in the developing diaphragm of the fetus leading to herniation of abdominal viscera into the thorax z Significant pulmonary, cardiac, and gastrointestinal sequelae z 1 in 2000 to 5000 live births Fanaroff and Martin’s Neonatal-Perinatal Medicine, 2006
Subtypes of CDH z Hernation
of abdominal contents occurs through a posterolateral defect (foramen of Bochdalek) in ~ 95% of cases z Retrosternal herniation occurs in ~ 5% of cases (foramen of Morgagni) z Left-sided CDH are more common (80%)
Lally et al. Congenital diaphragmatic hernia. Curr Opin Pediatr 2002;14:486-490.
Pathogenesis of CDH is Controversial z Is
CDH a primarily pulmonary or diaphragmatic pathology? z Classically the pathology was considered diaphragmatic – Incomplete embryologic formation of diaphragm – Protrusion of abdominal contents in thorax – Resultant pulmonary hypoplasia Harrison et al. Fetal diaphragmatic hernia: pathophysiology, natural history, and outcome. Clin Obstet Gynecol 1986;29:490-501.
Pulmonary Hypoplasia May be the Primary Pathology in CDH z Nitrofen
is a pulmonary teratogen in animal
models z Animals treated with Nitrofen developed pulmonary hypoplasia and CDH z Nitrofen is not believed to directly cause CDH (animals without CDH still developed pulmonary hypoplasia) Keijzer et al. Dual-hit hypothesis explains pulmonary hypoplasia in the nitrofen model of congenital diaphragmatic hernia. Am J Pathol 2000;156(4):1299-306.
Nitrofen Causes Pulmonary Hypoplasia in Animals
Cilley et al. Nitrofen dose-dependent gestational day-specific murine lung hypoplasia and left-sided diaphragmatic hernia. Am J Physiol 1997;272:L362-71.
Nitrofen Causes Pulmonary Hypoplasia in Animals
Cilley et al. Nitrofen dose-dependent gestational day-specific murine lung hypoplasia and left-sided diaphragmatic hernia. Am J Physiol 1997;272:L362-71.
Nitrofen Causes CDH in Animals
Kluth et al. Nitrofen-induced diaphragmatic hernia in rats: an animal model. J Pediatr Surg 1990;25(8):850-4.
Dual-Hit Hypothesis: Both Pulmonary and Diaphragmatic Factors may lead to CDH
Keijzer et al. Dual-hit hypothesis explains pulmonary hypoplasia in the nitrofen model of congenital diaphragmatic hernia. Am J Pathol 2000;156(4):1299-306.
Prenatal Diagnosis of CDH z High-Resolution
ultrasound in the first trimester can visualize the diaphragm z Important to evaluate for presence of liver or bowel in the thorax z Observe for other anomalies z If ultrasound is positive, consider MRI Deprest et al. Current consequences of prenatal diagnosis of congenital diaphragmatic hernia. Journal of Pediatric Surgery 2006;41:423-430.
40% of CDH Patients Have Anomalies or Genetic Syndromes
Pober et al. Genetic aspects of human congenital diaphragmatic hernia. Clin Genet 2008;74:1-15.
Increased Lung to Head Ratio (LHR) on Ultrasound Suggests Decreased Mortality
Metkus et al. Sonographic predictors of survival in fetal diaphragmatic hernia. Journal of Pediatric Surgery 1996;31(1):148-151.
Liver Herniation into Thorax Suggests Increased Mortality
Albanese et al. Fetal liver position and perinatal outcome for congenital diaphragmatic hernia. Prenatal Diagn 1998;18:1138-1142.
Antenatal MRI is Useful in Predicting Survival
Cannie et al. Prenatal prediction of survival in isolated diaphragmatic hernia using observed to expected total fetal lung volume determined by magnetic resonance imaging based on either gestational age of fetal body volume. Ultrasound Obstet Gynecol 2008;32:633-639.
Clinical Presentation of CDH z Respiratory
distress at birth
– Cyanosis, tachypnea, grunting, retractions
z Scaphoid
abdomen z Mediastinal shift z Breath sounds absent on affected side z Bowel sounds auscultated in the chest Fanaroff and Martin’s Neonatal-Perinatal Medicine, 2006
Delivery Room Management of the Infant with CDH z If
neonate is distressed: Immediate intubation z Avoidance of bag-mask ventilation z Nasogastric tube placement with gastric decompression Fanaroff and Martin’s Neonatal-Perinatal Medicine, 2006
Sequelae of CDH z Pulmonary Hypertension – Lung hypoplasia – Increased medial thickness of
pulmonary arteries – Blunted oxygen vasodilation
Fanaroff and Martin’s Neonatal-Perinatal Medicine, 2006
Patients Requiring Less Ventilatory Support Have Improved Mortality
Bohn et al. Blood gas and ventilatory parameters in predicting survival in congenital diaphragmatic hernia. Pediatr Surg Int 1987;2:336-340.
Patients with Lower Pre- and Post-ductal Differential Have Improved Mortality
Bohn et al. Blood gas and ventilatory parameters in predicting survival in congenital diaphragmatic hernia. Pediatr Surg Int 1987;2:336-340.
New Strategies for Treatment of CDH z Historically
treatment included emergent surgical repair and aggressive control of PPHN z Improved outcomes with gentler ventilation – Permissive hypercapnea/hypoxia – Avoid high ventilation pressures – Delayed repair when stable Deprest et al. Current consequences of prenatal diagnosis of congenital diaphragmatic hernia. Journal of Pediatric Surgery 2006;41:423-430.
Boloker et al. Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/elective repair. J Pediatr Surg 2002;37(3):357-366.
Conflicting Studies on Surfactant: Recent Studies Suggest Increased Mortality
Van Meurs et al. Is surfactant therapy beneficial in the treatment of the term newborn infant with congenital diaphragmatic hernia? J Pediatr 2004;145(3):312-316.
Nitric Oxide Does Not Improve Mortality
Finer et al. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 2006;4:CD000399.
Nitric Oxide Decreases Need for ECMO
Finer et al. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 2006;4:CD000399.
ECMO Improves Mortality in CDH
Mugford et al. Extracorporeal membrane oxygenation for severe respiratory failure in inewborn infants. Cochrane Database Syst Rev 2008;3:CD001340.
Significant Morbidity and Mortality Exists Despite Advances in Therapy z Permissive
hypercapnea strategy achieves survival approaching 90% z Significant morbidity – Developmental delay – GERD – Chronic lung disease – Hernia recurrence Lally et al. Congenital diaphragmatic hernia. Current Opinion in Pediatrics 2002, 14:486-490.
CONCLUSIONS I z CDH
is a relatively common congenital anomaly with significant sequelae
z Pathophysiology z Pulmonary z Diaphragm z Dual-Hit
is controversial:
CONCLUSIONS II z CDH
is commonly associated with other anomalies which affect outcomes
z Prenatal
Sonogram and MRI can diagnose CDH and predict outcome
z Less
ventilatory support and lower markers of pulmonary hypertension are associated with improved survival
CONCLUSIONS III z Postnatal
management strategies have changed resulting in improved outcomes
z Permissive
hypercapnea/hypoxia and delayed repair is beneficial
CONCLUSIONS IV z No
clear role for NO or Surfactant
z ECMO
improves survival
z While
mortality has improved with newer management strategies, significant long-term morbidity exists THANK YOU
