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Chapter 31 - Twin-to-Twin Transfusion Syndrome: Placental and Fetal Pathogenesis

from Complications of Monochorionic Multiple Pregnancy: Twin-to-Twin Transfusion Syndrome

Published online by Cambridge University Press:  21 October 2019

Mark D. Kilby
Affiliation:
University of Birmingham
Anthony Johnson
Affiliation:
University of Texas Medical School at Houston
Dick Oepkes
Affiliation:
Leids Universitair Medisch Centrum
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Summary

Twin-to-twin transfusion syndrome (TTTS) is a complication unique to monochorionic (MC) twins and affects 10–15% of MC twins, including MC twin pairs in higher order multiple pregnancies. 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 a very high perinatal loss rate. Since then, TTTS has provided many challenges, not only in terms of deciphering the underlying pathogenesis but also in attempting to alter the clinical course of a condition with a >90% perinatal loss rate untreated and very high (>50%) neurological morbidity in any surviving babies [2, 3]. Outcomes improve dramatically with treatment, which will be discussed in detail in Chapters 32, 33, and 35. However, even with treatment 12% of TTTS pregnancies will end with a double fetal loss, and only 62% with two survivors [4].

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
, pp. 344 - 352
Publisher: Cambridge University Press
Print publication year: 2020

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References

Schatz, F. Klinische Beiträge zur Physiologie des Fetus. Berlin: Hirschwald, 1900.Google Scholar
Berghella, V, Kaufmann, M. Natural history of twin-twin transfusion syndrome. J Reprod Med. 2001; 46: 480–4.Google Scholar
Lewi, L, Jani, J, Blickstein, I, Huber, A, Gucciardo, L, Van Mieghem, T, 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: 514. e1–8.Google Scholar
Akkermans, J, Peeters, S, Klumper, F, Lopriore, E, Middeldorp, J, Oepkes, D. Twenty-five years of fetoscopic laser coagulation in twin–twin transfusion syndrome: a systematic review. Fetal Diagn Ther. 2015; 38: 241–53.Google Scholar
Peeters, S, Devlieger, R, Middeldorp, J, DeKoninck, P, Deprest, J, Lopriore, E, et al. Fetal surgery in complicated monoamniotic pregnancies: case series and systematic review of the literature. Prenat Diagn. 2014; 34: 586–91.Google Scholar
Denbow, M, Welsh, A, Taylor, M, Blomley, M, Cosgrove, D, Fisk, N. Twin fetuses: intravascular microbubble US contrast agent administration – early experience. Radiology. 2000; 214: 724–8.Google Scholar
Gardiner, HM. Early changes in vascular dynamics in relation to twin-twin transfusion syndrome. Twin Res. 2001; 4: 371–7.CrossRefGoogle ScholarPubMed
Charnock-Jones, DS, Kaufmann, P, Mayhew, T. Aspects of human fetoplacental vasculogenesis and angiogenesis. I. Molecular regulation. Placenta. 2004; 25: 103–13.Google Scholar
Mayhew, T, Charnock-Jones, D, Kaufmann, P. Aspects of human fetoplacental vasculogenesis and angiogenesis. III. Changes in complicated pregnancies. Placenta. 2004; 25: 127–39.Google Scholar
Bdolah, Y, Lam, C, Rajakumar, A, Shivalingappa, V, Mutter, W, Sachs, BP, et al. Twin pregnancy and the risk of preeclampsia: bigger placenta or relative ischemia? Am J Obstet Gynecol. 2008; 198: 428. e1–6.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: 229–36.Google Scholar
Lewi, L, Deprest, J, Hecher, K. The vascular anastomoses in monochorionic twin pregnancies and their clinical consequences. Am J Obstet Gynecol. 2013; 208: 1930.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: 856–63.Google Scholar
Zhao, DP, de Villiers, SF, Slaghekke, F, Walther, FJ, Middeldorp, JM, Oepkes, D, et al. Prevalence, size, number and localization of vascular anastomoses in monochorionic placentas. Placenta. 2013; 34: 589–93.CrossRefGoogle ScholarPubMed
