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Vol. 92, No. 2, 2007
Issue release date: August 2007
Neonatology 2007;92:134–138

Risk of Persistent Pulmonary Hypertension of the Neonate in Twin-to-Twin Transfusion Syndrome

Delsing B. · Lopriore E. · Blom N. · Te Pas A.B. · Vandenbussche F.P. · Walther F.J.
aDivision of Neonatology, Department of Pediatrics, bDepartment of Pediatric Cardiology, and cDivision of Fetal Medicine, Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands

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Background: Chronic twin-to-twin transfusion syndrome (TTTS) is a complication of monochorionic twin gestations and is associated with high perinatal mortality and increased neurological, cardiovascular and renal morbidity. Objective: To report the risk of severe persistent pulmonary hypertension of the newborn (PPHN) in TTTS and discuss the possible association between severe PPHN and TTTS. Methods: All cases of monochorionic twins with severe PPHN at birth admitted to our nursery between June 2002 and July 2006 were reviewed retrospectively. We compared the incidence of severe PPHN in monochorionic twins with and without TTTS. Severe PPHN was diagnosed according to clinical and ultrasound criteria when an infant with a structurally normal heart had (1) severe hypoxemia and (2) evidence of a right-to-left shunt on persistent ductus arteriosus or foramen ovale, requiring treatment with inhaled nitric oxide (iNO). Results: In a consecutive series of 73 twin pregnancies with TTTS, 4 of the 135 live-born twins (3%) were affected by severe PPHN. All reacted promptly to treatment with iNO. The incidence of severe PPHN in monochorionic twins without TTTS was 0% (0/161). Conclusion: In view of the severe clinical course in PPHN and need for adequate and prompt treatment with iNO, perinatologists should be aware of the increased risk of severe PPHN in TTTS.

