Diaphragmatic Hernias 

In 1679, Lazarus Riverius (1589-1655) recorded the first reported case of a congenital diaphragmatic hernia (CDH); this was following postmortem examination of a 24-year-old male.^[1] The first attempt at surgical repair for congenital diaphragmatic hernia was by Nauman of Sweden in 1888; the 19-year-old patient presented with acute respiratory distress and an acute abdomen, and a laparotomy was performed. In 1889, J. O'Dwyer, MD, carried out the first repair of congenital diaphragmatic hernia in an infant. The first successful repair occurred in 1905. The patient was aged 9 years, and Heidenhain (at the Municipal Hospital for Worms, Germany) reduced the hernia and closed the diaphragmatic defect through a midline laparotomy incision. Approximately 20 years later, Carl Hedbolm reported a 58% mortality rate for patients undergoing surgical intervention for congenital diaphragmatic hernia.

See the image shown below.

In 1940, William Ladd and Robert Gross based their diagnosis of congenital diaphragmatic hernia on history, physical examination findings, and findings on chest radiography with or without a barium meal.^[2] They advocated early surgical intervention (within the first 48 h). Gross also described a 2-staged closure of the abdominal wall in difficult cases; closure of skin and subcutaneous fascia at the initial surgery and closure of the abdominal wall 5-6 days later. In 1950, C. Everett Koop and Julian Johnson suggested the transthoracic approach as a means of closing the defect under more direct vision.^[3]

As surgical expertise improved, innovative strategies were developed to address large diaphragmatic defects and agenesis of the hemidiaphragm. These techniques included the use of rotational muscle flaps, perirenal fascia, and synthetic patch repairs.

The exponential elucidation of the pathophysiology of congenital diaphragmatic hernia was instrumental in improving the survival rate in infants. Congenital diaphragmatic hernia was no longer considered a primarily surgical disease but rather a disease associated with pulmonary hypoplasia, pulmonary hypertension, pulmonary immaturity, and an increased susceptibility of the lungs to ventilation-induced lung injury. This led to a delayed approach to surgical repair and to a gentle but more ingenious respiratory support.

Associated anomalies are present in 10-50% of patients with congenital diaphragmatic hernias; these anomalies confer a 2-fold relative risk of mortality when compared with patients with isolated congenital diaphragmatic hernias.^[4] Frequently associated anomalies include cardiac defects, chromosomal anomalies (ie. trisomies 21, 18, and 13), renal anomalies, genital anomalies, and neural tube defects.

Frequency

Congenital diaphragmatic hernia occurs in 1 per 3000 live births.^[5]

Mortality

The Congenital Diaphragmatic Hernia Study Group recorded a 63% survival rate in 1995-1996 based on data from 62 centers in North America, Europe, and Australia.^[6] Survival rates are 60-90% for patients who present within the first few hours of life (see image below).^[7]

Relevant embryology

The diaphragm is derived from 4 embryonic structures: the septum transversum, the pleuroperitoneal membranes, mesoderm of the body wall, and esophageal mesenchyme. Following folding of the fetal head at 4-5 weeks' gestation, the septum transversum comes to lie as a semicircular shelf, which separates the heart from the liver. The septum transversum does not completely separate the thoracic cavity from the peritoneal cavity but allows pericardioperitoneal canals to exist on either side of the esophagus.

During the fifth week of gestation, the pleuroperitoneal membranes develop along a line connecting the root of the 12th rib with the tips of the 7th to 12th ribs. The pleuroperitoneal membranes grow ventrally to fuse with the posterior margins of the septum transversum and the dorsal mesentery of the esophagus. Hence, at 6-7 weeks' gestation, the pleuroperitoneal canals are closed; the left closes after the right. The mesentery of the esophagus condenses to form the left and right crura of the diaphragm, and the mesoderm of the body wall forms the outer rim of diaphragmatic muscle.

The posterolateral diaphragmatic defect is postulated to result from failure of closure of the pleuroperitoneal canals. The canal remains open when the intestines return to the abdomen at 10 weeks' gestation. Some intestine and other viscera enter the thorax and lead to compression of the developing lung at the crucial pseudoglandular stage and shifting of the mediastinum to the contralateral side. This causes compression of the heart and the contralateral lung as well.

In 1984, Iritani proposed a different concept of diaphragmatic development. He suggested that a posthepatic mesenchymal plate develops between the septum transversum and the pericardioperitoneal canals.^[8] Lateral growth of this plate leads to closure of the pericardioperitoneal canals, and congenital diaphragmatic hernia results from a disturbance in growth of the posthepatic mesenchymal plate.

Causes

• Genetic factors: The initiating factor responsible for the development of congenital diaphragmatic hernia is unknown. Wide variations have been noted in the reported prevalence of chromosomal abnormalities (7-31%) in patients with congenital diaphragmatic hernia. The prevalence is higher in cases of congenital diaphragmatic hernia associated with other defects.^[5] Familial occurrence has been noted in fewer than 2% of cases.
• Other causes: The role of drugs and environmental chemicals in the development of congenital diaphragmatic hernia is uncertain, but nitrofen, quinine, thalidomide, phenmetrazine, and polybrominated diphenyls have been used to induce congenital diaphragmatic hernia in various species. Current investigations are exploring the link between congenital diaphragmatic hernia and defects in the retinoid signaling pathway in experimental models.