Umur, A, Van Gemert, M, Nikkels, P, Ross, M. Monochorionic twins and twin-twin transfusion syndrome: the protective role of arterio-arterial anastomoses. Placenta. 2002; 23: 201–9.Google Scholar
de Villiers, S, Slaghekke, F, Middeldorp, J, Walther, F, Oepkes, D, Lopriore, E. Arterio-arterial vascular anastomoses in monochorionic placentas with and without twin-twin transfusion syndrome. Placenta. 2012; 33: 652–4.Google Scholar
Taylor, M, Denbow, M, Duncan, K, Overton, T, Fisk, N. Antenatal factors at diagnosis that predict outcome in twin-twin transfusion syndrome. Am J Obstet Gynecol. 2000; 183: 1023–8.CrossRefGoogle ScholarPubMed
De Villiers, SF, Zhao, DP, Cohen, D, Van Zwet, EW, Duan, T, Oepkes, D, et al. Correlation between veno-venous anastomoses, TTTS and perinatal mortality in monochorionic twin pregnancies. Placenta. 2015; 36: 603–6.Google Scholar
Zhao, DP, Cohen, D, Middeldorp, JM, Klumper, FJ, Haak, MC, Oepkes, D, et al. The role of veno-venous anastomoses in twin-twin transfusion syndrome. Placenta. 2014; 5: 334–6.Google Scholar
Kalafat, E, Thilaganathan, B, Papageorghiou, A, Bhide, A, Khalil, A. The significance of placental cord insertion site in twin pregnancy. Ultrasound Obstet Gynecol. 2018; 52: 378–84.CrossRefGoogle ScholarPubMed
Chmait, R, Kontopoulos, E, Korst, L, Llanes, A, Petisco, I, Quintero, R. Stage-based outcomes of 682 consecutive cases of twin-twin transfusion syndrome treated with laser surgery: the USFetus experience. Am J Obstet Gynecol. 2011; 204: 393. e1–6.Google ScholarPubMed
De Paepe, M, Shapiro, S, Greco, D, Luks, V, Abellar, R, Luks, C, 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: 269–76.CrossRefGoogle ScholarPubMed
Fries, MH, Goldstein, RB, Kilpatrick, SJ, Golbus, MS, Callen, PW, Filly, RA. 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, Oepkes, D, Walther, FJ, Vandenbussche, FPHA. Velamentous cord insertion and unequal placental territories in monochorionic twins with and without twin-to-twin-transfusion syndrome. Am J Obstet Gynecol. 2007; 196: 159. e1–5.Google Scholar
Tammela, T, Enholm, B, Alitalo, K, Paavonen, K. The biology of vascular endothelial growth factors. Cardiovasc Res. 2005; 65: 550–63.Google Scholar
Zhang, E, Smith, S, Baker, P, Charnock-Jones, D. The regulation and localization of angiopoietin-1, -2, and their receptor Tie2 in normal and pathologic human placentae. Mol Med. 2001; 7: 624–35.Google Scholar
Maisonpierre, P, Suri, C, Jones, P, Bartunkova, S, Wiegand, S, Radziejewski, C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997; 277: 5560.Google Scholar
St-Jacques, S, Forte, M, Lye, S, 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: 405–13.CrossRefGoogle ScholarPubMed
Venkatesha, S, Toporsian, M, Lam, C, Hanai, J, Mammoto, T, Kim, Y, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006; 12: 642–9.Google Scholar
Kaufmann, P, Mayhew, T, Charnock-Jones, D. Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta. 2004; 25: 114–26.Google Scholar
Burton, G, Charnock-Jones, D, Jauniaux, E. Regulation of vascular growth and function in the human placenta. Reproduction. 2009; 138: 895902.Google Scholar
Karumanchi, S, Bdolah, Y. Hypoxia and sFlt-1 in preeclampsia: the “chicken-and-egg” question. Endocrinology. 2004; 145: 4835–7.Google Scholar
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 VEGF 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: 923.Google Scholar
Levine, RJ, Maynard, SE, Qian, C, Lim, K-H, England, LJ, Yu, KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350: 672–83.Google Scholar
Crispi, F, Domínguez, C, Llurba, E, Martín-Gallán, P, Cabero, L, Gratacós, 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: 201–7.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: 1069–77.Google Scholar
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: 382. e1–8.Google Scholar
