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Am J Perinatol 2015; 32(09): 887-894
DOI: 10.1055/s-0035-1544949
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Management Practice and Mortality for Infants with Congenital Diaphragmatic Hernia

Jonathan R. Malowitz
1   Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
2   Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
,
Christoph P. Hornik
1   Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
2   Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
,
Matthew M. Laughon
3   Department of Pediatrics, North Carolina Children's Hospital, Chapel Hill, North Carolina
,
Daniela Testoni
2   Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
4   Division of Neonatal Medicine, Escola Paulista de Medicina – Universidade Federal de São Paulo, São Paulo, Brazil
,
C. Michael Cotten
1   Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
,
Reese H. Clark
5   Pediatrix Medical Group, Sunrise, Florida
,
P. Brian Smith
1   Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
2   Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
› Author Affiliations
Further Information

Publication History

27 June 2014

19 December 2014

Publication Date:
25 February 2015 (online)

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Abstract

Objective Congenital diaphragmatic hernia (CDH) is fatal in 20 to 40% of cases, largely due to pulmonary dysmaturity, lung hypoplasia, and persistent pulmonary hypertension. Evidence for survival benefit of inhaled nitric oxide (iNO), extracorporeal membrane oxygenation (ECMO), and other medical interventions targeting pulmonary hypertension is lacking. We assessed medical interventions and mortality over time in a large multicenter cohort of infants with CDH.

Study Design We identified all infants ≥ 34 weeks' gestation with CDH discharged from 29 neonatal intensive care units between 1999 and 2012 with an average of ≥ 2 CDH admissions per year. We examined mortality and the proportion of infants exposed to medical interventions, comparing four periods of time: 1999–2001, 2002–2004, 2005–2007, and 2008–2012.

Results We identified 760 infants with CDH. From 1999–2001 to 2008–2012, use of iNO increased from 20% of infants to 50%, sildenafil use increased from 0 to 14%, and milrinone use increased from 0 to 22% (p < 0.001). Overall mortality (28%) did not significantly change over time compared with the earliest time period.

Conclusion Despite changing use of iNO, sildenafil, and milrinone, CDH mortality has not significantly decreased in this population of infants.

Keywords

infants - congenital diaphragmatic hernia - lung dysmaturity - lung hypoplasia - pulmonary hypertension - respiratory management
 

