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Congenital diaphragmatic hernia:

prediction of pulmonary hypoplasia

JM Martínez, B Puerto, E Gratacós

1/2400-4000 neonates

– isolated: 1/5.000 (100/ year)

Localization

– 90% postero-lateral (Bochdaleck)

– 95% unilateral

• 80% left

• 20% right

Congenital diaphragmatic hernia (CDH)

1. Defect pleuroperitoneal membrane 8-12 wk

– Secondary pulmonary hypoplasia

2. Primary pulmonary hypoplasia

– Secondary CDH

CDH: etiopathogenesis

1. Defect pleuroperitoneal membrane 8-12 wk

– Secondary pulmonary hypoplasia

2. Primary pulmonary hypoplasia

– Secondary CDH

CDH: etiopathogenesis

PULMONARY HYPOPLASIA

+/-

PULMONARY HYPERTENSION

Canalicular 28 17

Pseudoglandular 18 7

Saccular 40 25

Alveolar 30 2 yrs

Embryonic 8 4

vascular

development

end of conduct

generation

IMPAIRMENT OF GROWTH

Normal lung development

Canalicular 28 17

Pseudoglandular 18 7

Saccular 40

25

Alveolar 30 2 yrs

Embryonic 8 4

vascular

development

end of conduct

generation

immaturity vascular damage Impaired airway number

IMPAIRMENT OF GROWTH

Lung hypoplasia

Ultrasound diagnosis of CDH

Normal thorax

─ Heterogeneous mass

─ Mediastinum shift

─ Abdominal viscera

─ PolyH, hydrothorax

Left CDH

─ Homogeneous mass

─ Mediastinum shift

─ Liver

─ PolyH, hydrothorax

Right CDH

30-40% associated anomalies

1. ultrasound

2. echocardio: 10-15%

3. Karyotype: 25%

t21,t18,iso12p

4. ¿MRI?

30-40% associated anomalies

1. ultrasound

2. echocardio: 10-15%

3. Karyotype: 25%

t21,t18,iso12p

4. ¿MRI?

Prognosis of CDH:

prediction of pulmonary hypoplasia

Isolated CDH: 60-70%

conflict obstetrical vs. pediatrical data

good prognosis poor prognosis

intrauterine prognostic factors

Euro-CDH group LHR and liver to predict outcome in left CDH:

a multicenter study. AJOG 2006

J. Jani1, A. Benachi2, R. Favre4, R. Keller3,

H. Vandecruys6, J. Becker5, M. Harrison7, J. Matis4,

E. Gratacos5, K. Nicolaides6, J. Deprest1

Leuven - Barcelona - London - Paris - Strasbourg - San Francisco

global perinatal mortality: 30-40%

Global mortality 30-40%

– LETHAL PULMONARY HYPOPLASIA

1. Respiratory insufficiency

2. Pulmonary hypertension

Isolated CDH: 1/5.000 (100/ year)

Pulmonary hypoplasia

• Pulmonary hypoplasia degree:

1. Size of the defect

2. Visceral herniation

• It is bilateral!!!

Ultrasound

– 3D-ultrasound

Doppler

– Pulsed

– Angio-power

MRI

– 3D-MRI

Prediction of pulmonary hypoplasia

30-40% perinatal mortality ‘qualified’:

o/e LHR + liver

Pulmonary hypoplasia

• Pulmonary hypoplasia degree:

1. Size of the defect

2. Visceral herniation

• It is bilateral!!!

‘Lung-to-head ratio’ (Metkus 1996)

1. 4 chamber view

2. 1 rib

3. Perpendicular max

diameters

Metkus 1996

‘Lung-to-head ratio’

1. 4 chamber view

2. 1 rib

3. Perpendicular max

diameters

LHR: 17.0x9.9/218= 0.78

‘Lung-to-head ratio’

o/e LHR (customization)

Jani et al UOG 2007

Poor prognosis: o/e LHR < 40-45%

Jani et al UOG 2007

LHR o/e LHR

>1.4 > 40%

1.0-1.4 25-40%

0.8-1.0 15-25%

< 0.8 < 15%

Correlation

o/e LHR and liver

bad prognosis ‘good’ prognosis

Prediction of survival according to o/e LHR and liver position

Left Right

CDH expectant management (n=100)

Prediction of morbidity

CDH expectant management (n=100)

