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Nihilism in the 1990s: The True Mortality of Congenital Diaphragmatic Hernia

From the Department of Child Health, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom

	ABSTRACT

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Objective. Reported survival in congenital diaphragmatic hernia (CDH) fails to allow for case selection bias. This study reports the incidence of CDH in a geographically defined population over 11 years and assesses the effect of new therapies (high-frequency oscillatory ventilation, extracorporeal membrane oxygenation, inhaled nitric oxide, and delayed surgery) on survival when case selection is avoided.

Methods. A retrospective review of cases from a regional case registry, the Northern Region Congenital Anomaly Survey, was conducted.

Results. A total of 185 cases were identified. Mortality was 62% and did not vary significantly during the study period. Mortality was unaffected by the introduction of new therapies. There was a significant inverse correlation between the rate of elective termination and survival of live borns. The presence of an additional anomaly increased mortality to 79%.

Conclusions. The mortality of CDH when complete case ascertainment is achieved is unaffected by new therapies. The survival rate is principally determined by the rate of antenatal termination and the incidence of associated anomalies. Reports of improved survival of CDH should be interpreted with caution, as variations in outcome are more likely to be explained by case selection artifact.

Key Words: congenital diaphragmatic hernia • survival

Abbreviations: CDH, congenital diaphragmatic hernia • ECMO, extracorporeal membrane oxygenation • HFOV, high-frequency oscillatory ventilation • iNO, inhaled nitric oxide • CI, confidence interval

Therapies used to treat congenital diaphragmatic hernia (CDH) include delayed surgery,¹ extracorporeal membrane oxygenation (ECMO),² high-frequency oscillatory ventilation (HFOV),³ inhaled nitric oxide (iNO),⁴ and surfactant⁵ with reports of improved survival. However, the hidden mortality either by antenatal termination or by postnatal death before transfer to referral centers is ignored.

The United Kingdom’s Northern health region is a geographically defined population of 3.2 million with 34 000 annual live births, within which the Northern Region Congenital Abnormality Survey registers infants with significant congenital abnormalities. The aims of this study were to identify variables that influenced survival in this population during a period when several new therapies were introduced.

	METHODS

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Cases were identified from the Northern Region Congenital Abnormality Survey database for the period January 1991 to December 2001, with case note and postmortem record review. Data retrieved included antenatal detection or termination; place of birth; age at onset of symptoms; side of defect; presence of associated anomalies; age at surgery; use of surfactant, iNO, HFOV, and ECMO; and outcome.

Outcome was classified as spontaneous abortion, elective termination, antepartum stillbirth, early neonatal death (death between birth and 24 hours), late neonatal death (death between 1 and 7 days), postnatal death (death between 7 days and 1 year), and survival to 1 year of age. Treatment of infants with congenital diaphragmatic hernia displaying respiratory distress at birth included intubation, paralysis, and ventilation, with manipulation of ventilator settings according to clinical criteria. New therapies were first used in the management of CDH as follows: HFOV (June 1995), iNO (October 1995), and surfactant (March 1998). After a prospective trial,⁶ delayed surgery was accepted as normal practice in 1993. ECMO was used between December 1994 and June 1999.

Statistical analysis used the ² test. Regression analysis was performed with the Minitab statistical package.

	RESULTS

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A total of 185 cases of CDH were identified (incidence 4.91/10 000 live births), 129 (70%) of whom were born alive. The termination rate (24%), spontaneous abortion rate (3%), and stillbirth rate (3%) did not vary during the study period (² = 10.0; P = .4). Of the 44 fetuses that were terminated electively, 32 had additional anomalies. Of the 58 live borns who subsequently died, 42 did so within the first 24 hours, 11 between 24 hours and 7 days, and 5 between 1 week and 1 year. Sixteen deaths occurred in peripheral hospitals. Fifty-two infants were born in the surgical center, 75 in peripheral hospitals, and 2 at home. Survival was 44%, 63%, and 100%, respectively. The better survival in peripheral hospitals was not statistically significant (² = 3.5; P = .06). Overall mortality was 62%, or 114 of 185 (95% confidence interval [CI]: 52.4%–69%), and did not vary during the period (² = 9.2; P = .5; Fig 1).

View larger version (25K): [in this window] [in a new window]   Fig 1. Annual mortality (%) of pregnancies involving CDH. Time periods of the new therapies are shown by the horizontal boxes.

View larger version (10K): [in this window] [in a new window]   Fig 2. The relationship between antenatal death and survival of liveborn infants with CDH.

