360.full

Congenital diaphragmatic herniation: antenatal detection

and outcome

E DILLON, FRCR, M RENWICK and C WRIGHT, MRCPath

Northern Region Congenital Abnormality Survey, Northern and Yorkshire Regional Health Authority,

Newcastle upon Tyne, UK

Abstract. 201 fetuses and babies with a congenital diaphragmatic herniation or eventration

(referred to collectively as CDH) were noti®ed to the Northern Region Congenital Abnormality

Survey (NorCAS) in the 13-year period from 1985 to 1997, an incidence of 0.25 per 1000 births.

The 1-year survival of all pregnancies associated with CDH was 37%. The 1-year survival of

livebirths was 50%. Antenatal scan detected the diaphragmatic defect or associated structural

abnormality in 50%. Another major structural abnormality was present in 62 (31%); one of these

babies survived and 26 pregnancies were terminated. This group contained four of the six

antepartum stillbirths, all three intrapartum stillbirths and four of the ®ve spontaneous

miscarriages. Non-isolated CDH occurred in association with Fryns (5), Goldenhar (1) and de

Lange (1) syndromes, and in 16 of 17 with a chromosome anomaly. 53% of the 139 fetuses with

isolated CDH survived to 1 year of age, and 59% of the 124 liveborn survived. Of 37 fetuses with

isolated CDH detected before 25 weeks gestation, 12 pregnancies were terminated. There were 11

survivors among the 25 continuing pregnancies (44%). The overall survival of babies with CDH is

very poor but, when a defect is identi®ed by ultrasound before 25 weeks gestation, chromosome

analysis and a careful ultrasound scan may suggest which fetuses have an isolated diaphragmatic

abnormality and a greater chance of survival.

Congenital diaphragmatic abnormalities occur

in 1 in 2000 to 1 in 4000 births [1, 2]. The

commonest defect is the congenital diaphragmatic

hernia, of which 90% are Bochdalek type;

Morgagni and paraoesophageal hernias and

diaphragmatic eventration are less common.Diaphragmatic hernias result from incomplete

closure of the pleuroperitoneal re¯ections, which

form the diaphragm by the tenth week after

conception. The Bochdalek hernia occurs postero-

laterally and, as nearly three-quarters are left

sided [3], the most frequent ®nding on antenatal

ultrasound is cardiac displacement and a ¯uid-

®lled stomach in the thorax.Hernias through the foramen of Morgagni

occur anteromedially and may therefore be

associated with de®ciencies of the pericardial sac

and anterior chest wall. However, all diaphrag-

matic abnormalities have the potential to cause

pulmonary hypoplasia and neonatal death.The association of chromosomal abnormality

with congenital diaphragmatic hernia is well

established, the reported incidence ranging from

5% [4] to 18% [5]. Genetically determined

disorders associated with congenital diaphrag-matic hernia include Fryns syndrome, Goldenharsyndrome [6], Fraser syndrome [7], Brachmann-deLange syndrome [8, 9] and Beckwith±Weidemannsyndrome [10].

There is an established association betweencongenital diaphragmatic hernia and Fryns syn-drome, ®rst described in 1978 by Fitch et al [11]and then in 1979 by Fryns et al [12], but morerecently rede®ned [13±15]. It is a lethal autosomalrecessive, multiple anomaly syndrome in whichdiaphragmatic herniation is associated with facialdysmorphism, central nervous system, cardiac andintestinal abnormalities, and digital hypoplasia.

In eventration, the diaphragm is a thinamuscular sheet dividing the thoracic and ab-dominal cavities. It is also associated with otherstructural abnormalities, pulmonary hypoplasiaand post-natal death.

The purpose of this study was to review theantenatal ultrasound detection of congenitaldiaphragmatic hernia and the outcome for allcases referred to the Northern Region CongenitalAbnormality Survey (NorCAS) for the years 1985to 1997.

Methods

The Northern Region Congenital AbnormalitySurvey (NorCAS), formerly known as the

Received 21 January 1999 and in revised form 27October 1999, accepted 3 November 1999.

