Outline Isolated Congenital Diaphragmatic Hernia Prenatal diagnosis - PDF document

20-3-2012 Prenatal management of the fetus with isolated Congenital Diaphragmatic Hernia Jan Deprest Center for Fetal Medicine Department Woman and Child, Division Woman University Hospitals Leuven Leuven, Belgium On behalf of the FETO consortium A number of instruments and devices are used of label The presenter has no financial interests to disclose Prenatal Diagnosis of CDH Diaphragm hypoechogenic line between lungs – viscera 13 wk 21 wk 27 wk Screening programmes should pick up CDH Raises the question of prognosis Outline Isolated Congenital Diaphragmatic Hernia • Prenatal diagnosis & prediction of outcome of i ‐ CDH • Planimetric methods • Volumetric methods • Vascular assessment • Prenatal therapy Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org • Rationale and experimental basis • Current clinical technique • Results • Currently investigated within randomized trial Experimental Experimental Clinical Clinical Issues & Issues & Outline Outline Prenatal Prediction Prenatal Prediction Results Results TOTAL trial TOTAL trial Fetal Therapy Fetal Therapy Fetal Therapy Fetal Therapy Questions Questions 1

20-3-2012 Congenital Diaphragmatic Hernia Increasingly being picked up in screening programmes Few in utero problems Postnatal: correctable defect ventilatory insufficiency pulmonary hypertension long term morbidity Overall outcome associated: 85% mortality isolated: 30% mortality Deprest et al, Sem Fet Neonat Med 2009 normal CDH Reduced and Reduced number of airways abnormal vessels Abnormal compliance Survival and hidden mortality Isolated CDH n TOP rate survival till discharge Gallot 2007 314 7% 63% Steege 2003 185 n.a. 70 % Schaible 2006 244* ‐ 70% Hedrick 2007 89 n.a. 66% Datin ‐ Dorrière 08 99 20% 63% Mettauer 09 147 postnatal series 77% Contact: eurofoetus@eurofoetus.org Grushka 2009 121 postnatal series 81% Mt Sinai (2000 ‐ 2009) ** 86 15% 65% Sick Kids (2002 ‐ 2009) ** 45 Postnatal series 85% * In utero referral in third trimester, ECMO policy of 50%; case load 35 cases/year ** isolated only, courtesy G Ryan & D Bohn , University of Toronto, Canada (May 2010) Prediction prognosis Liver position Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org Liver herniation Antenatal CDH registry 2006 Lung to Head Ratio (LHR) Mullasery UOG 2010 Metkus 1996 Mayer Prenat Diagn 2011 Antenatal CDH registry 2006 ‐ 8 Knox 2010 Survival: 74% → 45 % Alfarai 2011 Experimental Experimental Clinical Clinical Issues & Issues & Outline Outline Prenatal Prediction Prenatal Prediction Results Results TOTAL trial TOTAL trial Fetal Therapy Fetal Therapy Fetal Therapy Fetal Therapy Questions Questions 2

20-3-2012 Lung to head ratio • LHR increases with gestation (Peralta, 2005) • Different methods of which the tracing method is most accurate (Jani, 2006) Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org Using correct nomogram, • expressed as a percentage what is Peralta 2005 expected in normal fetus, provides gestational age Metkus et al, 1996 independent size estimation Jani et al, 2006 Observed/expected LHR area measured OBSERVED Fetal Lung Area 0.5 (fetus at risk for lung hypoplasia) O/E = 25% area predicted EXPECTED Fetal Lung Area 2.0 (matched normal fetus) matched fetus based on gestational age Methodology and discussion in Claus et al, Fet Diagn Ther 2010 O/E LHR discounts effect of gestational age Right lung 100 Lung area to head circumference ratio 4.0 90 Observed / Expected LHR (%) 3.5 80 70 3.0 60 2.5 50 2.0 40 1.5 30 1.0 20 0.5 10 0 0 18 22 26 30 34 38 18 22 26 30 34 38 Gestation (wks) Gestation (wks) Peralta et al 2005 Fetuses with left CDH (n=329) Jani et al 2007 3

20-3-2012 Current algorithm 100 extreme severe moderate mild 90 80 Survival rate (%) 70 60 50 40 30 20 10 0 Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org < 15 15 ‐ 25 26 ‐ 35 36 ‐ 45 O/E LHR (%) 46 and higher 1% 14% 45% 40% liver in thorax (“up”) liver in abdomen (“down”) Antenatal Registry – Jani et al, UOG 2008 (n=329 LCDH) ‐ Deprest J et al, Sem Neonat Fetl Med, 2008. Experimental Experimental Clinical Clinical Issues & Issues & Outline Outline Prenatal Prediction Prenatal Prediction Results Results TOTAL trial TOTAL trial Fetal Therapy Fetal Therapy Fetal Therapy Fetal Therapy Questions Questions Early neonatal morbidity indicators Isolated CDH eiter expectantly managed (n=100) Patch rate (%) Oxygen O 2 at 28d (%) Conventional ventilation Enteral feeding NICU** 100 100 60 60 60 90 90 days days days 80 80 50 50 50 70 70 40 40 40 60 60 50 50 30 30 30 40 40 20 20 20 Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org 30 30 20 20 10 10 10 10 10 0 0 0 0 0 ≤ 25 26 ‐ 45 >45 ≤ 25 26 ‐ 45 >45 ≤ 25 26 ‐ 45 >45 <25 26 ‐ 45 >45 <25 26 ‐ 45 >45 O/E LHR (%) O/E LHR (%) O/E LHR (%) O/E LHR (%) O/E LHR (%) Jani et al UOG 2009 Experimental Experimental Clinical Clinical Issues & Issues & Outline Outline Prenatal Prediction Prenatal Prediction Results Results TOTAL trial TOTAL trial Fetal Therapy Fetal Therapy Fetal Therapy Fetal Therapy Questions Questions 4