Effect of New Therapies
Before the use of ECMO, there were 69 cases; 51 were live births, with 22 surviving (68% overall mortality, 57% mortality of live births). During the period when ECMO was available, there were 73 cases; 48 were live births, 31 of whom survived (58% overall mortality, 45% mortality of live births). Six received ECMO, and there were 2 survivors. Since discontinuing ECMO, there have been 43 cases, 30 live births, and 18 survivors (58% overall mortality, 40% mortality of live births). There was no statistical difference in survival between any period when considering survival of all cases. When only live births are considered, the difference between the pre-ECMO and ECMO periods is significant (² = 4.5; P = .03), but there is no difference in survival since discontinuing the use of ECMO (² = 0.1; P = .7; 95% CIs for survival of live borns: pre-ECMO: 29.2%–78.8%; ECMO: 2.9%–66.6%; post-ECMO: –7.9% to 83.9%; Table 1, Fig 1).

	DISCUSSION

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We have found that survival for CDH has not improved in the past 10 years, despite new therapies. Extrapolated to England and Wales, this suggests that 298 fetuses with CDH can be expected annually and that 184 of them will die. Reports of improved survival for infants with CDH can be explained either by case selection bias^7–10 or by the use of inappropriate control groups.^2,11–14 CDH is an unusual congenital condition for the following reasons.

First, half of the cases are not detected by antenatal scanning,^15–17 leading to the birth of a infant with a life-threatening condition in an unprepared obstetric unit. Some die immediately after birth, are not subject to autopsy, and therefore remain undiagnosed; the mortality is worse than we have demonstrated.^18,19 Time of death was largely in the first 24 hours, with 28% of liveborn infants who died doing so in peripheral hospitals. Only infants with stable pathophysiology survive to transfer, resulting in case selection bias. For eliminating this bias, infants who are delivered and die in peripheral hospitals or are terminated electively must be identified. When this is done, the mortality rate is unchanging across different decades. Thus, although we report a mortality rate of 62% in the 1990s, in the 1980s, Wenstrom et al²⁰ recorded a 58% mortality, the current author reported 66% mortality,¹⁹ and Harrison et al²¹ recorded 66% for the early 1970s. In the early 1990s, Harrison revisited the subject of hidden mortality and reported 58% for antenatally diagnosed cases in an ECMO center.¹⁸ The close approximation of these figures suggests that without case selection bias, survival is unchanged. Because the new therapies that we have studied treat pulmonary hypertension and cannot affect pulmonary hypoplasia, this is unsurprising.

The second confounding feature of reports of survival in CDH is the unreliability of historical controls. In our study, the introduction of ECMO led to a fall in mortality in comparison with the previous period. However, having ceased to offer ECMO therapy, improved survival persisted. Comparison of current results with previous eras takes no account of general improvements in care or changes in referral patterns. The use of historical controls misleads investigators to believe that changes in outcome are the direct result of new therapies, without the rigor of prospective randomization of such therapies. Despite this, the majority of studies reporting improved survival of CDH continue to use historical controls from the same institution.^{2,11,14,22–25}

Strict criteria for the use of ECMO led to 6 infants from 48 cases (12.5%) receiving this therapy. The experience of Great Ormond Street Hospital, using the same criteria, was 11 (15%) of 72 infants receiving ECMO.²⁶ We ceased to offer this therapy because of poor outcome. Reports from North America record up to two thirds of infants with CDH receiving ECMO.^22,27 Whether this reflects severe pathology or different criteria for use of this therapy is speculative.

The 2 factors that clearly relate to postnatal mortality are the rate of termination and the presence of additional anomalies. The explanation of the inverse relationship between termination and postnatal survival is probably that the cases that are detected antenatally have more severe pathology. Previous reports have identified the poor prognosis of antenatally detected cases,^7,8,18 but this is the first series in which the direct relationship between the rate of antenatal termination and survival of live births has been documented. It is noticeable that when the effects of therapies are tabulated, for each apparent improvement in survival, there is a concomitant increase in the rate of antenatal death (Table 1). Although we have analyzed these therapies as independent variables, we recognize that they were not introduced independent of each other and that analysis by use of a statistical model would be appropriate. It is unlikely that any of the therapies that we have analyzed would be independently significant taking into account the 2 principal variables that we have identified of antenatal termination and the rate of associated anomalies. We urge all future reports to give details both of numbers dying in peripheral hospitals and of termination rates. Apparent improvements in survival are likely to have their explanation in these 2 areas.