The pathophysiology of congenital diaphragmatic hernia involves pulmonary hypoplasia, pulmonary hypertension, pulmonary immaturity, and potential deficiencies in the surfactant and antioxidant enzyme system.

Because of bowel herniation into the chest during crucial stages of lung development, airway divisions are limited to the 12th to 14th generation on the ipsilateral side and to the 16th to 18th generation on the contralateral side. Normal airway development results in 23-35 divisions. Because airspace development follows airway development, alveolarization is similarly reduced.

Development of the pulmonary arterial system parallels development of the bronchial tree, and, therefore, fewer arterial branches are observed in congenital diaphragmatic hernia. Abnormal medial muscular hypertrophy is observed as far distally as the acinar arterioles, and the pulmonary vessels are more sensitive to stimuli of vasoconstriction.^[9] Pulmonary hypertension resulting from these arterial anomalies leads to right-to-left shunting at atrial and ductal levels. This persistent fetal circulation leads to right-sided heart strain or failure and to the vicious cycle of progressive hypoxemia, hypercarbia, acidosis, and pulmonary hypertension observed in the neonatal period.

The surfactant system is demonstrably deficient in the lamb model of congenital diaphragmatic hernia.^[10] Postnatal administration of surfactant in these lambs is associated with dramatic increases in gas exchange, lung compliance, and pulmonary blood flow. However, in human neonates, reports on the status of the surfactant system are inconsistent.^{[11, 12]}

Infants with congenital diaphragmatic hernias also have impairment of the pulmonary antioxidant enzyme system and are more susceptible to hyperoxia-induced injury.

In addition, a left ventricular smallness and hypoplasia are observed with congenital diaphragmatic hernia. This is believed to arise from decreased in utero blood flow to the left ventricle, the mechanical compression of the herniated viscus similar to that observed in the lungs, and/or a primary yet unidentified developmental defect that simultaneously causes the diaphragmatic hernia and lung problems.

Prenatal

The diagnosis of congenital diaphragmatic hernia is frequently made prenatally prior to 25 weeks' gestation.

Congenital diaphragmatic hernia is usually detected in the antenatal period (46-97%), depending on the use of level II ultrasonography techniques. Ultrasonography reveals polyhydramnios, an absent intra-abdominal gastric air bubble, mediastinal shift, and hydrops fetalis. Ultrasonography demonstrates the dynamic nature of the visceral herniation observed with congenital diaphragmatic hernia. The visceral hernia has moved in and out of the chest in several fetuses.

Differential diagnoses on prenatal ultrasonography are as follows:

• Congenital cystic adenomatoid malformation
• Pulmonary sequestration (This can be an associated finding in CDH)
• Mediastinal cystic processes (eg, cystic teratoma, thymic cysts, foregut duplication cysts)
• Neurogenic tumors

Postnatal

History and clinical findings vary with the presence of associated anomalies and the degree of pulmonary hypoplasia and visceral herniation. In the infant presenting in the neonatal period without prenatal diagnosis, variable respiratory distress and cyanosis, feeding intolerance, and tachycardia are noted.

In the physical examination, the abdomen is scaphoid if significant visceral herniation is present (see image shown below).

Upon auscultation, breath sounds are diminished, bowel sounds may be heard in the chest, and heart sounds are distant or displaced.

Late presentation

Patients may present outside of the neonatal period with respiratory symptoms, intestinal obstruction, bowel ischemia, and necrosis following volvulus.

No time for repair of congenital diaphragmatic hernia (CDH) is ideal, but the authors suggest that the window of opportunity is 24-48 hours after birth to achieve normal pulmonary arterial pressures and satisfactory oxygenation and ventilation on minimal ventilator settings.

The diaphragm is a musculotendinous structure that separates the thoracic cavity from the abdominal cavity. It is composed of a central nonmuscular portion (central tendon) surrounded by a muscular rim in addition to the right and left diaphragmatic cura. The right and left diaphragmatic cura are 2 muscular bands that originate from vertebral bodies L1-L3 and L1-L2 respectively. These muscular bands insert into the dorsomedial diaphragm.

Most diaphragmatic defects are posterolateral, with 85-90% of these occurring on the left. The label "posterolateral" may be a misnomer because, frequently, much larger areas of the diaphragm are missing and only a posterior rim of muscle can be found. A hernial sac is present in 10-20% of cases.

The Morgagni defect occurs posterior to the sternum and results from failure of sternal and costal fibers to fuse at the site where the superior epigastric artery crosses the diaphragm. The Morgagni defect is rare and is rarely a cause for surgery in the newborn.

The association of congenital diaphragmatic hernia (CDH) with lethal congenital abnormalities is a relative contraindication to repair of the diaphragmatic defect.