**2.5. Embriology**

*The diaphragm* starts to develop at approximately 4 weeks of gestation. It develops from several structures. The anterior central tendon develops from an infolding of the ventral body wall: the septum transversum. Another infolding on the posterolateral sides establishes the pleuroperitoneal membranes. Closure of the pleuroperitoneal canals occurs when the septum transversum fuses to the structures surrounding the esophagus, the esophageal mesentery, and connects to the pleuroperitoneal membranes. Closure of the pleuroperitoneal canals normally occurs around the eighth week of gestation in humans. The right side of the diaphragm closes before the left side [6].

*The central portion and possibly anterior regions* are thought to develop from the septum transversum, which is initially fused to the liver during development and becomes the unmuscularized central tendon of the diaphragm [7].

*The posterolateral section*, the place where Bochdalek hernia occurs, develops from the pleuroperitoneal folds (PPFs), which are triangular structures derived from mesoderm that form in


**Table 3.** Syndromes in which CDH is less frequently a feature.

ventral hernias which are defects in the central tendon stemming from septum transversum impaired development. Hiatal hernias, as their name shows, develop more through the esophageal hiatus and do not involve the central tendon. Differentiating ventral mediastinal hernias from intrapleural hernias is important because the intrapleural hernias, usually, do not lead to pulmonary hypoplasia, which is the major complication of CHD [5] (**Table 4**).

**Mode of inheritance Gene**

Unknown XL *SMC1A*

Rare AR *DLL3* Rare *MESP2* Rare *LFNG* Rare *HES7*

Rare XL *GPC3*

affected than females)

*SMC3*

*EFNB1*

heterogeneity)

AR Unknown (possible etiologic

*The diaphragm* starts to develop at approximately 4 weeks of gestation. It develops from several structures. The anterior central tendon develops from an infolding of the ventral body wall: the septum transversum. Another infolding on the posterolateral sides establishes the pleuroperitoneal membranes. Closure of the pleuroperitoneal canals occurs when the septum transversum fuses to the structures surrounding the esophagus, the esophageal mesentery, and connects to the pleuroperitoneal membranes. Closure of the pleuroperitoneal canals normally occurs around the eighth week of gestation in humans. The right side of the diaphragm closes before the left side [6]. *The central portion and possibly anterior regions* are thought to develop from the septum transversum, which is initially fused to the liver during development and becomes the unmuscu-

*The posterolateral section*, the place where Bochdalek hernia occurs, develops from the pleuroperitoneal folds (PPFs), which are triangular structures derived from mesoderm that form in

**2.5. Embriology**

Spondylocostal dysostosis

Simpson-Golabi-Behmel

(SCDO)

syndrome

larized central tendon of the diaphragm [7].

**Syndrome Frequency of CDH in** 

190 Congenital Anomalies - From the Embryo to the Neonate

Fryns syndrome >80% (but ascertainment

**Table 2.** Selected syndromes in which CDH is a feature.

**this disorder**

Cornelia de Lange syndrome ?up to 5% AD *NIPBL*

Craniofrontonasal syndrome Rare XL (but males less severely

may be biased)

Denys-Drash syndrome Rare AD *WT1* Donnai-Barrow syndrome ~70% AR *LRP2*

Matthew-Wood syndrome ~50% AR *STRA6*

the thorax in the early development of the diaphragm. These PPFs are part of the diaphragmatic connective tissue. The membranous diaphragm is later muscularized by migrating muscle precursor cells to the PPF from the cervical somites. This phenomenon happens before these cells proliferate, differentiate, and migrate onto the membranous diaphragm [8, 9]. The hypothesis is that a Bochdalek hernia occurs if the PPFs do not fuse with the septum transversum and the dorsal mesentery of the esophagus by the 10th week of gestation [4].

*The lung* originates as an outpouch of the ventral wall of the posterior end of the laryngotracheal tube and divides into two bronchial buds at 3–4 weeks of gestation [10]. As the two buds elongate, the primitive tubular foregut tube begins to pinch into two tubes, namely, the dorsal esophagus and the ventral trachea [11]. Further outgrowth of the lung-buds produces the secondary bronchi. In humans, the right lung has three lobes, whereas, the left lung is composed of two lobes. The branching of the primary bronchial buds are monopodial. Every secondary bronchus then undergoes progressive dichotomous branching as each branch bifurcates repeatedly. Reproducible branching in humans is completed at 16 generations in 16 weeks of gestation [12]. The last seven generations of airway are completed during the last part of gestation. Alveolization starts after 28–30 weeks in humans and is completed in postnatal period [13]. Reid [14] presented this process in her laws of development of the human lung:


**2.6. Pathogenesis**

**2.7. Associated anomalies**

**2.8. Ultrasound diagnosis**

**Table 5.** Asociated anomalies.

every case diagnosed with CDH [19] (**Table 5**).

