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Chapter 48 - Congenital Diaphragmatic Hernia: In Utero Treatment Today and Tomorrow

from Congenital Diaphragmatic Hernia

Published online by Cambridge University Press:  21 October 2019

By
Jan Deprest ,
Anne Debeer ,
Lennart Van der Veeken ,
Karel Allegaert ,
Liesbeth Lewi  and
Luc De Catte
Edited by
Mark D. Kilby ,
Anthony Johnson  and
Dick Oepkes
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

Congenital diaphragmatic hernia (CDH) is a life-threatening surgically correctable congenital birth defect (3/10 000 live-born babies) [1]. Survival chances are dependent on the presence of associated malformations and severity of lung hypoplasia. Mortality remains up to 30% [2]. In the previous chapter we have outlined how fetuses with the suspicion of CDH should be assessed, using genetic testing and modern imaging techniques. Individualized prognosis of isolated CDH can be made prenatally by measurement of lung size, the presence of the liver in the thorax, and the side of the defect [3]. Patients with predicted poor prognosis are ideal candidates for an intervention that may improve the outcome. Such intervention is not aiming at repairing the diaphragmatic defect, as it can be easily closed after birth: it rather should reverse pulmonary hypoplasia (i.e. stimulate lung growth) before birth. Historically this was attempted by anatomical repair of the defect in utero, yet results were suboptimal [4].

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
 , pp. 503 - 511
Publisher: Cambridge University Press
Print publication year: 2020