20-3-2012 O/E LHR and CDH • Normative data for calculation expected LHR ‐ Peralta et al, UOG 2005 – Calculation formula based on the raw data – Deprest et al, Fet Diagn Ther 2010 – available as calculator on www.totaltrial.eu • Antenatal registry CDH: – Prediction of mortality : Jani et al, UOG 2006 (LHR), 2007 (O/E LHR) – Accuracy versus GA: Jani et al, UOG 2008 – Prediction of morbidity: Jani et al, UOG 2009 – Validation with pathology: Jani et al, UOG 2011 (on line) • Learning curve: Cruz ‐ Martinez et al, UOG 2010 • Recent meta ‐ analysis: Knox et al, J Mat Fet Med 2010 • Assessment methods reviewed in Claus et al, Fet Diagn Ther 2011 2 versus 3 dimensional Cross section at the 4 chamber view Of ONE lung volumetric measurement of two lungs and of liver herniation Multicenter studies prediction on volumetry Liver up 80 90 20% survival rate 70 80 60 70 o/e TFLV (%) 50 60 Survival rate (%) 50 40 40 30 30 20 20 Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org 10 10 0 ~ 33% 0 ≤ 25 26 ‐ 35 36 ‐ 45 > 45 0 10 20 30 40 50 Observed to expected total FLV (%) LiTR (%) o/e Total Fetal Lung Volume (TFLV) Liver to thorax ratio (LiTR) OR: 1.16 (1.04 ‐ 1.30) (p=0.09) OR survival: 0.87 (0.79 ‐ 0.95) (p=0.003) Cannie et al UOG 2008 Cannie et al UOG 2008 – n = 40 – 35 LCDH Experimental Experimental Clinical Clinical Issues & Issues & Outline Outline Prenatal Prediction Prenatal Prediction Results Results TOTAL trial TOTAL trial Fetal Therapy Fetal Therapy Fetal Therapy Fetal Therapy Questions Questions 5

20-3-2012 O/E LHR rather than volumetry ? 100 75 Sensitivity (%) 50 MRI 25 Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org 2D ‐ US 0 0 25 50 75 100 False positive rate (%) MRI may be better than 2D LHR in predicting outcome Cannie et al UOG 2008 Isolated CDH born alive >30 wks, paired observations (n=76 Experimental Experimental Clinical Clinical Issues & Issues & Outline Outline Prenatal Prediction Prenatal Prediction Results Results TOTAL trial TOTAL trial Fetal Therapy Fetal Therapy Fetal Therapy Fetal Therapy Questions Questions Prenatal prediction: lung vasculature Measurements of – Pulmonary artery diameters (Sokol et al.AJOG;2006) – Flow velocity waveforms (Laudy 1997; Sivan 2000; Fuke 2003, Moreno UOG 2008) – Resistance within (Rizzo, UOG 1996; Mitchell, UOG 1998; Chaoui, UOG 1999) Proximal branch – Power Doppler imaging intrapulmonary artery (Mahieu ‐ Caputo, 2004, Ruano 2004 ‐ 6) Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org Fractional Moving Blood – Fractional moving blood volume Volume (FMBV) (Hernandez ‐ Andrade, UOG 04; Moreno, UOG 2010; Cruz –Martinez , UOG 2010) – Hyperoxygenation test (Broth 2002, Doné UOG 2010) Experimental Experimental Clinical Clinical Issues & Issues & Outline Outline Prenatal Prediction Prenatal Prediction Results Results TOTAL trial TOTAL trial Fetal Therapy Fetal Therapy Fetal Therapy Fetal Therapy Questions Questions Anatomical repair → Tracheal Occlusion Congenital Contact: eurofoetus@eurofoetus.org Contact: eurofoetus@eurofoetus.org High Flake et al, 20000 Airway Obstruction Jost 1948 , Carmel 1960, Di Fiore & Wilson 1994 Lung growth is triggered by tracheal occlusion Luks & Deprest, Leuven 1995 ‐ 1996 Experimental Experimental Clinical Clinical Issues & Issues & Outline Outline Prenatal Prediction Prenatal Prediction Results Results TOTAL trial TOTAL trial Fetal Therapy Fetal Therapy Fetal Therapy Fetal Therapy Questions Questions 6