Download PDF
Am J Perinatol 2014; 31(S 01): S39-S46
DOI: 10.1055/s-0034-1384641
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Role of Adjunctive Medical Therapy in the Fetoscopic Surgical Treatment of Twin–Twin Transfusion Syndrome

Michael V. Zaretsky
1   Division of Maternal Fetal-Medicine, Colorado Institute of Maternal Fetal Health, The University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado
,
Stig Somme
2   Department of Pediatric General Thoracic and Fetal Surgery, Colorado Institute of Maternal Fetal Health, The University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado
,
Timothy M. Crombleholme
2   Department of Pediatric General Thoracic and Fetal Surgery, Colorado Institute of Maternal Fetal Health, The University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado
› Author Affiliations
Further Information

Publication History

13 February 2014

14 May 2014

Publication Date:
31 July 2014 (online)

Also available at
    Permissions and Reprints

Abstract

The underlying etiology of twin–twin transfusion syndrome (TTTS) is unknown, but our growing understanding of the cardiovascular features of TTTS suggests this may be a disease that could respond to transplacental medical therapy. Adjunctive medical therapy in TTTS with the calcium channel blocker nifedipine has been shown to improve recipient survival while having no effect on the donor. There is no significant difference in recipient survival from postoperative day 5 to birth suggesting that the survival benefit is confined to the effects of nifedipine in the perioperative period. Also, there is no significant effect of nifedipine on gestational age at delivery suggesting the survival benefit was unrelated to the tocolytic effects of nifedipine and more likely a result of hemodynamic effects in the recipient twins' cardiovascular system during the perioperative period. TTTS remains poorly understood but there appears to be good evidence suggesting twin–twin hypertensive cardiomyopathy is a large component of the pathophysiology in recipient twins. The initial findings of nifedipine's effectiveness as a targeted medical therapy to address TTTS cardiomyopathy and improve survival of recipient twins opens the door for further research for adjunctive medical therapies in TTTS.

Keywords

twin–twin transfusion syndrome - nifedipine - twin–twin transfusion syndrome cardiomyopathy - fetoscopic laser surgery
 