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References

EUROCAT (2015). EUROCAT Statistical Monitoring Report – 2012. www.eurocat-network.eu/content/Stat-Mon-Report-2012.pdfGoogle Scholar
Harting, MT, Lally, KP. The Congenital Diaphragmatic Hernia Study Group registry update. Semin Fetal Neonatal Med. 2014; 19: 370–5.Google Scholar
Claus, F, Sandaite, I, Dekoninck, P, Moreno, O, Cruz Martinez, R, Van Mieghem, T, et al. Prenatal anatomical imaging in fetuses with congenital diaphragmatic hernia. Fetal Diagn Ther. 2011; 29: 88–100.Google Scholar
Harrison, MR, Langer, JC, Adzick, NS, Golbus, MS, Filly, RA, Anderson, RL, et al. Correction of congenital diaphragmatic hernia in utero, V. Initial clinical experience. J Pediatr Surg. 1990; 25: 47–55; discussion 6–7.Google Scholar
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; discussion 1439–40.Google Scholar
Hedrick, MH, Estes, JM, Sullivan, KM, Bealer, JF, Kitterman, JA, Flake, AW, et al. Plug the lung until it grows (PLUG): a new method to treat congenital diaphragmatic hernia in utero. J Pediatr Surg. 1994; 29: 612–17.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
Marwan, AI, Shabeka, U, Dobrinskikh, E. Suggested mechanisms of tracheal occlusion mediated accelerated fetal lung growth: a case for heterogeneous topological zones. Front Pediatr. 2017; 5: 295.Google Scholar
Deprest, J, Gratacós, E, Nicolaides, KH, Group, FT. Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol. 2004; 24: 121–6.Google Scholar
Metkus, AP, Filly, RA, Stringer, MD, Harrison, MR, Adzick, NS. Sonographic predictors of survival in fetal diaphragmatic hernia. J Pediatr Surg. 1996; 31: 148–51; discussion 151–2.Google Scholar
Gallot, D, Boda, C, Ughetto, S, Perthus, I, Robert-Gnansia, E, Francannet, C, et al. Prenatal detection and outcome of congenital diaphragmatic hernia: a French registry-based study. Ultrasound Obstet Gynecol. 2007; 29: 276–83.CrossRefGoogle ScholarPubMed
Jani, J, Nicolaides, KH, Keller, RL, Benachi, A, Peralta, CF, Favre, R, 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.Google Scholar
Jani, JC, Nicolaides, KH, Gratacós, E, Valencia, CM, Done, E, Martinez, JM, et al. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009; 34: 304–10.Google Scholar
DeKoninck, P, Gomez, O, Sandaite, I, Richter, J, Nawapun, K, Eerdekens, A, et al. Right-sided congenital diaphragmatic hernia in a decade of fetal surgery. BJOG. 2015; 122: 940–6.CrossRefGoogle Scholar
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.Google Scholar
Seravalli, V, Jelin, EB, Miller, JL, Tekes, A, Vricella, L, Baschat, AA. Fetoscopic tracheal occlusion for treatment of non-isolated congenital diaphragmatic hernia. Prenat Diagn. 2017; 37: 1046–9.CrossRefGoogle ScholarPubMed
Van Mieghem, T, Cruz-Martinez, R, Allegaert, K, Dekoninck, P, Castanon, M, Sandaite, I, et al. Outcome of fetuses with congenital diaphragmatic hernia and associated intrafetal fluid effusions managed in the era of fetal surgery. Ultrasound Obstet Gynecol. 2012; 39: 50–5.CrossRefGoogle ScholarPubMed
Van Mieghem, T, Cruz-Martinez, R, Allegaert, K, Dekoninck, P, Castanon, M, Sandaite, I, et al. Outcome of fetuses with congenital diaphragmatic hernia and associated intrafetal fluid effusions managed in the era of fetal surgery. Ultrasound Obstet Gynecol. 2012; 39: 50-5.Google Scholar
Deprest, J, Brady, P, Nicolaides, K, Benachi, A, Berg, C, Vermeesch, J, et al. Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial. Semin Fetal Neonatal Med. 2014; 19: 338–48.Google Scholar
Friede, T, Kieser, M. Sample size recalculation in internal pilot study designs: a review. Biom J. 2006; 48: 537–55.Google Scholar
Friede, T, Mitchell, C, Muller-Velten, G. Blinded sample size reestimation in non-inferiority trials with binary endpoints. Biom J. 2007; 49: 903–16.Google Scholar
O’Brien, PC, Fleming, TR. A multiple testing procedure for clinical trials. Biometrics. 1979; 35: 549–56.Google Scholar
