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Right congenital diaphragmatic hernia: prenatal assessment and outcome
Right Congenital Diaphragmatic Hernia: Prenatal Assessment and Outcome By Holly L. Hedrick, Timothy M. Crombleholme, Alan W. Flake, Michael L. Nance, Daniel von Allmen, Lori J. Howell, Mark P. Johnson, R. Douglas Wilson, and N. Scott Adzick Philadelphia, Pennsylvania
Purpose: To understand the natural history of right congenital diaphragmatic hernia (CDH), the authors retrospectively reviewed 27 cases of right CDH that presented for prenatal evaluation or postnatal treatment. Methods: Between 1995 and September 2002, a total of 194 cases of fetal CDH were evaluated and included 22 rightsided defects. The authors reviewed prenatal diagnostic studies (ultrasound scan, magnetic resonance imaging [MRI] echocardiography) and pre- and postnatal outcomes in these 22 cases of right CDH. Five additional cases of right CDH without a prenatal diagnosis were reviewed. Results: The mean gestational age at evaluation was 26.1 weeks. The lung area to head circumference ratio (LHR) ranged from 0.32 to 2.5. In all cases, the fetal liver was herniated into the right chest. Associated anomalies were common. There were no karyotype abnormalities (17 of 22 tested). There were 4 terminations. Nine of the 18 (50%) continuing pregnancies had polyhydramnios, premature rupture of membranes, or preterm labor. The mean gestational age at birth was 36.8 weeks. One patient underwent
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IGHT-SIDED DEFECTS account for 8% to 21% of all cases of congenital diaphragmatic hernia (CDH).1-3 The current literature on right CDH and severity is contradictory. Several studies have described an increased mortality rate in right CDH compared with left CDH,3-9,10 whereas others have found the opposite effect,11 or no influence at all.1,12 To better understand the challenges facing the infant with the diagnosis of right CDH, we retrospectively reviewed 27 consecutive cases (22 prenatal diagnosis, 5 postnatal diagnosis) presenting to our institution over a 7-year period.
tracheal occlusion at 27 weeks, and 2 patients died before postnatal repair. Overall survival rate (22 prenatal plus 5 postnatal diagnoses) was 19 of 27 (70%). Postnatal survival rate was 19 of 23 (83%). A Gore-tex (W. L. Gore and Associates, Flagstaff, AZ) patch was utilized in 14 of 21 neonates undergoing surgery. Twelve of 23 (52%) required extracorporeal membrane oxygenation (ECMO) with a 75% survival rate. Significant morbidity occurred in 10 of 19 survivors and included neurologic sequelae in 6 of 19 (32%). Conclusions: MRI was helpful in the determination of liver position and confirmation of diagnosis. The high incidence of preterm complications, frequent need for ECMO, and high prevalence of comorbidities are indicative of the severity of this CDH population and warrant close prenatal surveillance and delivery at a tertiary care center with ECMO capability. J Pediatr Surg 39:319-323. © 2004 Elsevier Inc. All rights reserved. INDEX WORDS: Right congenital diaphragmatic hernia, prenatal diagnosis, outcome.
(1) termination of pregnancy if gestational age (GA) less than 24 weeks, (2) standard postnatal care, and (3) fetal tracheal occlusion (before January 1999) if the fetus and mother fit criteria. Because of the risk of intrauterine fetal demise,1 obstetric management included ultrasound surveillance and weekly nonstress testing beginning at 30 weeks GA. Several of these cases have been included in previously published reports.13-15 This study was approved by the Committee for Protection of Human Subjects Institutional Review Board at CHOP (IRB #20024-2786).
Prenatal Studies
MATERIALS AND METHODS
The left lung area to head circumference ratio (LHR) was calculated from an ultrasonographic cross-sectional image of the fetal thorax at the level of the 4-chamber view of the heart and consisted of the 2-dimensional area (greatest anteroposterior and lateral dimensions of
From September 1995 through September 2002, 22 fetuses with right congenital diaphragmatic hernia (CDH; from a total of 194 CDH cases) were evaluated at The Center for Fetal Diagnosis and Treatment at the Children’s Hospital of Philadelphia (CHOP). During the same period, 5 additional cases of right CDH without a prenatal diagnosis were admitted to CHOP. We retrospectively reviewed the maternal prenatal charts, postnatal hospital charts, outpatient office charts, and neonatal follow-up records for a total of 27 cases (22 prenatal diagnosis, 5 postnatal diagnosis) of right CDH. The initial prenatal evaluation at CHOP included detailed fetal ultrasonography, fetal ultrafast magnetic resonance imaging (MRI), and fetal echocardiography. After evaluation, all patients underwent nondirective counseling for management options. The options included
From The Center for Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia, Philadelphia, PA. Presented at the 34th Annual Meeting of the American Pediatric Surgical Association, Fort Lauderdale, Florida, May 25-28, 2003. Address reprint requests to Holly L. Hedrick, MD, The Center for Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia, 34th St and Civic Center Boulevard, Philadelphia, PA 191044399. © 2004 Elsevier Inc. All rights reserved. 0022-3468/04/3903-0013$30.00/0 doi:10.1016/j.jpedsurg.2003.11.006
Journal of Pediatric Surgery, Vol 39, No 3 (March), 2004: pp 319-323
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the left lung) divided by the head circumference.16 LHRs were measured at the presenting GA and then repeated between 23 and 25 weeks’ gestation in 7 of the pregnancies because this is the time period used for prognosis determination in left CDH.14 Ultrafast fetal MRI was obtained to confirm the diagnosis, further delineate liver position, visible lung tissue, and the presence of other anomalies.15 Fetal echocardiography assessed for the presence of coexistent congenital heart anomalies.13
Table 1. Summary of Right CDH Overall Outcomes Termination Fetal demise Neonatal demise Postnatal survival ECMO Neonatal demise Survival
4 0 4/23 (17%) 19/23 (83%) 12/23 (52%) 3/12 (25%) 9/12 (75%)
Criteria for Tracheal Occlusion Criteria for consideration of tracheal occlusion required the absence of maternal risk factors for anesthesia or surgery, a singleton pregnancy with normal karyotype analysis, diagnosis before 25 weeks’ gestation, and the absence of significant associated anomalies. For right-sided CDH, the criteria included massive herniation of the liver into the chest with inability to visualize significant contralateral lung tissue. The details of the tracheal occlusion procedure and maternal postoperative care have been discussed in detail in a prior report.14
Postnatal Management Postnatal management in the neonatal intensive care unit included the use of pressure ventilation, high-frequency oscillatory ventilation, and inhaled nitric oxide. If these therapies failed, then extracorporeal membrane oxygenation (ECMO) was used for salvage in neonates older than 34 weeks’ gestation and weighing greater than 2 kg. Repair of the CDH was performed in a delayed fashion once medical stability was achieved, the pulmonary vasculature became less reactive (absence of shunting), or weaning from ECMO was anticipated. The operating surgeon determined the need for patch placement based on the size of the diaphragmatic defect.
