Twin-to-twin transfusion syndrome

doi:10.1017/CBO9780511997778.017

Chapter 11.1 - Twin-to-twin transfusion syndrome

Scientific basis

from Section 2 - Fetal disease

Published online by Cambridge University Press: 05 February 2013

Enrico Lopriore and

Edited by

Anthony Johnson and

Mark D. Kilby: Affiliation:
Department of Fetal Medicine, University of Birmingham
Anthony Johnson: Affiliation:
Baylor College of Medicine, Texas
Dick Oepkes: Affiliation:
Department of Obstetrics, Leiden University Medical Center

Book contents

Get access

Summary

Introduction

Twin-to-twin transfusion syndrome (TTTS) may complicate multiple pregnancies where there is vascular conjoining within the hemochorial placenta, most commonly in monochorionic twins. The disease has fascinated obstetric specialists since it was first described in 1875 [1] when it was recognized as a condition not amenable to treatment and with very high perinatal loss rates. Since that time, this condition has offered many academic challenges. This is not only in terms of understanding the underlying pathophysiology but also a clinical challenge, in attempting to alter the clinical course of a condition that affects 10–15% of monochorionic twins. This is with a “backdrop” of a condition whose natural outcome would be at least 90% perinatal loss rates and very high (>50%) neuromorbidity in any surviving babies [2, 3].

TTTS is a relatively unusual condition as genetically concordant (i.e., monozygous) twins develop phenotypically discordant features as a consequence of monochorionic placentation and the conjoined angioarchitecture (see Chapter 11.2). In monozygous twins, placentation is dependent on the timing of the zygote splitting, post-fertilization of a single ovum and sperm. If this occurs after 72 hours, then a single placental disk develops, most commonly with two amnions. The “splitting” of the single cellular mass forms the most well-developed hypothesis in the formation of monozygous twins but a “co-dominant axis theory” (with the development of more than a single organizing axis) also exists. Whatever the mechanism, it is in these monochorionic diamniotic (MCDA) twins that TTTS commonly develops, complicating 20% overall and 10% severely (the clinical features of which are usually apparent by the mid-trimester) [3]. However, more rarely, this complication may occur in monochorionic, monoamniotic twin pregnancies when splitting of a single cellular mass occurs (days post-fertilization) (Figure 11.1.1).

Keywords

vascular leakage placental growth factor twin-to-twin transfusion syndrome vascular endothelial growth factor fetal cardiac function angioarchitecture angiogenic growth factors

Information

Type: Chapter
Information: Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
, pp. 145 - 155
DOI: https://doi.org/10.1017/CBO9780511997778.017 [Opens in a new window]
Publisher: Cambridge University Press
Print publication year: 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Schatz, F. Klinische Beiträge zur Physiologie des Fetus. Hirschwald, Berlin, 1900.

Berghella, V, Kaufmann, M. Natural history of twin-twin transfusion syndrome. J Reprod Med 2001;46(5):480–4.Google Scholar

Lewi, L, Jani, J, Blickstein, I, et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study. Am J Obstet Gynecol 2008;199(5):514–18.Google Scholar

Denbow, ML, Welsh, AW, Taylor, MJ, et al. Twin fetuses: intravascular microbubble US contrast agent administration – early experience. Radiology 2000;214(3):724–8.Google Scholar

Gardiner, HM. Early changes in vascular dynamics in relation to twin-twin transfusion syndrome. Twin Res 2001;4(5):371–7.Google Scholar

Charnock-Jones, DS, Kaufmann, P, Mayhew, TM. Aspects of human fetoplacental vasculogenesis and angiogenesis. I. Molecular regulation. Placenta 2004;25(2–3):103–13.Google Scholar

Mayhew, TM, Charnock-Jones, DS, Kaufmann, P. Aspects of human fetoplacental vasculogenesis and angiogenesis. III. Changes in complicated pregnancies. Placenta 2004;25(2–3):127–39.Google Scholar

Bdolah, Y, Lam, C, Rajakumar, A, et al. Twin pregnancy and the risk of preeclampsia: bigger placenta or relative ischemia? Am J Obstet Gynecol 2008;198(4):428–6.Google Scholar

