Published online August 31, 2007
PEDIATRICS Vol. 120 No. 3 September 2007, pp. e651-e657 (doi:10.1542/peds.2006-3040)
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ARTICLE

Defect Size Determines Survival in Infants With Congenital Diaphragmatic Hernia

The Congenital Diaphragmatic Hernia Study Group*


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVES. Congenital diaphragmatic hernia is a significant cause of neonatal mortality. The objective of this study was to evaluate the clinical factors associated with death in infants with congenital diaphragmatic hernia by using a large multicenter data set.

METHODS. This was a prospective cohort study of all liveborn infants with congenital diaphragmatic hernia who were cared for at tertiary referral centers belonging to the Congenital Diaphragmatic Hernia Study Group between 1995 and 2004. Factors thought to influence death included birth weight, Apgar scores, size of defect, and associated anomalies. Survival to hospital discharge, duration of mechanical ventilation, and length of hospital stay were evaluated as end points.

RESULTS. A total of 51 centers in 8 countries contributed data on 3062 liveborn infants. The overall survival rate was 69%. Five hundred thirty-eight (18%) patients did not undergo an operation and died. The defect size was the most significant factor that affected outcome; infants with a near absence of the diaphragm had a survival rate of 57% compared with infants having a primary repair with a survival rate of 95%. Infants without agenesis but who required a patch for repair had a survival rate of 79% compared with primary repair.

CONCLUSIONS. The size of the diaphragmatic defect seems to be the major factor influencing outcome in infants with congenital diaphragmatic hernia. It is likely that the defect size is a surrogate marker for the degree of pulmonary hypoplasia. Future research efforts should be directed to accurately quantitate the degree of pulmonary hypoplasia or defect size antenatally. Experimental therapies can then be targeted to prospectively identify high-risk patients who are more likely to benefit.

Key Words: congenital diaphragmatic hernia • pulmonary hypoplasia • neonatal surgery • ECMO

Abbreviations: CDH—congenital diaphragmatic hernia • ROC—receiver operating characteristic

Congenital diaphragmatic hernia (CDH) has a reported incidence of between 1 in 2500 and 1 in 4000 live births.1,2 With improvements in neonatal intensive care in the 1970s and 1980s, sicker patients survived to receive surgery in tertiary centers. During this time, mortality rates from CDH approximated 50%.3,4 Because of this persistently high mortality rate, newer techniques for the management of neonatal respiratory failure including extracorporeal membrane oxygenation, high-frequency oscillatory ventilation, exogenous surfactant, and inhaled nitric oxide were rapidly adopted. Attempts at CDH repair in utero were pioneered by Harrison and colleagues,5–7 but recent data have not shown a survival advantage for patients who undergo fetal surgery. Survival to hospital discharge seems to have improved over the past 2 decades, although some authors dispute these conclusions.8–11 The reported mortality rate in liveborn infants of 20% to 40% makes CDH responsible for >1% of the annual infant mortality in the United States.12 Furthermore, CDH ranks among the most costly of neonatal conditions. Metkus and colleagues13 reported that CDH had an estimated hospital cost of $250000 per case to hospital discharge, and an estimated yearly cost of $264000000 in the United States (1995 dollars) for the initial hospital care alone.

The relative rarity of the condition makes the conduct of well-designed clinical studies extremely difficult because no single center can accrue sufficient patients to reach meaningful conclusions. Therefore, the management of CDH has evolved based largely on retrospective reviews from centers with small numbers of patients and differing treatment algorithms. A number of factors complicate interpretation of these studies. Institutions differ with respect to referral patterns and hospital resources such that the case mix or range of severity in patients treated may not be comparable. Some centers do not offer surgical repair for certain infants that are deemed "nonsalvageable," whereas others do, and this bias can clearly affect comparisons of survival rates.14,15 Stratification systems that have been reported to date, however, have been unwieldy or have not proven useful when applied to other centers or other populations of infants.16,17

The purpose of this study was to evaluate hospital-based outcomes for infants with CDH from a large number of institutions and to determine clinical factors associated with a poor outcome.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patients
The CDH Study Group was formed in 1995 to compile data on liveborn infants with CDH at participating institutions to assess therapies and outcomes. The CDH Study Group consists of tertiary referral centers that voluntarily provide data to a central registry. Data on all infants with CDH who are born at or transferred to a participating center are entered into the database. Data were collected prospectively on all liveborn patients with CDH between 1995 and 2004 in participating hospitals and included information on delivery and subsequent hospital care (including surgery where applicable) until death or hospital discharge. Institutions were included in this analysis if they had ≥4 consecutive years of data submission. The data from the registry forms were entered into a Microsoft (Redmond, WA) Access database and were cross-checked against the original forms. Patient demographics, birth information, Apgar scores, treatments received, and outcome were recorded. The Apgar scores were recoded into 3 categories (0–3, 4–6, and 7–10) for analysis.

