Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia

Abstract

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease. METHODS: In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age. RESULTS: In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk , 1.27; 95% confidence interval [CI], 0.99 to 1.63; two-sided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal. CONCLUSIONS: This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.).

Shown for reading. Its publisher allows quoting it, not republishing it.

References 40

1. 1.

   Ameis D, Khoshgoo N, Keijzer R. Abnormal lung development in congenital diaphragmatic hernia. Semin Pediatr Surg. 2017;26:123-8.

   Not in our library10.1053/j.sempedsurg.2017.04.011

2. 2.

   Harting MT, Lally KP. The Congenital Diaphragmatic Hernia Study Group registry update. Semin Fetal Neonatal Med. 2014;19:370-5.

   Not in our library10.1016/j.siny.2014.09.004

3. 3.

   Postdischarge follow-up of infants with congenital diaphragmatic hernia. Pediatrics. 2008;121:627-32.

   Not in our library10.1542/peds.2007-3282

4. 4.

   Jani J, Nicolaides KH, Keller RL, et al. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol. 2007;30:67-71.

   Not in our library10.1002/uog.4052

5. 5.

   Dekoninck P, Gratacos E, Van Mieghem T, et al. Results of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia and the set up of the randomized controlled TOTAL trial. Early Hum Dev. 2011;87:619-24.

   Not in our library10.1016/j.earlhumdev.2011.08.001

6. 6.

   Lusk LA, Wai KC, Moon-Grady AJ, Basta AM, Filly R, Keller RL. Fetal ultrasound markers of severity predict resolution of pulmonary hypertension in congenital diaphragmatic hernia. Am J Obstet Gynecol. 2015;213(2):216.e1-8.

   Not in our library10.1016/j.ajog.2015.03.036

7. 7.

   Jani JC, Benachi A, Nicolaides KH, et al. Prenatal prediction of neonatal morbidity in survivors with congenital diaphragmatic hernia: a multicenter study. Ultrasound Obstet Gynecol. 2009;33:64-9.

   Not in our library10.1002/uog.6141

8. 8.

   Doné E, Gratacos E, Nicolaides KH, et al. Predictors of neonatal morbidity in fetuses with severe isolated congenital diaphragmatic hernia undergoing fetoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2013;42:77-83.

   Not in our library10.1002/uog.12445

9. 9.

   Wilson JM, DiFiore JW, Peters CA. Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated with fetal nephrectomy: possible application for congenital diaphragmatic hernia. J Pediatr Surg. 1993;28:1433-9.

   Not in our library10.1016/0022-3468(93)90426-l

10. 10.

    Khan PA, Cloutier M, Piedboeuf B. Tracheal occlusion: a review of obstructing fetal lungs to make them grow and mature. Am J Med Genet C Semin Med Genet. 2007;145C:125-38.

    Not in our library10.1002/ajmg.c.30127

11. 11.

    Flageole H, Evrard VA, Piedboeuf B, Laberge JM, Lerut TE, Deprest JA. The plug-unplug sequence: an important step to achieve type II pneumocyte maturation in the fetal lamb model. J Pediatr Surg. 1998;33:299-303.

    Not in our library10.1016/s0022-3468(98)90451-1

12. 12.

    Deprest J, Gratacos E, Nicolaides KH. Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol. 2004;24:121-6.

    Not in our library10.1002/uog.1711

13. 13.

    Jani JC, Nicolaides KH, Gratacós E, et al. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009;34:304-10.

    Not in our library10.1002/uog.6450

14. 14.

    Al-Maary J, Eastwood MP, Russo FM, Deprest JA, Keijzer R. Fetal tracheal occlusion for severe pulmonary hypoplasia in isolated congenital diaphragmatic hernia: a systematic review and meta-analysis of survival. Ann Surg. 2016;264:929-33.

    Not in our library10.1097/sla.0000000000001675

15. 15.

    Araujo E, Tonni G, Martins WP, Ruano R. Procedure-related complications and survival following fetoscopic endotracheal occlusion (FETO) for severe congenital diaphragmatic hernia: systematic review and meta-analysis in the FETO era. Eur J Pediatr Surg. 2017;27:297-305.

    Not in our library10.1055/s-0036-1587331

16. 16.

    Nawapun K, Eastwood MP, Diaz-Cobos D, et al. In vivo evidence by magnetic resonance volumetry of a gestational age dependent response to tracheal occlusion for congenital diaphragmatic hernia. Prenat Diagn. 2015;35:1048-56.

    Not in our library10.1002/pd.4642

17. 17.

    FETO Task Group, Jani JC, Nicolaides KH, Gratacós E, Vandecruys H, Deprest JA. Fetal lung-to-head ratio in the prediction of survival in severe left-sided diaphragmatic hernia treated by fetal endoscopic tracheal occlusion (FETO). Am J Obstet Gynecol. 2006;195:1646-50.

    Not in our library10.1016/j.ajog.2006.04.004

18. 18.

    Reiss I, Schaible T, van den Hout L, et al. Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO Consortium consensus. Neonatology. 2010;98:354-64.

    Not in our library10.1159/000320622

19. 19.

    Snoek KG, Reiss IK, Greenough A, et al. Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO Consortium consensus — 2015 update. Neonatology. 2016;110:66-74.

    Not in our library10.1159/000444210

20. 20.