Address correspondence to Dr E Dillon, Department ofRadiology, The Memorial Hospital, Hollyhurst Road,Darlington DL3 6HX, UK.

The British Journal of Radiology, 73 (2000), 360±365 E 2000 The British Institute of Radiology

360 The British Journal of Radiology, April 2000

Northern Region Fetal Abnormality Survey, hasbeen in existence since 1984. It provides a centralregister on all babies born with a signi®cantabnormality in the former Northern Region (nowpart of the Northern and Yorkshire Region),which is a well de®ned geographical area of 3million people. In 1984 there were 40 000 birthseach year in the region but this has subsequentlyfallen to 35 000 per year.

There are 16 maternity units within theNorthern Region, each with its own antenatalultrasound facility, and four General Practitionerunits. The Fetal Assessment Unit and PaediatricSurgical Centre for this population is inNewcastle upon Tyne. Very few babies arethought to have escaped registration, as only asmall proportion of the population living in thesouth-west of the region refer to Manchester.

Cases of proven or suspected abnormality arenoti®ed to the survey mainly by obstetricians,midwives, radiologists, paediatricians, patholo-gists and cytogeneticists. The survey aims tocollect information on all babies with a suspectedor proven signi®cant abnormality since August1984. The register details how and when eachdiagnosis was made together with managementand outcome, including follow-up to 1 year ofage.

Results

201 fetuses and babies with a congenitaldiaphragmatic abnormality were noti®ed to theNorthern Region Congenital Abnormality Survey(NorCAS) in the 13-year period from 1985 to1997. 187 had diaphragmatic herniation and 14had diaphragmatic eventration, subsequentlyreferred to collectively as CDH. CDH was

bilateral in two cases. A previous sibling had

CDH in three families.The overall survival of babies with CDH at 1

year of age was 37%. There were 74 survivors

from 149 livebirths (50%), of which 73 had

isolated defects. In three of those with an isolated

defect, pleural effusion was identi®ed in three, at

27, 29 (with ascites) and 37 weeks gestation. 66

deaths occurred in the ®rst week of life, seven

from 7 to 28 days, and two from 28 days to 1 year

of age. Five pregnancies resulted in spontaneous

miscarriage, six in antepartum stillbirth and three

in intrapartum stillbirth (Table 1). 26 termina-

tions of pregnancy occurred in babies with CDH

and other abnormalities, and 12 in babies with

isolated defects.CDH occurred in isolation in 139 pregnancies

(69%). The overall survival of babies with isolated

CDH was therefore 53%, or 57% if terminations

were excluded. 73 (59%) of the 124 live-

born babies with isolated CDH survived. One

spontaneous miscarriage, two antepartum still-

births and a single chromosome anomaly (of

chromosome 9) occurred in babies with isolated

CDH. 37 fetuses with isolated CDH were

identi®ed between 17 and 25 weeks gestation,

and the 1-year survival, including the 12 termina-

tions of pregnancy, was 30%. Of the 25 continu-

ing pregnancies, 11 (44%) babies were alive at 1

year of age, representing 46% of livebirths.Another structural abnormality was present in

62 babies (31%), including two of those with

eventration (Table 2). Of the 25 livebirths, only

one baby with a unilateral limb reduction defect

survived. The pregnancy was terminated in 26. All

babies with Fryns syndrome (5), Goldenhar

syndrome (1) and de Lange syndrome (1), and

16 of the 17 with aneuploidy had abnormalities in

Table 1. The outcome of diaphragmatic abnormalities occurring in each year of the survey. Data relating to iso-lated diaphragmatic defects are in parenthesis

Year: 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 Total

Total 17 17 12 14 8 19 18 19 17 14 21 9 16 201(11) (15) (8) (12) (4) (16) (13) (11) (11) (10) (14) (5) (9) (139)

Total surviving at1 year

5 (5) 8 (8) 5 (5) 8 (8) 1 (1) 8 (8) 4 (4) 7 (7) 4 (4) 5 (5) 8 (8) 4 (4) 7 (6) 74 (73)

Spontaneousmiscarriage

0 0 1 0 0 0 1 2 (1) 1 0 0 0 0 5 (1)