The size of the diaphragm defect was determined by the surgeon at the time of repair and coded as "agenesis" if the diaphragm or most of the diaphragm was absent (based on surgeons' reports and/or operative notes with findings of "absent or missing rim of diaphragm" or repair requiring "suturing the patch to the ribs anteriorly and posteriorly"). All patients with diaphragm agenesis required a patch to repair the defect. In those patients without agenesis, either the defect could be repaired primarily, or a patch was required to close the defect. A fourth group of patients never underwent operation; most had a combination of either severe other anomalies or were thought to have fatal pulmonary hypoplasia. Central or bilateral diaphragmatic defects comprise a rare variant with a very high mortality; patients with these defects were not included in the analysis.

Significant associated anomalies, including chromosomal anomalies, syndromes, and complex congenital heart disease, were evaluated to see whether their presence with CDH affected outcomes. The most common chromosomal anomalies were trisomies 13, 18, and 21; the most common syndrome was Fryns syndrome. Complex congenital heart disease included hypoplastic left heart syndrome, coarctation of the aorta, and tetralogy of Fallot. An isolated ventricular septal defect or atrial septal defect was considered minor.

Statistical Analysis
Death before hospital discharge was the primary outcome variable. The length of stay in the hospital and duration of mechanical ventilation were secondary outcomes. Univariate logistic regressions were used to evaluate the associations between clinical variables and death before hospital discharge. Those variables associated with death are presented as unadjusted odds ratios and their 95% confidence intervals. The Wald test statistic was used to evaluate statistical significance. A P value of .05 was considered significant. Patients who did not undergo repair were not included in the analysis.

Multiple logistic regression models including the clinical variables evaluated (inborn status, birth weight, prenatal diagnosis, major cardiac anomalies, chromosomal anomalies, 5-minute Apgar score, and defect size) were calculated. Receiver operating characteristic (ROC) curves of these models were evaluated to determine how well they classified patients that died before discharge. The area under the ROC curve was used to summarize the classification accuracy of the logistic regression models. The classification accuracies of full (including all the clinical variables) and reduced models were contrasted to identify the minimal set of clinical variables predictive of death before discharge. Kruskal-Wallis rank order 1-way analyses of variance were used to compare outcomes among patients grouped by defect size for length of hospital stay and duration of mechanical ventilation. Analysis of the database was approved by the University of Texas Institutional Review Board. Participating centers filed a waiver of consent for data submission or signed a data use agreement for a limited data set. The analyses were conducted using the NCSS 2004 (NCSS, Kaysville, UT) statistical software package.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
There were 3062 liveborn infants from 51 centers who met criteria for the analysis. There were 39 centers from the United States and 12 centers from 7 other countries. The overall survival until hospital discharge for all infants was 69%. Descriptive statistics for all patients are shown in Table 1.


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  		TABLE 1 Descriptive Statistics for All Patients

 
Five hundred thirty-eight (18%) of the patients did not undergo operation, and all died. One hundred fifty-three of nonrepaired patients (28%) were noted to have severe anomalies (major cardiac, syndromal, or chromosomal) compared with 165 (7%) of repaired patients. Most of the remainder of unrepaired patients was believed to be unsalvageable based on hemodynamic instability or blood gas values. Autopsy data on defect size was only available on 50 patients, but of these, 23 (68%) had agenesis of the diaphragm, suggesting that the incidence of agenesis was much higher in patients thought to be nonsalvageable.

Survival in the surgically repaired patients was 2100 (83%) of 2524. A number of factors were significantly associated with death in the surgically repaired patients by univariate analysis (Table 2). Younger gestational age and lower birth weight were highly correlated, and both were associated with worse outcomes. Other significant factors included inborn status, prenatal diagnosis, presence of cardiac and chromosomal anomalies, low Apgar score, and large defect size (either a patch repair or diaphragm agenesis).