    Engels AC, DeKoninck P, van der Merwe JL, et al. Does website-based information add any value in counseling mothers expecting a baby with severe congenital diaphragmatic hernia? Prenat Diagn. 2013;33:1027-32.

    Not in our library10.1002/pd.4190

21. 21.

    TOTAL trial.

    Not in our library

22. 22.

    Van der Veeken L, Russo FM, De Catte L, et al. Fetoscopic endoluminal tracheal occlusion and reestablishment of fetal airways for congenital diaphragmatic hernia. Gynecol Surg. 2018;15:9.

    Not in our library10.1186/s10397-018-1041-9

23. 23.

    Jiménez JA, Eixarch E, DeKoninck P, et al. Balloon removal after fetoscopic endoluminal tracheal occlusion for congenital diaphragmatic hernia. Am J Obstet Gynecol. 2017;217(1):78.e1-78.e11.

    Not in our library10.1016/j.ajog.2017.02.041

24. 24.

    Bancalari E, Claure N. Definitions and diagnostic criteria for bronchopulmonary dysplasia. Semin Perinatol. 2006;30:164-70.

    Not in our library10.1053/j.semperi.2006.05.002

25. 25.

    O’Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979;35:549-56.

    Not in our library

26. 26.

    Alfaraj MA, Shah PS, Bohn D, et al. Congenital diaphragmatic hernia: lung-to-head ratio and lung volume for prediction of outcome. Am J Obstet Gynecol. 2011;205(1):43.

    Not in our library10.1016/j.ajog.2011.02.050

27. 27.

    Snoek KG, Capolupo I, van Rosmalen J, et al. Conventional mechanical ventilation versus high-frequency oscillatory ventilation for congenital diaphragmatic hernia: a randomized clinical trial (The VICI-trial). Ann Surg. 2016;263:867-74.

    Not in our library10.1097/sla.0000000000001533

28. 28.

    Snoek KG, Peters NCJ, van Rosmalen J, et al. The validity of the observed-to-expected lung-to-head ratio in congenital diaphragmatic hernia in an era of standardized neonatal treatment; a multicenter study. Prenat Diagn. 2017;37:658-65.

    Not in our library10.1002/pd.5062

29. 29.

    Grivell RM, Andersen C, Dodd JM. Prenatal interventions for congenital diaphragmatic hernia for improving outcomes. Cochrane Database Syst Rev. 2015;11(11):CD008925.

    Not in our library10.1002/14651858.cd008925.pub2

30. 30.
    Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia · 2021

    No notice
31. 31.

    Bouchghoul H, Dumery G, Russo FM, et al. Optimal gestational age at delivery for congenital diaphragmatic hernia. Ultrasound Obstet Gynecol. 2020.

    Not in our library10.1002/uog.22133

32. 32.

    Basurto D, Russo FM, Van der Veeken L, et al. Prenatal diagnosis and management of congenital diaphragmatic hernia. Best Pract Res Clin Obstet Gynaecol. 2019;58:93-106.

    Not in our library10.1016/j.bpobgyn.2018.12.010

33. 33.

    Snoek KG, Greenough A, van Rosmalen J, et al. Congenital diaphragmatic hernia: 10-year evaluation of survival, extracorporeal membrane oxygenation, and foetoscopic endotracheal occlusion in four high-volume centres. Neonatology. 2018;113:63-8.

    Not in our library10.1159/000480451

34. 34.

    van den Hout L, Schaible T, Cohen-Overbeek TE, et al. Actual outcome in infants with congenital diaphragmatic hernia: the role of a standardized postnatal treatment protocol. Fetal Diagn Ther. 2011;29:55-63.

    Not in our library10.1159/000322694

35. 35.

    Deprest J. Prenatal treatment of severe congenital diaphragmatic hernia: there is still medical equipoise. Ultrasound Obstet Gynecol. 2020;56:493-7.

    Not in our library10.1002/uog.22182

36. 36.

    Ruano R, Duarte SA, Pimenta EJ, et al. Comparison between fetal endoscopic tracheal occlusion using a 1.0-mm fetoscope and prenatal expectant management in severe congenital diaphragmatic hernia. Fetal Diagn Ther. 2011;29:64-70.

    Not in our library10.1159/000311944

37. 37.

    Mari G, Deprest J, Schenone M, et al. A novel translational model of percutaneous fetoscopic endoluminal tracheal occlusion — baboons (Papio spp.). Fetal Diagn Ther. 2014;35:92-100.

    Not in our library10.1159/000357139

38. 38.

    Basurto D, Sananès N, Verbeken E, et al. New device permitting non-invasive reversal of fetal endoscopic tracheal occlusion: ex-vivo and in-vivo study. Ultrasound Obstet Gynecol. 2020;56:522-31.

    Not in our library10.1002/uog.22132

39. 39.

    Basurto D, Sananès N, Bleeser T, et al. Safety and efficacy of smart tracheal occlusion device in diaphragmatic hernia lamb model. Ultrasound Obstet Gynecol. 2021;57:105-12.

    Not in our library10.1002/uog.23135

40. 40.

    Cannie MM, Jani JC, De Keyzer F, Allegaert K, Dymarkowski S, Deprest J. Evidence and patterns in lung response after fetal tracheal occlusion: clinical controlled study. Radiology. 2009;252:526-33.

    Not in our library10.1148/radiol.2522081955

Cited by papers we hold 2

• Anesthesia for fetal operative procedures: A systematic review · 2022
  Not checked
• Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia · 2021
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.