Machin, G, Still, K, Lalani, T. Correlations of placental vascular anatomy and clinical outcomes in 69 monochorionic twin pregnancies. Am J Med Genet 1996;61(3):229–36.Google Scholar

Sebire, NJ, Talbert, D, Fisk, NM. Twin-to-twin transfusion syndrome results from dynamic asymmetrical reduction in placental anastomoses: a hypothesis. Placenta 2001;22(5):383–91.Google Scholar

Bajoria, R, Wigglesworth, J, Fisk, NM. Angioarchitecture of monochorionic placentas in relation to the twin-twin transfusion syndrome. Am J Obstet Gynecol 1995;172(3):856–63.Google Scholar

Umur, A, Van Gemert, MJC, Nikkels, PGJ, Ross, MG. Monochorionic twins and twin-twin transfusion syndrome: the protective role of arterio-arterial anastomoses. Placenta 2002;23(2–3):201–9.Google Scholar

Denbow, ML, Cox, P, Taylor, M, Hammal, DM, Fisk, NM. Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome. Am J Obstet Gynecol 2000;182(2):417–26.Google Scholar

De Paepe, ME, Shapiro, S, Greco, D, et al. Placental markers of twin-to twin transfusion syndrome in diamniotic-monochorionic twins: a morphometric analysis of deep artery-to vein anastomoses. Placenta 2010;31(4):269–76.Google Scholar

Taylor, MJ, Denbow, ML, Duncan, KR, Overton, TG, Fisk, NM. Antenatal factors at diagnosis that predict outcome in twin-twin transfusion syndrome. Am J Obstet Gynecol 2000;183:1023–8.Google Scholar

Fries, MH, Goldstein, RB, Kilpatrick, SJ, et al. The role of velamentous cord insertion in the etiology of twin-twin transfusion syndrome. Obstet Gynecol 1993;81:569–74.Google Scholar

Machin, GA. Velamentous cord insertion in monochorionic twin gestation. An added risk factor. J Reprod Med 1997;42:785–9.Google Scholar

Lopriore, E, Sueters, M, Middeldorp, JM, et al. Velamentous cord insertion and unequal placental territories in monochorionic twins with and without twin-twin transfusion syndrome. Am J Obstet Gynecol 2007;196(2):159.e1–5.Google Scholar

Jain, V, Fisk, NM. The twin-twin transfusion syndrome. Clin Obstet Gynecol 2004;47:181–202.Google Scholar

Umur, A, Van Gemert, MJC, Ross, MG. Amniotic fluid and hemodynamic model in monochorionic twin pregnancies and twin-twin transfusion syndrome. AmJ Physiol Regul Integr Comp Physiol 2001;280(5):R1499–R1509.Google Scholar

van Gemert, MJ, Sterenborg, HJ. Haemodynamic model of twin-twin transfusion syndrome in monochorionic twin pregnancies. Placenta 1998;19(2–3):195–208.Google Scholar

van Gemert, MJ, Scherjon, SA, Major, AL, Borst, C. Twin-twin transfusion syndrome. Three possible pathophysiologic mechanisms. J Reprod Med 1997;42(11):708–14.Google Scholar

Denbow, ML, Fisk, NM. The consequences of monochorionic placentation. Baillieres Clin Obstet Gynaecol 1998;12(1):37–51.Google Scholar

Tammela, T, Enholm, B, Alitalo, K, Paavonen, K. The biology of vascular endothelial growth factors. Cardiovasc Res 2005;65(3):550–63.Google Scholar

de Villiers, S, Slaghekke, F, Middeldorp, JM, et al. Arterio-arterial vascular anastomoses in monochorionic twin placentas with and without twin anemia-polycythemia sequence. Placenta 2012;33(3):227–9.Google Scholar

Zhang, EG, Smith, SK, Baker, PN, Charnock-Jones, DS. The regulation and localization of angiopoietin-1, -2, and their receptor Tie2 in normal and pathologic human placentae. Mol Med 2001;7(9):624–35.Google Scholar

Maisonpierre, PC, Suri, C, Jones, PF, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997;277(5322):55–60.Google Scholar