TOP, multipleabnormalities

3 1 1 0 2 1 0 2 3 3 3 3 4 26

TOP, isolated CDH (0) (0) (0) (0) (0) (1) (1) (1) (0) (2) (3) (1) (3) (12)Antepartum stillbirth 0 1 1 1 0 1 0 0 2 (1) 0 0 0 0 6 (1)Intrapartum stillbirth 2 0 1 0 0 0 0 0 0 0 0 0 0 3Post-natal deaths total 75 (52)

in ®rst week of life 7 (6) 7 (7) 3 (3) 5 (4) 4 (3) 8 (7) 9 (5) 6 (2) 6 (5) 2 (1) 6 (3) 1 (0) 2 (0) 66 (46)7±28 days 1 3 (3) 1 2 (2) 7 (5)28 days±1 year 1 (1) 1 2 (1)

TOP, termination of pregnancy; CDH, congenital diaphragmatic herniation or diaphragmatic eventration.

Congenital diaphragmatic herniation

361The British Journal of Radiology, April 2000

Table 2. The signi®cant structural abnormalities occurring with congenital diaphragmatic defects and the outcome.Underlined are the abnormalities detected by scan and the gestation at diagnosis is given in parenthesis

1985 CDH Lumbar meningomyelocele (20w) TOPCDH Cardiac single ventricle Died 2dCDH Anencephaly, spina bi®da (36w) Intrapartum stillbirthCDH Exomphalos, elevated serum afp TOPEventration Exomphalos, cervico-dorsal meningocele (19w) TOPCDH Cervical meningomyelocele and hydrocephalus (33w) Intrapartum stillbirth

1986 CDH Exomphalos, cervical meningocele, facial cleft, absent L arm(16w)

TOP of twin pregnancy

CDH Spina bi®da, hydrocephalus, renal agenesis Not screened Antepartum stillbirth (31w)1987 CDH Unilateral renal agenesis Antepartum stillbirth (32w)

CDH Anencephaly Not screened Intrapartum stillbirthCDH Exomphalos (Trisomy 18 diagnosed by amnio) TOP trisomy 18CDH Spina bi®da (17w) Spontaneous miscarriage

1988 Eventration Hydrocephalus, cardiac ASD, cervical deformity (30w) Died ,1dCDH Large VSD Antepartum stillbirth (30w)

1989 CDH Facial clefting, Pierre Robin syndrome Died .7d 46xy, 3q4 deletionCDH Exomphalos (35w) Died ,1dCDH Lumbar meningomyelocele, hydrocephalus (17w) TOPCDH Ectopia cordis, unil renal agenesis (17w) TOP

1990 CDH Facial and palatal clefting (36w) Died 1dCDH Situs inversus, bilateral renal dysplasia Died 1dCDH Hydrocephalus, TOF, L renal agenesis, imperf anus, facial

cleft (21w)TOP Fryns syndrome

1991 CDH Bilateral renal dysplasia (24w) Spont misc deletion 3q1.1CDH Bulging eyes, large extremities, R cystic dysp (37w) Died ,1d. Fryns syndromeCDH Hypoplastic left heart (26w) Died ,1dCDH Nuchal thickening, cleft lip and palate, VSD (36w) Died ,1d. Fryns syndromeCDH VSD+tracheo-oesophageal atresia (25w) Died 2d. trisomy 18

1992 CDH L hydronephrosis, facial clefting (19w) Died ,1d. Fryns syndromeCDH Nuchal thickening, facial clefting (20w) Died ,1d. Fryns syndromeEventration Amnion rupture seq ± abd wall and spinal defect (16w) TOPCDH VSD+coarctation (17w) Died 2dCDH Duodenal atresia (21w) trisomy 13 on aminocentesis Died ,1d trisomy 13CDH (bilat) Transposition and single ventricle Died ,1dCDH Exomphalos, dorsal scloiosis, cardiac VSD (22w) TOPEventration Amnion rupture seq ± abd wall and spinal abn (20w) Sp miscarriage trans 13q 14q

