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Foetal therapy, what works? An overview

Published online by Cambridge University Press:  28 August 2014

Mats Mellander*
Affiliation:
The Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Göteborg, Sweden
Helena Gardiner
Affiliation:
Texas Fetal Center, University of Texas, Houston, Texas, United States of America
*
Correspondence to: Dr M. Mellander, MD, PhD, Department of Paediatric Cardiology, The Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Göteborg, Sweden. Tel: +00 463 134 346 59; Fax: +00 463 184 5029; E-mail: [email protected]

Abstract

The update course in foetal cardiology held by the Fetal Working Group of the Association for European Paediatric and Congenital Cardiology in Istanbul in May 2012 included a session on foetal cardiac therapy. In the introductory overview to this symposium, we critically examine the level of evidence supporting or refuting proposed foetal cardiac therapies including transplacental treatment of foetal tachyarrhythmias, steroid treatment in foetal atrioventricular block, and foetal aortic valvuloplasty. In summary, the evidence for the efficiency and safety of currently available foetal cardiac therapies is low, with no therapy based on a randomised controlled trial. Transplacental treatment of foetal tachycardia is generally accepted as effective and safe, based on extensive and widespread clinical experience; however, there is no consensus on which drugs are the most effective in different electrophysiological situations. Randomised studies may be able to resolve this, but this is complicated because tachyarrhythmias are relatively rare conditions, the foetus is not accessible for direct treatment, and it is the healthy mother who accepts treatment she does not need on behalf of her foetus. The indications for steroid treatment in foetal atrioventricular block and for foetal valvuloplasty are even more controversial. Although randomised trials would be desirable, the practical issues of recruiting sufficient sample sizes and controlling for variation in practice across multiple sites is not to be underestimated. Multicentre registries, analysed free of bias, may be an alternative way to improve the evidence base of foetal cardiac therapy.