St-Jacques, S, Forte, M, Lye, SJ, Letarte, M. Localization of endoglin, a transforming growth factor-beta binding protein, and of CD44 and integrins in placenta during the first trimester of pregnancy. Biol Reprod 1994;51(3):405–13.Google Scholar

Kaufmann, P, Mayhew, TM, Charnock-Jones, DS. Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta 2004;25(2–3):114–26.Google Scholar

Burton, GJ, Charnock-Jones, DS, Jauniaux, E. Regulation of vascular growth and function in the human placenta. Reproduction 2009;138(6):895–902.Google Scholar

Karumanchi, SA, Bdolah, Y. Hypoxia and sFlt-1 in preeclampsia: the “chicken-and-egg” question. Endocrinology 2004;145(11):4835–7.Google Scholar

Venkatesha, S, Toporsian, M, Lam, C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006;12(6):642–9.Google Scholar

Levine, RJ, Qian, C, Maynard, SE, et al. Serum sFlt1 concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women. Am J Obstet Gynecol 2006;194(4):1034–41.Google Scholar

Moore Simas, TA, Crawford, SL, Solitro, MJ, et al. Angiogenic factors for the prediction of preeclampsia in high-risk women. Am J Obstet Gynecol 2007;197(3):244–8.Google Scholar

Romero, R, Nien, JK, Espinoza, J, 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.Google Scholar

Chaiworapongsa, T, Romero, R, Gotsch, F, et al. Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age. J Matern Fetal Neonatal Med 2008;21(1):41–52.Google Scholar

Gotsch, F, Romero, R, Kusanovic, JP, et al. Preeclampsia and small-for-gestational age are associated with decreased concentrations of a factor involved in angiogenesis: soluble Tie-2. J Matern Fetal Neonatal Med 2008;21(6):389–402.Google Scholar

Crispi, F, Dominguez, C, Llurba, E, et al. 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.Google Scholar

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.Google Scholar

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.Google Scholar

Espinoza, J, Chaiworapongsa, T, Romero, R, et al. Unexplained fetal death: another anti-angiogenic state. J Matern Fetal Neonatal Med 2007;20(7):495–507.Google Scholar

Kumazaki, K, Nakayama, M, Suehara, N, Wada, Y. Expression of vascular endothelial growth factor, placental growth factor, and their receptors Flt-1 and KDR in human placenta under pathologic conditions. Hum Pathol 2002;33(11):1069–77.Google Scholar

Kusanovic, JP, Romero, R, Espinoza, J, et al. Twin-to-twin transfusion syndrome: an antiangiogenic state? Am J Obstet Gynecol 2008;198(4):382–8.Google Scholar

Fox, CE, Lash, GE, Pretlove, SJ, et al. Maternal plasma and amniotic fluid angiogenic factors and their receptors in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2010;35(6):695–701.Google Scholar

Quintero, RA, Morales, WJ, Allen, MH, et al. Staging of twin-twin transfusion syndrome. J Perinatol 1999;19(8 Pt 1):550–5.Google Scholar

Galea, P, Barigye, O, Wee, L, et al. The placenta contributes to activation of the renin angiotensin system in twin-twin transfusion syndrome. Placenta 2008;29(8):734–42.Google Scholar

Barrea, C, Alkazaleh, F, Ryan, G, et al. Prenatal cardiovascular manifestations in the twin-to-twin transfusion syndrome recipients and the impact of therapeutic amnioreduction. Am J Obstet Gynecol 2005;192(3):892–902.Google Scholar

Karatza, AA, Wolfenden, JL, Taylor, MJO, et al. Influence of twin-twin transfusion syndrome on fetal cardiovascular structure and function: prospective case-control study of 136 monochorionic twin pregnancies. Heart 2002;88(3):271–7.Google Scholar

Gardiner, HM, Taylor, MJ, Karatza, A, et al. Twin-twin transfusion syndrome: the influence of intrauterine laser photocoagulation on arterial distensibility in childhood. Circulation 2003;107(14):1906–11.Google Scholar

Mahieu-Caputo, D, Salomon, LJ, Le, BJ, et al. Fetal hypertension: an insight into the pathogenesis of the twin-twin transfusion syndrome. Prenat Diagn 2003;23(8):640–5.Google Scholar