Jani et al 2007

≤ 25 26-45 >45

Patch rate (%)

0

10

20

30

40

50

60

70

80

90

100

O/E LHR (%)

0

10

20

30

40

50

60

Conventional ventilation

days

≤ 25 26-45 >45

O/E LHR (%)

0

10

20

30

40

50

60

Enteral feeding

days

<25 26-45 >45

O/E LHR (%)

0

10

20

30

40

50

60

NICU

days

<25 26-45 >45

O/E LHR (%)

0

10

20

30

40

50

60

70

80

90

≤ 25 26-45 >45

O/E LHR (%)

Oxygen O2 at 28d (%)

100

sagital coronal transversal

3D ultrasound / MRI … not yet

Risk prediction by LHR

LHR predicts

lethal hypoplasia

LHR predicts

nothing

Arkovitz MS, JPS 07

Heiling KS, UOG 05

Bashat, UOG 07

review & meta-analysis most published studies excluded

Metkus, JPS 96

Lipshutz GS, JPS 97

Laudy JA, Pren Diag 03

Keller RL, UOG 03

Jani J, UOG 2006

Jani J, AJOG 06

Yang SH, AJOG 07

Hedrick,AJOG 07(worse than liver)

Datin-D,AJOG07(better than liver)

It is not perfect but it is the

BEST AVAILABLE PARAMETER

Options for isolated CDH

1. TOP

2. ‘Standard’ postnatal treatment

3. Postnatal treatment + FETAL THERAPY

• if survival ≤ 60%

Prenatal therapy for CDH

Fetal therapy: fetoscopic tracheal occlusion

• Mecanism: Induces accelerated lung growth

1. Direct mechanical stimuli: prevents exit of normal

tracheobronchial fluid

2. Secretion of growth factors

• Timing

– 27-29 wk if LHR O/E < 25%

– 30-32 wk if LHR O/E > 25-40%

FETO: Leuven-BCN-London (n> 350)

Post-fetoscopy

Post-fetoscopy

elegible: FETO: ‘update’ results: 210 cases (october 2008)

FETO: removal of balloon

Fetal therapy for CDH: survival

Left CDH: 24.1% to 49.1%

Right CDH: 0% to 35.3%

Aive and well 73%

Respiratory 4%

Feeding 7%

Neurodevelopmental 2%

Scoliosis 2%

Fetal therapy for CDH: morbidity (6-60 months)

Fetal therapy for CDH : complications

Rotura de tràquea: 4 (1.9%)

– 3 fetoscopia 8-14 días

Polihidramnios severo: 18 (8.5%)

Hemorragia intramaniótica (transfusión): 1 (0.5%)

Corioamnionitis: 5 (2.3%)

Future challenges in CDH

FETO survival + 30% S

urv

ival ra

te (

%)

≤15% 16%-25% 25%- 40% ≥41%

0

10

20

30

40

50

60

70

80

90

100

1. 50-60%: good response

high survival

2. 25%: lung growth BUT severe PHT

high mortality

3. 15-20%: no response

extreme mortality

¿How can we identify those cases with good or

poor lung response to FETO?

Conduct randomized studies

Improved thecnological issues

Refine pathophysiological understanding

– Define subgrups at risk

• Survival

• Morbidity

Fetal therapy for CDH: future challenges

Eurofetus vs randomized USA

US diagnosis

•US (LHR)

•MRI (liver-up)

•detailed US scan

•karyotype

O/E < 15%

(LHR< 0.6)

pilot study TO 22-24w

+

eventually RCT

O/E 15-25%

(LHR 0.7-0.99)

TO vs expectant

SURVIVAL

O/E 25-40%

(LHR 1.0-1.4)

TO 30-32 w vs expectant

MORBIDITY

EURO-CDH - RCT STUDIES ON CDH IN UTERO TREATMENT EURO-CDH: Barcelona-Leuven-London

RCT studies on CDH in utero treatment

CDH: Doppler evalaution

PSV

PERDF

CDH: Doppler evalaution

PSV

PERDF

Doppler prediction of response after FETO

+

Doppler evaluation of perfusion

1. Isolated: only 50%

2. Global mortality 30-40%

3. Variable and predictable outcome (o/e LHR)

4. Fetal therapy: 30-35 % survival

5. If survives: good quality of life

CDH: conclusions