1993 CDH Hydrocephalus, skeletal abnorm, L renal agenesis, facial cleft(22w)

TOP Goldenhar syndrome

CDH Blepharophimosis, facial dysmorphism (18w) APSB 3q2.2 deletionEventration Facial dysmorphism (20w) amniocentesis TOP trisomy 18CDH Coarctation. (21w) aminocentesis TOP trisomy 18CDH Exomphalos, secundum ASD Died ,1d trisomy 13CDH Lumbar meningomyelocele, exomphalos, bladder extrophy (16) Spontaneous miscarriage

1994 CDH Renal agenesis (28w) Died 1d. induced at 30wCDH Anencephaly (15w) TOPCDH Hydranencephaly (22w) TOPCDH Facial cleft, hydrocephalus, cerebellar hypoplasia, VSD (21w) TOP

1995 CDH Cantrell's pentalogy (13w) TOPCDH Hypoplastic left heart Died 2dCDH Unilateral cystic dysplasia (26w) Died ,1dCDH Cleft palate (24w) Died 28d trisomy 22CDH Dextrocardia and VSD (20w) TOPCDH Tracheo-oesophageal ®stula (15w) TOPCDH Cystic hygroma, arm reduction defect, transposition (19w) Died ,1d

1996 CDH Fallots tetralogy (32w) Died 1dCDH Anencephaly (17w) TOP Unbal 46XX 3q4 deletCDH Exomphalos, agenesis corpus callosum, bilat hydronephrosis

(20w)TOP trisomy 13

CDH Soft tissue oedema and nuchal thickening (30w) TOP Turner's syndrome

1997 CDH Absent R forearm AliveCDH Abdominal wall defect part of body stalk anomaly (19w) Died 1dCDH Deformity left forearm and hand (20w) in a twin Died 1d srom @24w, twinCDH Anencephaly (16w) TOPCDH Exomphalos, abnormal post fossa, ascites (20w) trisomy 18 TOP trisomy 18CDH Bilateral ulnar agenesis, facial dysmorphism, cleft palate (18w) TOP de Lange syndromeCDH Holoprosencephaly (17w) TOP 3q2.2 deletion

E Dillon, M Renwick and C Wright


addition to the CDH, all potentially detectable byroutine ultrasound scan.

The chromosome abnormalities encounteredwere trisomy 18 (5), trisomy 13 (3), trisomy 22(1), deletions 3q/4 (2), 3q1.1 (1) and 3q2.2 (2),translocation 13q14q (1), Turner's syndrome (1)and ring chromosome 9 (1). The latter wasassociated with isolated CDH.

Antenatal scan identi®ed an abnormality, eitherthe diaphragmatic defect and/or another struc-tural abnormality, in 100 (50%) of cases; 73 (36%)before 25 weeks gestation. In the ®nal 3 years ofthe study, the corresponding ®gures were 61% and50%, respectively (Table 3). The antenatal detec-tion of CDH was 15% of all defects in 1985±87and 59% of isolated defects in 1995±97. In six, theCDH was undiagnosed until 3 and 4 days, 2 and 4weeks, and 9 and 10 months of age.

Hydramnios was reported in eight pregnancies.This occurred in the second trimester in only twopregnancies, in one with bilateral CDH and inanother with Fryns syndrome. Oligohydramnioswas reported in the second trimester in a babywith Fryns syndrome and multiple other abnor-malities.

Discussion

The 13 years of this study have seen consider-able advances in the antenatal diagnosis of CDH.Ultrasound scanning is able to diagnose thediaphragmatic abnormality at an earlier gesta-tional stage and more reliably identi®es associatedabnormalities. In the Northern region, the rate ofantenatal detection was 15% of all CDH in 1985±1987 and 59% of isolated defects in 1995±1997,

22% of which were identi®ed before 25 weeks

gestation.Newer management techniques, such as delayed

surgery, improved respiratory support and extra-

corporeal membrane oxygenation, have become

established over the same period, although in

utero surgery such as tracheal ablation remain

dif®cult and semi-experimental [16±18].