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  1. Lopriore E, Vandenbussche FP, Tiersma ES, de Beaufort AJ, de Leeuw JP: Twin-to-twin transfusion syndrome: new perspectives. J Pediatr 1995;127:675–680.
  2. Barrea C, Alkazaleh F, Ryan G, McCrindle BW, Roberts A, Bigras JL, Barrett J, Seaward GP, Smallhorn JF, Hornberger LK: Prenatal cardiovascular manifestations in the twin-to-twin transfusion syndrome recipients and the impact of therapeutic amnioreduction. Am J Obstet Gynecol 2005;192:892–902.
  3. Bajoria R, Sullivan M, Fisk NM: Endothelin concentrations in monochorionic twins with severe twin-twin transfusion syndrome. Hum Reprod 1999;14:1614–1618.
  4. Mahieu-Caputo D, Salomon LJ, Le Bidois J, Fermont L, Brunhes A, Jouvet P, Dumez Y, Dommergues M: Fetal hypertension: an insight into the pathogenesis of the twin-twin transfusion syndrome. Prenat Diagn 2003;23:640–645.
  5. Lopriore E, Nagel HT, Vandenbussche FP, Walther FJ: Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome. Am J Obstet Gynecol 2003;189:1314–1319.
  6. Zosmer N, Bajoria R, Weiner E, Rigby M, Vaughan J, Fisk NM: Clinical and echographic features of in utero cardiac dysfunction in the recipient twin in twin-twin transfusion syndrome. Br Heart J 1994;72:74–79.
  7. Karatza AA, Wolfenden JL, Taylor MJ, 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;88:271–277.
  8. Fesslova V, Villa L, Nava S, Mosca F, Nicolini U: Fetal and neonatal echocardiographic findings in twin-twin transfusion syndrome. Am J Obstet Gynecol 1998;179:1056–1062.
  9. Simpson LL, Marx GR, Elkadry EA, D’Alton ME: Cardiac dysfunction in twin-twin transfusion syndrome: a prospective, longitudinal study. Obstet Gynecol 1998;92:557–562.
  10. Lougheed J, Sinclair BG, Fung Kee FK, Bigras JL, Ryan G, Smallhorn JF, Hornberger LK: Acquired right ventricular outflow tract obstruction in the recipient twin in twin-twin transfusion syndrome. J Am Coll Cardiol 2001;38:1533–1538.
  11. Rennie JM (ed): Roberton’s Textbook of Neonatology, ed 4. Amsterdam, Elsevier, 2005.
  12. Walsh-Sukys MC, Tyson JE, Wright LL, Bauer CR, Korones SB, Stevenson DK, Verter J, Stoll BJ, Lemons JA, Papile LA, Shankaran S, Donovan EF, Oh W, Ehrenkranz RA, Fanaroff AA: Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics 2000;105:14–20.
  13. Muraskas JK, Juretschke LJ, Weiss MG, Bhola M, Besinger RE: Neonatal-perinatal risk factors for the development of persistent pulmonary hypertension of the newborn in preterm newborns. Am J Perinatol 2001;18:87–91.
  14. Wittmann BK, Baldwin VJ, Nichol B: Antenatal diagnosis of twin transfusion syndrome by ultrasound. Obstet Gynecol 1981;58:123–127.
  15. Nicolaides KH, Thilaganathan B, Mibashan RS: Cordocentesis in the investigation of fetal erythropoiesis. Am J Obstet Gynecol 1989;161:1197–1200.
  16. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723–1729.
  17. Hislop AA, Pierce CM: Growth of the vascular tree. Paediatr Respir Rev 2000;1:321–327.
  18. Dakshinamurti S: Pathophysiologic mechanisms of persistent pulmonary hypertension of the newborn. Pediatr Pulmonol 2005;39:492–503.
  19. Robyr R, Lewi L, Salomon LJ, Yamamoto M, Bernard JP, Deprest J, Ville Y: Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome. Am J Obstet Gynecol 2006;194:796–803.
  20. Rychik J: Fetal cardiovascular physiology. Pediatr Cardiol 2004;25:201–209.
  21. Levin DL, Mills LJ, Weinberg AG: Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus. A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant. Circulation 1979;60:360–364.
  22. Manchester D, Margolis HS, Sheldon RE: Possible association between maternal indomethacin therapy and primary pulmonary hypertension of the newborn. Am J Obstet Gynecol 1976;126:467–469.
  23. Fouron JC, Bard H, Riopel L, De M, X, Van Ameringen MR, Urfer F: Circulatory changes in newborn lambs with experimental polycythemia: comparison between fetal and adult type blood. Pediatrics 1985;75:1054–1060.
  24. Mukhtar AI, Halliday HL: Eisenmenger syndrome in pregnancy: a possible cause of neonatal polycythemia and persistent fetal circulation. Obstet Gynecol 1982;60:651–652.
  25. Mahieu-Caputo D, Muller F, Joly D, Gubler MC, Lebidois J, Fermont L, Dumez Y, Dommergues M: Pathogenesis of twin-twin transfusion syndrome: the renin-angiotensin system hypothesis. Fetal Diagn Ther 2001;16:241–244.
  26. Mahieu-Caputo D, Dommergues M, Delezoide AL, Lacoste M, Cai Y, Narcy F, Jolly D, Gonzales M, Dumez Y, Gubler MC: Twin-to-twin transfusion syndrome. Role of the fetal renin-angiotensin system. Am J Pathol 2000;156:629–636.
  27. Mahieu-Caputo D, Meulemans A, Martinovic J, Gubler MC, Delezoide AL, Muller F, Madelenat P, Fisk NM, Dommergues M: Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient. Pediatr Res 2005;58:685–688.
  28. Abman SH: Neonatal pulmonary hypertension: a physiologic approach to treatment. Pediatr Pulmonol Suppl 2004;26:127–128.
  29. Rosenberg AA, Kennaugh J, Koppenhafer SL, Loomis M, Chatfield BA, Abman SH: Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension. J Pediatr 1993;123:109–114.
  30. De Vroomen M, Lopes Cardozo RH, Steendijk P, Frolich M, Baan J, van Bel F: Endothelin-1 plasma concentration increases in the early phase of pulmonary hypertension development during respiratory distress syndrome: a study in newborn lambs. Early Hum Dev 2001;63:9–21.
  31. Bajoria R, Sooranna SR, Ward S, D’Souza S, Hancock M: Placental transport rather than maternal concentration of amino acids regulates fetal growth in monochorionic twins: implications for fetal origin hypothesis. Am J Obstet Gynecol 2001;185:1239–1246.
  32. Pearson DL, Dawling S, Walsh WF, Haines JL, Christman BW, Bazyk A, Scott N, Summar ML: Neonatal pulmonary hypertension – urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med 2001;344:1832–1838.

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