956; 63 (3): 372–74.
106.Goodlin, RC. Impending fetal death in utero due to isoimmunization. Obstet Gynecol 1957; 10 (3): 299302.
107.Scott, JS. Pregnancy toxaemia associated with hydrops foetalis, hydatidiform mole and hydramnios. J Obstet Gynaecol Br Emp 1958; 65 (5): 689701.
108.Cohen, A. Maternal syndrome in Rh iso-immunization: report of a case. J Obstet Gynaecol Br Emp 1960; 67: 325–27.
109.Hirsch, MR, Mark, MS. Pseudotoxemia and erythroblastosis. Report of a case. Obstet Gynecol 1964; 24: 47–8.
110.John, AH, Duncan, AS. The Maternal Syndrome associated with hydrops foetalis. J Obstet Gynaecol Br Commonw 1964; 71: 61–5.
111.Quagliarello, JR, Passalaqua, AM, Greco, MA, Zinberg, S, Young, BK. Ballantyne's triple edema syndrome: prenatal diagnosis with ultrasound and maternal renal biopsy findings. Am J Obstet Gynecol 1978; 132 (5): 580–81.
112.Duthie, SJ, Walkinshaw, SA. Parvovirus associated fetal hydrops: reversal of pregnancy-induced proteinuric hypertension by in utero fetal transfusion. Br J Obstet Gynaecol 1995; 102 (12): 1011–13.
113.Carbillon, L, Oury, JF, Guerin, JM, Azancot, A, Blot, P. Clinical biological features of Ballantyne syndrome and the role of placental hydrops. Obstet Gynecol Surv 1997; 52 (5): 310–14.
114.Ordorica, SA, Marks, F, Frieden, FJ, Hoskins, IA, Young, BK. Aneurysm of the vein of Galen: a new cause for Ballantyne syndrome. Am J Obstet Gynecol 1990; 162 (5): 1166–67.
115.Midgley, DY, Harding, K. The Mirror syndrome. Eur J Obstet Gynecol Reprod Biol 2000; 88 (2): 201–2.
116.Finamore, PS, Kontopoulos, E, Price, M, Giannina, G, Smulian, JC. Mirror syndrome associated with sacrococcygeal teratoma: a case report. J Reprod Med 2007; 52 (3): 225–7.
117.Dorman, SL, Cardwell, MS. Ballantyne syndrome caused by a large placental chorioangioma. Am J Obstet Gynecol 1995; 173 (5): 1632–33.
118.Barker, G, Boyd, RD, D’Souza, SW, Donnai, P, Fox, H, Sibley, CP. Placental water content and distribution. Placenta 1994; 15 (1): 4756.
119.Kovalovszki, L, Villanyi, E, Benko, G. Placental villous edema: a possible cause of antenatal hypoxia. Acta Paediatr Hung 1990; 30 (2): 209–15.
120.Naeye, RL, Maisels, MJ, Lorenz, RP, Botti, JJ. The clinical significance of placental villous edema. Pediatrics 1983; 71 (4): 588–94.
121.Alvarez, H, Sala, MA, Benedetti, WL. Intervillous space reduction in the edematous placenta. Am J Obstet Gynecol 1972; 112 (6): 819–20.
122.Stepan, H, Faber, R. Cytomegalovirus-induced mirror syndrome associated with elevated levels of angiogenic factors. Obstet Gynecol 2007; 109 (5): 1205–6.
123.Koga, K, Osuga, Y, Tajima, T, Hirota, Y, Igarashi, T, Fujii, T, et al.Elevated serum soluble fms-like tyrosine kinase 1 (sFlt1) level in women with hydatidiform mole. Fertil Steril 2009; 94 (1): 305–8.
124.Soto-Wright, V, Bernstein, M, Goldstein, DP, Berkowitz, RS. The changing clinical presentation of complete molar pregnancy. Obstet Gynecol 1995; 86 (5): 775–9.
125.Jauniaux, E. Partial moles: from postnatal to prenatal diagnosis. Placenta 1999; 20 (5–6): 379–88.
126.Prasannan-Nair, C, Reynolds, SF, Budden, G. Partial molar pregnancy with severe pre-eclampsia at 19 weeks’ gestation. J Obstet Gynaecol 2006; 26 (8): 817.
127.Stefos, T, Plachouras, N, Mari, G, Cosmi, E, Lolis, D. A case of partial mole and atypical type I triploidy associated with severe HELLP syndrome at 18 weeks’ gestation. Ultrasound Obstet Gynecol 2002; 20 (4): 403–4.
128.Sherer, DM, Dalloul, M, Stimphil, R, Hellmann, M, Khoury-Collado, F, Osho, J, et al.Acute onset of severe hemolysis, elevated liver enzymes, and low platelet count syndrome in a patient with a partial hydatidiform mole at 17 weeks gestation. Am J Perinatol 2006; 23 (3): 163–6.