  • References

  • 1 Hall JG. Twinning. Lancet 2003; 362 (9385) 735-743
    CrossrefPubMedSearch in Google Scholar
  • 2 Habli M, Lim F-Y, Crombleholme T. Twin-to-twin transfusion syndrome: a comprehensive update. Clin Perinatol 2009; 36 (2) 391-416 , x
    CrossrefPubMedSearch in Google Scholar
  • 3 Quintero RA. Twin-twin transfusion syndrome. Clin Perinatol 2003; 30 (3) 591-600
    CrossrefPubMedSearch in Google Scholar
  • 4 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
    CrossrefPubMedSearch in Google Scholar
  • 5 Habli M, Michelfelder E, Livingston J , et al. Acute effects of selective fetoscopic laser photocoagulation on recipient cardiac function in twin-twin transfusion syndrome. Am J Obstet Gynecol 2008; 199 (4) e1-e6
    PubMedSearch in Google Scholar
  • 6 Crombleholme TM, Lim F-Y, Habli M , et al. Improved recipient survival with maternal nifedipine in twin-twin transfusion syndrome complicated by TTTS cardiomyopathy undergoing selective fetoscopic laser photocoagulation. Am J Obstet Gynecol 2010; 203 (4) e1-e9
    CrossrefPubMedSearch in Google Scholar
  • 7 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) 189-194
    CrossrefPubMedSearch in Google Scholar
  • 8 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) 121-127
    CrossrefPubMedSearch in Google Scholar
  • 9 Van Mieghem T, Doné E, Gucciardo L , et al. Amniotic fluid markers of fetal cardiac dysfunction in twin-to-twin transfusion syndrome. Am J Obstet Gynecol 2010; 202 (1) e1-e7
    PubMedSearch in Google Scholar
  • 10 Crombleholme TM, Shera D, Lee H , et al. A prospective, randomized, multicenter trial of amnioreduction vs selective fetoscopic laser photocoagulation for the treatment of severe twin-twin transfusion syndrome. Am J Obstet Gynecol 2007; 197 (4) e1-e9
    PubMedSearch in Google Scholar
  • 11 Huhta JC. Guidelines for the evaluation of heart failure in the fetus with or without hydrops. Pediatr Cardiol 2004; 25 (3) 274-286
    PubMedSearch in Google Scholar
  • 12 Huhta JC. Fetal congestive heart failure. Semin Fetal Neonatal Med 2005; 10 (6) 542-552
    CrossrefPubMedSearch in Google Scholar
  • 13 Shah AD, Border WL, Crombleholme TM, Michelfelder EC. Initial fetal cardiovascular profile score predicts recipient twin outcome in twin-twin transfusion syndrome. J Am Soc Echocardiogr 2008; 21 (10) 1105-1108
    CrossrefPubMedSearch in Google Scholar
  • 14 Michelfelder E, Gottliebson W, Border W , et al. Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin transfusion syndrome: relation to Quintero stage. Ultrasound Obstet Gynecol 2007; 30 (7) 965-971
    CrossrefPubMedSearch in Google Scholar
  • 15 Tei C, Ling LH, Hodge DO , 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 cardiomyopathy. J Cardiol 1995; 26 (6) 357-366
    PubMedSearch in Google Scholar
  • 16 Bui YK, Kipps AK, Brook MM, Moon-Grady AJ. Tissue Doppler is more sensitive and reproducible than spectral pulsed-wave Doppler for fetal right ventricle myocardial performance index determination in normal and diabetic pregnancies. J Am Soc Echocardiogr 2013; 26 (5) 507-514
    CrossrefPubMedSearch in Google Scholar
  • 17 Rychik J, Tian Z, Bebbington M , 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 (4) e1-e8
    PubMedSearch in Google Scholar
  • 18 Gratacós E, Van Schoubroeck D, Carreras E , et al. Impact of laser coagulation in severe twin-twin transfusion syndrome on fetal Doppler indices and venous blood flow volume. Ultrasound Obstet Gynecol 2002; 20 (2) 125-130
    CrossrefPubMedSearch in Google Scholar
  • 19 Faye-Petersen OM, Crombleholme TM. Twin-to-twin transfusion syndrome: part 1. Types and pathogenesis. NeoReviews 2008; 9: e370-e379
    CrossrefPubMedSearch in Google Scholar
  • 20 Harkness UF, Crombleholme TM. Twin-twin transfusion syndrome: where do we go from here?. Semin Perinatol 2005; 29 (5) 296-304
    CrossrefPubMedSearch in Google Scholar
  • 21 Tolosa JE, Zoppini C, Ludomirsky A, Bhutani V, Weil SR, Huhta JC. Fetal hypertension and cardiac hypertrophy in the discordant twin syndrome. Am J Obstet Gynecol 1993; 168: 292
    PubMedSearch in Google Scholar
  • 22 Mahieu-Caputo D, Salomon LJ, Le Bidois J , et al. Fetal hypertension: an insight into the pathogenesis of the twin-twin transfusion syndrome. Prenat Diagn 2003; 23 (8) 640-645
    CrossrefPubMedSearch in Google Scholar
  • 23 Moretti MM, Fairlie FM, Akl S, Khoury AD, Sibai BM. The effect of nifedipine therapy on fetal and placental Doppler waveforms in preeclampsia remote from term. Am J Obstet Gynecol 1990; 163 (6 Pt 1) 1844-1848
    CrossrefPubMedSearch in Google Scholar
  • 24 Fenakel K, Fenakel G, Appelman Z, Lurie S, Katz Z, Shoham Z. Nifedipine in the treatment of severe preeclampsia. Obstet Gynecol 1991; 77 (3) 331-337
    PubMedSearch in Google Scholar