With an additional anomaly, mortality is 79%, which is in accordance with previous reports.^28–30 Why these anomalies should have such a devastating effect on survival is less clear. However, in terms of antenatal counseling, obstetricians, pediatricians, and pediatric surgeons should be aware of the implications of such an association.

This study has shown that when complete ascertainment of cases is attempted, there has been no improvement in the outcome of CDH in the past decade. The 2 factors that are related to survival are the rate of antenatal termination and the presence of associated anomalies. New therapies continue to be promulgated for this condition.³¹ We urge caution in accepting reports of improved survival after the introduction of new therapies where rates of antenatal termination and details of deaths in peripheral hospitals are omitted or where historical controls are used. Such reports have profound flaws.

	ACKNOWLEDGMENTS

 
We are grateful to Professor J. N. Mathews for comments on the statistical sections and to Professor Dan Young, whose comments suggested the title.

	FOOTNOTES

 
Received for publication Jan 2, 2003; Accepted Mar 19, 2003.

Address correspondence to Bruce Jaffray, ChM, Department of Child Health, Sir James Spence Institute, University of Newcastle upon Tyne, Queen Victoria Rd, Newcastle upon Tyne NE1 4LP, United Kingdom. E-mail: bruce.jaffray{at}ncl.ac.uk

	REFERENCES

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1. Goh DW, Drake DP, Brereton RJ, et al. Delayed surgery for congenital diaphragmatic hernia. Br J Surg.1992; 79 :644 –646[Medline]
2. Weber TR, Kountzman B, Dillon PA, et al. Improved survival in congenital diaphragmatic hernia with evolving therapeutic strategies. Arch Surg.1998; 133 :498 –502[Abstract/Free Full Text]
3. Miguet D, Claris O, Lapillonne A, et al. Preoperative stabilization using high-frequency oscillatory ventilation in the management of congenital diaphragmatic hernia. Crit Care Med.1994; 22(9 suppl) :S77 –S82[ISI][Medline]
4. Somaschini M, Locatelli G, Salvoni L, et al. Impact of new treatments for respiratory failure on outcome of infants with congenital diaphragmatic hernia. Eur J Pediatr.1999; 158 :780 –784[CrossRef][Medline]
5. Lotze A, Knight GR, Anderson KD, et al. Surfactant (beractant) therapy for infants with congenital diaphragmatic hernia on ECMO: evidence of persistent surfactant deficiency. J Pediatr Surg.1994; 29 :407 –412[CrossRef][ISI][Medline]
6. de-la-Hunt MN, Madden N, Scott JE, et al. Is delayed surgery really better for congenital diaphragmatic hernia? A prospective randomized clinical trial. J Pediatr Surg.1996; 31 :1554 –1556[Medline]
7. Adzick NS, Vacanti JP, Lillehei CW, et al. Fetal diaphragmatic hernia: ultrasound diagnosis and clinical outcome in 38 cases. J Pediatr Surg.1989; 24 :654 –658[ISI][Medline]
8. Adzick NS, Harrison MR, Glick PL, et al. Diaphragmatic hernia in the fetus: prenatal diagnosis and outcome in 94 cases. J Pediatr Surg.1985; 20 :357 –361[CrossRef][ISI][Medline]
9. Al-Shanafey S, Giacomantonio M, Henteleff H. Congenital diaphragmatic hernia: experience without extracorporeal membrane oxygenation. Pediatr Surg Int.2002; 18 :28 –31[CrossRef][Medline]
10. Charlton AJ, Bruce J, Davenport M. Timing of surgery in congenital diaphragmatic hernia. Low mortality after pre-operative stabilisation. Anaesthesia.1991; 46 :820 –823[ISI][Medline]
11. vd Staak FHJM, de Haan AJF, Geven WB, et al. Improving survival for patients with high-risk congenital diaphragmatic hernia by using extracorporeal membrane oxygenation. J Pediatr Surg.1995; 30 :1463 –1467[CrossRef][ISI][Medline]
12. Breaux CW, Rouse TM, Cain WS, et al. Improved survival of patients with congenital diaphragmatic hernia utilizing a strategy of delayed repair after medical and/or extracorporeal membrane oxygenation stabilisation. J Pediatr Surg.1991; 26 :333 –338[Medline]
13. Weber TR, Connors RH, Pennington DG, et al. Neonatal diaphragmatic hernia. An improving outlook with extracorporeal membrane oxygenation. Arch Surg.1987; 122 :615 –618[Abstract]