Rodrigues, HC, Deprest, J, Berg, PP. When referring physicians and researchers disagree on equipoise: the TOTAL trial experience. Prenat Diagn. 2011; 31: 589–94.CrossRefGoogle ScholarPubMed
Van der Veeken, L, Russo, FM, De Catte, L, Gratacós, E, Benachi, A, Ville, Y, et al. Fetoscopic endoluminal tracheal occlusion and reestablishment of fetal airways for congenital diaphragmatic hernia. Gynecol Surg. 2018; 15: 9.Google Scholar
Deprest, J, Jani, J, Cannie, M, Debeer, A, Vandevelde, M, Done, E, et al. Prenatal intervention for isolated congenital diaphragmatic hernia. Curr Opin Obstet Gynecol. 2006; 18: 355–67.CrossRefGoogle ScholarPubMed
Peralta, CF, Jani, JC, Van Schoubroeck, D, Nicolaides, KH, Deprest, JA. Fetal lung volume after endoscopic tracheal occlusion in the prediction of postnatal outcome. Am J Obstet Gynecol. 2008; 198: 60. e1–5.CrossRefGoogle ScholarPubMed
Done, E, Gratacós, E, Nicolaides, KH, Allegaert, K, Valencia, C, Castanon, M, 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.CrossRefGoogle ScholarPubMed
Jimenez, JA, Eixarch, E, DeKoninck, P, Bennini, JR, Devlieger, R, Peralta, CF, et al. Balloon removal after fetoscopic endoluminal tracheal occlusion for congenital diaphragmatic hernia. Am J Obstet Gynecol. 2017; 217: 78. e1–11.Google Scholar
Vijfhuize, S, Schaible, T, Kraemer, U, Cohen-Overbeek, TE, Tibboel, D, Reiss, I. Management of pulmonary hypertension in neonates with congenital diaphragmatic hernia. Eur J Pediatr Surg. 2012; 22: 374–83.CrossRefGoogle ScholarPubMed
Villamor, E, Le Cras, TD, Horan, MP, Halbower, AC, Tuder, RM, Abman, SH. Chronic intrauterine pulmonary hypertension impairs endothelial nitric oxide synthase in the ovine fetus. Am J Physiol. 1997; 272: L1013–20.Google Scholar
Hanson, KA, Ziegler, JW, Rybalkin, SD, Miller, JW, Abman, SH, Clarke, WR. Chronic pulmonary hypertension increases fetal lung cGMP phosphodiesterase activity. Am J Physiol. 1998; 275: L931–41.Google Scholar
Barnett, CF, Machado, RF. Sildenafil in the treatment of pulmonary hypertension. Vasc Health Risk Manag. 2006; 2: 411–22.CrossRefGoogle ScholarPubMed
Wharton, J, Strange, JW, Moller, GM, Growcott, EJ, Ren, X, Franklyn, AP, et al. Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med. 2005; 172: 105–13.CrossRefGoogle ScholarPubMed
Barst, RJ, Ivy, DD, Gaitan, G, Szatmari, A, Rudzinski, A, Garcia, AE, et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation. 2012; 125: 324–34.Google Scholar
Barst, RJ, Beghetti, M, Pulido, T, Layton, G, Konourina, I, Zhang, M, et al. STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation. 2014; 129: 1914–23.Google Scholar
Steinhorn, RH, Kinsella, JP, Pierce, C, Butrous, G, Dilleen, M, Oakes, M, et al. Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. J Pediatr. 2009; 155: 841–7. e1.Google Scholar
Sanchez Luna, M, Franco, ML, Bernardo, B. Therapeutic strategies in pulmonary hypertension of the newborn: where are we now? Curr Med Chem. 2012; 19: 4640–53.Google Scholar
Lacassie, HJ, Germain, AM, Valdes, G, Fernandez, MS, Allamand, F, Lopez, H. Management of Eisenmenger syndrome in pregnancy with sildenafil and L-arginine. Obstet Gynecol. 2004; 103: 1118–20.Google Scholar
Molelekwa, V, Akhter, P, McKenna, P, Bowen, M, Walsh, K. Eisenmenger’s syndrome in a 27 week pregnancy –management with bosentan and sildenafil. Ir Med J. 2005; 98: 87–8.Google Scholar
Streit, M, Speich, R, Fischler, M, Ulrich, S. Successful pregnancy in pulmonary arterial hypertension associated with systemic lupus erythematosus: a case report. J Med Case Rep. 2009; 3: 7255.CrossRefGoogle ScholarPubMed
Samangaya, RA, Mires, G, Shennan, A, Skillern, L, Howe, D, McLeod, A, et al. A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia. Hypertens Pregnancy. 2009; 28: 369–82.Google Scholar
von Dadelszen, P, Dwinnell, S, Magee, LA, Carleton, BC, Gruslin, A, Lee, B, et al. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG. 2011; 118: 624–8.Google Scholar
Maher, MA, Sayyed, TM, Elkhouly, N. Sildenafil citrate therapy for oligohydramnios: a randomized controlled trial. Obstet Gynecol. 2017; 129: 615–20.Google Scholar