Fox, CE, Lash, GE, Pretlove, SJ, Chan, BC, Holder, R, Kilby, MD. 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: 695701.Google Scholar
Mackie, FL, Whittle, R, Morris, RK, Hyett, J, Riley, R, Kilby, MD. First trimester ultrasound measurements and maternal serum biomarkers as prognostic factors in monochorionic twins: a cohort study. Diagn Progn Res. 2019; 3: 9.Google Scholar
Galea, P, Barigye, O, Wee, L, Jain, V, Sullivan, M, Fisk, NM. The placenta contributes to activation of the renin angiotensin system in twin-twin transfusion syndrome. Placenta. 2008; 29: 734–42.Google Scholar
Barrea, C, Alkazaleh, F, Ryan, G, McCrindle, BW, Roberts, A, Bigras, JL, 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: 892902.CrossRefGoogle ScholarPubMed
Habli, M, Michelfelder, E, Livingston, J, Harmon, J, Lim, F, Polzin, W, et al. Acute effects of selective fetoscopic laser photocoagulation on recipient cardiac function in twin-twin transfusion syndrome. Am J Obstet Gynecol. 2008; 199: 412. e1–6.Google Scholar
Tei, C, Ling, L, Hodge, D, Bailey, K, Oh, J, Rodeheffer, R, et al. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function—a study in normals and dilated. J Cardiol. 1995; 26: 357–66.Google ScholarPubMed
Rychik, J, Tian, Z, Bebbington, M, Xu, F, McCann, M, Mann, S, et al. The twin-twin transfusion syndrome: spectrum of cardiovascular abnormality and development of a cardiovascular score to assess severity of disease. Am J Obstet Gynecol. 2007; 197: 392. e1–8.CrossRefGoogle ScholarPubMed
Van Mieghem, T, Klaritsch, P, Doné, E, Gucciardo, L, Lewi, P, Verhaeghe, J, et al. Assessment of fetal cardiac function before and after therapy for twin-to-twin transfusion syndrome. Am J Obstet Gynecol. 2009; 200: 400. e1–7.Google Scholar
Gapp-Born, E, Sananes, N, Weingertner, AS, Guerra, F, Kohler, M, Fritz, G, et al. Predictive value of cardiovascular parameters in twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol. 2014; 44: 427–33.Google Scholar
Habli, M, Michelfelder, E, Cnota, J, Wall, D, Polzin, W, Lewis, D, et al. Prevalence and progression of recipient-twin cardiomyopathy in early stage twin-twin transfusion syndrome. Ultrasound Obstet Gynecol. 2012; 39: 63–8.Google Scholar
Ortiz, J, Torres, X, Eixarch, E, Bennasar, M, Cruz-Lemini, M, Gómez, O, et al. Differential changes in myocardial performance index and its time intervals in donors and recipients of twin-to-twin transfusion syndrome before and after laser therapy. Fetal Diagn Ther. 2018; 44: 305–10.Google Scholar
Karatza, AA, Wolfenden, JL, Taylor, MJO, Wee, L, Fisk, NM, Gardiner, HM. Influence of twin-twin transfusion syndrome on fetal cardiovascular structure and function: Prospective case-control study of 136 monochorionic twin pregnancies. Heart. 2002; 88: 271–7.Google Scholar
Wohlmuth, C, Boudreaux, D, Moise, KJ Jr., Johnson, A, Papanna, R, Bebbington, M, et al. Cardiac pathophysiology in twin-twin transfusion syndrome: new insights into its evolution. Ultrasound Obstet Gynecol. 2017: 51: 341–8.Google Scholar
Gardiner, H, Matsui, H, Roughton, M, Greenwald, S, Diemert, A, Taylor, M, et al. Cardiac function in 10-year-old twins following different fetal therapies for twin-twin transfusion syndrome. Ultrasound Obstet Gynecol. 2014; 43: 652–7.Google Scholar
Gardiner, H, Taylor, M, Karatza, A, Vanderheyden, T, Huber, A, Greenwald, S, et al. Twin-twin transfusion syndrome: the influence of intrauterine laser photocoagulation on arterial distensibility in childhood. Circulation. 2003; 107: 1906–11.Google Scholar
Gardiner, H, Barlas, A, Matsui, H, Diemert, A, Taylor, M, Preece, J, et al. Vascular programming in twins: the effects of chorionicity and fetal therapy for twin-to-twin transfusion syndrome. J Dev Orig Health Dis. 2012; 3: 182–9.Google Scholar