RESULTS
Patient Population and Associated Anomalies For the 22 cases of right CDH diagnosed before birth, the mean gestational age at presentation was 26.1 weeks (range, 19 to 36 weeks). There were no karyotype abnormalities in 17 of 22 who underwent amniocentesis. In 2 patients, the referring diagnosis of a fetal lung lesion was corrected to right CDH. An additional patient was misdiagnosed as a cystic fetal lung lesion by ultrasound scan in 1995 before the use of ultrafast fetal MRI. In all other cases, the fetal liver was herniated into the right chest by fetal MRI. The lung area to head circumference ratio (LHR) ranged from 0.32 to 2.5, and was obtained at 19 to 36 weeks. Only 7 fetuses had ultrasound examinations at 23 to 25 weeks. The contralateral lung was too small to visualize in 2 of these cases. In the remaining 5 cases, mean LHR was 0.8 (range, 0.66 to 1.0). One of these fetuses underwent fetal tracheal occlusion and survived. Other outcomes in the group undergoing ultrasound examination at 23 to 25 weeks were termination (n ⫽ 2), neonatal death (n ⫽ 1), survival with ECMO (n ⫽ 2), and survival without ECMO (n ⫽ 1). Associated anomalies were common. Cardiovascular anomalies included ventricular septal defect (n ⫽ 3), pulmonary artery stenosis (n ⫽ 4), right anomalous pulmonary venous return (n ⫽ 1), and interrupted infe-
rior vena cava (n ⫽ 1). Central nervous system anomalies included microcephaly and Dandy Walker malformation. Three fetuses had associated extralobar pulmonary sequestrations. Gastrointestinal anomalies included choledochal cyst (n ⫽ 1), Meckel’s diverticulum (n ⫽ 1), and omphalocele (n ⫽ 1). Genitourinary anomalies included hydronephrosis (n ⫽ 3), horseshoe kidney (n ⫽ 1), and undescended testes (n ⫽ 1). One fetus had transient hydrops secondary to maternal parvovirus infection. Overall Outcomes Outcomes (Table 1) in the prenatal diagnosis group included 4 terminations, 3 neonatal deaths (2 with ECMO), and 15 survivors (8 with ECMO). The mean gestational age at birth was 36.8 weeks (range, 33.3 to 39.1 weeks). Outcomes in the postnatal presentation group were 1 neonatal death (with ECMO) and 4 survivors (1 with ECMO). Overall survival rate (22 prenatal plus 5 postnatal diagnoses) was 19 of 27 (70%). Postnatal survival rate for those not electing termination was 19 of 23 (83%). Twelve of 23 (52%) neonates required ECMO with a 75% survival rate. CDH was repaired with Gore-tex (W.L. Gore and Associates, Flagstaff, AZ) patch in 14 of 21 neonates undergoing surgery. Among the 19 survivors, 16 had postnatal care at CHOP with mean length of mechanical ventilation 32.9 days (range, 0 to 79 days) and mean length of hospital stay 50.4 days (range, 6 to 139). Significant morbidity occurred in 10 of 19 survivors and included severe neurologic sequelae in 6 of 19 (32%; Table 2). Termination. Of the 4 terminations at mean GA 22.1 weeks (range, 19 to 24), 2 were syndromic at postmortem examination. LHR measurements in these fetuses were 0.76, 0.95, 0.87, and too small to measure. Neonatal Demise. Three neonatal deaths occurred in the prenatal diagnosis group. Mean GA at delivery was 35 weeks (range, 33.3 to 36.7). Two patients died before postnatal repair. In 1 case, the mother had polyhydramnios and premature rupture of membranes at 33.3 weeks. The 1.78-kg neonate was not a candidate for ECMO because of prematurity and birth weight. The neonate had bilateral pulmonary hemorrhage and progressive hemodynamic instability and died at 23 hours of life. In the second case, prenatal diagnosis showed a
RIGHT-SIDED CDH
Table 2. Summary of Right CDH Complications Neurologic Bilateral occipital hemorrhage, right subdural hematoma Hearing loss Left middle cerebral artery infarct Periventricular leukomalacia Right occipital infarct Right subarachnoid hemorrhage Pulmonary Chylothorax Pulmonary hemorrhage Reactive airway disease Tracheomalacia Tracheitis Gastrointestinal Cholangitis secondary to undiagnosed choledochal cyst Dysmotility Failure to thrive requiring gastrostomy tube Gastroesophageal reflux 7 Nissen fundoplication/gastrostomy tube 2 Hyperalimentation cholestasis Liver necrosis Infectious disease Sepsis Endocrine Hypothyroidism Surgical complications Adhesive small bowel obstruction Chest wall asymmetry Intraoperative bleeding Jejunal perforation
ventricular septal defect. The mother had polyhydramnios and premature rupture of membranes at 34.9 weeks. The newborn was maintained on ECMO for 18 days and then died of multisystem organ failure at 20 days of life before surgical repair. In the third case, the patient exhibited severe pulmonary hypertension necessitating ECMO in the first 24 hours of life. Pulmonary hypertension remained severe with right heart decompensation requiring inhaled nitric oxide and milrinone. CDH repair with patch was performed on ECMO at 21 days of life, but postoperatively the patient had seizure activity and global ischemic injury by head ultrasound scan. Support was withdrawn at 31 days of life. The fourth neonatal death was a 39-week-gestation neonate with right CDH diagnosed after suffering respiratory distress in the delivery room. After transfer to CHOP, the baby exhibited severe pulmonary hypertension requiring ECMO for 26 days. CDH repair with patch and resection of an extralobar sequestration were performed on ECMO at day 15. After decannulation, the baby had persistent pulmonary hypertension and poor gas exchange treated with nitric oxide and high-frequency oscillatory ventilation. By day-of-life 37, a left parietal-temporal infarct was diagnosed by ultrasound scan, and life support was withdrawn. On postmortem
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examination, there was evidence of multiple myocardial infarcts and severe pulmonary hypoplasia. Survivor fetal intervention. One patient, with a leftsided lung too small to calculate LHR, underwent tracheal occlusion at 27 weeks and delivery by ex utero intrapartum therapy after preterm labor at 31.4 weeks.14 Birth weight was 1.8 kg. Patch repair of the diaphragmatic agenesis was performed at 9 days of life. The patient was ventilated mechanically for 50 days, hospitalized for 66 days, and maintained on oxygen for 18 months. The patient has had 4 subsequent hospitalizations for gastroesophageal reflux, failure to thrive, viral pneumonia, and diaphragmatic reconstruction caused by chest wall tethering by the patch. Long-term complications include profound developmental delay, autism, failure to thrive, and hearing loss. Survivors standard postnatal care. Mean GA at CHOP evaluation in the prenatal diagnosis survival group was 29.4 weeks (range, 21 to 36) with mean GA at birth 37.6 weeks (range, 36 to 39.1). Eight patients required ECMO for a mean of 13.3 days. One patient had a second course of ECMO for 9 days. In the ECMO group, the mean number of days on ventilator support for 7 of the patients was 48 days (range, 25 to 79 days), and 4 were discharged on oxygen. Seven of the 8 ECMO patients underwent patch repair of the diaphragm on ECMO at mean 10.9 days of life. One patient cared for at another institution was readmitted after a respiratory arrest at home. Tracheomalacia and severe gastroesophageal reflux were diagnosed, and the patient subsequently underwent tracheostomy and Nissen fundoplication. The mean hospital stay was 77.6 days (range, 45 to 139), and mean age now is 3.7 years (range, 0.7 to 7.3). Short-term complications included intraoperative bleeding (n ⫽ 1), sepsis (n ⫽ 3), chylothorax (n ⫽ 1), pulmonary hemorrhage (n ⫽ 2), cholestasis (n ⫽ 2), tamponade/arrythmias after cardiac surgery (n ⫽ 1), hypothyroidism (n ⫽ 1), and adhesive small bowel obstruction (n ⫽ 1). Long-term complications included central nervous system hemorrhage or infarct with developmental delay (n ⫽ 4), profound hearing loss (n ⫽ 2), tracheomalacia (n ⫽ 1), reactive airway disease (n ⫽ 3), gastroesophageal reflux (n ⫽ 6), severe gastrointestinal dysmotility (n ⫽ 1), and failure to thrive (n ⫽ 1). The remaining 6 survivors in the prenatal diagnosis group did not require ECMO and were mechanically ventilated for mean 15 days (range, 7 to 30). Mean age at surgical repair was 4.3 days, and 2 required a patch reconstruction. Three of these patients with presentations at 35, 27, and 30 weeks had a hernia sac noted at the time of surgical repair and did not require a patch. The mean hospital stay was 30.7 days (range, 17 to 49), and none of the 6 patients surviving without ECMO required supplemental oxygen at discharge. Follow-up is 2 months to 5
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years. Complications included cholangitis at 6 weeks of life secondary to previously undiagnosed cholecochal cyst (n ⫽ 1) and gastroesophageal reflux (n ⫽ 2). In the postnatal diagnosis group, 3 of the 5 patients presented with symptoms in the delivery room of a community hospital and were then transferred to CHOP. The neonatal death requiring ECMO was discussed in detail previously. A second patient required ECMO for 16 days, underwent CDH repair with patch on ECMO at day 11 of life, was ventilated for 50 days, and was discharged from the hospital at 81 days on oxygen. Her complications included grade I intraventricular hemorrhage, sepsis, liver necrosis, and jejunal perforation. The remaining patient with symptoms in the delivery room was stabilized, underwent primary CDH repair at 4 days, extubation at 35 days, and discharge from the hospital at 39 days. Two patients in the postnatal diagnosis group presented with gastrointestinal symptoms and liver down at 3 months and 7 months of age, respectively. Both patients underwent primary CDH repair and were extubated postoperatively. Hospital stay was 13 days and 6 days, respectively. Maternal Morbidity Nine of the 18 (50%) continuing pregnancies in the prenatal diagnosis group had polyhydramnios (n ⫽ 8), premature rupture of membranes (n ⫽ 2), and/or preterm labor (n ⫽ 3). DISCUSSION
In our population, right-sided CDH occurred in 11% (22 of 194) of patients presenting with a confirmed prenatal diagnosis of CDH. Before the development of high-resolution ultrasound scan, color flow Doppler, and ultrafast MRI, the accurate prenatal diagnosis of right CDH was difficult because of the liver’s solid echotexture.15,17-19 Clues in distinguishing right CDH from fetal lung lesions include the direction of portal blood flow, ascites in the chest (may also simulate pleural effusion associated with sequestrations), or the gallbladder in the thoracic cavity.20 The diagnosis was corrected from fetal
lung lesion to right CDH in 2 of our patients. The correct diagnosis may significantly affect the vigilance of prenatal surveillance and subsequent resuscitative efforts. One patient in our series received a misdiagnosis, was severely depressed at birth, and required 2 courses of ECMO before eventual survival. In comparison with the hidden mortality series reported by the University of California, San Francisco,1,6 our series contains no cases of intrauterine fetal demise. This may be in part because of close follow-up by ultrasound scan and nonstress testing beginning at 30 weeks GA. In contrast to left CDH,14-16,19,21,22 liver position and LHR measurements were not helpful in determining prognosis in our group of right CDH patients. The fetal liver was herniated into the chest in all of our prenatal diagnosis patients, yet at least 6 did not require ECMO, and 4 did not require patch placement. For LHR measurements, the numbers are very small in the 23- to 25-week prognostic window. Only 7 patients underwent ultrasound scan in this time period and in 2 of the patients the contralateral lung was too small to measure. The remaining patients’ outcomes included termination, neonatal death, and survival with and without ECMO. The high mortality rate of prenatally diagnosed CDH has been confirmed by several reports.1,6,23 Recent reports on CDH using strategies of surfactant,24 highfrequency oscillatory ventilation,25 nitric oxide,26-28 partial liquid ventilation,29 ECMO,30-32 and gentilation33-36 show improvements in the outcomes at some tertiary medical centers but still carry a “hidden mortality” because of the successful transport of the patient and incidence of exclusion criteria in some cases. The overall survival rate of 70% and postnatal survival rate of 83% in our series of right CDH were better than expected but must be tempered by the very high incidence of severe complications. Fifty-two percent of our patients required ECMO, and many of these patients have long-term developmental, pulmonary, and gastrointestinal issues that have required rehospitalizations and ongoing care. This high morbidity despite a surprisingly low mortality reflects the severity of this population of CDH.
REFERENCES 1. Harrison MR, Adzick NS, Estes JM: A prospective study of the outcome of fetuses with congenital diaphragmatic hernia. JAMA 271: 382-384, 1994 2. Clark RH, Hardin WD Jr, Hirschl RB, et al: Current surgical management of congenital diaphragmatic hernia: A report from the Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg 33: 1004-1009, 1998 3. Skari H, Bjornland K, Haugen G, et al: Congenital diaphragmatic hernia: A meta-analysis of mortality factors. J Pediatr Surg 35:11871197, 2000 4. Azarow K, Messineo A, Pearl R, et al: Congenital diaphragmatic hernia—A tale of two cities: The Toronto experience. J Pediatr Surg 32:395-400, 1997
5. Jaffray B, MacKinlay GA: Real and apparent mortality from congenital diaphragmatic hernia. Br J Surg 83:79-82, 1996 6. Harrison MR, Bjordal RI, Langmark F, et al: Congenital diaphragmatic hernia: The hidden mortality. J Pediatr Surg 13:227-230, 1978 7. Touloukian RJ, Markowitz RI: A preoperative x-ray scoring system for risk assessment of newborns with congenital diaphragmatic hernia. J Pediatr Surg 19:252-257, 1984 8. Gibson C, Fonkalsrud EW: Iatrogenic pneumothorax and mortality in congenital diaphragmatic hernia. J Pediatr Surg 18:555-559, 1983 9. Skari H, Bjornland K, Frenckner B, et al: Congenital diaphragmatic hernia in Scandinavia from 1995 to 1998: Predictors of mortality. J Pediatr Surg 37:1269-1275, 2002
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10. Geary M: Management of congenital diaphragmatic hernia diagnosed prenatally: An update. Prenatal Diagnosis 18:1155-1158, 1998 11. Macken MB, Thompson DL: Antenatal diagnosis of congenital diaphragmatic hernia. Can Assoc Radiol J 44:439-442, 1993 12. Wilson JM, Lund DP, Lillehei CW, et al: Congenital diaphragmatic hernia—A tale of two cities: The Boston experience. J Pediatr Surg 32:401-405, 1997 13. Cohen MS, Rychik J, Bush DM, et al: Influence of congenital heart disease on survival in children with congenital diaphragmatic hernia. J Pediatr 141:25-30, 2002 14. Flake AW, Crombleholme TM, Johnson MP, et al: Treatment of severe congenital diaphragmatic hernia by fetal tracheal occlusion: Clinical experience with fifteen cases. Am J Obstet Gynecol 183:10591066, 2000 15. Hubbard AM, Crombleholme TM, Adzick NS, et al: Prenatal MRI evaluation of congenital diaphragmatic hernia. Am J Perinatol 16:407-413, 1999 16. Metkus AP, Filly RA, Stringer MD, et al: Sonographic predictors of survival in fetal diaphragmatic hernia. J Pediatr Surg 31:148151; discussion 151-152, 1996 17. Fu RH, Hsieh WS, Yang PH, et al: Diagnostic pitfalls in congenital right diaphragmatic hernia. Acta Paediatr Taiwan 41:251254, 2000 18. Izquierdo LA, Ramos C, Gonzalez JL, et al: Prenatal diagnosis of right-sided diaphragmatic hernia: The use of color flow Doppler. Bol Asoc Med PR 89:189-191, 1997 19. Walsh DS, Hubbard AM, Olutoye OO, et al: Assessment of fetal lung volumes and liver herniation with magnetic resonance imaging in congenital diaphragmatic hernia. Am J Obstet Gynecol 183:1067-1069, 2000 20. Callen PW: Ultrasonography in Obstetric and Gynecology. Philadelphia, PA, Saunders, 2000 21. Albanese CT, Lopoo J, Goldstein RB, et al: Fetal liver position and perinatal oucome for congenital diaphragmatic hernia. Prenat Diagn 18:1138, 1998 22. Lipshutz GS, Albanese CT, Feldstein VA, et al: prospective analysis of lung-to-head ratio predicts survival for patients with prenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg 32:1634, 1997 23. Adzick NS, Vacanti JP, Lillehei CW, et al: Fetal diaphragmatic hernia: Ultrasound diagnosis and clinical outcome in 38 cases from a single medical center. J Pediatr Surg 24:654-660, 1981 24. Glick PL, Leach CL, Besner GE, et al: Pathophysiology of
congenital diaphragmatic hernia. III: Exogenous surfactant therapy for the high-risk neonate with CDH. J Pediatr Surg 27:866-869, 1992 25. 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 22:S77-S82, 1994 26. Frostell CG, Lonnqvist PA, Sonesson SE, et al: Near-fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia. Successful use of inhaled nitric oxide. Anaesthesist 48:679-683, 1993 27. Henneberg SW, Jespen S, Andersen PD, et al: Inhalation of nitric oxide as a treatment of pulmonary hypertension in congenital diphragmatic hernia. J Pediatr Surg 30:853-855, 1995 28. Dillon PW, Cilley RE, Hudome SM, et al: Nitric oxide reversal of recurrent pulmonary hypertension and respiratory failure in an infant with CDH after successful ECMO therapy. J Pediatr Surg 30:743-744, 1995 29. Hirschl RB, Fox W, Glick PL, et al: A prospective, randomized pilot trial of perfluorocarbon-induced lung growth in newborns with congenital diaphragmatic hernia. J Pediatr Surg 38:283-289, 2003 30. Bartlett RH, Gazzaniga AB, Toomasian J, et al: Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases. Ann Surg 204:236-245, 1986 31. Langham MR Jr, Krummel TM, Bartlett RH, et al: Mortality with extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernia in 93 infants. J Pediatr Surg 22:11501154, 1987 32. Redmond C, Heaton J, Calix J, et al: A correlation of pulmonary hypoplasia, mean airway pressure, and survival in congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation. J Pediatr Surg 22:1143-1149, 1987 33. Wung JT, James LS, Kilchevsky E, et al: Management of infants with severe respiratory failure and persistence of the fetal circulation without hyperventilation. Pediatrics 76:488-494, 1985 34. Kayes DW, Langham MR Jr, Ledbetter DJ, et al: Detrimental effects of standard medical therapy in congenital diaphragmatic hernia. Ann Surg 230:340-348; discussion 348-351, 1999 35. Wung JT, Sahni R, Moffitt ST, et al: Congenital diaphragmatic hernia: Survival treated with very delayed surgery, spontaneous respiraton, and no chest tube. J Pediatr Surg 30:406-409, 1995 36. Frenckner B, Ehren H, Granholm T, et al: Improved results in patients who have congenital diaphragmatic hernia using preoperative stablization, extracorporeal membrane oxygenation, and delayed surgery. J Pediatr Surg 32:1185-1189, 1997
Discussion D. Cass (Houston, TX): Alan, thank you very much for sharing your experience with us. I have 2 questions. First, what happened to the 5 patients that were diagnosed postnatally? It is a small number, but did any of those patients die? A. W. Flake (response): We had 1 death in the postnatal group, and we had 3 that required ECMO out of the 5.
D. Cass: Second, this is a high patch rate. What are your indications for using a patch? Do you have a similar rate of patching on the left side? A. W. Flake (response): My indication is pretty simple. If I can’t close the diaphragm primarily, I will use a patch. That was the case in this series as well. I think the patch rates are fairly similar between right and left, perhaps a little higher on the left in fact in our group.
Purpose: To understand the natural history of right congenital diaphragmatic hernia (CDH), the authors retrospectively reviewed 27 cases of right CDH that presented for prenatal evaluation or postnatal treatment. Methods: Between 1995 and September 2002, a total of 194 cases of fetal CDH were evaluated and included 22 rightsided defects. The authors reviewed prenatal diagnostic studies (ultrasound scan, magnetic resonance imaging [MRI] echocardiography) and pre- and postnatal outcomes in these 22 cases of right CDH. Five additional cases of right CDH without a prenatal diagnosis were reviewed. Results: The mean gestational age at evaluation was 26.1 weeks. The lung area to head circumference ratio (LHR) ranged from 0.32 to 2.5. In all cases, the fetal liver was herniated into the right chest. Associated anomalies were common. There were no karyotype abnormalities (17 of 22 tested). There were 4 terminations. Nine of the 18 (50%) continuing pregnancies had polyhydramnios, premature rupture of membranes, or preterm labor. The mean gestational age at birth was 36.8 weeks. One patient underwent
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IGHT-SIDED DEFECTS account for 8% to 21% of all cases of congenital diaphragmatic hernia (CDH).1-3 The current literature on right CDH and severity is contradictory. Several studies have described an increased mortality rate in right CDH compared with left CDH,3-9,10 whereas others have found the opposite effect,11 or no influence at all.1,12 To better understand the challenges facing the infant with the diagnosis of right CDH, we retrospectively reviewed 27 consecutive cases (22 prenatal diagnosis, 5 postnatal diagnosis) presenting to our institution over a 7-year period.
tracheal occlusion at 27 weeks, and 2 patients died before postnatal repair. Overall survival rate (22 prenatal plus 5 postnatal diagnoses) was 19 of 27 (70%). Postnatal survival rate was 19 of 23 (83%). A Gore-tex (W. L. Gore and Associates, Flagstaff, AZ) patch was utilized in 14 of 21 neonates undergoing surgery. Twelve of 23 (52%) required extracorporeal membrane oxygenation (ECMO) with a 75% survival rate. Significant morbidity occurred in 10 of 19 survivors and included neurologic sequelae in 6 of 19 (32%). Conclusions: MRI was helpful in the determination of liver position and confirmation of diagnosis. The high incidence of preterm complications, frequent need for ECMO, and high prevalence of comorbidities are indicative of the severity of this CDH population and warrant close prenatal surveillance and delivery at a tertiary care center with ECMO capability. J Pediatr Surg 39:319-323. © 2004 Elsevier Inc. All rights reserved. INDEX WORDS: Right congenital diaphragmatic hernia, prenatal diagnosis, outcome.
(1) termination of pregnancy if gestational age (GA) less than 24 weeks, (2) standard postnatal care, and (3) fetal tracheal occlusion (before January 1999) if the fetus and mother fit criteria. Because of the risk of intrauterine fetal demise,1 obstetric management included ultrasound surveillance and weekly nonstress testing beginning at 30 weeks GA. Several of these cases have been included in previously published reports.13-15 This study was approved by the Committee for Protection of Human Subjects Institutional Review Board at CHOP (IRB #20024-2786).
Prenatal Studies
MATERIALS AND METHODS
The left lung area to head circumference ratio (LHR) was calculated from an ultrasonographic cross-sectional image of the fetal thorax at the level of the 4-chamber view of the heart and consisted of the 2-dimensional area (greatest anteroposterior and lateral dimensions of
From September 1995 through September 2002, 22 fetuses with right congenital diaphragmatic hernia (CDH; from a total of 194 CDH cases) were evaluated at The Center for Fetal Diagnosis and Treatment at the Children’s Hospital of Philadelphia (CHOP). During the same period, 5 additional cases of right CDH without a prenatal diagnosis were admitted to CHOP. We retrospectively reviewed the maternal prenatal charts, postnatal hospital charts, outpatient office charts, and neonatal follow-up records for a total of 27 cases (22 prenatal diagnosis, 5 postnatal diagnosis) of right CDH. The initial prenatal evaluation at CHOP included detailed fetal ultrasonography, fetal ultrafast magnetic resonance imaging (MRI), and fetal echocardiography. After evaluation, all patients underwent nondirective counseling for management options. The options included
From The Center for Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia, Philadelphia, PA. Presented at the 34th Annual Meeting of the American Pediatric Surgical Association, Fort Lauderdale, Florida, May 25-28, 2003. Address reprint requests to Holly L. Hedrick, MD, The Center for Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia, 34th St and Civic Center Boulevard, Philadelphia, PA 191044399. © 2004 Elsevier Inc. All rights reserved. 0022-3468/04/3903-0013$30.00/0 doi:10.1016/j.jpedsurg.2003.11.006
Journal of Pediatric Surgery, Vol 39, No 3 (March), 2004: pp 319-323
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the left lung) divided by the head circumference.16 LHRs were measured at the presenting GA and then repeated between 23 and 25 weeks’ gestation in 7 of the pregnancies because this is the time period used for prognosis determination in left CDH.14 Ultrafast fetal MRI was obtained to confirm the diagnosis, further delineate liver position, visible lung tissue, and the presence of other anomalies.15 Fetal echocardiography assessed for the presence of coexistent congenital heart anomalies.13
Table 1. Summary of Right CDH Overall Outcomes Termination Fetal demise Neonatal demise Postnatal survival ECMO Neonatal demise Survival
4 0 4/23 (17%) 19/23 (83%) 12/23 (52%) 3/12 (25%) 9/12 (75%)
Criteria for Tracheal Occlusion Criteria for consideration of tracheal occlusion required the absence of maternal risk factors for anesthesia or surgery, a singleton pregnancy with normal karyotype analysis, diagnosis before 25 weeks’ gestation, and the absence of significant associated anomalies. For right-sided CDH, the criteria included massive herniation of the liver into the chest with inability to visualize significant contralateral lung tissue. The details of the tracheal occlusion procedure and maternal postoperative care have been discussed in detail in a prior report.14
Postnatal Management Postnatal management in the neonatal intensive care unit included the use of pressure ventilation, high-frequency oscillatory ventilation, and inhaled nitric oxide. If these therapies failed, then extracorporeal membrane oxygenation (ECMO) was used for salvage in neonates older than 34 weeks’ gestation and weighing greater than 2 kg. Repair of the CDH was performed in a delayed fashion once medical stability was achieved, the pulmonary vasculature became less reactive (absence of shunting), or weaning from ECMO was anticipated. The operating surgeon determined the need for patch placement based on the size of the diaphragmatic defect.
RESULTS
Patient Population and Associated Anomalies For the 22 cases of right CDH diagnosed before birth, the mean gestational age at presentation was 26.1 weeks (range, 19 to 36 weeks). There were no karyotype abnormalities in 17 of 22 who underwent amniocentesis. In 2 patients, the referring diagnosis of a fetal lung lesion was corrected to right CDH. An additional patient was misdiagnosed as a cystic fetal lung lesion by ultrasound scan in 1995 before the use of ultrafast fetal MRI. In all other cases, the fetal liver was herniated into the right chest by fetal MRI. The lung area to head circumference ratio (LHR) ranged from 0.32 to 2.5, and was obtained at 19 to 36 weeks. Only 7 fetuses had ultrasound examinations at 23 to 25 weeks. The contralateral lung was too small to visualize in 2 of these cases. In the remaining 5 cases, mean LHR was 0.8 (range, 0.66 to 1.0). One of these fetuses underwent fetal tracheal occlusion and survived. Other outcomes in the group undergoing ultrasound examination at 23 to 25 weeks were termination (n ⫽ 2), neonatal death (n ⫽ 1), survival with ECMO (n ⫽ 2), and survival without ECMO (n ⫽ 1). Associated anomalies were common. Cardiovascular anomalies included ventricular septal defect (n ⫽ 3), pulmonary artery stenosis (n ⫽ 4), right anomalous pulmonary venous return (n ⫽ 1), and interrupted infe-
rior vena cava (n ⫽ 1). Central nervous system anomalies included microcephaly and Dandy Walker malformation. Three fetuses had associated extralobar pulmonary sequestrations. Gastrointestinal anomalies included choledochal cyst (n ⫽ 1), Meckel’s diverticulum (n ⫽ 1), and omphalocele (n ⫽ 1). Genitourinary anomalies included hydronephrosis (n ⫽ 3), horseshoe kidney (n ⫽ 1), and undescended testes (n ⫽ 1). One fetus had transient hydrops secondary to maternal parvovirus infection. Overall Outcomes Outcomes (Table 1) in the prenatal diagnosis group included 4 terminations, 3 neonatal deaths (2 with ECMO), and 15 survivors (8 with ECMO). The mean gestational age at birth was 36.8 weeks (range, 33.3 to 39.1 weeks). Outcomes in the postnatal presentation group were 1 neonatal death (with ECMO) and 4 survivors (1 with ECMO). Overall survival rate (22 prenatal plus 5 postnatal diagnoses) was 19 of 27 (70%). Postnatal survival rate for those not electing termination was 19 of 23 (83%). Twelve of 23 (52%) neonates required ECMO with a 75% survival rate. CDH was repaired with Gore-tex (W.L. Gore and Associates, Flagstaff, AZ) patch in 14 of 21 neonates undergoing surgery. Among the 19 survivors, 16 had postnatal care at CHOP with mean length of mechanical ventilation 32.9 days (range, 0 to 79 days) and mean length of hospital stay 50.4 days (range, 6 to 139). Significant morbidity occurred in 10 of 19 survivors and included severe neurologic sequelae in 6 of 19 (32%; Table 2). Termination. Of the 4 terminations at mean GA 22.1 weeks (range, 19 to 24), 2 were syndromic at postmortem examination. LHR measurements in these fetuses were 0.76, 0.95, 0.87, and too small to measure. Neonatal Demise. Three neonatal deaths occurred in the prenatal diagnosis group. Mean GA at delivery was 35 weeks (range, 33.3 to 36.7). Two patients died before postnatal repair. In 1 case, the mother had polyhydramnios and premature rupture of membranes at 33.3 weeks. The 1.78-kg neonate was not a candidate for ECMO because of prematurity and birth weight. The neonate had bilateral pulmonary hemorrhage and progressive hemodynamic instability and died at 23 hours of life. In the second case, prenatal diagnosis showed a
RIGHT-SIDED CDH
Table 2. Summary of Right CDH Complications Neurologic Bilateral occipital hemorrhage, right subdural hematoma Hearing loss Left middle cerebral artery infarct Periventricular leukomalacia Right occipital infarct Right subarachnoid hemorrhage Pulmonary Chylothorax Pulmonary hemorrhage Reactive airway disease Tracheomalacia Tracheitis Gastrointestinal Cholangitis secondary to undiagnosed choledochal cyst Dysmotility Failure to thrive requiring gastrostomy tube Gastroesophageal reflux 7 Nissen fundoplication/gastrostomy tube 2 Hyperalimentation cholestasis Liver necrosis Infectious disease Sepsis Endocrine Hypothyroidism Surgical complications Adhesive small bowel obstruction Chest wall asymmetry Intraoperative bleeding Jejunal perforation
ventricular septal defect. The mother had polyhydramnios and premature rupture of membranes at 34.9 weeks. The newborn was maintained on ECMO for 18 days and then died of multisystem organ failure at 20 days of life before surgical repair. In the third case, the patient exhibited severe pulmonary hypertension necessitating ECMO in the first 24 hours of life. Pulmonary hypertension remained severe with right heart decompensation requiring inhaled nitric oxide and milrinone. CDH repair with patch was performed on ECMO at 21 days of life, but postoperatively the patient had seizure activity and global ischemic injury by head ultrasound scan. Support was withdrawn at 31 days of life. The fourth neonatal death was a 39-week-gestation neonate with right CDH diagnosed after suffering respiratory distress in the delivery room. After transfer to CHOP, the baby exhibited severe pulmonary hypertension requiring ECMO for 26 days. CDH repair with patch and resection of an extralobar sequestration were performed on ECMO at day 15. After decannulation, the baby had persistent pulmonary hypertension and poor gas exchange treated with nitric oxide and high-frequency oscillatory ventilation. By day-of-life 37, a left parietal-temporal infarct was diagnosed by ultrasound scan, and life support was withdrawn. On postmortem
