Congenital diaphragmatic hernia (ORPHA:2140)
A rare developmental defect during embryogenesis which can be a non-syndromic (70%) or syndromic (30%) diaphragmatic malformation characterized by a posterolateral defect of the diaphragm that allows passage of abdominal viscera into the thorax, leading to respiratory insufficiency and persistent pulmonary hypertension.
Epidemiology
Congenital diaphragmatic hernia (CDH) is a rare condition occuring in 1-5/10,000 births.
Clinical description
Newborns display respiratory distress with hypoxia, excavated abdomen with sternal protrusion and in severe cases low APGAR scores at 1 and 5 minutes. Auscultation may reveal a contralateral cardiac displacement and respiratory bruits are absent or decreased on the affected side. Insufficient gas exchange and persistent pulmonary hypertension are associated with hypoplastic lungs. Pulmonary hypertension may become manifest after a brief period of adaptation to post-natal circulation. The defect and hence herniation of the intestine and/or the liver into the thorax occurs more often on the left side. Malrotation or malfixation of the intestine are frequent. One third of cases present with cardiovascular malformations and lesser proportions with skeletal, neural, genitourinary, gastrointestinal or other defects. CDH may be isolated (non-syndromic) or a component of Fryns, Denys-Drash and Donnai-Barrow syndromes as well as certain chromosomal anomalies.
Etiology
The causes of CDH are largely unknown; abnormal embryogenesis due to retinoid signaling dysfunction is likely involved as are mutations of ZFPM2 and GATA6 in some cases. Persistent pulmonary hypertension is due to arteriolar constriction and closure of the pulmonary arterial bed.
Diagnostic methods
Thoracic and abdominal X-rays locate herniated viscera. Blood gases and pH status, and other derived indexes, reflect the efficiency of gas exchange. Echocardiography of the heart is necessary to exclude associated malformations, to measure the right-to-left shunt and to estimate the severity of pulmonary hypertension.
Differential diagnosis
CDH should be differentiated from cystic malformation of the lung.
Antenatal diagnosis
Prenatal ultrasonography reveals herniation, polyhydramnios may appear. Genetic testing for associated chromosomal aberrations and syndromes may indicate syndromic CDH if other manifestations are present. Small lungs size related to the size of the head indicates lung hypoplasia and can be prognostic.
Genetic counseling
Most cases are sporadic and appear to be multifactorial, two thirds are male. Recurrence in siblings is 2%. Genetic counseling should be offered.
Management and treatment
Termination of pregnancy may be offered when chromosomal aberrations and syndromes are present. Fetoscopic endoluminal tracheal occlusion (FETO) with a balloon, particularly for fetuses considered otherwise unviable, has yielded survival rates approaching 50%. Gestation should be prolonged until near term if possible; maternal corticosteroids have also been proposed. In newborns, pre- and post-ductal percutaneous oxygen saturation measurements may assess the pulmonary function. Spontaneous ventilation or high frequency, low pressure ventilation (<20-25 cm H2O), no relaxation, alkalinization and adoption of modest gasometric goals (pre-ductal saturation of 80-95%, PaO2 60 mm Hg, hypercapnia <60 mm Hg) are now the standard. Extra-corporeal membrane oxygenation (ECMO) has also been used. Inotropic drugs (eg: dobutamine, dopamine) may be used to treat cardiac anomalies. Surgical repair of the hernia, undertaken only after cardio-respiratory functions are stable, replaces viscera into the abdomen and closes the diaphragmatic defect; a prosthetic patch may be necessary to repair the defect. Some surgeons perform this operation by video-assisted thoracoscopy.
Prognosis
Considering prenatal and preoperative fatalities, mortality is 50-60%. Post-operative survival rate is 70-80%, up to 90% in certain institutions, particularly in non-syndromic CDH. Right-sided hernias seem to have a worse prognosis and may require more ECMO support. After surgical repair, pleural effusions and chronic respiratory tract disease are frequent, along with gastroesophageal reflux. Neurodevelopmental deficits are a risk following bouts of cerebral hypoxia. Neurosensorial deafness has been reported in a small proportion of patients.

                            Last update: 
                            August 2020


                            - Expert reviewer(s): 
                            Pr Richard KEIJZER