  • References

  • 1 Colvin J, Bower C, Dickinson JE, Sokol J. Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia. Pediatrics 2005; 116 (3) e356-e363
    CrossrefPubMedGoogle Scholar
  • 2 Langham Jr MR, Kays DW, Ledbetter DJ, Frentzen B, Sanford LL, Richards DS. Congenital diaphragmatic hernia. Epidemiology and outcome. Clin Perinatol 1996; 23 (4) 671-688
    CrossrefPubMedGoogle Scholar
  • 3 Philip N, Gambarelli D, Guys JM, Camboulives J, Ayme S. Epidemiological study of congenital diaphragmatic defects with special reference to aetiology. Eur J Pediatr 1991; 150 (10) 726-729
    CrossrefPubMedGoogle Scholar
  • 4 Logan JW, Rice HE, Goldberg RN, Cotten CM. Congenital diaphragmatic hernia: a systematic review and summary of best-evidence practice strategies. J Perinatol 2007; 27 (9) 535-549
    CrossrefPubMedGoogle Scholar
  • 5 Seetharamaiah R, Younger JG, Bartlett RH, Hirschl RB ; Congenital Diaphragmatic Hernia Study Group. Factors associated with survival in infants with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: a report from the Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg 2009; 44 (7) 1315-1321
    CrossrefPubMedGoogle Scholar
  • 6 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 (1) 55-63
    CrossrefPubMedGoogle Scholar
  • 7 Abdullah F, Zhang Y, Sciortino C , et al. Congenital diaphragmatic hernia: outcome review of 2,173 surgical repairs in US infants. Pediatr Surg Int 2009; 25 (12) 1059-1064
    CrossrefPubMedGoogle Scholar
  • 8 George DK, Cooney TP, Chiu BK, Thurlbeck WM. Hypoplasia and immaturity of the terminal lung unit (acinus) in congenital diaphragmatic hernia. Am Rev Respir Dis 1987; 136 (4) 947-950
    CrossrefPubMedGoogle Scholar
  • 9 Congenital Diaphragmatic Hernia Study Group. Estimating disease severity of congenital diaphragmatic hernia in the first 5 minutes of life. J Pediatr Surg 2001; 36 (1) 141-145
    CrossrefPubMedGoogle Scholar
  • 10 Tsao K, Allison ND, Harting MT, Lally PA, Lally KP. Congenital diaphragmatic hernia in the preterm infant. Surgery 2010; 148 (2) 404-410
    CrossrefPubMedGoogle Scholar
  • 11 Rocha G, Azevedo I, Pinto JC, Guimarães H. Follow-up of the survivors of congenital diaphragmatic hernia. Early Hum Dev 2012; 88 (4) 255-258
    CrossrefPubMedGoogle Scholar
  • 12 Lally KP, Engle W ; American Academy of Pediatrics Section on Surgery; American Academy of Pediatrics Committee on Fetus and Newborn. Postdischarge follow-up of infants with congenital diaphragmatic hernia. Pediatrics 2008; 121 (3) 627-632
    CrossrefPubMedGoogle Scholar
  • 13 Friedman S, Chen C, Chapman JS , et al. Neurodevelopmental outcomes of congenital diaphragmatic hernia survivors followed in a multidisciplinary clinic at ages 1 and 3. J Pediatr Surg 2008; 43 (6) 1035-1043
    CrossrefPubMedGoogle Scholar
  • 14 Muratore CS, Kharasch V, Lund DP , et al. Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic. J Pediatr Surg 2001; 36 (1) 133-140
    CrossrefPubMedGoogle Scholar
  • 15 Ng GY, Derry C, Marston L, Choudhury M, Holmes K, Calvert SA. Reduction in ventilator-induced lung injury improves outcome in congenital diaphragmatic hernia?. Pediatr Surg Int 2008; 24 (2) 145-150
    CrossrefPubMedGoogle Scholar
  • 16 van den Hout L, Reiss I, Felix JF , et al; Congenital Diaphragmatic Hernia Study Group. Risk factors for chronic lung disease and mortality in newborns with congenital diaphragmatic hernia. Neonatology 2010; 98 (4) 370-380
    CrossrefPubMedGoogle Scholar
  • 17 Maier S, Zahn K, Wessel LM, Schaible T, Brade J, Reinshagen K. Preventive antireflux surgery in neonates with congenital diaphragmatic hernia: a single-blinded prospective study. J Pediatr Surg 2011; 46 (8) 1510-1515
    CrossrefPubMedGoogle Scholar
  • 18 Morini F, Capolupo I, Masi R , et al. Hearing impairment in congenital diaphragmatic hernia: the inaudible and noiseless foot of time. J Pediatr Surg 2008; 43 (2) 380-384
    CrossrefPubMedGoogle Scholar
  • 19 Muratore CS, Utter S, Jaksic T, Lund DP, Wilson JM. Nutritional morbidity in survivors of congenital diaphragmatic hernia. J Pediatr Surg 2001; 36 (8) 1171-1176