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examination, there was evidence of multiple myocardial infarcts and severe pulmonary hypoplasia. Survivor fetal intervention. One patient, with a leftsided lung too small to calculate LHR, underwent tracheal occlusion at 27 weeks and delivery by ex utero intrapartum therapy after preterm labor at 31.4 weeks.14 Birth weight was 1.8 kg. Patch repair of the diaphragmatic agenesis was performed at 9 days of life. The patient was ventilated mechanically for 50 days, hospitalized for 66 days, and maintained on oxygen for 18 months. The patient has had 4 subsequent hospitalizations for gastroesophageal reflux, failure to thrive, viral pneumonia, and diaphragmatic reconstruction caused by chest wall tethering by the patch. Long-term complications include profound developmental delay, autism, failure to thrive, and hearing loss. Survivors standard postnatal care. Mean GA at CHOP evaluation in the prenatal diagnosis survival group was 29.4 weeks (range, 21 to 36) with mean GA at birth 37.6 weeks (range, 36 to 39.1). Eight patients required ECMO for a mean of 13.3 days. One patient had a second course of ECMO for 9 days. In the ECMO group, the mean number of days on ventilator support for 7 of the patients was 48 days (range, 25 to 79 days), and 4 were discharged on oxygen. Seven of the 8 ECMO patients underwent patch repair of the diaphragm on ECMO at mean 10.9 days of life. One patient cared for at another institution was readmitted after a respiratory arrest at home. Tracheomalacia and severe gastroesophageal reflux were diagnosed, and the patient subsequently underwent tracheostomy and Nissen fundoplication. The mean hospital stay was 77.6 days (range, 45 to 139), and mean age now is 3.7 years (range, 0.7 to 7.3). Short-term complications included intraoperative bleeding (n ⫽ 1), sepsis (n ⫽ 3), chylothorax (n ⫽ 1), pulmonary hemorrhage (n ⫽ 2), cholestasis (n ⫽ 2), tamponade/arrythmias after cardiac surgery (n ⫽ 1), hypothyroidism (n ⫽ 1), and adhesive small bowel obstruction (n ⫽ 1). Long-term complications included central nervous system hemorrhage or infarct with developmental delay (n ⫽ 4), profound hearing loss (n ⫽ 2), tracheomalacia (n ⫽ 1), reactive airway disease (n ⫽ 3), gastroesophageal reflux (n ⫽ 6), severe gastrointestinal dysmotility (n ⫽ 1), and failure to thrive (n ⫽ 1). The remaining 6 survivors in the prenatal diagnosis group did not require ECMO and were mechanically ventilated for mean 15 days (range, 7 to 30). Mean age at surgical repair was 4.3 days, and 2 required a patch reconstruction. Three of these patients with presentations at 35, 27, and 30 weeks had a hernia sac noted at the time of surgical repair and did not require a patch. The mean hospital stay was 30.7 days (range, 17 to 49), and none of the 6 patients surviving without ECMO required supplemental oxygen at discharge. Follow-up is 2 months to 5
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years. Complications included cholangitis at 6 weeks of life secondary to previously undiagnosed cholecochal cyst (n ⫽ 1) and gastroesophageal reflux (n ⫽ 2). In the postnatal diagnosis group, 3 of the 5 patients presented with symptoms in the delivery room of a community hospital and were then transferred to CHOP. The neonatal death requiring ECMO was discussed in detail previously. A second patient required ECMO for 16 days, underwent CDH repair with patch on ECMO at day 11 of life, was ventilated for 50 days, and was discharged from the hospital at 81 days on oxygen. Her complications included grade I intraventricular hemorrhage, sepsis, liver necrosis, and jejunal perforation. The remaining patient with symptoms in the delivery room was stabilized, underwent primary CDH repair at 4 days, extubation at 35 days, and discharge from the hospital at 39 days. Two patients in the postnatal diagnosis group presented with gastrointestinal symptoms and liver down at 3 months and 7 months of age, respectively. Both patients underwent primary CDH repair and were extubated postoperatively. Hospital stay was 13 days and 6 days, respectively. Maternal Morbidity Nine of the 18 (50%) continuing pregnancies in the prenatal diagnosis group had polyhydramnios (n ⫽ 8), premature rupture of membranes (n ⫽ 2), and/or preterm labor (n ⫽ 3). DISCUSSION
In our population, right-sided CDH occurred in 11% (22 of 194) of patients presenting with a confirmed prenatal diagnosis of CDH. Before the development of high-resolution ultrasound scan, color flow Doppler, and ultrafast MRI, the accurate prenatal diagnosis of right CDH was difficult because of the liver’s solid echotexture.15,17-19 Clues in distinguishing right CDH from fetal lung lesions include the direction of portal blood flow, ascites in the chest (may also simulate pleural effusion associated with sequestrations), or the gallbladder in the thoracic cavity.20 The diagnosis was corrected from fetal
lung lesion to right CDH in 2 of our patients. The correct diagnosis may significantly affect the vigilance of prenatal surveillance and subsequent resuscitative efforts. One patient in our series received a misdiagnosis, was severely depressed at birth, and required 2 courses of ECMO before eventual survival. In comparison with the hidden mortality series reported by the University of California, San Francisco,1,6 our series contains no cases of intrauterine fetal demise. This may be in part because of close follow-up by ultrasound scan and nonstress testing beginning at 30 weeks GA. In contrast to left CDH,14-16,19,21,22 liver position and LHR measurements were not helpful in determining prognosis in our group of right CDH patients. The fetal liver was herniated into the chest in all of our prenatal diagnosis patients, yet at least 6 did not require ECMO, and 4 did not require patch placement. For LHR measurements, the numbers are very small in the 23- to 25-week prognostic window. Only 7 patients underwent ultrasound scan in this time period and in 2 of the patients the contralateral lung was too small to measure. The remaining patients’ outcomes included termination, neonatal death, and survival with and without ECMO. The high mortality rate of prenatally diagnosed CDH has been confirmed by several reports.1,6,23 Recent reports on CDH using strategies of surfactant,24 highfrequency oscillatory ventilation,25 nitric oxide,26-28 partial liquid ventilation,29 ECMO,30-32 and gentilation33-36 show improvements in the outcomes at some tertiary medical centers but still carry a “hidden mortality” because of the successful transport of the patient and incidence of exclusion criteria in some cases. The overall survival rate of 70% and postnatal survival rate of 83% in our series of right CDH were better than expected but must be tempered by the very high incidence of severe complications. Fifty-two percent of our patients required ECMO, and many of these patients have long-term developmental, pulmonary, and gastrointestinal issues that have required rehospitalizations and ongoing care. This high morbidity despite a surprisingly low mortality reflects the severity of this population of CDH.
