Diaphragmatic hernia in the fetus: Prenatal diagnosis and outcome in 94 cases

D i a p h r a g m a t i c Hernia in the Fetus: Prenatal D i a g n o s i s and Outcome in 94 Cases By N. Scott Adzick, Michael R. Harrison, Philip L. Glick, Donald K. Nakayama, Frank A. Manning, and Alfred A. deLorimier San Francisco, Cafifornia 9 Most babies born with congenital diaphragmatic hernia (CDH) die after birth. The natural course of CDH in the human fetus is not known. W e found 94 cases of fetal CDH in the records of surgeons and obstetricians surveyed in the United States and Canada. W e found the following: (1) prenatal diagnosis of CDH is accurate and current techniques can detect lethal n o n p u l m o n a r y anomalies and prevent diagnostic errors; (2) despite optimal conventional therapy, most fetuses with detectable CDH will die in the neonatal period (80% mortality); (3) polyhydramnios is both a common prenatal marker for CDH (present in 7 6 % of fetuses) and a predictor for poor clinical outcome (only 11% survived); (4) fetal CDH is a dynamic p r o c e s s - nonsurvivors have larger defects and may have more viscera displaced into the chest at an earlier stage of development. Surgical intervention before birth may be necessary to improve survival of the fetus with CDH and polyhydramnios. 9 1985 by G r u n e & S t r a t t o n , Inc.

INDEX W O R D S : surgery.

Congenital diaphragmatic

hernia; fetal

E N A T A L D I A G N O S I S of congenital diap Rphragmatic hernia (CDH) makes it possible to define the natural history of this lesion, determine the pathophysiologic features that affect clinical outcome, and formulate management based on prognosis. Our initial clinical experience with fetal CDH was very discouraging--there were no survivors out of seven fetuses prospectively diagnosed before birth. 1 This prompted us to examine the experience at other pediatric surgical centers by means of a survey. We obtained 94 cases of fetal CDH from surgeons and obstetricians in North America, and obtained detailed information by follow-up telephone conversation and questionnaire. Not all questionnaires were completed for all items. Consequently, the total number of valid responses for each item is indicated, and percentages are calculated according to this number.

diagnosis was made by ultrasound in 97% of cases with confirmation by amniogram or single-section computerized tomography scan in a total of 14 instances (Table 2). The ultrasound findings were remarkably consistent, and included herniated abdominal viscera, abnormal upper abdominal anatomy, and mediastinal shift away from the side of herniation. Polyhydramnios was present in 76% of cases. An important ultrasound finding was that herniated abdominal viscera moved in-and-out of the chest in several fetuses, so fetal CDH appears to be a dynamic process. The earliest diagnosis was made at 17 weeks gestation; the range was 17 to 40 weeks (Fig 1). Survivors and nonsurvivors showed no significant difference with regard to mean gestational age of diagnosis, which was about 29 weeks. The average gestational age at time of delivery was about 37 weeks (Fig 2). There were several errors in diagnosis. These included six additional cases in which C D H was misdiagnosed prenatally and proved to be cystic adenomatoid malformation in four fetuses, lung leiomyosarcoma in one, and mediastinal cystic teratoma in one. There were also some errors made regarding the diagnosis of hernia side. In the four cases of bilateral CDH, only one side was diagnosed prenatally. Two cases of right CDH were thought to be left-sided before birth. In addition, there was one case of CDH that was misdiagnosed prenatally as esophageal atresia with tracheoesophageal fistula. OUTCOME

Ninety percent of the cases had optimal perinatal care with maternal transport, planned delivery, and immediate resuscitation. Despite sophisticated postna-

Prenatal diagnosis was made initially in 88 cases, and retrospectively in six cases. The maternal indications for prenatal study are shown in Table 1. In the majority of cases (66%), the mother was large-fordates because of polyhydramnios. Nineteen percent of the studies were part of a routine obstetrical evaluation. Other indications were much less common. The

From the Fetal Treatment Program and Division of Pediatric Surgery, University of California, San Francisco. Supported by Grant No. A M 29890 and a N R S A from the National Institutes of Health, Basic Research Grant No. 10803 from the March of Dimes Birth Defects Foundation, and the 13th American College of Surgeons Scholarship. Presented at the 33rd Annual Meeting of the Surgical Section of the American Academy of Pediatrics, Chicago, September 15-16, 1984. Address reprint requests to Michael R. Harrison, MD, Room 585 HSE, University of California, San Francisco, CA 94143. 9 1985 by Grune & Stratton, Inc. 0022-3468/85/2004-0013503.00/0

Journal of Pediatric Surgery, Vo120, No 4 (August), 1985: pp 357-361

357

PRENATAL DIAGNOSIS AND PERINATAL MANAGEMENT

358

ADZICK ET AL

Survivor M e a n = 3 7 . 8 w k s ; N o n s u r v i v o r M e a n = 3 6 . 5 wks N = 6 9 ; Range=26-42 w k s