    CrossrefPubMedGoogle Scholar
  • 20 Azarow K, Messineo A, Pearl R, Filler R, Barker G, Bohn D. Congenital diaphragmatic hernia—a tale of two cities: the Toronto experience. J Pediatr Surg 1997; 32 (3) 395-400
    CrossrefPubMedGoogle Scholar
  • 21 Bagolan P, Casaccia G, Crescenzi F, Nahom A, Trucchi A, Giorlandino C. Impact of a current treatment protocol on outcome of high-risk congenital diaphragmatic hernia. J Pediatr Surg 2004; 39 (3) 313-318 , discussion 313–318
    CrossrefPubMedGoogle Scholar
  • 22 Bohn D. Congenital diaphragmatic hernia. Am J Respir Crit Care Med 2002; 166 (7) 911-915
    CrossrefPubMedGoogle Scholar
  • 23 Wung JT, James LS, Kilchevsky E, James E. Management of infants with severe respiratory failure and persistence of the fetal circulation, without hyperventilation. Pediatrics 1985; 76 (4) 488-494
    PubMedGoogle Scholar
  • 24 Rocha GM, Bianchi RF, Severo M , et al. Congenital diaphragmatic hernia - the neonatal period (part I). Eur J Pediatr Surg 2008; 18 (4) 219-223
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Rozmiarek AJ, Qureshi FG, Cassidy L, Ford HR, Hackam DJ. Factors influencing survival in newborns with congenital diaphragmatic hernia: the relative role of timing of surgery. J Pediatr Surg 2004; 39 (6) 821-824 , discussion 821–824
    CrossrefPubMedGoogle Scholar
  • 26 Tracy ET, Mears SE, Smith PB , et al. Protocolized approach to the management of congenital diaphragmatic hernia: benefits of reducing variability in care. J Pediatr Surg 2010; 45 (6) 1343-1348
    CrossrefPubMedGoogle Scholar
  • 27 Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 2006; (4) CD000399
    PubMedGoogle Scholar
  • 28 The Neonatal Inhaled Nitric Oxide Study Group (NINOS). Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. Pediatrics 1997; 99 (6) 838-845
    CrossrefPubMedGoogle Scholar
  • 29 Van Meurs K ; Congenital Diaphragmatic Hernia Study Group. Is surfactant therapy beneficial in the treatment of the term newborn infant with congenital diaphragmatic hernia?. J Pediatr 2004; 145 (3) 312-316
    CrossrefPubMedGoogle Scholar
  • 30 Noori S, Friedlich P, Wong P, Garingo A, Seri I. Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension. Neonatology 2007; 91 (2) 92-100
    CrossrefPubMedGoogle Scholar
  • 31 Downey LC, Benjamin Jr DK, Clark RH , et al. Urinary tract infection concordance with positive blood and cerebrospinal fluid cultures in the neonatal intensive care unit. J Perinatol 2013; 33 (4) 302-306
    CrossrefPubMedGoogle Scholar
  • 32 Frenckner B, Ehrén H, Granholm T, Lindén V, Palmér K. Improved results in patients who have congenital diaphragmatic hernia using preoperative stabilization, extracorporeal membrane oxygenation, and delayed surgery. J Pediatr Surg 1997; 32 (8) 1185-1189
    CrossrefPubMedGoogle Scholar
  • 33 Wung JT, Sahni R, Moffitt ST, Lipsitz E, Stolar CJ. Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatr Surg 1995; 30 (3) 406-409
    CrossrefPubMedGoogle Scholar
  • 34 Jacobs P, Finer NN, Robertson CM, Etches P, Hall EM, Saunders LD. A cost-effectiveness analysis of the application of nitric oxide versus oxygen gas for near-term newborns with respiratory failure: results from a Canadian randomized clinical trial. Crit Care Med 2000; 28 (3) 872-878
    CrossrefPubMedGoogle Scholar
  • 35 Downard CD, Jaksic T, Garza JJ , et al. Analysis of an improved survival rate for congenital diaphragmatic hernia. J Pediatr Surg 2003; 38 (5) 729-732
    CrossrefPubMedGoogle Scholar
  • 36 Kim H, Park JD, Kim HS , et al. Survival rate changes in neonates with congenital diaphragmatic hernia and its contributing factors. J Korean Med Sci 2007; 22 (4) 687-692
    CrossrefPubMedGoogle Scholar
  • 37 Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics 2006; 117 (4) 1077-1083
    CrossrefPubMedGoogle Scholar
  • 38 Carroll WD, Dhillon R. Sildenafil as a treatment for pulmonary hypertension. Arch Dis Child 2003; 88 (9) 827-828
    CrossrefPubMedGoogle Scholar