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  		TABLE 2 Clinical Variables Associated with Death Prior to Discharge in Patients Undergoing Repair

 
A logistic regression analysis was performed by using the variables in Table 2 for the equation. The low-Apgar-score group (0–3) and the 2 larger defect-size groups remained significant predictors in the full model. The area under the ROC curve for death in this model (full model) was 0.803. A logistic regression model with defect size as the only predictor variable was calculated. Using the defect size alone, the area under the ROC curve for death was 0.764. The more complicated full model added little predictive accuracy when compared with a simple model using defect size alone. The size of the defect had a significant effect on outcome. The odds of dying for patients with diaphragm agenesis were 14.07 (95% confidence interval: 10.35–19.13) times that of patients whose defect was small enough to undergo primary repair. Patients without agenesis, but who required a patch to close the diaphragm were also at increased risk for death (odds ratio: 5.04 [95% confidence interval: 3.71–6.86]) compared with infants who had a primary repair of the diaphragm.

We examined the impact of defect size on length of hospitalization and duration of mechanical ventilation as well. In patients who underwent repair and survived to transfer or hospital discharge, the size of the hernia defect was strongly associated with duration of mechanical ventilation and length of hospital stay (Fig 1).


Figure 1
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  		FIGURE 1 A, Duration of mechanical ventilation according to defect size in survivors. Data are presented as median with interquartile range; bars represent 1.5 times the interquartile range. B, Length of hospital stay according to defect size in survivors. Data are presented as median with interquartile range; bars represent 1.5 times the interquartile range.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
CDH remains an important cause of neonatal mortality despite many advances in neonatal critical care. The main determinant of survival in CDH remains the severity of pulmonary hypoplasia and pulmonary hypertension. Techniques to determine the degree of pulmonary hypoplasia have not been successful to date.18 Because many infants in whom a certain preductal arterial PaO2 or PaCO2 cannot be achieved do not survive, some institutions have used these measures to select candidates for repair.8,19 Others have used measures such as birth weight, prenatal diagnosis, associated anomalies, and Apgar scores as predictors of outcome.16,17,20 Some of these measures are not disease-specific; low Apgar scores, low birth weight, and presence of comorbid conditions such as cardiac anomalies are associated with increased morbidity and mortality in a large number of neonatal conditions.

This analysis shows that the size of the diaphragm defect correlates well with mortality, as well as morbidity in liveborn infants with CDH. Patients with diaphragm agenesis have previously been reported to have a high mortality.21–26 Defect size is likely to be a marker for the degree of pulmonary hypoplasia. Animal models suggest that a large defect is associated with much smaller lungs. It is possible to modify the degree of lung hypoplasia in the lamb model by the size of the defect created. In transgenic mice and toxicology models, timing of the insult is a contributing factor in determining size of the defect and outcome.27

An important criticism of this study is the accurate determination of the size of the defect. Clearly, there is some overlap between the groups defined by defect size because there is not an absolute value that defines agenesis or a "large" defect. There are also variations in surgical practice that determine whether a patch is used. However, there is a clear trend to liberal use of a patch to repair the defect.12,28 Also, it is not possible to close the defect in a patient with agenesis or a very large defect without a patch of some kind. Similarly, the definition of agenesis is likely to vary between centers. Despite this limitation, there is a clear differentiation in outcome by defect size in this data set.

The CDH Registry was formed to allow collection and analysis of data on presentation, treatment, and outcome of CDH from a large number of centers. Registries have proven to be a good way of collecting data on rare conditions and of mitigating institutional bias in patient selection and treatment. As with any data from registries, there are caveats to their interpretation. The database is observational, and conclusions about therapies should be interpreted cautiously. The data are collected from institutions that differ significantly in their patient recruitment and selection. These differences are especially important when interpreting patients in the nonrepaired category because criteria for "nonsalvageable" patients vary between centers. Many infants with severe cardiac and chromosomal anomalies did not undergo repair making the true impact of these factors difficult to determine. Furthermore, these data only represent outcome to hospital transfer or discharge; both long-term survival and morbidity are likely to be worse.30–33 Nonetheless, these data do represent a significant collection of patients with an uncommon disease process.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Approximately two thirds of liveborn infants with CDH will survive to hospital discharge. Outcome for these infants is largely dependent on the size of the diaphragm defect. Future efforts should be directed to accurately determine defect size preoperatively or optimally prenatally to correlate the defect size with actual lung hypoplasia. Ultimately, it would be ideal to stage patients prenatally by the severity of lung hypoplasia using a system validated across multiple institutions. Additional characterization of the patients who do not undergo diaphragmatic hernia repair would also be useful. Identifying patients with small defects before intervention will allow those patients to be treated with less invasive therapies, reserving the high-risk interventions for those with more severe disease. Improved accuracy in categorizing patients will also help in counseling families about survival, expected lengths of stay in the hospital, and long-term outcomes.