129.Jank, A, Kratzsch, J, Stepan, H. Effect of terminated fetal circulation on maternal angiogenic factors in severe early preeclampsia. Hypertens Pregnancy 2012.
130.Benirschke, K, Kaufmann, P, Baergen, R. Molar pregnancies. In: Benirschke, K, Kaufmann, P, Baergen, R (eds.) Pathology of the Human Placenta. New York, NY: Springer, 2006; 797–836.
131.Qiao, S, Nagasaka, T, Nakashima, N. Numerous vessels detected by CD34 in the villous stroma of complete hydatidiform moles. Int J Gynecol Pathol 1997; 16 (3): 233–8.
132.Sibai, BM, Stella, CL. Diagnosis and management of atypical preeclampsia-eclampsia. Am J Obstet Gynecol 2009; 200 (5): 481–7.
133.Burton, GJ, Charnock-Jones, DS, Jauniaux, E. Regulation of vascular growth and function in the human placenta. Reproduction 2009; 138 (6): 895902.
134.Espinoza, J, Espinoza, AF. Pre-eclampsia: a maternal manifestation of a fetal adaptive response? Ultrasound Obstet Gynecol 2011; 38 (4): 367–70.
135.Espinoza, J, Espinoza, AF, Power, GG. High fetal plasma adenosine concentration: a role for the fetus in preeclampsia? Am J Obstet Gynecol 2011; 205 (5): 485.e24-7.
136.Jeyabalan, A, McGonigal, S, Gilmour, C, Hubel, CA, Rajakumar, A. Circulating and placental endoglin concentrations in pregnancies complicated by intrauterine growth restriction and preeclampsia. Placenta 2008; 29 (6): 555–63.
137.Lin, S, Shimizu, I, Suehara, N, Nakayama, M, Aono, T. Uterine artery Doppler velocimetry in relation to trophoblast migration into the myometrium of the placental bed. Obstet Gynecol 1995; 85 (5, Pt 1): 760–5.
138.Olofsson, P, Laurini, RN, Marsal, K. A high uterine artery pulsatility index reflects a defective development of placental bed spiral arteries in pregnancies complicated by hypertension and fetal growth retardation. Eur J Obstet Gynecol Reprod Biol 1993; 49 (3): 161–8.
139.Aardema, MW, Oosterhof, H, Timmer, A, van, R, I, Aarnoudse, JG. Uterine artery Doppler flow and uteroplacental vascular pathology in normal pregnancies and pregnancies complicated by pre-eclampsia and small for gestational age fetuses. Placenta 2001; 22 (5): 405–11.
140.Madazli, R, Somunkiran, A, Calay, Z, Ilvan, S, Aksu, MF. Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries. Placenta 2003; 24 (5): 510–16.
141.Voigt, HJ, Becker, V. Doppler flow measurements and histomorphology of the placental bed in uteroplacental insufficiency. J Perinat Med 1992; 20 (2): 139–47.
142.Espinoza, J, Romero, R, Mee, KY, Kusanovic, JP, Hassan, S, Erez, O, et al.Normal and abnormal transformation of the spiral arteries during pregnancy. J Perinat Med 2006; 34 (6): 447–58.
143.Pijnenborg, R, Vercruysse, L, Hanssens, M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta 2006; 27 (9–10): 939–58.
144.Kosaka, K, Fujiwara, H, Yoshioka, S, Fujii, S. Vascular endothelial growth factor production by circulating immune cells is elevated in ovarian hyperstimulation syndrome. Hum Reprod 2007; 22 (6): 1647–51.
145.Pau, E, Alonso-Muriel, I, Gomez, R, Novella, E, Ruiz, A, Garcia-Velasco, JA, et al.Plasma levels of soluble vascular endothelial growth factor receptor-1 may determine the onset of early and late ovarian hyperstimulation syndrome. Hum Reprod 2006; 21 (6): 1453–60.
146.Gomez, R, Simon, C, Remohi, J, Pellicer, A. Administration of moderate and high doses of gonadotropins to female rats increases ovarian vascular endothelial growth factor (VEGF) and VEGF receptor-2 expression that is associated to vascular hyperpermeability. Biol Reprod 2003; 68 (6): 2164–71.
147.Gomez, R, Simon, C, Remohi, J, Pellicer, A. Vascular endothelial growth factor receptor-2 activation induces vascular permeability in hyperstimulated rats, and this effect is prevented by receptor blockade. Endocrinology 2002; 143 (11): 4339–48.
148.Luttun, A, Tjwa, M, Carmeliet, P. Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders. Ann N Y Acad Sci 2002; 979: 8093.
149.Li, Z, Zhang, Y, Ying, MJ, Kapoun, AM, Shao, Q, Kerr, I, et al.Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia. Hypertension 2007; 50 (4): 686–92.
150.Thadhani, R, Kisner, T, Hagmann, H, Bossung, V, Noack, S, Schaarschmidt, W, et al.Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase-1 in preeclampsia. Circulation 2011; 124 (8): 940–50.




Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed