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Prenatal diagnosis and natural history of the fetus with a congenital diaphragmatic hernia: Initial clinical experience
Prenatal Diagnosis and Natural History of the Fetus With a Congenital Diaphragmatic Hernia: Initial Clinical Experience By Don K. Nakayama, Michael R. Harrison, Daryl H. Chinn, Peter W. Callen, Roy A. Filly, Mitchell S. Golbus, and Alfred A. De Lorimier San Francisco, California 9 To study the accuracy of prenatal diagnosis and define the natural history of fetal congenital diaphragmatic hernia (CDH), w e reviewed experience with CDH at The University of California, San Francisco (UCSF) over the last three years. All nine babies born in our institution (inborns) and six of 11 babies referred from other hospitals after birth (outborns) died, an overall mortality of 75%. All had pulmonary hypoplasia. Forty percent had associated malformations or chromosomal abnormalities, a higher incidence than generally reported. Prenatal sonograms w e r e available in all nine inborn cases. CDH was correctly diagnosed prospectively in only five, but could be recognized retrospectively in all nine cases using the sonographic criteria developed from the study. Polyhydramnios was present in all nine cases; in seven cases sonography was performed because the w o m a n was large-for-dates clinically. There w e r e no false positive interpretations, and w h e n necessary the diagnosis was confirmed by amniography. All nine cases of CDH detected in utero died. Seven deteriorated so rapidly that surgical repair could not even be attempted. T w o w h o had optimal care (maternal transport, immediate resuscitation and operation) died after repair despite maximal intensive care including vasodilator therapy. Despite the theoretical advantages of maternal transport to pediatric surgical specialty centers, a majority of fetuses with a prenatal diagnosis of CDH will die because their lungs are inadequate to support extra-uterine life even at term. 9 1 9 8 5 by Grune & Stratton. Inc. INDEX W O R D S : Congenital diaphragmatic hernia; prenatal sonography; fetal surgery.
E C A U S E T H E m o r t a l i t y of c o n g e n i t a l diaphragmatic hernia (CDH) remains high d e s p i t e significant a d v a n c e s in p e r i n a t a l a n d n e o n a t a l intensive care, 1'2 f u r t h e r i m p r o v e m e n t in o u t c o m e m a y lie in t h e p r e n a t a l s u r g i c a l r e p a i r
B
From the Fetal Treatment Program, Division o f Pediatric Surgery, Departments o f Surgery, Radiology, Obstetrics, Gynecology, and Reproductive Sciences, University o f California, San Francisco. Address reprint requests to Michael R. Harrison, MD, Room 585 HSE, University of California, San Francisco, CA 94143. 9 1985 by Grune & Stratton, Inc. 0022-3468/85/2002-0003503.00/0 118
of C D H . 3 In t h e o r y , the fetus w o u l d r e t a i n t h e vital gas e x c h a n g e f u n c t i o n s of t h e p l a c e n t a , w h i l e t h e lungs, r e l i e v e d of c o m p r e s s i o n by surgical r e d u c t i o n of t h e hernia, c o u l d g r o w a n d a c h i e v e a f u n c t i o n a l l y a d e q u a t e size by t e r m . A discussion o f t h e p o t e n t i a l benefit o f in u t e r o s u r g i c a l r e p a i r of C D H m u s t i n c l u d e t h e a c c u r a c y of p r e n a t a l u l t r a s o u n d diagnosis, and t h e n a t u r a l history o f a fetus w i t h t h e s o n o g r a p h i c findings of C D H . T h e r e f o r e we r e v i e w e d all cases of C D H a d m i t t e d to t h e U n i v e r s i t y of California, San Francisco (UCSF) during the p a s t t h r e e years, a p e r i o d o f i n c r e a s i n g i n t e r e s t in p r e n a t a l d i a g n o s i s a n d t r e a t m e n t at o u r institution. MATERIALS AND METHODS We reviewed the clinical records of babies with CDH at birth from July 1979 through June 1982 at UCSF. The group included babies born at our institution (inborns) and those transferred from other hospitals (outborns). We reviewed the prenatal sonograms in those cases in which obstetric ultrasonographic examinations were performed. In those cases where an accurate prenatal diagnosis of CDH was made, the sonographic features, the prenatal management, and the postnatal outcome were noted. If the prenatal diagnosis was missed, then sonograms were reviewed for features that may have allowed the prenatal detection of CDH in retrospect. These included a fluid-filled viscus in the thorax; shift in the position of the heart, indicating a mediastinal shift; a pleural effusion; an asymmetery in the echogenicity of the thorax; ascites; polyhydramnios; and the presence of associated malformations. These were reviewed by one of us (DHC) who did not know the cases or their outcomes. The sonograms and the details are further described in a separate report. 4 The available obstetrical history was reviewed for any clinical problems during the prenancy and labor. The postnatal course was reviewed. Details of postnatal management at our institution have been published previously. 1The period of study coincided with a period of active use of vasodilator (tolazoline) therapy in infants suffering from pulmonary hypertension associated with CDH, and other cardiotonic drugs (dopamine or isoproterenol) were also used frequently. The timing of operative ~'epair was noted in cases coming to surgery. The presence of associated malformations was determined from clinical examinations in the charts or from autopsy reports. Patent ductus arteriosus and patent foramen ovale were excluded because of their relationship to persistent fetal circulation (PFC) complicating CDH. 1'5 Journal of Pediatric Surgery, Vo120, No 2 (April), 1985: pp 118-124
FETAL DIAPHRAGMATIC HERNIA
RESULTS
Twenty babies had clinically recognized CDH at birth during the past three years, nine inborn (Table 1) and 11 outborn (Table 2). All inborn babies died. Five babies survived, all outborn babies. Fifteen cases of CDH were fatal, a mortality of 75%. All deaths were due to respiratory insufficiency, and pulmonary hypoplasia was present at autopsy. Death occurred within one hour of birth in five inborn cases. One outborn case was transported to UCSF within four hours of birth, but the baby was moribund on arrival and could not be resuscitated. Surgery was deferred in one inborn and one outborn because of severe anomalies associated with trisomy 18 and 13, respectively, and the babies were allowed to expire. One fetus demonstrated irregularities in heart rate on admission and died in utero before a delivery could be performed. Hernia repairs were performed in 11 cases, all within 24 hours of birth. Six operated cases ended fatally within three days of operation, an operative mortality of 55%. No unoperated babies survived. Prenatal ultrasonographic examinations of the fetuses were performed in ten cases, nine inborn and one outborn (Table 1). An accurate diagnosis of CDH was made in five cases. This allowed maternal transport for delivery in our institution in cases 1 and 6. Despite the logistical advantage of having a neonatal resuscitation team close at hand at delivery, both babies died of respiratory insufficiency soon after birth. Prenatal diagnosis allowed an attempt at prenatal treatment in case 5. At 33 menstrual weeks the fetus was found to have a right-sided CDH and a massive amount of fetal ascites. Because the volume of abdominal fluid was thought to be compressing the fetal thorax from below, a fine needle was passed percutaneously through the maternal abdomen and 225 mL of fetal ascites was aspirated. This decreased intraabdominal volume by nearly one half. The right hemidiaphragm appeared to move inferiorly during the procedure. The fetal abdomen was again aspirated one week later because of reaccumulation of fluid. Because the positions of the diaphragm and mediastinum were partially dependent on the volume of ascites, at 36 weeks a catheter was inserted percutaneously into the fetal abdomen to drain intraabdominal fluid into the amniotic
1 19
sac in an attempt at chronic drainage in utero. The catheter decompressed the fetal abdomen, and the right hemidiaphragm and mediastinum moved toward their normal positions, although not completely. The baby was delivered at 37 weeks, but died one hour after birth of irreversible respiratory insufficiency due to bilateral pulmonary hypoplasia (Figure 1). On review of the sonograms in which the diagnosis was missed, findings were present that allowed an accurate retrospective diagnosis of fetal CDH to be made in three cases. Careful reexamination revealed abdominal viscera in the fetal thorax which was easily recognizable as liver and gallbladder in one case and stomach in two. In all three cases the heart was abnormally positioned, reflecting a shift in the mediastinum due to herniated intrathoracic viscera. The diagnosis of CDH was therefore considered possible in these false-negative cases. In case 7 the prenatal ultrasound diagnosis was confirmed by amniography and computerized tomography (Figure 2). These additional tests were necessary to avoid a false-positive diagnosis of fetal CDH, because prenatal intervention was being considered. All cases that demonstrated features of CDH on prenatal ultrasonography ended fatally within 72 hours of birth. Polyhydramnios was present in nine of ten cases of CDH in which prenatal ultrasonography was performed. In those cases examined by prenatal ultrasound, associated anomalies were detected prenatally in five (two urinary tract obstructions, two nonimmune ascites, and one congenital heart defect). One baby, normal on prenatal ultrasound evaluation, was born with an unsuspected trisomy 18 and cleft palate. Associated malformations were present in five inborn and three outborn babies, a total incidence of 4O%. DISCUSSION
Our series confirms the very high mortality of CDH. The mortality of previous reports from surgical series have been shown to be biased by referral patterns. 2 Operative series from referral centers report mortalities of 10% to 30%; these do not include cases ending in death prior to transfer. When birth registries are reviewed for all deaths due to CDH, the mortality increases to 50% to 80%. Our series of nine cases of CDH
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Table 1. Congenital Diaphragmatic Hernia (CDH): Prenatal Sonography, Management, and Outcome Among Infants Born at U.C.S.F. (Inborns)
Case No 1
2
3
4
5
Maternal Indication 36 YO G4 P3 Sono @ 30 wks Large for dates 31 YO G2 PO Ab 1 Sono @ 38 wks Large for dates 25 YO G 1 PO Sono @ 33 wks Large for dates
35 YO G4 P3 Sono @ 30 wks Large for dates 22 YO G3 P 1 Ab 1 Sono @ 33 wks Large for dates
Abnormal Upper Polyhydramnios Abdomen
Mediastinai Shift
Viscus in Thorax
Other Findings
CDH Recognized initial/ Retrospect
+
+
Left
Liver, gallbladder
Hydrops, ascites, pleural effusion
No/Yes
4-
+
Right
Stomach
? SGA
No/yes
4-
4-
Anterior
Stomach
Bilateral hydronephrosis (UPJ obstruction)
No/Yes
+
Outside sonogram
No/?
+
+
Left
Liver, gallbladder
Massive ascites
Yes/Yes
6
28 YO G3 P2 Sono @ 34 wks Large for dates
+
§
Left
Liver, gallbladder
Right heart enlargement, dysplastic tricuspid valve
Yes/Yes
7
23 YO G2 P 1 Sono @ 26 wks Large for dates
+
+
Right
Stomach, bowel
? Mild, left hydronephrosis
Yes/Yes
8
27 Y0 G 1 P0 Sono @ 37 wks Check dates
--
+
Right
Stomach, bowel
9
23 YO G3 P2 Sono @ 26 wks Large for dates
+
+
Left
Liver
Yes/Yes
Hydrops, ascites
Yes/Yes
Abbrev: ASD, atrial septal defect; C/S, cesarean section; CT, computerized tomography; Dx, diagnosis; L/S, lecithin-to-sphingomyelin; PROM, premature rupture of membranes; Rx, treatment; SGA, small for gestational age; UP J, ureteropelvic junction; VSD, ventricular septal defect.
FETAL DIAPHRAGMATIC HERNIA
121
Table 1. (Continued)
Prenatal Management
Postnatal Management
Outcome
Right CDH, & hydrops; follow sono; materal transport; PROM; spontaneous vaginal delivery @ 33 wks Left CDH; ? SGA; follow sono; spontaneous vaginal delivery @ 41 wks
2100 gram female; Severe respiratory distress; hydrops; prune belly; not resuscitated 2440 gram female; severe respiratory distress; dysmorphic (cleft lip, etc) probable trisomy; not resuscitated 4 6 0 0 gram male; respiratory distress; left CDH repaired; pulmonary sequestration; left nephrectomy, right nephrostomy
Died; Autopsy: right CDH (eventration), pulmonary hypoplasia, ascites, fetal hydrops Died; Autopsy: left CDH, pulmonary hypoplasia, bilateral cleft lip & palate (Trisomy 18) Died 1 day postop; Autopsy: repaired CDH, pulmonary hypoplasia, bilateral UPJ obstruction, (left nephrectomy, right nephrostomy), pulmonary sequestration Died; Autopsy: bilateral CDH pulmonary hypoplasia, otherwise normal
Hydronephrosis; serial sonograms; C/S at term
Polyhydramnios; follow sono; spontaneous vaginal delivery @ 42 wks Right CDH; ascites; serial sonograms; repeated aspiration ascites (225, 2 1 5 , 2 6 0 ) with lowering of the right hemidiaphragm; lungs immature on repeat amnio; catheter shunt drainage of ascites into amniotic cavity at 36 wks; amniocentesis ( 1000 mL) for polyhydramnios; spontaneous vaginal delivery @ 37 wks, betamethasone given Right CDH; congenital heart disease; L/S ratio 0.9 at 36 wks; maternal transport with irregular contractions X 2d; planned elective repeat C/S (Breech); PROM & fetal distress led to urgent C/S Left CDH; unilateral hydronephrosis; preterm labor; referred for in utero repair; DX confirmed by amniography and CT; ameiocentesis (1000 mL); ritodrine used to Rx contractions; surgery refused because active preterm labor increased risk; spontaneous preterm delivery at 27 wks Left CDH; maternal transport induced vaginal delivery at 38 wks
Right CDH & hydrops; referred for repair; DX confirmed, but Rx refused because lesion severe & hydrops; follow sono; fetal demise at 32 wks induced vaginal delivery
3800 gram male; severe respiratory distress; CXR--bilateral CDH; died before operation 2640 gram male; severe respiratory distress; massive ascites; Bilateral thoracentesis; no further resuscitation
1960 gram female; right CDH & congenital heart disease; not resuscitated
1200 gram male; severe respiratory distress; not resuscitated
3000 gram female; severe respiratory distress; immediate CDH repair
Died; Autopsy: bilateral CDH, pulmonary hypoplasia, otherwise normal
Stillborn; Autopsy: right CDH, small lungs, multiple anomalies (double outlet right ventricle VSD, ASD, bilateral hydronephrosis and hydroureter cleft palate, 2-vessel cord, small pleural effusions and ascites) Died; Autopsy: left CDH, pulmonary hypoplasia, ascites, otherwise normal
Died 10 hrs postop despite Priscoline/ Dopamine/Prostaglandin D2; Autopsy: left CDH, pulmonary hypoptasia, anasarca consistent with resuscitative efforts; otherwise normal infant Stillborn; hydropic; autopsy refused.
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Table 2. Congenital Diaphragmatic Hernia: Outcome Among Infants Transfered From Other Hospitals (Outborns)
Case
Obstetric History
10
Large-for-dates with polhydramnios on ultrasound
Gestational Age at Birth (Weeks)
Birthweight (g)
40
3,200
Left
1d
Survived
--
Otherwise normal
38
2,890
Left
ld
Survived
--
Otherwise normal
41
3,000
Right
ld
Died, 2d
Yes
PDA, ASD
40 Term 40
3,320 3,360 4,080
Left Left Left
11 h ld 1d
Survived Survived Survived
----
Otherwise normal Otherwise normal
39
3,520
Left
ld
Died, 3d
Yes
CDH
Age at Hernia Repair
Outcome
Pulmonary Hypoplasia
Other Findings
exam at 26 wks CDH not noted initially, but pres11
ent on retrospect Large-for-dates with clinical polyhydramnios; no prenatal sonography. Polydramios noted at de-
12
livery Large-for-dates with clinical polyhydramios: no prena-
13 14 15
tal sonography Unremarkable Unremarkable Unremarkable
16
Unremarkeble
17
Unremarkable
Term
3,500
Left
1Oh
Died, 12h
Yes
18 19
Unremarkable Unremarkable
Term Term
3,180 3,200
Left Left
1d None
Died, 2d Died, 4h
Yes Yes
20
Unremarkable
34
1,680
Left
None
Died, 6h
Yes
Otherwise normal Heavy, edematous lungs: bilateral bronchopneumonia with organizing alveolar damage Single umbilical artery absent IVC, PDA, ASD VSD, PDA, ASD PDA, ASD Trisomy 13, hypoplastic LV, VSD, truncus arteriosus
*Abbreviations same as in Table 1, including PDA, patent ductus arteriosus; IVC, inferior vena cava; LV, left ventricle.
detected prenatally reflects the general population of affected fetuses. Therefore, it is not surprising that all nine died shortly after birth. The prenatal diagnosis depends on demonstration of abdominal organs in the thorax on sonography. Although difficult to detect on routine sonograms, three easily detected features--polyhydramnios, shift of the mediastinum, and absence of an intraabdominal stomach bubble-should prompt a more careful search for herniated abdominal organs in the fetal chest. 4 When we applied these criteria to sonograms of fetuses with CDH previously misread as being normal, we felt that all the cases in our series could have been correctly diagnosed. Still, falsenegative diagnoses are certain to occur. If necessary, the diagnosis can be easily confirmed by amniography. Contrast material placed in the amniotic fluid and swallowed by the fetus opacifies the stomach or intestines in the fetal chest on plain radiograph or computerized tomogram of the maternal abdomen. False-positive interpretations may arise in cases of cystic lung disease (ie, congenital lobar emphysema, cystic adenoma-
told malformation). 6 Mediastinal cystic processes (ie, neurenteric cysts, bronchogenic cysts, thymic cysts) 6 may produce a fluid-filled structure within the chest that displaces the mediastinum, presenting a diagnostic challenge. We have been consulted by phone about a fetus thought to have a left CDH by sonogram at 25 weeks. On follow-up sonogram, the diagnosis was in doubt and the possibility of cystic lung disease was raised. The baby girl born at term had cystic lung disease (probably cystic adenomatoid malformation) but has remained asymptomatic and not required surgery thus far. In these difficult cases, we predict that the fetal upper abdominal anatomy would be normal on amniography and thereby exclude a large CDH (Figure 2). Multiple associated morphologic and chromosomal abnormalities were a common finding, occurring in 40% of our total series and seven of nine cases undergoing prenatal ultrasonography. Although previous reports have noted that associated anomalies are rare in CDH, with estimates ranging from "extreme paucity" to 10%, l'v these may reflect the influence of referral pat-
FETAL DIAPHRAGMATIC HERNIA
123
Fig 1. A u t o p s y findings in Case 5. Massive ascites associated w i t h a right-sided CDH was aspirated and then s h u n t e d into the a m n i o t i c sac before birth to d e c r e a s e the lung compression by the intact hernia sac, but the lungs w e r e already too hypoplastic. The right lobe of the liver is herniated into the right chest. Before birth, the hernia sac w a s distended by massive fetal ascites and the right lobe of the liver. The hernia compressed t h e developing lung resulting in fatal pulmonary hypoplasia.
terns at those institutions. Although our numbers are limited, our incidence of 40% suggests that associated anomalies in CDH are common. Because this is a higher frequency than is generally appreciated, all fetuses suspected of having CDH should have a thorough examination by an experienced sonographer to detect major cardiac, urologic, and other structural anomalies. Amniocentesis for karyotype analysis should also be performed. Polyhydramnios, a nonspecific sign that has been associated with numerous congenital anomalies, was seen in nine of ten cases examined. Although the etiology of polyhydramnios is unclear in CDH, impaired fetal swallowing of amniotic fluid due to the compression of the esophagus from herniated abdominal organs may play a role. Despite its lack of specificity for
Fig 2. (A) Amniogram in case 7 confirmed the diagnosis of a left CDH. On conventional radiograph, the contrastfilled intestine can be seen only faintly. (B) Single section CT at the level of the fetal t h o r a x shows the contrast-filled intestine abnormally positioned in the fetal chest. Note the greater contrast density in the small bowel (SB} relative to the stomach (St). This is due to w a t e r resorption within t h e small bowel. Note large amount of amniotic fluid (AF). Polyhydramnios is common w i t h fetal CDH and may lead to ultrasonographic diagnosis.
CDH, polyhydramnios signals the possibility of anomalies being present and is an indication for sonography. 6
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NAKAYAMA ET AL
A t present the principal a d v a n t a g e of p r e n a t a l detection of C D H is t h a t postnatal care can be facilitated. T h e m o t h e r can be t r a n s p o r t e d to a neonatal center where the b a b y can be electively delivered, resuscitated, and r e p a i r e d by a fully p r e p a r e d t e a m of neonatologists and surgeons. T h e fetus with congenital d i a p h r a g m a t i c h e r n i a is in no d a n g e r until birth, so m a t e r n a l t r a n s p o r t is far safer than resuscitation and t r a n s p o r t of the critically ill neonate. 8'9 However, even with these advantages, most fetuses with a p r e n a t a l diagnosis of C D H will die shortly after birth. D e a t h s in C D H a r e due to r e s p i r a t o r y insufficiency related to p u l m o n a r y hypoplasia. T h e p u l m o n a r y hypoplasia universally seen with congenital d i a p h r a g m a t i c hernia has been well documented, both clinically and experimentally, and is p r e s u m a b l y secondary to the presence of bowel in the chest during development of the lung in utero. 5'1~ Survival a p p e a r s to be independent of surgical reduction of herniated i n t r a t h o r a c i c viscera, and depends instead upon the severity of r e s p i r a t o r y distress and the degree of p u l m o n a r y hypoplasia at birth. 7'~2 S o m e babies have mild hypoplasia and will survive with a p p r o p r i a t e care. A few babies with m o d e r a t e hypoplasia m a y be salvaged by m a n i p u l a t i o n of p u l m o n a r y h e m o d y n a m i c s with p u l m o n a r y vasodilators or
possibly by t e m p o r a r y m e m b r a n e o x y g e n a tion. 13A4 However, most babies with C D H have severe p u l m o n a r y hypoplasia and cannot survive even with p r o m p t surgical correction and optim u m neonatal intensive care. These babies simply do not have a d e q u a t e p u l m o n a r y function to support life at birth. If the p u l m o n a r y hypoplasia is a developmental consequence of compression by the h e r n i a t e d viscera, removal of this space-occupying lesion in utero m a y allow pulm o n a r y development to proceed normally. Thus, correcting C D H in utero m a y allow the lung to develop sufficiently to support life at b i r t h ] 5 T h e p r o b l e m in the m a j o r i t y of cases is not how to get the lung to grow after neonatal correction, but how to get the lung to grow and develop before birth to the point where it can support life at birth. W e have d e m o n s t r a t e d t h a t correction of C D H in utero is physiologically s o u n d a n d t e c h n i c a l l y f e a s i b l e in f e t a l lambs,~ ~,~5,16but e x t r a p o l a t i o n to the h u m a n fetus with C D H is not yet possible. In utero surgical intervention should not be a t t e m p t e d until anesthetic and surgical techniques to control uterine contractility are proven effective and a high degree of success is achieved in the rigorous n o n h u m a n p r i m a t e model.
REFERENCES
1. Harrison MR, de Lorimier AA: Congenital diaphragmatic hernia, in Grosfeld JL (ed): Neonatal Surgery. Surgery Clinics of North America, 61:1023-1035, 1981 2. Harrison MR, Bjordal RI, Landmark F, et al: Congenital diaphragmatic hernia: The hidden mortality. J Pediatr Surg 13:227-232, 1979 3. Harrison MR, Golbus MS, Filly RA: Management of the fetus with a correctable congenital defect. JAMA 246:774 776, 1981 4. Chinn DH, Filly RA, Callen PW, et al: Prenatal ultrasonographic diagnosis of congenital diaphragmatic hernia. Radiology 148:119 123, 1983 5. Inselman LS, Mellins RB: Growth and development of the lung. Pediatr 98:1, 1981 6. Knochel JQ, Lee TG, Melendez MG, et al: Fetal anomalies involving the thorax and abdomen, in Callen PW (ed): Ultrasonography in Obstetrics and Gynecology. Philadelphia, WB Saunders, 1983, pp 61 80 7. Johnson DG, Deaner RM, Koop CE: Diaphragmatic hernia in infancy: Factors affecting the mortality rate. Surgery 62:1082-1091, 1967 8. Harri BA Jr, Wirtschafter DD, Huddleston JF, et al: In utero versus neonatal transportation of high-risk perinates: A comparison. Obstet Gynecol 57:496-499, 1981 9. Levy DL, Noelke K, Goldsmith JP: Maternal and infant transport program in Louisiana. Obstet Gynecol 57:50(~504, 198t
10. Levin DL: Morphologic analysis of the pulmonary vascular bed in congenital left-sided diaphragmatic hernia. J Pediatr 92:805-809, 1973 11. Harrison MR, Jester JA, Ross NA: Correction of congenital diaphragmatic hernia in utero. I. The Model: Intrathoracic balloon produces fatal pulmonary hypoplasia. Surgery 88:174-182, 1980 12. Dibbins AW, Wiener ES: Mortality from neonatal diaphragmatic hernia. J Pediatr Surg 9:653 662, 1974 13. Bloss RS, Arando JV, Beardmore HE: Congenital diaphragmatic hernia: Pathophysiology and pharmacolic support. Surgery 89:418, t981 14. German JC, Gazzaniga AB, Amlie R, et al: Management of pulmonary insufficiency in diaphragmatic hernia using extracorporeal circulation with membrane oxygenator. J Pediatr Surg 12:905, 1977 15. Harrison MR, Bressack MA, Churg AM, et al: Correction of congenital diaphragmatic hernia in utero. II. Simulated correction permits fetal lung growth with survival at birth. Surgery 88:260-268, 1980 16. Harrison MR, Ross NA, de Lorimier AA: Correction of congenital diaphragmatic hernia in utero. III. Development of a successful surgical techniques using abdominoplasty to avoid compromise of umbilical blood flow. J Pediatr Surg 16:934-942, 1981
E C A U S E T H E m o r t a l i t y of c o n g e n i t a l diaphragmatic hernia (CDH) remains high d e s p i t e significant a d v a n c e s in p e r i n a t a l a n d n e o n a t a l intensive care, 1'2 f u r t h e r i m p r o v e m e n t in o u t c o m e m a y lie in t h e p r e n a t a l s u r g i c a l r e p a i r
B
From the Fetal Treatment Program, Division o f Pediatric Surgery, Departments o f Surgery, Radiology, Obstetrics, Gynecology, and Reproductive Sciences, University o f California, San Francisco. Address reprint requests to Michael R. Harrison, MD, Room 585 HSE, University of California, San Francisco, CA 94143. 9 1985 by Grune & Stratton, Inc. 0022-3468/85/2002-0003503.00/0 118
of C D H . 3 In t h e o r y , the fetus w o u l d r e t a i n t h e vital gas e x c h a n g e f u n c t i o n s of t h e p l a c e n t a , w h i l e t h e lungs, r e l i e v e d of c o m p r e s s i o n by surgical r e d u c t i o n of t h e hernia, c o u l d g r o w a n d a c h i e v e a f u n c t i o n a l l y a d e q u a t e size by t e r m . A discussion o f t h e p o t e n t i a l benefit o f in u t e r o s u r g i c a l r e p a i r of C D H m u s t i n c l u d e t h e a c c u r a c y of p r e n a t a l u l t r a s o u n d diagnosis, and t h e n a t u r a l history o f a fetus w i t h t h e s o n o g r a p h i c findings of C D H . T h e r e f o r e we r e v i e w e d all cases of C D H a d m i t t e d to t h e U n i v e r s i t y of California, San Francisco (UCSF) during the p a s t t h r e e years, a p e r i o d o f i n c r e a s i n g i n t e r e s t in p r e n a t a l d i a g n o s i s a n d t r e a t m e n t at o u r institution. MATERIALS AND METHODS We reviewed the clinical records of babies with CDH at birth from July 1979 through June 1982 at UCSF. The group included babies born at our institution (inborns) and those transferred from other hospitals (outborns). We reviewed the prenatal sonograms in those cases in which obstetric ultrasonographic examinations were performed. In those cases where an accurate prenatal diagnosis of CDH was made, the sonographic features, the prenatal management, and the postnatal outcome were noted. If the prenatal diagnosis was missed, then sonograms were reviewed for features that may have allowed the prenatal detection of CDH in retrospect. These included a fluid-filled viscus in the thorax; shift in the position of the heart, indicating a mediastinal shift; a pleural effusion; an asymmetery in the echogenicity of the thorax; ascites; polyhydramnios; and the presence of associated malformations. These were reviewed by one of us (DHC) who did not know the cases or their outcomes. The sonograms and the details are further described in a separate report. 4 The available obstetrical history was reviewed for any clinical problems during the prenancy and labor. The postnatal course was reviewed. Details of postnatal management at our institution have been published previously. 1The period of study coincided with a period of active use of vasodilator (tolazoline) therapy in infants suffering from pulmonary hypertension associated with CDH, and other cardiotonic drugs (dopamine or isoproterenol) were also used frequently. The timing of operative ~'epair was noted in cases coming to surgery. The presence of associated malformations was determined from clinical examinations in the charts or from autopsy reports. Patent ductus arteriosus and patent foramen ovale were excluded because of their relationship to persistent fetal circulation (PFC) complicating CDH. 1'5 Journal of Pediatric Surgery, Vo120, No 2 (April), 1985: pp 118-124