Table 1. Maternal Indication for Prenatal Study Indication

Number of Cases

Size/Dates discrepancy

55

Routine

16

Advanced maternal age

4

Threatened abortion

3

Medical/obstetrical problem

4

Previous child with CDH

11

I

DEAD [ E ~

'~ IdJ

25

~klJ

20

0

15

'~

10

Id. ii

1

Not stated

ALIVE I

3O

~/////////// ///////////[~

i///////11/11

Table 2. Method of Prenatal Diagnosis

V//////////~

~44<44~44<44 Y//////////Z

z

Number of Cases U/S alone

~//////iiii/~

Y//////////~

73

A alone

0

3

U/S + A U/S + A + CT scan

2

Not stated

4

25

ALIVE

I

1

DEAD

20

It L,U

,,,

10

z

5

39-42

Fig 2. Gestational age of fetus at time of delivery (69 valid responses).

Survivor Mean= 29.0 wks; N o n s u r v i v o r M e a n = 2 8 . 5 w k s N = 61 ; Range = 17-40 wks

15

35-38

WEEKS

tal therapy, the overall outcome was very disappointing (Fig 3). Only 20% of these babies survived (19 out of 94 cases). Although most of the survivors did well, three of these infants developed severe bronchopulmonary dysplasia during prolonged postoperative respiratory support. One infant subsequently died at age 6 months from cardiomyopathy. There were 27 prenatal or preoperative deaths, and almost half of these were due to lethal associated anomalies (Table 3). Five deaths occurred prior to transport, and ten neonates deteriorated so rapidly that surgical repair could not even be attempted. There were 46 postoperative and two intraoperative deaths. Many of these infants were moribund in the operating room. Seventy four percent died during the first 24 hours postoperatively, usually secondary to the sequelae of persistent fetal circulation. Two infants treated with extracorporeal membrane oxygenation

-ii O

31-34

26-30

12

Abbrevs: U/S = ultrasound; A = amniogram.

iii

5

~////////X

OUTCOME:

20%

94

29%

SURVIVORS

PRENATAL OR PREOPERATIVE DEATH

Fig 3.

CASES

51% POSTOPERATIVE O R INTRAOPERATIVE DEATH

Overall outcome in 94 oases.

(ECMO) succumbed at 36 and 60 hours of life, respectively. MORTALITY FACTORS

Sixteen percent of the fetuses in this series had lethal associated anomalies (Fig 4). These anomalies were detected prospectively in seven of 11 cases in which good prenatal diagnostic data was available. In addition, three fetuses with right CDH and one fetus with bilateral CDH were hydropic. Isolated nonlethal anomalies were present in six cases (Table 4). An important prognostic indicator was the presence of polyhydramnios (Fig 5). Polyhydramnios was not Table 3. Prenatal or Preoperative Deaths Number of Cases Stillborn

~////A ] 7-23

24-27

28-30

31-34

35-40

1*

No resuscitation

8*

Outborn death

WEEKS Fig 1. Gestational age of fetus at time of diagnosis (61 valid responses).

3*

Therapeutic abortion

5

Maximal resuscitation

10

Total

27

*Lethal anomalies.

FETAL DIAPHRAGMATIC HERNIA

359

LETHAL ASSOCIATED A N O M A L I E S

(81 valid responses)

POLYHYDRAMNIOS: INCIDENCE AND RELATIONSHIP TO SURVIVAL (82 valid responses) YES

CARDIAC CNS TRISOMY MULTIPLE LUNG AGENESIS TOTA L

5 2 4 3 1

7/11 Detected on Prenatal Evaluation

Fig 4.

POLYHYDRAMNIOS 62 CASES

11%

NO POLYHYDRAMNIOS 20 CASES Fig 5. vival.

15

I,o,,;.i

9

Alive [ Dead

I

Incidence of polyhydramnios and relationship to sur-

Lethal associated anomalies.

only common, but was also a predictor of extremely poor clinical outcome (only 11% survived). The survival rate was 55% for fetuses in which polyhydramnios was not present. With regard to management of delivery, there was a high incidence of cesarean section (Fig 6). Oftentimes there were side-by-side operating rooms set u ~ n e for the mother's cesarean section and the other for the newborn's CDH repair. In terms of survival, however, cesarean section did not appear to have any advantage over vaginal delivery. Early delivery for ex utero repair also did not improve overall survival; only three infants survived out of 17 born prior to 35 weeks gestation. When cases were analyzed according to hernia side, left-sided defects were seven times more common than right-sided ones. There was no difference in survival of infants with left- or right-sided hernias. All four fetuses that had bilateral CDH died (Fig 7). With respect to hernia closure, nonsurvivors tended to have large diaphragmatic defects. More than onehalf of the nonsurvivors who came to operation required closure with either prosthetic material or a muscle flap (Fig 8). DISCUSSION Prenatal diagnosis permits elucidation of the important pathophysiologic features of fetal CDH. Since

Duodenal atresia Multicystic kidney Ureteropelvic junction obstruction Pectus carinatum Malrotation, patent ductus arteriosus, excluded.