  • 39 FDA Drug Safety Communication. FDA recommends against use of Revatio in children with pulmonary hypertension. 2012; Available at: http://www.fda.gov/Drugs/DrugSafety/ucm317123.htm
    PubMedGoogle Scholar
  • 40 Barst RJ, Ivy DD, Gaitan G , 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 (2) 324-334
    CrossrefPubMedGoogle Scholar
  • 41 Hunter L, Richens T, Davis C, Walker G, Simpson JH. Sildenafil use in congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed 2009; 94 (6) F467
    PubMedGoogle Scholar
  • 42 Patel N. Use of milrinone to treat cardiac dysfunction in infants with pulmonary hypertension secondary to congenital diaphragmatic hernia: a review of six patients. Neonatology 2012; 102 (2) 130-136
    CrossrefPubMedGoogle Scholar
  • 43 Bassler D, Kreutzer K, McNamara P, Kirpalani H. Milrinone for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev 2010; (11) CD007802
    PubMedGoogle Scholar
  • 44 Khazin V, Kaufman Y, Zabeeda D , et al. Milrinone and nitric oxide: combined effect on pulmonary artery pressures after cardiopulmonary bypass in children. J Cardiothorac Vasc Anesth 2004; 18 (2) 156-159
    CrossrefPubMedGoogle Scholar
  • 45 Frenckner B, Broomé M, Lindström M, Radell P. Platelet-derived growth factor inhibition—a new treatment of pulmonary hypertension in congenital diaphragmatic hernia?. J Pediatr Surg 2008; 43 (10) 1928-1931
    CrossrefPubMedGoogle Scholar
  • 46 Inamura N, Kubota A, Nakajima T , et al. A proposal of new therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg 2005; 40 (8) 1315-1319
    CrossrefPubMedGoogle Scholar
  • 47 Hofmann SR, Stadler K, Heilmann A , et al. Stabilisation of cardiopulmonary function in newborns with congenital diaphragmatic hernia using lung function parameters and hemodynamic management. Klin Padiatr 2012; 224 (4) e1-e10
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Shiyanagi S, Okazaki T, Shoji H , et al. Management of pulmonary hypertension in congenital diaphragmatic hernia: nitric oxide with prostaglandin-E1 versus nitric oxide alone. Pediatr Surg Int 2008; 24 (10) 1101-1104
    CrossrefPubMedGoogle Scholar
  • 49 Lally KP, Lally PA, Langham MR , et al; Congenital Diaphragmatic Hernia Study Group. Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia. J Pediatr Surg 2004; 39 (6) 829-833
    CrossrefPubMedGoogle Scholar
  • 50 Bucher BT, Guth RM, Saito JM, Najaf T, Warner BW. Impact of hospital volume on in-hospital mortality of infants undergoing repair of congenital diaphragmatic hernia. Ann Surg 2010; 252 (4) 635-642
    PubMedGoogle Scholar
  • 51 Clark RH, Hardin Jr WD, Hirschl RB , et al. Current surgical management of congenital diaphragmatic hernia: a report from the Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg 1998; 33 (7) 1004-1009
    CrossrefPubMedGoogle Scholar
  • 52 Evans MJ, McKeever PA, Pearson GA, Field D, Firmin RK. Pathological complications of non-survivors of newborn extracorporeal membrane oxygenation. Arch Dis Child 1994; 71 (2) F88-F92
    CrossrefPubMedGoogle Scholar
  • 53 Hanekamp MN, Mazer P, van der Cammen-van Zijp MH , et al. Follow-up of newborns treated with extracorporeal membrane oxygenation: a nationwide evaluation at 5 years of age. Crit Care 2006; 10 (5) R127
    CrossrefPubMedGoogle Scholar
  • 54 McNally H, Bennett CC, Elbourne D, Field DJ ; UK Collaborative ECMO Trial Group. United Kingdom collaborative randomized trial of neonatal extracorporeal membrane oxygenation: follow-up to age 7 years. Pediatrics 2006; 117 (5) e845-e854
    CrossrefPubMedGoogle Scholar
  • 55 Grushka JR, Laberge JM, Puligandla P, Skarsgard ED ; Canadian Pediatric Surgery Network. Effect of hospital case volume on outcome in congenital diaphragmatic hernia: the experience of the Canadian Pediatric Surgery Network. J Pediatr Surg 2009; 44 (5) 873-876
    CrossrefPubMedGoogle Scholar
  • 56 Su W, Berry M, Puligandla PS, Aspirot A, Flageole H, Laberge JM. Predictors of gastroesophageal reflux in neonates with congenital diaphragmatic hernia. J Pediatr Surg 2007; 42 (10) 1639-1643
    CrossrefPubMedGoogle Scholar