FETAL DIAPHRAGMATIC HERNIA
RESULTS
Twenty babies had clinically recognized CDH at birth during the past three years, nine inborn (Table 1) and 11 outborn (Table 2). All inborn babies died. Five babies survived, all outborn babies. Fifteen cases of CDH were fatal, a mortality of 75%. All deaths were due to respiratory insufficiency, and pulmonary hypoplasia was present at autopsy. Death occurred within one hour of birth in five inborn cases. One outborn case was transported to UCSF within four hours of birth, but the baby was moribund on arrival and could not be resuscitated. Surgery was deferred in one inborn and one outborn because of severe anomalies associated with trisomy 18 and 13, respectively, and the babies were allowed to expire. One fetus demonstrated irregularities in heart rate on admission and died in utero before a delivery could be performed. Hernia repairs were performed in 11 cases, all within 24 hours of birth. Six operated cases ended fatally within three days of operation, an operative mortality of 55%. No unoperated babies survived. Prenatal ultrasonographic examinations of the fetuses were performed in ten cases, nine inborn and one outborn (Table 1). An accurate diagnosis of CDH was made in five cases. This allowed maternal transport for delivery in our institution in cases 1 and 6. Despite the logistical advantage of having a neonatal resuscitation team close at hand at delivery, both babies died of respiratory insufficiency soon after birth. Prenatal diagnosis allowed an attempt at prenatal treatment in case 5. At 33 menstrual weeks the fetus was found to have a right-sided CDH and a massive amount of fetal ascites. Because the volume of abdominal fluid was thought to be compressing the fetal thorax from below, a fine needle was passed percutaneously through the maternal abdomen and 225 mL of fetal ascites was aspirated. This decreased intraabdominal volume by nearly one half. The right hemidiaphragm appeared to move inferiorly during the procedure. The fetal abdomen was again aspirated one week later because of reaccumulation of fluid. Because the positions of the diaphragm and mediastinum were partially dependent on the volume of ascites, at 36 weeks a catheter was inserted percutaneously into the fetal abdomen to drain intraabdominal fluid into the amniotic
1 19
sac in an attempt at chronic drainage in utero. The catheter decompressed the fetal abdomen, and the right hemidiaphragm and mediastinum moved toward their normal positions, although not completely. The baby was delivered at 37 weeks, but died one hour after birth of irreversible respiratory insufficiency due to bilateral pulmonary hypoplasia (Figure 1). On review of the sonograms in which the diagnosis was missed, findings were present that allowed an accurate retrospective diagnosis of fetal CDH to be made in three cases. Careful reexamination revealed abdominal viscera in the fetal thorax which was easily recognizable as liver and gallbladder in one case and stomach in two. In all three cases the heart was abnormally positioned, reflecting a shift in the mediastinum due to herniated intrathoracic viscera. The diagnosis of CDH was therefore considered possible in these false-negative cases. In case 7 the prenatal ultrasound diagnosis was confirmed by amniography and computerized tomography (Figure 2). These additional tests were necessary to avoid a false-positive diagnosis of fetal CDH, because prenatal intervention was being considered. All cases that demonstrated features of CDH on prenatal ultrasonography ended fatally within 72 hours of birth. Polyhydramnios was present in nine of ten cases of CDH in which prenatal ultrasonography was performed. In those cases examined by prenatal ultrasound, associated anomalies were detected prenatally in five (two urinary tract obstructions, two nonimmune ascites, and one congenital heart defect). One baby, normal on prenatal ultrasound evaluation, was born with an unsuspected trisomy 18 and cleft palate. Associated malformations were present in five inborn and three outborn babies, a total incidence of 4O%. DISCUSSION
Our series confirms the very high mortality of CDH. The mortality of previous reports from surgical series have been shown to be biased by referral patterns. 2 Operative series from referral centers report mortalities of 10% to 30%; these do not include cases ending in death prior to transfer. When birth registries are reviewed for all deaths due to CDH, the mortality increases to 50% to 80%. Our series of nine cases of CDH
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Table 1. Congenital Diaphragmatic Hernia (CDH): Prenatal Sonography, Management, and Outcome Among Infants Born at U.C.S.F. (Inborns)
Case No 1
2
3
4
5
Maternal Indication 36 YO G4 P3 Sono @ 30 wks Large for dates 31 YO G2 PO Ab 1 Sono @ 38 wks Large for dates 25 YO G 1 PO Sono @ 33 wks Large for dates
35 YO G4 P3 Sono @ 30 wks Large for dates 22 YO G3 P 1 Ab 1 Sono @ 33 wks Large for dates
Abnormal Upper Polyhydramnios Abdomen
Mediastinai Shift
Viscus in Thorax
Other Findings
CDH Recognized initial/ Retrospect
+
+
Left
Liver, gallbladder
Hydrops, ascites, pleural effusion
No/Yes
4-
+
Right
Stomach
? SGA
No/yes
4-
4-
Anterior
Stomach
Bilateral hydronephrosis (UPJ obstruction)
No/Yes
+
Outside sonogram
No/?
+
+
Left
Liver, gallbladder
Massive ascites
Yes/Yes
6
28 YO G3 P2 Sono @ 34 wks Large for dates
+
§
Left
Liver, gallbladder
Right heart enlargement, dysplastic tricuspid valve
Yes/Yes
7
23 YO G2 P 1 Sono @ 26 wks Large for dates
+
+
Right
Stomach, bowel
? Mild, left hydronephrosis
Yes/Yes
8
27 Y0 G 1 P0 Sono @ 37 wks Check dates
--
+
Right
Stomach, bowel
9
23 YO G3 P2 Sono @ 26 wks Large for dates
+
+
Left
Liver
Yes/Yes
Hydrops, ascites
Yes/Yes
Abbrev: ASD, atrial septal defect; C/S, cesarean section; CT, computerized tomography; Dx, diagnosis; L/S, lecithin-to-sphingomyelin; PROM, premature rupture of membranes; Rx, treatment; SGA, small for gestational age; UP J, ureteropelvic junction; VSD, ventricular septal defect.
FETAL DIAPHRAGMATIC HERNIA
121
Table 1. (Continued)
Prenatal Management
Postnatal Management
Outcome
Right CDH, & hydrops; follow sono; materal transport; PROM; spontaneous vaginal delivery @ 33 wks Left CDH; ? SGA; follow sono; spontaneous vaginal delivery @ 41 wks
2100 gram female; Severe respiratory distress; hydrops; prune belly; not resuscitated 2440 gram female; severe respiratory distress; dysmorphic (cleft lip, etc) probable trisomy; not resuscitated 4 6 0 0 gram male; respiratory distress; left CDH repaired; pulmonary sequestration; left nephrectomy, right nephrostomy
Died; Autopsy: right CDH (eventration), pulmonary hypoplasia, ascites, fetal hydrops Died; Autopsy: left CDH, pulmonary hypoplasia, bilateral cleft lip & palate (Trisomy 18) Died 1 day postop; Autopsy: repaired CDH, pulmonary hypoplasia, bilateral UPJ obstruction, (left nephrectomy, right nephrostomy), pulmonary sequestration Died; Autopsy: bilateral CDH pulmonary hypoplasia, otherwise normal
Hydronephrosis; serial sonograms; C/S at term
Polyhydramnios; follow sono; spontaneous vaginal delivery @ 42 wks Right CDH; ascites; serial sonograms; repeated aspiration ascites (225, 2 1 5 , 2 6 0 ) with lowering of the right hemidiaphragm; lungs immature on repeat amnio; catheter shunt drainage of ascites into amniotic cavity at 36 wks; amniocentesis ( 1000 mL) for polyhydramnios; spontaneous vaginal delivery @ 37 wks, betamethasone given Right CDH; congenital heart disease; L/S ratio 0.9 at 36 wks; maternal transport with irregular contractions X 2d; planned elective repeat C/S (Breech); PROM & fetal distress led to urgent C/S Left CDH; unilateral hydronephrosis; preterm labor; referred for in utero repair; DX confirmed by amniography and CT; ameiocentesis (1000 mL); ritodrine used to Rx contractions; surgery refused because active preterm labor increased risk; spontaneous preterm delivery at 27 wks Left CDH; maternal transport induced vaginal delivery at 38 wks
Right CDH & hydrops; referred for repair; DX confirmed, but Rx refused because lesion severe & hydrops; follow sono; fetal demise at 32 wks induced vaginal delivery
3800 gram male; severe respiratory distress; CXR--bilateral CDH; died before operation 2640 gram male; severe respiratory distress; massive ascites; Bilateral thoracentesis; no further resuscitation
1960 gram female; right CDH & congenital heart disease; not resuscitated
1200 gram male; severe respiratory distress; not resuscitated
3000 gram female; severe respiratory distress; immediate CDH repair
Died; Autopsy: bilateral CDH, pulmonary hypoplasia, otherwise normal
Stillborn; Autopsy: right CDH, small lungs, multiple anomalies (double outlet right ventricle VSD, ASD, bilateral hydronephrosis and hydroureter cleft palate, 2-vessel cord, small pleural effusions and ascites) Died; Autopsy: left CDH, pulmonary hypoplasia, ascites, otherwise normal
Died 10 hrs postop despite Priscoline/ Dopamine/Prostaglandin D2; Autopsy: left CDH, pulmonary hypoptasia, anasarca consistent with resuscitative efforts; otherwise normal infant Stillborn; hydropic; autopsy refused.
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Table 2. Congenital Diaphragmatic Hernia: Outcome Among Infants Transfered From Other Hospitals (Outborns)
Case
Obstetric History
10
Large-for-dates with polhydramnios on ultrasound
Gestational Age at Birth (Weeks)
Birthweight (g)
40
3,200
Left
1d
Survived
--
Otherwise normal
38
2,890
Left
ld
Survived
--
Otherwise normal
41
3,000
Right
ld
Died, 2d
Yes
PDA, ASD
40 Term 40
3,320 3,360 4,080
Left Left Left
11 h ld 1d
Survived Survived Survived
----
Otherwise normal Otherwise normal
39
3,520
Left
ld
Died, 3d
Yes
CDH
Age at Hernia Repair
Outcome
Pulmonary Hypoplasia
Other Findings
exam at 26 wks CDH not noted initially, but pres11
ent on retrospect Large-for-dates with clinical polyhydramnios; no prenatal sonography. Polydramios noted at de-
12
livery Large-for-dates with clinical polyhydramios: no prena-
13 14 15
tal sonography Unremarkable Unremarkable Unremarkable
16
Unremarkeble
17
Unremarkable
Term
3,500
Left
1Oh
Died, 12h
Yes
18 19
Unremarkable Unremarkable
Term Term
3,180 3,200
Left Left
1d None
Died, 2d Died, 4h
Yes Yes
20
Unremarkable
34
1,680
Left
None
Died, 6h
Yes
Otherwise normal Heavy, edematous lungs: bilateral bronchopneumonia with organizing alveolar damage Single umbilical artery absent IVC, PDA, ASD VSD, PDA, ASD PDA, ASD Trisomy 13, hypoplastic LV, VSD, truncus arteriosus
*Abbreviations same as in Table 1, including PDA, patent ductus arteriosus; IVC, inferior vena cava; LV, left ventricle.