DELIVERY: TYPE AND RELATIONSHIP TO SURVIVAL (71 valid responses) I

VAGINAL

55%

VAGINAL 123%~ 39 CASES

Table 4. Isolated Nonlethal Anomalies Anomaly

fetal CDH appears to have a dynamic variation in the timing and amount of herniated viscera, this probably accounts for the spectrum of severity seen postnatally. One interesting finding was that one survivor clearly had CDH present at 26 weeks gestation, but not at 20 weeks gestation by ultrasound. In addition, we know of three survivors, not included in this series, that had good quality sonograms at 20, 26, and 38 weeks gestation, respectively. On careful retrospective review of the sonograms, CDH could not be demonstrated in any of the three cases. All of these findings suggest that survivors have late gestational herniation of viscera or smaller hernias that are missed by ultrasound. Conversely, nonsurvivors tended to have large defects, and may have more viscera displaced into the chest at an earlier stage of development with consequent severe pulmonary hypoplasia (Fig 9). It is important that prenatal diagnosis of CDH not only be accurate but also predict clinical outcome. Ultrasound may not detect small CDH in utero, but it does apparently detect those fetuses that are most

Number of Cases 2 1 2 1

IC-SECTION /

/

45% I

~

C'SECTION i31% ~ 32 CASES Alive Dead

and patent foramen ovale Fig 6.

Type of delivery and relationship to survival.

360

ADZICK ET AL

CDH SIDE: R E L A T I O N S H I P TO S U R V I V A L ( 8 4 v a l i d responses) LEFTCDH 123% ~ 70 CASES RIGHT CDH

~

10 CASES

Ir//A

20% BILATERAL ~ 4 CASES CDH O% Fig 7.

Alive I Dead

LUNG HYPOPLASIA

I

Fig 9. Fetal CDH appears to be a dynamic process and early herniation of a large volume of viscera through a large defect leads to severe lung hypoplasia and neonatal death.

Anatomic side of CDH and relationship to survival.

severely affected. Most importantly, polyhydramnios is not only a good prenatal marker for the presence of fetal CDH, but also is a good predictor for severe cases with poor prognosis. Although there were several instances in which diaphragmatic hernia was either misdiagnosed or the correct hernia side was inacurately defined by prenatal ultrasound, it is likely that diagnostic errors can be avoided by confirming the ultrasound findings by amniography with or without computerized tomography, z Previous reports have noted that the incidence of associated lethal anomalies with CDH varied from "rare" to 56%, 3~ and in this series the incidence was 16%. Current prenatal diagnostic techniques can detect virtually all of these defects. Consequently, a thorough sonographic examination of the fetus with CDH is essential to detect the presence of other structural anomalies. Amniocentesis for karyotype analysis may also be indicated, since our review also included four cases of trisomy. The prenatal diagnosis of CDH has made it possible to define the natural history of this lesion. In the past, the wide range of mortality figures from numerous

METHOD OF CDH CLOSURE: RELATIONSHIP TO SURVIVAL (56 valid responses) PRIMARY

CLOSURE

[

PROSTHESIS OR I FLAP CLOSURE 5%

49% ~

~

/

/ ~ 35 CASES

A 21 CASES

Alive I

I

Dead NONSURVIVORS TENDED TO HAVE LARGER DEFECTS THAT REQUIRED CLOSURE WITH PROSTHESIS OR FLAP Fig 8.

Method of CDH closure and relationship to survival.

--" VOLUME + TIMING OF HERNIATION

surveys of C D H related more to patterns of referral than to specific therapy. 7 Referral centers frequently do not have an opportunity to treat high-risk outborn infants with severe pulmonary hypoplasia, simply because these neonates do not survive long enough for transport. This series demonstrates that most fetuses with detectable CDH will die, and that the outcome for the fetus with CDH and polyhydramnios is particularly dismal. The principal advantage of prenatal detection of CDH is that it allows maternal transport, planned delivery, and immediate resuscitation. In the vast majority of cases, these infants had prompt, sophisticated postnatal intervention that even included ECMO in two instances. Yet, 80% of fetuses with detectable CDH died in the neonatal period despite optimal conventional therapy. This is consistent with six previously reported cases of antenatally diagnosed CDH, in which only one infant survived. 8-12 The extent of pulmonary hypoplasia at birth appears to be the major mortality factor, rather than the skill or promptness of postnatal surgical repair and intensive care. Prenatal diagnosis also makes it possible to induce preterm delivery for early decompression of the fetal thorax. However, this appears to add the problem of pulmonary immaturity to the existing problem of lung hypoplasia, and survival was not improved. In the future, prenatal diagnosis may permit surgical intervention before birth. Six years of experimental and clinical investigation suggests that prenatal repair offers great hope for the fetus with CDH. However, prenatal intervention carries considerable risk for both fetus and mother, and we remain convinced that it should not be attempted until the following criteria are met: (1) the physiologic rationale, efficacy, and feasibility are demonstrated experimentally13-~7; (2) the safety of hysterotomy and control of preterm labor are established in the non-human primateS8; (3) the natu-

