Congenital posterolateral diaphragmatic hernia : pathophysiological studies and clinical picture

Congenital diaphragmatic hernias are classified according to the location of the defect: posterolateral hernia with or without a sac (Bochdalek-type), parasternal hernia through the foramen of Morgagni, central hernia, and diaphragmatic eventration. The so-called hiatal hernia has a different pathophysiology and a different clinical presentation. Posterolateral defects account for 85% of congenital diaphragmatic herniasY Left-sided posterolateral defects occur eight times more frequently than right-sided defects in the neonatal period. Bilateral defects are rare and estimated at 3 to 5%.3 Children at the highest risk of dying are they who are symptomatic in the delivery room or within six hours after birth.' The mortality rate reported in this group ranges from 40 to 50%." Conversely, those who do not develop respiratory failure in the first 24 hours of life have an almost 100% chance of survival. In contrast to other major congenital anomalies the mortality due to congenital posterolateral diaphragmatic hernia remains high despite improvements in neonatal intensive care and pediatric surgery.'~ The main reason is that pulmonary hypoplasia and pulmonary hypertension form the pathophysiological basis for the clinical picture of respiratory distress and right-to-left shunting that frustrates so many clinicians responsible for newborns with a diaphragmatic defect. This thesis presents the research into clinical aspects of congenital posterolateral diaphragmatic hernia related to pulmonary hypoplasia and pulmonary hypertension; the pathophysiological background of these disorders was studied in an animal model. The clinical studies were all carried out in the Pediatric Surgical Intensive Care Unit of the Sophia Children's Hospital. The animal model was developed by TenBrinck and coworkers in the Laboratory of Experimental Surgery of the Erasmus University in Rotterdam.' In this model congenital diaphragmatic hernia is induced in fetal rats by means of administering a single dose of Nitrofen (2,4-dichlorophenylp- nitrophenyl ether) on the lOth day of gestation. The model interferes with lung development in an early stage, thus providing the opportunity to study several aspects of lung development in relation to both ventilatory capacity and pulmonary vascular reactivity. The results of the conducted studies, as they have been reported and discussed in papers either published or accepted by international journals, form the core of this thesis. These papers are preceded by a review of the literature focussed on historical aspects, clinical picture and normal and abnormal lung development. They are followed by a concluding chapter in which changing concepts concerning pathogenesis and treatment are discussed

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