The pathogenesis of CDH is poorly understood. The diaphragmatic defect is caused by delayed or impaired separation of the two compartments: thoracic and abdominal. This is due to closure of embryonic pleuroperitoneal canals influenced by the growth of the post-hepatic mesenchymal plate and of the pleuroperitoneal folds [15, 16]. In CDH, respiratory failure at birth is the result of pulmonary hypoplasia (PH), reduced airway branching, and surfactant deficiency. Extensive muscularization of the pulmonary vessels may result in persistent pulmonary hypertension (PPH) of the newborn. Historically, PH was believed to be the result of compression of the lungs by the herniating intrathoracic abdominal organs. However, our understanding of abnormal pulmonary development in relation to CDH has significantly improved and we know that pulmonary development is already affected prior to development of the diaphragmatic hernia, implicating that the lungs are primarily disturbed in their

Congenital Diaphragmatic Hernia

193

http://dx.doi.org/10.5772/intechopen.74500

The most common associated anomalies are cardiovascular in 40–60% of live-born infants and in 95% of fetal demise; therefore, a detailed ultrasound examination must be performed in

Ultrasound evaluation of the thorax can be carried out easily until 25–26 weeks of gestation; after this period, the increased mineralization of the ribs limits the display of intrathoracic organs, especially for coronal or sagittal views. A number of thoracic anomalies evolve; they can appear only in the third trimester or they can regress before birth. Therefore, if an initial assessment of the thorax can be performed as early as at the 12th week of gestation, in order

*Scanning planes*: the most important view for the assessment of intrathoracic anatomy is the classic *four chamber view* of the fetal heart. In this plane, most thoracic viscera can be visualized, including the ribs, the sternum, and the cutaneous outline. The *midsagittal* and *parasagittal views* allow display of the diaphragm as a hypoechoic line below the lungs and the heart and above the liver and the stomach. The diaphragm shows a curved outline, convex toward the thorax.

development before mechanical compression can happen [17, 18].

to follow up abnormal cases, late third-trimester scans may be needed.

Cardiovascular VSD, ASD, tetralogy of fallot, hypoplastic left heart syndrome

Central nervous system Neural tube defects, hydrocephalus, agenesis of corpus callosum

Genitourinary abnormalities Cryptorhydia, absent testes, ectopic kidney, horseshoe kidney

Gastrointestinal abnormalities Meckel diverticulum, anal atresia

Eye abnormalities Microphtalmia and anophtalmia

Limb abnormalities Absence defects, polydactyly, syndactyly

**3.** Blood vessels are remodeled and increase, as new alveoli form, probably until the chest growth is complete.

**Figure 1.** Types of congenital diaphragmatic hernia.


**Table 4.** Texas Children's Fetal Center classification of CDH.

#### **2.6. Pathogenesis**

**1.** The bronchial tree is completed by the 16th gestational weeks.

chest wall finishes growing.

192 Congenital Anomalies - From the Embryo to the Neonate

**Figure 1.** Types of congenital diaphragmatic hernia.

**Table 4.** Texas Children's Fetal Center classification of CDH.

Morgagni Anteromedial, small, typically isolated

Mediastinal

**Hernia type Location Contents Associated findings**

sized portions of the liver

Hiatal Posterior and central Stomach, sometimes other organs Congenital short esophagus

Ventral Anterior and central Liver, bowel Pericardial effusion, pentalogy of Cantrell

Pulmonary hypoplasia

Liver, bowel No pericardial communication

Intrapleural Lateral, usually left-sided Stomach, bowel, spleen, variable-

growth is complete.

**2.** Alveoli, developed after birth, increase in number until 8 years of age and in size until the

**3.** Blood vessels are remodeled and increase, as new alveoli form, probably until the chest

The pathogenesis of CDH is poorly understood. The diaphragmatic defect is caused by delayed or impaired separation of the two compartments: thoracic and abdominal. This is due to closure of embryonic pleuroperitoneal canals influenced by the growth of the post-hepatic mesenchymal plate and of the pleuroperitoneal folds [15, 16]. In CDH, respiratory failure at birth is the result of pulmonary hypoplasia (PH), reduced airway branching, and surfactant deficiency. Extensive muscularization of the pulmonary vessels may result in persistent pulmonary hypertension (PPH) of the newborn. Historically, PH was believed to be the result of compression of the lungs by the herniating intrathoracic abdominal organs. However, our understanding of abnormal pulmonary development in relation to CDH has significantly improved and we know that pulmonary development is already affected prior to development of the diaphragmatic hernia, implicating that the lungs are primarily disturbed in their development before mechanical compression can happen [17, 18].