   ACKNOWLEDGMENTS
 
This work was supported in part by National Institutes of Health grants K24RR17050 and M01RR002558.

The centers that contributed to the CDH Registry were Arnold Palmer Hospital for Women and Children (Orlando, FL), Astrid Lindgren Children's Hospital (Stockholm, Sweden), Central Hospital Aichi Prefectural Colony (Kasugai Aichi, Japan), Children's Hospital at Carolinas Medical Center (Charlotte, NC), Children's Hospital Boston (Boston, MA), Children's Hospital of Akron (Akron, OH), Children's Hospital of Alabama (Birmingham, AL), Children's Hospital of Illinois (Peoria, IL), Children's Hospital of Los Angeles (Los Angeles, CA), Children's Hospital of Minneapolis (Minneapolis, MN), Children's Hospital of Oakland (Oakland, CA), Children's Hospital of Oklahoma (Oklahoma City, OK), Children's Hospital of Wisconsin (Milwaukee, WI), Cincinnati Children's Hospital Medical Center (Cincinnati, OH), Cleveland Clinic Foundation-Children's Hospital (Cleveland, OH), Columbus Children's Hospital, Columbus, OH), DeVos Children's Hospital (Grand Rapids, MI), Emory University (Atlanta, GA), Hershey Medical Center (Hershey, PA), James Whitcomb Riley Children's Hospital (Indianapolis, IN), Kosair Children's Hospital (Louisville, KY), Legacy Emanuel Children's Hospital (Portland, OR), Loma Linda University Children's Hospital (Loma Linda, CA), Lucile Salter Packard Children's Hospital (Palo Alto, CA), Mattel Children's Hospital at UCLA (Los Angeles, CA), Medical College of Georgia (Augusta, GA), Children's Memorial Hermann Hospital (Houston, TX), Miami Valley Hospital (Dayton, OH), National Center for Child Health and Development (Tokyo, Japan), Oespedale Pediatrico Bambino Gesu (Rome, Italy), Oespedale Riunite Bergamo (Bergamo, Italy), Osaka University Graduate School of Medicine (Osaka, Japan), Phoenix Children's Hospital (Phoenix, AZ), Rainbow Babies & Children's Hospital (Cleveland, OH), Royal Alexandra Hospital (Edmonton, Alberta, Canada), Royal Children's Hospital Parkville (Victoria, Australia), Royal Hospital for Sick Children (Glasgow, Yorkhill, Scotland), San Diego Children's Hospital (San Diego, CA), Santa Rosa Children's Hospital (San Antonio, TX), Shands Children's Hospital/University of Florida (Gainesville, FL), Sophia Children's Hospital (Rotterdam, Netherlands), St Francis Children's Hospital (Tulsa, OK), St Joseph's Hospital and Medical Center (Phoenix, AZ), Strong Children's Hospital (Rochester, NY), Sydney Children's Hospital (Randwick NWS, Australia), Hospital for Sick Children (Toronto, Ontario, Canada), University of Michigan Medical Center (Ann Arbor, MI), University of Nebraska Medical Center (Omaha, NE), University of Texas Medical Branch (Galveston, TX), University of Virginia Health System (Charlottesville, VA), and Vanderbilt Children's Hospital (Nashville, TN).