  • 25 Sibai BM, Barton JR, Akl S, Sarinoglu C, Mercer BM. A randomized prospective comparison of nifedipine and bed rest versus bed rest alone in the management of preeclampsia remote from term. Am J Obstet Gynecol 1992; 167 (4 Pt 1) 879-884
    CrossrefPubMedSearch in Google Scholar
  • 26 Hanretty KP, Whittle MJ, Howie CA, Rubin PC. Effect of nifedipine on Doppler flow velocity waveforms in severe pre-eclampsia. BMJ 1989; 299 (6709) 1205-1206
    CrossrefPubMedSearch in Google Scholar
  • 27 Martins-Costa S, Ramos JG, Barros E, Bruno RM, Costa CA, Goldin JR. Randomized controlled trial of hydralazine versus nifedipine in preeclamptic women with acute hypertension. Hypertens Pregnancy 1992; 11: 25-44
    PubMedSearch in Google Scholar
  • 28 Kwawukume EY, Ghosh TS. Oral nifedipine therapy in the management of severe preeclampsia. Int J Gynaecol Obstet 1995; 49 (3) 265-269
    CrossrefPubMedSearch in Google Scholar
  • 29 Vermillion ST, Scardo JA, Newman RB, Chauhan SP. A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy. Am J Obstet Gynecol 1999; 181 (4) 858-861
    CrossrefPubMedSearch in Google Scholar
  • 30 Scardo JA, Vermillion ST, Newman RB, Chauhan SP, Hogg BB. A randomized, double-blind, hemodynamic evaluation of nifedipine and labetalol in preeclamptic hypertensive emergencies. Am J Obstet Gynecol 1999; 181 (4) 862-866
    CrossrefPubMedSearch in Google Scholar
  • 31 Smith P, Anthony J, Johanson R. Nifedipine in pregnancy. BJOG 2000; 107 (3) 299-307
    CrossrefPubMedSearch in Google Scholar
  • 32 Nifedipine versus expectant management in mild to moderate hypertension in pregnancy. Gruppo di Studio Ipertensione in Gravidanza. Br J Obstet Gynaecol 1998; 105 (7) 718-722
    CrossrefPubMedSearch in Google Scholar
  • 33 Papatsonis DNM, Lok CAR, Bos JM, Geijn HP, Dekker GA. Calcium channel blockers in the management of preterm labor and hypertension in pregnancy. Eur J Obstet Gynecol Reprod Biol 2001; 97 (2) 122-140
    CrossrefPubMedSearch in Google Scholar
  • 34 Andrade SE, Raebel MA, Brown J , et al. Outpatient use of cardiovascular drugs during pregnancy. Pharmacoepidemiol Drug Saf 2008; 17 (3) 240-247
    CrossrefPubMedSearch in Google Scholar
  • 35 Lyell DJ, Pullen KM, Mannan J , et al. Maintenance nifedipine tocolysis compared with placebo: a randomized controlled trial. Obstet Gynecol 2008; 112 (6) 1221-1226
    CrossrefPubMedSearch in Google Scholar
  • 36 Fox NS, Gelber SE, Kalish RB, Chasen ST. Contemporary practice patterns and beliefs regarding tocolysis among u.s. Maternal-fetal medicine specialists. Obstet Gynecol 2008; 112 (1) 42-47
    CrossrefPubMedSearch in Google Scholar
  • 37 Barton JR, Prevost RR, Wilson DA, Whybrew WD, Sibai BM. Nifedipine pharmacokinetics and pharmacodynamics during the immediate postpartum period in patients with preeclampsia. Am J Obstet Gynecol 1991; 165 (4 Pt 1) 951-954
    CrossrefPubMedSearch in Google Scholar
  • 38 Prevost RR, Akl SA, Whybrew WD, Sibai BM. Oral nifedipine pharmacokinetics in pregnancy-induced hypertension. Pharmacotherapy 1992; 12 (3) 174-177
    PubMedSearch in Google Scholar
  • 39 Juon AM, Kühn-Velten WN, Burkhardt T, Krähenmann F, Zimmermann R, von Mandach U. Nifedipine gastrointestinal therapeutic system (GITS) as an alternative to slow-release for tocolysis—tolerance and pharmacokinetic profile. Eur J Obstet Gynecol Reprod Biol 2008; 140 (1) 27-32
    CrossrefPubMedSearch in Google Scholar
  • 40 Breimer DD, Schellens JH, Soons PA. Nifedipine: variability in its kinetics and metabolism in man. Pharmacol Ther 1989; 44 (3) 445-454
    CrossrefPubMedSearch in Google Scholar
  • 41 van Geijn HP, Lenglet JE, Bolte AC. Nifedipine trials: effectiveness and safety aspects. BJOG 2005; 112 (Suppl. 01) 79-83
    CrossrefPubMedSearch in Google Scholar
  • 42 Houtzager BA, Hogendoorn SM, Papatsonis DN , et al. Long-term follow up of children exposed in utero to nifedipine or ritodrine for the management of preterm labour. BJOG 2006; 113 (3) 324-331
    CrossrefPubMedSearch in Google Scholar
  • 43 Martin RA, Jones KL, Mendoza A, Barr Jr M, Benirschke K. Effect of ACE inhibition on the fetal kidney: decreased renal blood flow. Teratology 1992; 46 (4) 317-321
    CrossrefPubMedSearch in Google Scholar
  • 44 von Dadelszen P, Dwinnell S, Magee LA , et al; Research into Advanced Fetal Diagnosis and Therapy (RAFT) Group. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011; 118 (5) 624-628
    CrossrefPubMedSearch in Google Scholar
  • 45 Villanueva-García D, Mota-Rojas D, Hernández-González R , et al. A systematic review of experimental and clinical studies of sildenafil citrate for intrauterine growth restriction and pre-term labour. J Obstet Gynaecol 2007; 27 (3) 255-259
    CrossrefPubMedSearch in Google Scholar
  • 46 Arabin B, Laurini RN, van Eyck J, Nicolaides KH. Treatment of twin-twin transfusion syndrome by laser and digoxin. Biophysical and angiographic evaluation. Fetal Diagn Ther 1998; 13 (3) 141-146
    CrossrefPubMedSearch in Google Scholar