Nevertheless, CDH still has a poor prognosis;

only 37% in our study overall, and 50% of

livebirths, reaching 1 year of age. It is therefore

not surprising that with earlier and more frequent

diagnosis by ultrasound, termination of babies

including those with isolated CDH occurs.It is still dif®cult to give parents an accurate

prediction of their baby's chance of survival. In

order to correctly interpret reported survival

rates, we need to know whether data refer to

isolated defects and whether all the in utero and

post-natal deaths were recognized and hence

included. For example, 74% of livebirths referred

to an obstetric±paediatric surgical unit survived

[3], 60% from Minnesota birth and death records

[19], and 42% of isolated defects identi®ed before

24 weeks gestation [20]. Although our data are

very comprehensive, collected over a 13-year

period by NorCAS, and include antenatal,

perinatal and post-natal information, the chance

of survival when identi®ed at a speci®c gestation

remains dif®cult to predict.Our study shows that an important indicator of

poor prognosis is the presence of an associated

structural abnormality, which occurred in almost

one-third of fetuses. Only one baby in this group

survived to 1 year of age (1.6%), representing 4%

Table 3. The congenital diaphragmatic defects that occurred in each year and how they were diagnosed

Year: 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 Total

Total CDH andeventration

17 17 12 14 8 19 18 19 17 14 21 9 16 201

Isolated CDH 11 15 8 12 4 16 13 11 11 10 14 5 9 139Identi®ed by scan

before 25 w1 0 0 1 2 4 3 4 7 5 5 2 3 37

Identi®ed by scanafter 25 w

0 0 0 2 1 4 1 2 1 1 1 1 0 1451a

CDH+other structuralabnormalities

6 2 4 2 4 3 5 8 6 4 7 4 7 62

Identi®ed by scanbefore 25 w

2 1 0 0 2 1 2 7 5 3 5 2 6 36

Identi®ed by scanafter 25 w

3 0 0 1 1 1 3 0 0 1 1 2 0 1349b

Total detected byscan

6 1 0 4 6 10 9 13 13 10 12 7 9 100 (50%)

Total detectedbefore 25 w

3 1 0 1 4 5 5 11 12 8 10 4 9 73 (36%)

CDH, congenital diaphragmatic hernia; w, weeks gestation.aTotal isolated CDH identi®ed by scan; btotal non-isolated CDH identi®ed by scan.



of livebirths, whereas survival of those withisolated CDH was 53% overall and 59% oflivebirths. Also dif®cult to quantify is thereliability of ultrasound in the detection ofabnormalities associated with CDH. However,with modern ultrasound equipment it is possibleto identify facial dysmorphism and clefting,nuchal thickening or cardiac abnormalities,which may be the only indicators of chromosomeor syndromic abnormality. Identi®cation of CDHshould prompt chromosome analysis and detailedcardiac examination.

The gestation at which CDH is identi®ed mayalso in¯uence survival. Babies have a reduced riskof pulmonary hypoplasia and a better chance ofsurvival if herniation of abdominal viscerathrough the diaphragmatic defect occurs later inpregnancy. Delayed herniation is considered to bea reason for failure of ultrasound to identify CDHbefore 25 weeks gestation [21, 22]. However,failure is more commonly due to inadequateequipment performance or scanning technique[23]. Our multicentre study encompassed unitswith diverse equipment and expertise, particularlyin the earlier years. There was improvement inantenatal CDH detection over the study period,and we assume that many diaphragmatic defectswith visceral herniation were initially missed onultrasound. We anticipate that the numbers offalse negative scans will continue to fall, but lateherniation will remain unidenti®ed by routine scan.

There are many ultrasound criteria that aim topredict the degree of pulmonary hypoplasia, suchas reduced lung:thoracic transverse area ratio [24],abnormal fetal breathing characteristics based onnasal ¯uid ¯ow parameters [25], or abdominalcircumference below the third percentile.However, they require further evaluation [26,27]. Although polyhydramnios indicates a pooroutcome [28], it usually develops later [29], andwas documented by NorCAS only twice before 24weeks gestation in 13 years. Mediastinal shift andthe presence of the stomach in the chest has beensuggested as a poor prognostic indicator [30], butmerely indicates left visceral herniation and doesnot necessarily prejudice survival [31]. Liverherniation with right lung to head circumferenceratio of less than 0.6 has a poor prognosis [32] butis of limited value in antenatal management.