Taylor, GM, Peart, WS, Porter, KA, Zondek, LH, Zondek, T. Concentration and molecular forms of active and inactive renin in human fetal kidney, amniotic fluid and adrenal gland: evidence for renin-angiotensin system hyperactivity in 2nd trimester of pregnancy. J Hypertens 1986;4(1):121–9.Google Scholar

Paul, M, Poyan, MA, Kreutz, R. Physiology of local renin-angiotensin systems. Physiol Rev 2006;86(3):747–803.Google Scholar

Kilby, MD, Platt, C, Whittle, MJ, Oxley, J, Lindop, GB. Renin gene expression in fetal kidneys of pregnancies complicated by twin-twin transfusion syndrome. Pediatr Dev Pathol 2001;4(2):175–9.Google Scholar

Wee, LY, Sullivan, M, Humphries, K, Fisk, NM. Longitudinal blood flow in shared (arteriovenous anastomoses) and non-shared cotyledons in monochorionic placentae. Placenta 2007;28(5–6):516–22.Google Scholar

Mahieu-Caputo, D, Meulemans, A, Martinovic, J, et al. Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient. Pediatr Res 2005;58(4):685–8.Google Scholar

Bajoria, R, Ward, S, Chatterjee, R. Natriuretic peptides in the pathogenesis of cardiac dysfunction in the recipient fetus of twin-twin transfusion syndrome. Am J Obstet Gynecol 2002;186(1):121–7.Google Scholar

Hynynen, MM, Khalil, RA. The vascular endothelin system in hypertension – recent patents and discoveries. Recent Pat Cardiovasc Drug Discov 2006;1(1):95–108.Google Scholar

Bajoria, R, Sullivan, M, Fisk, NM. Endothelin concentrations in monochorionic twins with severe twin-twin transfusion syndrome. Hum Reprod 1999;14(6):1614–18.Google Scholar

Bajoria, R, Ward, S, Chatterjee, R. Brain natriuretic peptide and endothelin-1 in the pathogenesis of polyhydramnios-oligohydramnios in monochorionic twins. Am J Obstet Gynecol 2003;189(1):189–94.Google Scholar

Wilkins, MR, Redondo, J, Brown, LA. The natriuretic-peptide family. Lancet 1997;349(9061):1307–10.Google Scholar

Chen, HH, Burnett, JC. Natriuretic peptides in the pathophysiology of congestive heart failure. Curr Cardiol Rep 2000;2(3):198–205.Google Scholar

Butt, RP, Laurent, GJ, Bishop, JE. Mechanical load and polypeptide growth factors stimulate cardiac fibroblast activity. Ann N Y Acad Sci 1995;752:387–93.Google Scholar

Cao, L, Gardner, DG. Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. Hypertension 1995;25(2):227–34.Google Scholar

Omland, T, Aakvaag, A, Bonarjee, VV, et al. Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide. Circulation 1996;93(11):1963–9.Google Scholar

Bajoria, R, Ward, S, Sooranna, SR. Atrial natriuretic peptide mediated polyuria: pathogenesis of polyhydramnios in the recipient twin of twin-twin transfusion syndrome. Placenta 2001;22(8–9):716–24.Google Scholar

Kiowski, W, Sutsch, G, Hunziker, P, et al. Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure. Lancet 1995;346(8977):732–6.Google Scholar

Yorikane, R, Sakai, S, Miyauchi, T, et al. Increased production of endothelin-1 in the hypertrophied rat heart due to pressure overload. FEBS Lett 1993;332(1–2):31–4.Google Scholar

Garcia, R, Lachance, D, Thibault, G. Positive inotropic action, natriuresis and atrial natriuretic factor release induced by endothelin in the conscious rat. J Hypertens 1990;8(8):725–31.Google Scholar

Kanno, K, Hirata, Y, Tsujino, M, et al. Up-regulation of ETB receptor subtype mRNA by angiotensin II in rat cardiomyocytes. Biochem Biophys Res Commun 1993;194(3):1282–7.Google Scholar

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the PDF of this chapter is currently unknown and may be updated in the future.