Type
Original Article
Copyright
© Cambridge University Press 2014 

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References

1.Liley, AW. Intrauterine transfusion of foetus in haemolytic disease. BMJ 1963: 11071109; (Evidence level III).Google Scholar
2.Liggins, GC, Howie, RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972; 50: 515525; (Evidence level III).CrossRefGoogle ScholarPubMed
3.Carpenter, RJ, Strasburger, JF, Garson, A, et al. Fetal ventricular pacing for hydrops secondary to complete atrioventricular block. J Am Coll Cardiol 1986; 8: 14341436; (Evidence level III).CrossRefGoogle ScholarPubMed
4.Guyatt, GH, Oxman, AD, Vist, G, et al; for the GRADE Working Group. Rating quality of evidence and strength of recommendations GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336: 924926.Google Scholar
5.Roberts, D, Dalziel, S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006; 19: CD004454(Evidence level Ia).Google Scholar
6.Senat, MV, Deprest, J, Boulvain, M, Paupe, A, Winer, N, Ville, Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med 2004; 351: 136144; (Evidence level Ib).CrossRefGoogle ScholarPubMed
7.Harrison, MR, Keller, RL, Hawgood, SB, et al. Tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med 2003; 349: 19161924; (Evidence level Ib).CrossRefGoogle ScholarPubMed
8.Adzick, NS, Thom, EA, Spong, CY, et al. A randomised trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011; 364: 9931004; (Evidence level Ib).CrossRefGoogle ScholarPubMed
9.Morris, RK, Malin, GL, Quinlan-Jones, E, et al. Percutaneous vesicoamniotic shunting in Lower Urinary Tract Obstruction (PLUTO) Collaborative Group. Lancet 2013; 382: 14961506; (Evidence level Ib).Google Scholar
10.Skinner, JR, Sharland, G. Detection and management of life threatening arrhythmias in the perinatal period. Early Hum Dev 2008; 84: 161172; (Evidence level III).CrossRefGoogle ScholarPubMed
11.Jaeggi, ET, Carvalho, JS, De Groot, E, et al. Comparison of transplacental treatment of fetal supraventricular tachyarrhythmias with digoxin, flecainide, and sotalol. Results of a nonrandomised multicentre study. Circulation 2011; 124: 17471754; (Evidence level III).CrossRefGoogle Scholar
12.Van den Heuvel, F, Bink-Boelkens, M, Du Marchie Sarvaas, GJ, Berger, RMF. Drug management of fetal tachyarrhythmias: are we ready for a systematic and evidence-based approach? Pace 2008; 31: S54S57.Google Scholar
13.Saul, JP, Cain, NB. Can we do a prospective trial for fetal tachycardia? The barriers to clinical trials in small patient populations. Circulation 2011; 124: 17031705.Google Scholar
14.Bergman, G, Eliasson, H, Bremme, K, Wahren-Herlenius, M, Sonesson, SE. Anti-Ro52/SSA antibody-exposed fetuses with prolonged atrioventricular time intervals show signs of decreased cardiac performance. Ultrasound Obstet Gynecol 2009; 34: 543549; (Evidence level III).Google Scholar
15.Jaeggi, ET, Silverman, ED, Laskin, C, Kingdom, J, Golding, F, Weber, R. Prolongation of the atrioventricular conduction in fetuses exposed to maternal anti-Ro/SSA and anti-La/SSB antibodies did not predict progressive heart block. A prospective observational study on the effects of maternal antibodies on 165 fetuses. J Am Coll Cardiol 2011; 57: 14871492; (Evidence level III).CrossRefGoogle Scholar
16.Askanase, AD, Friedman, DM, Copel, J, et al. Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies. Lupus 2002; 11: 145151; (Evidence level III).CrossRefGoogle ScholarPubMed
17.Eliasson, H, Sonesson, SE, Sharland, G, et al. Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients. Circulation 2011; 124: 19191926; (Evidence level III).Google Scholar
18.Breur, JM, Visser, GH, Kruize, AA, Stoutenbeek, P, Meijboom, EJ. Treatment of fetal heart block with maternal steroid therapy: case report and review of the literature. Ultrasound Obstet Gynecol 2004; 24: 467472; (Evidence level III).CrossRefGoogle ScholarPubMed
19.Jaeggi, ET, Fouron, JC, Silverman, ED, Ryan, G, Smallhorn, J, Hornberger, LK. Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 2004; 110: 15421548; (Evidence level III).Google Scholar
20.Allan, LD, Sharland, G, Tynan, MJ. The natural history of the hypoplastic left heart syndrome. Int J Cardiol 1989; 25: 343346; (Evidence level III).CrossRefGoogle ScholarPubMed
21.Hornberger, LK, Sanders, SP, Rein, AJ, Spevak, PJ, Parness, IA, Colan, SD. Left heart obstructive lesions and left ventricular growth in the mid-trimester fetus. A longitudinal study. Circulation 1995; 92: 15311538; (Evidence level III).Google Scholar
22.Maxwell, D, Allan, LD, Tynan, M. Balloon dilatation of the aortic valve in the fetus: a report of two cases. Br Heart J 1991; 65: 256258; (Evidence level III).CrossRefGoogle ScholarPubMed
23.McElhinney, DB, Marshall, AC, Wilkins-Haug, LE, et al. Predictors of technical success and postnatal biventricular outcome after in utero aortic valvuloplasty for aortic stenosis with evolving hypoplastic left heart syndrome. Circulation 2009; 120: 14821490; (Evidence level III).Google Scholar
24.Artzt, W, Wertaschnigg, D, Veit, I, Klement, F, Gitter, R, Tulzer, G. Intrauterine aortic valvuloplasty in fetuses with critical aortic stenosis: experience and results of 24 procedures. Ultrasound Obstet Gynecol 2011; 37: 689695; (Evidence level III).CrossRefGoogle Scholar
25.Mäkikallio, K, McElhinney, DB, Levine, JC, et al. Fetal aortic valve stenosis and the evolution of hypoplastic left heart syndrome: patient selection for fetal intervention. Circulation 2006; 113: 14011405; (Evidence level III).Google Scholar
26.Oepkes, D, Moon-Grady, AJ, Wilkins-Haug, L, Tworetzky, W, Arzt, W, Devlieger, R. 2010 report from the ISPD special interest group fetal therapy: fetal cardiac interventions. Prenat Diagn 2011; 31: 249251.Google Scholar
27.Marshall, AC, Levine, J, Morash, D, et al. Results of in utero atrial septoplasty in fetuses with hypoplastic left heart syndrome. Prenat Diagn 2008; 28: 10231028; (Evidence level III).CrossRefGoogle ScholarPubMed
28.Kalish, BT, Tworetzky, W, Benson, CB, et al. Technical challenges of atrial septal stent placement in fetuses with hypoplastic left heart syndrome and intact atrial septum. Catheter Cardiovasc Interv 2013; 84: 7785; (Evidence level III).Google Scholar
29.Quintero, RA, Huhta, J, Suh, E, Chmait, R, Romero, R, Angel, J. In utero cardiac fetal surgery: laser atrial septotomy in the treatment of hypoplastic left heart syndrome with intact atrial septum. Am J Obstet Gynecol 2005; 193: 14241428; (Evidence level III).Google Scholar
30.Tulzer, G, Arzt, W, Franklin, RC, Loughna, PV, Mair, R, Gardiner, HM. Fetal pulmonary valvuloplasty for critical pulmonary stenosis or atresia with intact septum. Lancet 2002; 360: 15671568; (Evidence level III).Google Scholar
31.Gardiner, HM, Belmar, C, Tulzer, G, et al. Morphologic and functional predictors of eventual circulation in the fetus with pulmonary atresia or critical pulmonary stenosis with intact septum. J Am Coll Cardiol 2008; 51: 12991308; (Evidence level III).CrossRefGoogle ScholarPubMed