The Congenital Diaphragmatic Hernia Study Group writing committee is as follows: Kevin P. Lally, MD, MS (University of Texas Medical School and Children's Memorial Hermann Hospital), Pamela A. Lally, MD (University of Texas Medical School and Children's Memorial Hermann Hospital), Robert E. Lasky, PhD (University of Texas Medical School and Children's Memorial Hermann Hospital), Dick Tibboel, MD (Sophia Children's Hospital), Tom Jaksic, MD, PhD (Children's Hospital Boston), Jay M. Wilson, MD (Children's Hospital Boston), Bjorn Frenckner, MD (Astrid Lindgren Children's Hospital), Krista P. Van Meurs, MD (Stanford University School of Medicine and Lucile Packard Children's Hospital), Desmond J. Bohn, MD (Hospital for Sick Children), Carl F. Davis, MD (Royal Hospital for Sick Children), and Ronald B. Hirschl, MD (University of Michigan).


   FOOTNOTES
 
Accepted Feb 1, 2007.

Address correspondence to Kevin P. Lally, MD, MS, Department of Surgery, University of Texas Health Sciences Center, 6431 Fannin St, Suite 5.258, Houston, TX 77030. E-mail: kevin.p.lally{at}uth.tmc.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.

* See "Acknowledgments" for complete listing of writing committee. Back


   REFERENCES
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 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Wenstrom KD, Weiner CP, Hanson JW. A five-year statewide experience with congenital diaphragmatic hernia. Am J Obstet Gynecol. 1991;165 :838 –842[ISI][Medline]
  2. Langham MR Jr, Kays DW, Ledbetter DJ, Frentzen B, Sanford LL, Richards DS. Congenital diaphragmatic hernia: epidemiology and outcome. Clin Perinatol. 1996;23 :671 –688[ISI][Medline]
  3. Wilson JM, Lund DP, Lillehei CW, Vacanti JP. Congenital diaphragmatic hernia: a tale of two cities: the Boston experience. J Pediatr Surg. 1997;32 :401 –405[CrossRef][ISI][Medline]
  4. Mishalany HG, Nakada K, Woolley MM. Congenital diaphragmatic hernias: eleven years' experience. Arch Surg. 1979;114 :1118 –1123[Abstract]
  5. Harrison MR, Adzick NS, Longaker MT, et al. Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax. N Engl J Med. 1990;322 :1582 –1584[ISI][Medline]
  6. Harrison MR, Keller RL, Hawgood SB, et al. A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med. 2003;349 :1916 –1924[Abstract/Free Full Text]
  7. Cass DL. Fetal surgery for congenital diaphragmatic hernia: the North American experience. Semin Perinatol. 2005;29 :104 –111[CrossRef][ISI][Medline]
  8. Boloker J, Bateman DA, Wung JT, Stolar CJ. Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/elective repair. J Pediatr Surg. 2002;37 :357 –366[CrossRef][ISI][Medline]
  9. Kays DW, Langham MR, Jr, Ledbetter DJ, Talbert JL. Detrimental effects of standard medical therapy in congenital diaphragmatic hernia. Ann Surg. 1999;230 :340 –348[CrossRef][ISI][Medline]
  10. Javid PJ, Jaksic T, Skarsgard ED, Lee S; Canadian Neonatal Network. Survival rate in congenital diaphragmatic hernia: the experience of the Canadian Neonatal Network. J Pediatr Surg. 2004;39 :657 –660[CrossRef][ISI][Medline]
  11. Stege G, Fenton A, Jaffray B. Nihilism in the 1990s: the true mortality of congenital diaphragmatic hernia. Pediatrics. 2003;112 :532 –535[Abstract/Free Full Text]
  12. Clark RH, Hardin WD Jr, Hirschl RB, et al. Current surgical management of congenital diaphragmatic hernia: a report from the congenital diaphragmatic study group. J Pediatr Surg. 1998;33 :1004 –1009[CrossRef][ISI][Medline]
  13. Metkus AP, Esserman L, Sola A, Harrison MR, Adzick NS. Cost per anomaly: what does a diaphragmatic hernia cost? J Pediatr Surg. 1995;30 :226 –230[CrossRef][ISI][Medline]
  14. Newman KD, Anderson KD, Van Meurs K, Parson S, Loe W, Short B. Extracorporeal membrane oxygenation and congenital diaphragmatic hernia: should any infant be excluded? J Pediatr Surg. 1990;25 :1048 –1052[CrossRef][ISI][Medline]
