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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