Although earlier identi®cation of isolated CDHresulted in a modest increase in the number ofterminations of affected pregnancies, 44% ofbabies of continuing pregnancies and 46% oflivebirths survived, in keeping with previousstudies [18].

As well as survival rates varying with thegestation at diagnosis of CDH and whetheradditional abnormalities are present, child-hood morbidity may result from congenital

diaphragmatic herniation and its treatment [33].In conclusion, our data indicate that if isolatedCDH is identi®ed between 17 and 25 weeksgestation, chromosome analysis and detailedanomaly scan including cardiac examination isnormal, parents may be advised that their baby'schance of survival is at least 40%, and terminationmay not be their preferred option.

Acknowledgments

We wish to thank other members of theNorthern Region Fetal Abnormality SteeringGroup for access to data: Mr J Atkins, DrH Cameron, Dr H Lambert, Mr J Scott,Professor R Bhopal, Dr M Coulthard, DrS Pearson, Mr L Rangecroft, Dr S Richmond,Dr J Wolstenholme, Professor J Burn, ProfessorS Robson and Dr C Wren. Also we wish to thankall the Link Clinicians in the Northern Region fortheir continued collaboration and support ofNorCAS.

References

1. Wenstrom KD, Weiner CP, Hanson JW. A ®ve yearstatewide experience with congenital diaphragmatichernia. Am J Obstet Gynecol 1991;165:838±42.

2. Bonham-Carter RE, Waterson DJ, Aberdeen E.Hernia and eventration of the diaphragm in child-hood. Lancet 1962;1:656±9.

3. Shaw KS, Filiatrault D, Yasbeck S, St-Vil D.Improved survival for congenital diaphragmatichernia, based on prenatal ultrasound diagnosisand referral to a combined obstetric±paediatricsurgical centre. J Pediatr Surg 1994;29:1268±9.

4. Cunniff C, Jones KL, Jones MC. Patterns ofmalformation in children with congenital diaphrag-matic defects. J Pediatr 1990;116:258±61.

5. Bollmann R, Kalache K, Mau H, Chaoui R,Tennstedt C. Associated malformations and chro-mosomal defects in congenital diaphragmatichernia. Fetal Diagn Ther 1995;10:52±9.

6. Rollnick BR, Kaye CI. Hemifacial microsomia andvariants: pedigree data. Am J Med Genet 1983;15:233±53.

7. Philip N, Gambarelli D, Guys JM, Camboulives J,Ayme S. Epidemiological study of congenitaldiaphragmatic defects with special reference toaetiology. Eur J Pediatr 1991;150:726±9.

8. Fitzgerald RJ. Congenital diaphragmatic hernia: astudy of mortality factors. Ir J Med Sci 1977;146:280±4.

9. Jelsema RS, Isada NB, Kazzi NJ, Sargent K,Harrison MR, Johnson MP, et al. Prenataldiagnosis of congenital diaphragmatic hernia notamenable to prenatal or neonatal repair:Brachmann-de-Lange syndrome. Am J Med Genet1993;47:1022±3.

10. Thorburn MJ, Wright ES, Miller CG, Smith-ReadE. Exomphalos-macroglossia-gigantism syndromein Jamaican infants. Am J Dis Child 1970;119:316±21.

11. Fitch N, Srolovitz H, Robitaille Y, Guttman F.Absent left hemidiaphragm, arhinencephaly andcardiac malformations. J Med Genet 1978;15:399±401.

E Dillon, M Renwick and C Wright


12. Fryns JP, Moerman F, Goddeeris P, Bossuyt C, vanden Berghe H. A new lethal syndrome with cloudycornea, diaphragmatic defects and distal limbdeformities. Hum Genet 1979;50:65±70.

13. McPherson EW, Ketterer DM, Salsburey DJ.Pallister±Killian and Fryns syndromes. Am J MedGenet 1993;47:241±5.

14. Pinar H, Carpenter MW, Abuelo D, Singer DB.Fryns syndrome: a new de®nition. Pediat Pathol1994;14:467±78.

15. Langer JC, Winthrop AL, Whelan D. Frynssyndrome: a rare familial cause of congenitaldiaphragmatic hernia. J Pediatr Surg 1994;29:1266±7.