FETAL DIAPHRAGMATIC HERNIA

361

ral history a n d o u t c o m e of C D H in t h e u n t r e a t e d h u m a n fetus is defined by serial observations~9; a n d (4) t h e p r e n a t a l d i a g n o s i s o f C D H is s h o w n to be a c c u r a t e , c a p a b l e of e x c l u d i n g o t h e r a n o m a l i e s , a n d a b l e to p r e d i c t w h i c h fetuses h a v e sufficiently b a d p r o g n o s i s to

j u s t i f y in u t e r o i n t e r v e n t i o n . A l t h o u g h we a r e now close to s a t i s f y i n g t h e s e c r i t e r i a , t h e r e p a i r of h u m a n fetal CDH remains a formidable challenge that should not be a t t e m p t e d u n d e r a n y b u t t h e m o s t r i g o r o u s conditions.

REFERENCES

1. Nakayama DK, Harrison MR, Chinn DH, et al: Prenatal diagnosis and natural history of the fetus with a congenital diaphragmatic hernia: Initial clinical experience. J Pediatr Surg (in press) 2. Chinn DH, Filly RA, Callen PW, et aI: Congenital diaphragmatic hernia diagnosed prenatally by ultrasound. Radiology 148:199-123, 1983 3. Johnson DG, Deaner RM, Koop CE: Diaphragmatic hernia in infancy: Factors affecting the mortality rate. Surgery 62:10821091, 1967 4. Fitzgerald R J: Congenital diaphragmatic hernia: A study of mortality factors Ir J Med Sci 146:280-284, 1979 5. Butler N, Claireaux AE: Congenital diaphragmatic hernia as a cause of perinatal mortality. Lancet 1:659-663, 1962 6. Puri P, Gorman F: Lethal nonpulmonaryanomalies associated with congenital diaphragmatic hernia: Implications for early intrauterine surgery. J Pediatr Surg 19:29-32, 1984 7. Harrison MR, Bjordal RI, Landmark F, et al: Congenital diaphragmatic hernia: The hidden mortality. J Pediatr Surg 13:227 232, 1979 8. Marwood RP, Davison OW: Antenatal diagnosis of diaphragmatic hernia: Case report. Br J Obstet Gynaecol 88:77-72, 1981 9. Touloukian R J, Hobbins JC: Maternal ultrasonography in the antenatal diagnosis of surgically correctable fetal abnormalities. J Pediatr Surg 15:373-377, 1980 10. Fleischer AC, Killan AP, Boehm FH, et al: Hydrops fetalis: Sonographic evaluation and clinical implications. Radiology 141:163-168, 1981

11. Perrelli L, Calisti A, Romagnoli C, et al: Antenatal ultrasonic demonstration of congenital diaphragmatic hernia. Z Kinderchir 38:108-109, 1983 12. Bell MJ, Ternberg JL: Antenatal diagnosis of diaphragmatic hernia. Pediatrics 60:738-740, 1977 13. 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 9 14. Harrison MR, Bressack MC, Churg AM, et al: Correction of congenital diaphragmatic hernia in utero. I1. Simulated correction permits fetal lung growth with survival at birth. Surgery 88:260268, 1980 15. Harrison MR, Ross NA, deLorimier AA: Correction of congenital diaphragmatic hernia in utero. III. Development of a successful surgical technique using abdominoplasty to avoid compromise of umbilical blood flow. J Pediatr Surg 16:934-942, 1981 16. Soper RT, Pringle KC, and Scofield JC: Creation and repair of diaphragmatic hernia in the fetal lamb. Techniques and survival. J Pediatr Surg 19:33-40, 1984 17. Harrison MR, and deLorimier AA: Congenital diaphragmatic hernia. Surg Clin N A m e r 61:1023-1035, 1981 18. Harrison MR, Anderson J, Rosen MA, et al: Fetal surgery in the primate I. Anesthetic, surgical, and tocolytic management to maximize fetal-neonatal survival. J Pediatr Surg 17:115-121, 1982 19. Harrison MR, Golbus MS, Filly RA: The Unborn Patient. New York, Grune & Stratton, 1984, pp 237-276