14. Lessin MS, Thompson IM, Deprez MF, et al. Congenital diaphragmatic hernia with or without extracorporeal membrane oxygenation: are we making progress? J Am Coll Surg.1995; 181 :65 –71[ISI][Medline]
15. Shaw KS, Filiatrault D, Yazbeck S, et al. Improved survival for congenital diaphragmatic hernia, based on prenatal ultrasound diagnosis and referral to a combined obstetric-pediatric surgical center. J Pediatr Surg.1994; 29 :1268 –1269[Medline]
16. Lewis DA, Reickert C, Bowerman R, et al. Prenatal ultrasonography frequently fails to diagnose congenital diaphragmatic hernia. J Pediatr Surg.1997; 32 :352 –356[CrossRef][ISI][Medline]
17. Garne E, Haeusler M, Barisic I, et al. Congenital diaphragmatic hernia: evaluation of prenatal diagnosis in 20 European regions. Ultrasound Obstet Gynecol.2002; 19 :329 –333[Medline]
18. Harrison MR, Adzick NS, Estes JM, et al. A prospective study of the outcome for fetuses with diaphragmatic hernia. JAMA.1994; 271 :382 –384[Abstract]
19. Jaffray B, MacKinlay GA. Real and apparent mortality from congenital diaphragmatic hernia. Br J Surg.1996; 83 :79 –82[Medline]
20. Wenstrom KD, Weiner CP, Hanson JW. A five-year statewide experience with congenital diaphragmatic hernia. Am J Obstet Gynecol.1991; 165 :838 –842[Medline]
21. Harrison MR, Bjordal RI, Langmark F, et al. Congenital diaphragmatic hernia: the hidden mortality. J Pediatr Surg.1978; 13 :227 –230[ISI][Medline]
22. D’Agostino JA, Bernbaum JC, Gerdes M, et al. Outcome for infants with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: the first year. J Pediatr Surg.1995; 30 :10 –15[CrossRef][Medline]
23. Ssemakula N, Stewart DL, Goldsmith LJ, et al. Survival of patients with congenital diaphragmatic hernia during the ECMO era: an 11-year experience. J Pediatr Surg.1997; 32 :1683 –1689[CrossRef][ISI][Medline]
24. Desfrere L, Jarreau PH, Dommergues M, et al. Impact of delayed repair and elective high-frequency oscillatory ventilation on survival of antenatally diagnosed congenital diaphragmatic hernia: first application of these strategies in the more "severe" subgroup of antenatally diagnosed newborns. Intensive Care Med.2000; 26 :934 –941[CrossRef][ISI][Medline]
25. Cacciari A, Ruggeri G, Mordenti M, et al. High-frequency oscillatory ventilation versus conventional mechanical ventilation in congenital diaphragmatic hernia. Eur J Pediatr Surg.2001; 11 :3 –7[Medline]
26. Schoeman L, Pierro A, Macrae D, et al. Late death after extracorporeal membrane oxygenation for congenital diaphragmatic hernia. J Pediatr Surg.1999; 34 :357 –359[Medline]
27. Wilson JM, Lund DP, Lillehei CW, et al. Delayed repair and preoperative ECMO does not improve survival in high-risk congenital diaphragmatic hernia. J Pediatr Surg.1992; 27 :368 –372[CrossRef][ISI][Medline]
28. Sweed Y, Puri P. Congenital diaphragmatic hernia: influence of associated malformations on survival. Arch Dis Child.1993; 69 :68 –70[Abstract]
29. Cohen MS, Rychik J, Bush DM, et al. Influence of congenital heart disease on survival in children with congenital diaphragmatic hernia. J Pediatr.2002; 141 :25 –30[Medline]
30. Witters I, Legius E, Moerman P, et al. Associated malformations and chromosomal anomalies in 42 cases of prenatally diagnosed diaphragmatic hernia. Am J Med Genet.2001; 103 :278 –282[CrossRef][Medline]
31. Fauza DO, Hirschl RB, Wilson JM. Continuous intrapulmonary distension with perfluorocarbon accelerates lung growth in infants with congenital diaphragmatic hernia: initial experience. J Pediatr Surg.2001; 36 :1237 –1240[CrossRef][Medline]

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This Article Abstract Full Text (PDF) P3Rs: Submit a response Alert me when this article is cited Alert me when P3Rs are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via ISI Web of Science (90) Citing Articles via Google Scholar Google Scholar Articles by Stege, G. Articles by Jaffray, B. Search for Related Content PubMed PubMed Citation Articles by Stege, G. Articles by Jaffray, B. Related Collections Surgery

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