Luong, C, Rey-Perra, J, Vadivel, A, Gilmour, G, Sauve, Y, Koonen, D, et al. Antenatal sildenafil treatment attenuates pulmonary hypertension in experimental congenital diaphragmatic hernia. Circulation. 2011; 123: 2120–31.Google Scholar
Yamamoto, Y, Thebaud, B, Vadivel, A, Eaton, F, Jain, V, Hornberger, LK. Doppler parameters of fetal lung hypoplasia and impact of sildenafil. Am J Obstet Gynecol. 2014; 211: 263. e1–8.Google Scholar
Kattan, J, Cespedes, C, Gonzalez, A, Vio, CP. Sildenafil stimulates and dexamethasone inhibits pulmonary vascular development in congenital diaphragmatic hernia rat lungs. Neonatology. 2014; 106: 74–80.Google Scholar
Lemus-Varela Mde, L, Soliz, A, Gomez-Meda, BC, Zamora-Perez, AL, Ornelas-Aguirre, JM, Melnikov, V, et al. Antenatal use of bosentan and/or sildenafil attenuates pulmonary features in rats with congenital diaphragmatic hernia. World J Pediatr. 2014; 10: 354–9.Google Scholar
Burgos, CM, Pearson, EG, Davey, M, Riley, J, Jia, H, Laje, P, et al. Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia following prenatal maternal dexamethasone and/or sildenafil. Pediatr Res. 2016; 80: 577–85.Google Scholar
Mous, DS, Kool, HM, Buscop-van Kempen, MJ, Koning, AH, Dzyubachyk, O, Wijnen, RM, et al. Clinically relevant timing of antenatal sildenafil treatment reduces pulmonary vascular remodeling in congenital diaphragmatic hernia. Am J Physiol Lung Cell Mol Physiol. 2016; 311: L734–42.Google Scholar
Russo, FM, Toelen, J, Eastwood, MP, Jimenez, J, Miyague, AH, Vande Velde, G, et al. Transplacental sildenafil rescues lung abnormalities in the rabbit model of diaphragmatic hernia. Thorax. 2016; 71: 517–25.Google Scholar
Russo, FM, Toelen, J, Eastwood, MP, Jimenez, J, Miyague, AH, Vande Velde, G, et al. Transplacental sildenafil rescues lung abnormalities in the rabbit model of diaphragmatic hernia. Thorax. 2016; 71: 517–25.Google Scholar
Russo, et al. Am J Obstet Gynecol. 2018 (will be added in galley proof phase)Google Scholar
Russo, FM, Conings, S, Allegaert, K, van Mieghem, T, Toelen, J, van Calsteren, K, et al. Sildenafil crosses the placenta at therapeutic levels in a dually perfused human cotyledon model. Am J Obstet Gynecol. 2018; 219: 619. e1–619. e10.Google Scholar
Russo, FM, Benachi, A, Van Mieghem, T, De Hoon, J, Van Calsteren, K, Annaert, P, et al. Antenatal sildenafil administration to prevent pulmonary hypertension in congenital diaphragmatic hernia (SToP-PH): study protocol for a phase I/IIb placenta transfer and safety study. Trials. 2018; 19: 524.Google Scholar
Khoshgoo, N, Kholdebarin, R, Iwasiow, BM, Keijzer, R. MicroRNAs and lung development. Pediatr Pulmonol. 2013; 48: 317–23.CrossRefGoogle ScholarPubMed
Pereira-Terra, P, Deprest, JA, Kholdebarin, R, Khoshgoo, N, DeKoninck, P, Munck, AA, et al. Unique tracheal fluid microRNA signature predicts response to FETO in patients with congenital diaphragmatic Hernia. Ann Surg. 2015; 262: 1130–40.Google Scholar
Khoshgoo, N, Kholdebarin, R, Pereira-Terra, P, Mahood, TH, Falk, L, Day, CA, et al. Prenatal microRNA miR-200b therapy improves nitrofen-induced pulmonary hypoplasia associated with congenital diaphragmatic hernia. Ann Surg. 2019; 269: 979–87.Google Scholar
Eastwood, MP, Deprest, J, Russo, FM, Wang, H, Mulhall, D, Iwasiow, B, et al. MicroRNA 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia. Prenat Diagn. 2018; 38: 645–53.Google Scholar
Jani, JC, Nicolaides, KH, Gratacós, E, Vandecruys, H, Deprest, JA, Group, FT. 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.Google Scholar
Russo, FM, De Coppi, P, Allegaert, K, Toelen, J, van der Veeken, L, Attilakos, G, et al. Current and future antenatal management of isolated congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2017; 22: 383–90.Google Scholar
Bancalari, E, Claure, N. Definitions and diagnostic criteria for bronchopulmonary dysplasia. Semin Perinatol. 2006; 30: 164–70.Google Scholar

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