  15. Stolar C, Dillon P, Reyes C. Selective use of extracorporeal membrane oxygenation in the management of congenital diaphragmatic hernia. J Pediatr Surg. 1998;23 :207 –211
  16. Skari H, Bjornland K, Frenckner B, et al. Congenital diaphragmatic hernia in Scandinavia from 1995 to 1998: predictors of mortality. J Pediatr Surg. 2002;37 :1269 –1275[CrossRef][ISI][Medline]
  17. The Congenital Diaphragmatic Hernia Study Group. Estimating disease severity of congenital diaphragmatic hernia in the first 5 minutes of life. J Pediatr Surg. 2001;36 :141 –145[CrossRef][ISI][Medline]
  18. Holt PD, Arkovitz MS, Berdon WE, Stolar CJ. Newborns with diaphragmatic hernia: initial chest radiography does not have a role in predicting clinical outcome. Pediatr Radiol. 2004;34 :462 –464[CrossRef][ISI][Medline]
  19. Boix-Ochoa J, Peguero G, Seijo G, Natal A, Canals J. Acid-base balance and blood gases in prognosis and therapy of congenital diaphragmatic hernia. J Pediatr Surg. 1974;9 :49 –57[CrossRef][ISI][Medline]
  20. Skari H, Bjornland, Haugen G, Egeland T, Emblem R. Congenital diaphragmatic hernia: a meta-analysis of mortality factors. J Pediatr Surg. 2000;35 :1187 –1197[CrossRef][ISI][Medline]
  21. Singh SJ, Cummins GE, Cohen RC, et al. Adverse outcome of congenital diaphragmatic hernia is determined by diaphragmatic agenesis, not by antenatal diagnosis. J Pediatr Surg. 1999;34 :1740 –1742[CrossRef][ISI][Medline]
  22. Tsang TM, Tam PK, Dudley NE, Stevens J. Diaphragmatic agenesis as a distinct clinical entity. J Pediatr Surg. 1994;29 :1439 –1441[CrossRef][ISI][Medline]
  23. Baglaj M, Spicer R, Ashworth M. Unilateral agenesis of the diaphragm: a separate entity or an extremely large defect? Pediatr Surg Int. 1999;15 :206 –209[CrossRef][ISI][Medline]
  24. Eichelberger MR, Kettrick RG, Hoelzer DJ, Swedlow DB, Schnaufer L. Agenesis of the left diaphragm: surgical repair and physiologic consequences. J Pediatr Surg. 1980;15 :395 –397[CrossRef][ISI][Medline]
  25. Fumino S, Shimotake T, Kume Y, et al. A clinical analysis of prognostic parameters of survival in children with congenital diaphragmatic hernia. Eur J Pediatr Surg. 2005;15 :399 –403[CrossRef][ISI][Medline]
  26. Lally KP, Lally PA, Van Meurs KP, et al. Treatment evolution in high-risk congenital diaphragmatic hernia: ten years' experience with diaphragmatic agenesis. Ann Surg. 2006;244 :505 –513[ISI][Medline]
  27. Keijzer R, Liu J, Deimling J, Tibboel D, Post M. Dual-hit hypothesis explains pulmonary hypoplasia in the nitrofen model of congenital diaphragmatic hernia. Am J Pathol. 2000;156 :1299 –1306[Abstract/Free Full Text]
  28. Loff S, Wirth H, Jester I, et al. Implantation of a cone-shaped double-fixed patch increases abdominal space and prevents recurrence of large defects in congenital diaphragmatic hernia. J Pediatr Surg. 2005;40 :1701 –1705[CrossRef][ISI][Medline]
  29. Davis PJ, Firmin RK, Manktelow B, et al. Long-term outcome following extracorporeal membrane oxygenation for congenital diaphragmatic hernia: the UK experience. J Pediatr. 2004;144 :309 –315[CrossRef][ISI][Medline]
  30. Cortes RA, Keller RL, Townsend T, et al. Survival of severe congenital diaphragmatic hernia has morbid consequences. J Pediatr Surg. 2005;40 :36 –45[CrossRef][ISI][Medline]
  31. Trachsel D, Selvadurai H, Bohn D, Langer JC, Coates AL. Long-term pulmonary morbidity in survivors of congenital diaphragmatic hernia. Pediatr Pulmonol. 2005;39 :433 –439[CrossRef][ISI][Medline]
  32. Chiu PP, Sauer C, Mihailovic A, et al. The price of success in the management of congenital diaphragmatic hernia: is improved survival accompanied by an increase in long-term morbidity? J Pediatr Surg. 2006;41 :888 –892[CrossRef][ISI][Medline]
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics




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