16. Harrison MR, Adzick NS, Flake AW. Congenitaldiaphragmatic hernia: an unsolved problem. SeminPaediatr Surg 1993;2:109±12.

17. Luks FI. Fetal surgery. BMJ 1995;311:1449.18. Hedrick MH, Estes JM, Sullivan KM, et al. Plug

the lung until it grows (PLUG): a new method totreat congenital diaphragmatic hernia in-utero.J Pediatr Surg 1994;29:612±7.

19. Steinhorn RH, Kriesmer PJ, Green TP, McKay CJ,Payne NR. Congenital diaphragmatic hernia inMinnesota. Impact of antenatal diagnosis onsurvival. Arch Paediatr Adolesc Med 1994;148:626±31.

20. Harrison MR, Adzick NS, Estes JM, Howell LJ. Aprospective study of the outcome for fetuses withdiaphragmatic hernia. JAMA 1994;271:382±4.

21. Stringer MD, Goldstein RB, Filly RA, Howell LJ,Sola A, Adzick NS, et al. Fetal diaphragmatichernia without visceral herniation. J Pediatr Surg1995;39:1264±6.

22. Bronshtein M, Lewit N, Sujov PO, Makhoul IR,Blazer S. Prenatal diagnosis of congenital diaphrag-matic hernia: timing of visceral herniation andoutcome. Prenat Diagn 1995;15:695±8.

23. Lewis DA, Reickert C, Bowerman R, Hirschl RB.Prenatal ultrasonography frequently fails to diag-nose congenital diaphragmatic hernia. J PediatrSurg 1997;32:352±6.

24. Kamata S, Hasegawa T, Ishikawa S, Usui N,Okuyama H, Kawahara H, et al. Prenatal diagnosisof congenital diaphragmatic hernia and perinatalcare: assessment of lung hypoplasia. Early HumDev 1992;29:375±9.

25. Badalian SS, Fox HE, Chao CR, Timor-Tritsch IE,Stolar CJ. Fetal breathing characteristics andpostnatal outcome in cases of congenital diaphrag-matic hernia. Am J Obstet Gynecol 1994;171:970±6.

26. Fox HE, Badalian SS. Ultrasound prediction offetal pulmonary hypoplasia in pregnancies compli-cated by oligohydramnios and in cases of congenitaldiaphragmatic hernia: a review. Am J Perinatol1994;11:104±8.

27. Dommergues M, Louis-Sylvestre C, Mandelbrot L,Oury JF, Herlicoviez M, Body G, et al. Congenitaldiaphragmatic hernia: can prenatal ultrasonographypredict outcome? Am J Obstet Gynecol 1996;174:1377±81.

28. Adzick NS, Vacanti JP, Lillehei CW, O'Rourke PP,Crone RK, Wilson JM. Fetal diaphragmatic hernia:ultrasound diagnosis and clinical outcome in 38cases. J Pediatr Surg 1989;24:654±8.

29. Moore A, Umstad MP, Stewart M, Stokes KB.Prognosis of congenital diaphragmatic hernia. AustN Z J Obstet Gynaecol 1998;38:16±21.

30. Burge DM, Atwell JD, Freeman NV. Could thestomach site help predict outcome in babies withleft sided congenital diaphragmatic hernia diag-nosed antenatally? J Pediatr Surg 1989;24:654±8.

31. Dillon E, Renwick M. Antenatal detection ofcongenital diaphragmatic hernias: the NorthernRegion experience. Clin Radiol 1993;48:264±7.

32. Metkus AP, Filly RA, Stringer MD, Harrison MR,Adzick AS. Sonographic predictors of survival infetal diaphragmatic hernia. J Pediatr Surg 1996;31:148±51.

33. Lund DP, Mitchell J, Kharasch V, Quigley S,Kuehn M, Wilson JM. Congenital diaphragmatichernia: the hidden morbidity. J Pediatr Surg 1994;29:258±62.



Documents

360.full