Mahieu-Caputo, D, Salomon, L, Le Bidois, J, Fermont, L, Brunhes, A, Jouvet, P, et al. Fetal hypertension: An insight into the pathogenesis of the twin-twin transfusion syndrome. Prenat Diagn. 2003; 23: 640–5.Google Scholar
Stagnati, V, Zanardini, C, Fichera, A, Pagani, G, Quintero, RA, Bellocco, R, et al. Early prediction of twin-to-twin transfusion syndrome: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2017; 49: 573–82.Google Scholar
Sebire, NJ, Souka, A, Skentou, H, Geerts, L, Nicolaides, KH. Early prediction of severe twin-to-twin transfusion syndrome. Hum Reprod. 2000; 15: 2008–10.Google Scholar
Dunn, WB, Shek, N, Fox, CE, Mackie, F, van Mieghem, T, Kilby, M. Non-targeted metabolomics in recipient amniotic fluid of MC twin pregnancies complicated by severe twin to twin transfusion syndrome (TTTS) and treated by fetoscopic laser ablation (FLC). BJOG. 2015; 122(Suppl. 8): 8.Google Scholar
Taylor, G, Peart, W, Porter, K, Zondek, L, 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: 121–9.Google Scholar
Paul, M, Poyan, M, Kreutz, R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006; 86: 747803.Google Scholar
Kilby, M, Platt, C, Whittle, M, Oxley, J, Lindop, G. Renin-gene expression in fetal kidneys of pregnancies complicated by twin-twin transfusion syndrome. Pediatr Dev Pathol. 2001; 4: 175–9.Google Scholar
Wee, L, Sullivan, M, Humphries, K, Fisk, N. Longitudinal blood flow in shared (arteriovenous anastomoses) and non-shared cotyledons in monochorionic placentae. Placenta. 2007; 28: 516–22.Google Scholar
Mahieu-Caputo, D, Meulemans, A, Martinovic, J, Gubler, M, Delezoide, A, Muller, F, 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: 685–8.Google Scholar
Verbeek, L, Joemmanbaks, F, Quak, J, Sukhai, R, Middeldorp, J, Oepkes, D, et al. Renal function in neonates with twin-twin transfusion syndrome treated with or without fetoscopic laser surgery. Eur J Pediatr. 2017; 176: 1209–15.CrossRefGoogle ScholarPubMed
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: 121–7.CrossRefGoogle ScholarPubMed
Hynynen, M, Khalil, R. The vascular endothelin system in hypertension – recent patents and discoveries. Recent Pat Cardiovasc Drug Discov. 2006; 1: 95108.Google Scholar
Bajoria, R, Sullivan, M, Fisk, NM. Endothelin concentrations in monochorionic twins with severe twin-twin transfusion syndrome. Hum Reprod. 1999; 14: 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: 189–94.Google Scholar
Wilkins, M, Redondo, J, Brown, L. The natriuretic-peptide family. Lancet. 1997; 349: 1307–10.Google Scholar
Chen, H, Burnett, J. Natriuretic peptides in the pathophysiology of congestive heart failure. Curr Cardiol Rep. 2000; 2: 198205.Google Scholar
Butt, R, Laurent, G, Bishop, J. Mechanical load and polypeptide growth factors stimulate cardiac fibroblast activity. Ann N Y Acad Sci. 1995; 752: 387–93.Google Scholar
Cao, L, Gardner, D. Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. Hypertension. 1995; 25: 227–34.Google Scholar
Omland, T, Aakvaag, A, Bonarjee, V, Caidahl, K, Lie, R, Nilsen, D, 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: 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: 716–24.Google Scholar
Kiowski, W, Sütsch, G, Hunziker, P, Müller, P, Kim, J, Oechslin, E, et al. Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure. Lancet. 1995; 346: 732–6.Google Scholar
Yorikane, R, Sakai, S, Miyauchi, T, Sakurai, T, Sugishita, Y, Goto, K. Increased production of endothelin-1 in the hypertrophied rat heart due to pressure overload. FEBS Lett. 1993; 332: 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: 725–31.CrossRefGoogle ScholarPubMed
Kanno, K, Hirata, Y, Tsujino, M, Imai, T, Shichiri, M, Ito, H, et al. Up-regulation of ETB receptor subtype mRNA by angiotensin II in rat cardiomyocytes. Biochem Biophys Res Commun. 1993; 194: 1282–7.Google Scholar

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