detected prenatally reflects the general population of affected fetuses. Therefore, it is not surprising that all nine died shortly after birth. The prenatal diagnosis depends on demonstration of abdominal organs in the thorax on sonography. Although difficult to detect on routine sonograms, three easily detected features--polyhydramnios, shift of the mediastinum, and absence of an intraabdominal stomach bubble-should prompt a more careful search for herniated abdominal organs in the fetal chest. 4 When we applied these criteria to sonograms of fetuses with CDH previously misread as being normal, we felt that all the cases in our series could have been correctly diagnosed. Still, falsenegative diagnoses are certain to occur. If necessary, the diagnosis can be easily confirmed by amniography. Contrast material placed in the amniotic fluid and swallowed by the fetus opacifies the stomach or intestines in the fetal chest on plain radiograph or computerized tomogram of the maternal abdomen. False-positive interpretations may arise in cases of cystic lung disease (ie, congenital lobar emphysema, cystic adenoma-
told malformation). 6 Mediastinal cystic processes (ie, neurenteric cysts, bronchogenic cysts, thymic cysts) 6 may produce a fluid-filled structure within the chest that displaces the mediastinum, presenting a diagnostic challenge. We have been consulted by phone about a fetus thought to have a left CDH by sonogram at 25 weeks. On follow-up sonogram, the diagnosis was in doubt and the possibility of cystic lung disease was raised. The baby girl born at term had cystic lung disease (probably cystic adenomatoid malformation) but has remained asymptomatic and not required surgery thus far. In these difficult cases, we predict that the fetal upper abdominal anatomy would be normal on amniography and thereby exclude a large CDH (Figure 2). Multiple associated morphologic and chromosomal abnormalities were a common finding, occurring in 40% of our total series and seven of nine cases undergoing prenatal ultrasonography. Although previous reports have noted that associated anomalies are rare in CDH, with estimates ranging from "extreme paucity" to 10%, l'v these may reflect the influence of referral pat-
FETAL DIAPHRAGMATIC HERNIA
123
Fig 1. A u t o p s y findings in Case 5. Massive ascites associated w i t h a right-sided CDH was aspirated and then s h u n t e d into the a m n i o t i c sac before birth to d e c r e a s e the lung compression by the intact hernia sac, but the lungs w e r e already too hypoplastic. The right lobe of the liver is herniated into the right chest. Before birth, the hernia sac w a s distended by massive fetal ascites and the right lobe of the liver. The hernia compressed t h e developing lung resulting in fatal pulmonary hypoplasia.
terns at those institutions. Although our numbers are limited, our incidence of 40% suggests that associated anomalies in CDH are common. Because this is a higher frequency than is generally appreciated, all fetuses suspected of having CDH should have a thorough examination by an experienced sonographer to detect major cardiac, urologic, and other structural anomalies. Amniocentesis for karyotype analysis should also be performed. Polyhydramnios, a nonspecific sign that has been associated with numerous congenital anomalies, was seen in nine of ten cases examined. Although the etiology of polyhydramnios is unclear in CDH, impaired fetal swallowing of amniotic fluid due to the compression of the esophagus from herniated abdominal organs may play a role. Despite its lack of specificity for
Fig 2. (A) Amniogram in case 7 confirmed the diagnosis of a left CDH. On conventional radiograph, the contrastfilled intestine can be seen only faintly. (B) Single section CT at the level of the fetal t h o r a x shows the contrast-filled intestine abnormally positioned in the fetal chest. Note the greater contrast density in the small bowel (SB} relative to the stomach (St). This is due to w a t e r resorption within t h e small bowel. Note large amount of amniotic fluid (AF). Polyhydramnios is common w i t h fetal CDH and may lead to ultrasonographic diagnosis.
CDH, polyhydramnios signals the possibility of anomalies being present and is an indication for sonography. 6
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A t present the principal a d v a n t a g e of p r e n a t a l detection of C D H is t h a t postnatal care can be facilitated. T h e m o t h e r can be t r a n s p o r t e d to a neonatal center where the b a b y can be electively delivered, resuscitated, and r e p a i r e d by a fully p r e p a r e d t e a m of neonatologists and surgeons. T h e fetus with congenital d i a p h r a g m a t i c h e r n i a is in no d a n g e r until birth, so m a t e r n a l t r a n s p o r t is far safer than resuscitation and t r a n s p o r t of the critically ill neonate. 8'9 However, even with these advantages, most fetuses with a p r e n a t a l diagnosis of C D H will die shortly after birth. D e a t h s in C D H a r e due to r e s p i r a t o r y insufficiency related to p u l m o n a r y hypoplasia. T h e p u l m o n a r y hypoplasia universally seen with congenital d i a p h r a g m a t i c hernia has been well documented, both clinically and experimentally, and is p r e s u m a b l y secondary to the presence of bowel in the chest during development of the lung in utero. 5'1~ Survival a p p e a r s to be independent of surgical reduction of herniated i n t r a t h o r a c i c viscera, and depends instead upon the severity of r e s p i r a t o r y distress and the degree of p u l m o n a r y hypoplasia at birth. 7'~2 S o m e babies have mild hypoplasia and will survive with a p p r o p r i a t e care. A few babies with m o d e r a t e hypoplasia m a y be salvaged by m a n i p u l a t i o n of p u l m o n a r y h e m o d y n a m i c s with p u l m o n a r y vasodilators or
possibly by t e m p o r a r y m e m b r a n e o x y g e n a tion. 13A4 However, most babies with C D H have severe p u l m o n a r y hypoplasia and cannot survive even with p r o m p t surgical correction and optim u m neonatal intensive care. These babies simply do not have a d e q u a t e p u l m o n a r y function to support life at birth. If the p u l m o n a r y hypoplasia is a developmental consequence of compression by the h e r n i a t e d viscera, removal of this space-occupying lesion in utero m a y allow pulm o n a r y development to proceed normally. Thus, correcting C D H in utero m a y allow the lung to develop sufficiently to support life at b i r t h ] 5 T h e p r o b l e m in the m a j o r i t y of cases is not how to get the lung to grow after neonatal correction, but how to get the lung to grow and develop before birth to the point where it can support life at birth. W e have d e m o n s t r a t e d t h a t correction of C D H in utero is physiologically s o u n d a n d t e c h n i c a l l y f e a s i b l e in f e t a l lambs,~ ~,~5,16but e x t r a p o l a t i o n to the h u m a n fetus with C D H is not yet possible. In utero surgical intervention should not be a t t e m p t e d until anesthetic and surgical techniques to control uterine contractility are proven effective and a high degree of success is achieved in the rigorous n o n h u m a n p r i m a t e model.
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