REFERENCES 1. Harrison MR, Adzick NS, Estes JM: A prospective study of the outcome of fetuses with congenital diaphragmatic hernia. JAMA 271: 382-384, 1994 2. Clark RH, Hardin WD Jr, Hirschl RB, et al: Current surgical management of congenital diaphragmatic hernia: A report from the Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg 33: 1004-1009, 1998 3. Skari H, Bjornland K, Haugen G, et al: Congenital diaphragmatic hernia: A meta-analysis of mortality factors. J Pediatr Surg 35:11871197, 2000 4. Azarow K, Messineo A, Pearl R, et al: Congenital diaphragmatic hernia—A tale of two cities: The Toronto experience. J Pediatr Surg 32:395-400, 1997
5. Jaffray B, MacKinlay GA: Real and apparent mortality from congenital diaphragmatic hernia. Br J Surg 83:79-82, 1996 6. Harrison MR, Bjordal RI, Langmark F, et al: Congenital diaphragmatic hernia: The hidden mortality. J Pediatr Surg 13:227-230, 1978 7. Touloukian RJ, Markowitz RI: A preoperative x-ray scoring system for risk assessment of newborns with congenital diaphragmatic hernia. J Pediatr Surg 19:252-257, 1984 8. Gibson C, Fonkalsrud EW: Iatrogenic pneumothorax and mortality in congenital diaphragmatic hernia. J Pediatr Surg 18:555-559, 1983 9. Skari H, Bjornland K, Frenckner B, et al: Congenital diaphragmatic hernia in Scandinavia from 1995 to 1998: Predictors of mortality. J Pediatr Surg 37:1269-1275, 2002
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10. Geary M: Management of congenital diaphragmatic hernia diagnosed prenatally: An update. Prenatal Diagnosis 18:1155-1158, 1998 11. Macken MB, Thompson DL: Antenatal diagnosis of congenital diaphragmatic hernia. Can Assoc Radiol J 44:439-442, 1993 12. Wilson JM, Lund DP, Lillehei CW, et al: Congenital diaphragmatic hernia—A tale of two cities: The Boston experience. J Pediatr Surg 32:401-405, 1997 13. Cohen MS, Rychik J, Bush DM, et al: Influence of congenital heart disease on survival in children with congenital diaphragmatic hernia. J Pediatr 141:25-30, 2002 14. Flake AW, Crombleholme TM, Johnson MP, et al: Treatment of severe congenital diaphragmatic hernia by fetal tracheal occlusion: Clinical experience with fifteen cases. Am J Obstet Gynecol 183:10591066, 2000 15. Hubbard AM, Crombleholme TM, Adzick NS, et al: Prenatal MRI evaluation of congenital diaphragmatic hernia. Am J Perinatol 16:407-413, 1999 16. Metkus AP, Filly RA, Stringer MD, et al: Sonographic predictors of survival in fetal diaphragmatic hernia. J Pediatr Surg 31:148151; discussion 151-152, 1996 17. Fu RH, Hsieh WS, Yang PH, et al: Diagnostic pitfalls in congenital right diaphragmatic hernia. Acta Paediatr Taiwan 41:251254, 2000 18. Izquierdo LA, Ramos C, Gonzalez JL, et al: Prenatal diagnosis of right-sided diaphragmatic hernia: The use of color flow Doppler. Bol Asoc Med PR 89:189-191, 1997 19. Walsh DS, Hubbard AM, Olutoye OO, et al: Assessment of fetal lung volumes and liver herniation with magnetic resonance imaging in congenital diaphragmatic hernia. Am J Obstet Gynecol 183:1067-1069, 2000 20. Callen PW: Ultrasonography in Obstetric and Gynecology. Philadelphia, PA, Saunders, 2000 21. Albanese CT, Lopoo J, Goldstein RB, et al: Fetal liver position and perinatal oucome for congenital diaphragmatic hernia. Prenat Diagn 18:1138, 1998 22. Lipshutz GS, Albanese CT, Feldstein VA, et al: prospective analysis of lung-to-head ratio predicts survival for patients with prenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg 32:1634, 1997 23. Adzick NS, Vacanti JP, Lillehei CW, et al: Fetal diaphragmatic hernia: Ultrasound diagnosis and clinical outcome in 38 cases from a single medical center. J Pediatr Surg 24:654-660, 1981 24. Glick PL, Leach CL, Besner GE, et al: Pathophysiology of
congenital diaphragmatic hernia. III: Exogenous surfactant therapy for the high-risk neonate with CDH. J Pediatr Surg 27:866-869, 1992 25. 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 22:S77-S82, 1994 26. Frostell CG, Lonnqvist PA, Sonesson SE, et al: Near-fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia. Successful use of inhaled nitric oxide. Anaesthesist 48:679-683, 1993 27. Henneberg SW, Jespen S, Andersen PD, et al: Inhalation of nitric oxide as a treatment of pulmonary hypertension in congenital diphragmatic hernia. J Pediatr Surg 30:853-855, 1995 28. Dillon PW, Cilley RE, Hudome SM, et al: Nitric oxide reversal of recurrent pulmonary hypertension and respiratory failure in an infant with CDH after successful ECMO therapy. J Pediatr Surg 30:743-744, 1995 29. Hirschl RB, Fox W, Glick PL, et al: A prospective, randomized pilot trial of perfluorocarbon-induced lung growth in newborns with congenital diaphragmatic hernia. J Pediatr Surg 38:283-289, 2003 30. Bartlett RH, Gazzaniga AB, Toomasian J, et al: Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases. Ann Surg 204:236-245, 1986 31. Langham MR Jr, Krummel TM, Bartlett RH, et al: Mortality with extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernia in 93 infants. J Pediatr Surg 22:11501154, 1987 32. Redmond C, Heaton J, Calix J, et al: A correlation of pulmonary hypoplasia, mean airway pressure, and survival in congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation. J Pediatr Surg 22:1143-1149, 1987 33. Wung JT, James LS, Kilchevsky E, et al: Management of infants with severe respiratory failure and persistence of the fetal circulation without hyperventilation. Pediatrics 76:488-494, 1985 34. Kayes DW, Langham MR Jr, Ledbetter DJ, et al: Detrimental effects of standard medical therapy in congenital diaphragmatic hernia. Ann Surg 230:340-348; discussion 348-351, 1999 35. Wung JT, Sahni R, Moffitt ST, et al: Congenital diaphragmatic hernia: Survival treated with very delayed surgery, spontaneous respiraton, and no chest tube. J Pediatr Surg 30:406-409, 1995 36. Frenckner B, Ehren H, Granholm T, et al: Improved results in patients who have congenital diaphragmatic hernia using preoperative stablization, extracorporeal membrane oxygenation, and delayed surgery. J Pediatr Surg 32:1185-1189, 1997
Discussion D. Cass (Houston, TX): Alan, thank you very much for sharing your experience with us. I have 2 questions. First, what happened to the 5 patients that were diagnosed postnatally? It is a small number, but did any of those patients die? A. W. Flake (response): We had 1 death in the postnatal group, and we had 3 that required ECMO out of the 5.
D. Cass: Second, this is a high patch rate. What are your indications for using a patch? Do you have a similar rate of patching on the left side? A. W. Flake (response): My indication is pretty simple. If I can’t close the diaphragm primarily, I will use a patch. That was the case in this series as well. I think the patch rates are fairly similar between right and left, perhaps a little higher on the left in fact in our group.