1. Definition

   Presence of abdominal contents in thoracic cavity during fetal life results in acute neonatal respiratory distress.

   1. Often the sickest infants in the NICU

   2. Associated with long-term respiratory, gastrointestinal, and neuro-cognitive difficulties

2. Incidence

   Estimated to occur in one per 3000 live births (true incidence unknown)

   1. “Hidden mortality”—early deaths among severely affected fetuses and infants

3. Pathophysiology

   Abnormal or incomplete formation of diaphragm between weeks 8 and 10 of gestation allows herniation of abdominal contents into chest cavity, impairing proper lung growth and development (Figure 31-1).

   1. Occurs at critical stage of lung embryogenesis, during pulmonary artery and bronchial branching

   2. Subsequent pulmonary parenchymal and vascular hypoplasia with fewer airways, vessels, and alveolar structures

   3. Lung hypoplasia most significant on ipsilateral side, contralateral lung also affected

      Epidemiology: Three CDH subtypes based on location of diaphragmatic defect

      1. Bochdalek: posterolateral diaphragmatic defect (most common)

      2. Morgagni: anterior diaphragmatic defect

      3. Pars sternalis: central diaphragmatic defect

         Additional facts about CDH

      1. 85% occur on left side, 13% occur on right, 2% bilateral absence of diaphragm (universally fatal)

      2. Right-sided defects associated with higher mortality due to presence of liver in chest

      3. Can be isolated finding (50% to 60%) or occur as part of syndrome

         • ∼1/3 associated with cardiac, renal, gastrointestinal, or central nervous system anomalies

      4. Overall survival ranges between 50% and 80% for isolated CDH

         • Lower survival rates if other anomalies present

4. Risk factors

   None proven, many postulated

   1. Genetic factors

   2. Maternal nutritional deficiency during pregnancy

   3. Disturbances in retinoid-signaling pathway during organogenesis

5. Clinical presentation

   1. Signs and symptoms

      1. Most present with respiratory distress and cyanosis soon after birth.

         • Intestines dilate with swallowed air and compromise cardiorespiratory function.

      2. Physical examination: Scaphoid abdomen, barrel-shaped chest, increased work of breathing.

      3. Auscultation: Decreased aeration over ipsilateral chest, displacement of heart tones, bowel sounds appreciated in chest.

      4. Imaging: Radiography shows gas-filled loops of bowel in chest, displacement of heart, and mediastinum to right (left-sided) (Figure 31-2).

   2. Condition variability

      Severity of respiratory distress corresponds to degree of pulmonary hypoplasia (related to timing and degree of compression of fetal lungs).

      1. Mild: May not present until later in newborn course or early infancy

      2. Severe or unrecognized: Swallowed air following delivery results in intestinal distention, leads to worsening mediastinal shift, compromised venous return, hypoperfusion, and systemic hypotension

6. Diagnosis

   1. Prenatal: Most cases identified antenatally between 16 and 24 weeks’ gestation.

      1. Characteristic findings on ultrasound

         • Fluid-filled stomach detected in chest cavity

         • Polyhydramnios

         • Small abdominal circumference

         • Mediastinal or cardiac shift away from side of hernia

   2. Postnatal: Chest radiography shows multiple gas-filled loops of bowel in thorax (Figure 31-2).

7. Management

   Antenatal

   1. Medical

      1. Detailed anatomic ultrasonography to detect other anomalies

      2. Amniocentesis for chromosomal studies

      3. Determination of liver position and lung-to-head ratio to assess degree of pulmonary hypoplasia and predict outcome

      4. Parental counseling

      5. Expectant management, close monitoring for development of complications

      6. Induction of labor ∼38 weeks’ gestation at tertiary care center

   2. Surgical

      1. Many trials of fetal surgery to correct diaphragmatic defect and promote fetal lung growth

      2. Disappointing results due to increased rates of preterm delivery; none have demonstrated significant benefit compared with standard therapy

         Postnatal (Table 31-1)

   3. Medical

      1. Resuscitation and stabilization

         • Immediate postnatal endotracheal intubation (avoid bag-valve-mask ventilation)

         • Nasogastric tube to continuous suction

         • Pre- and post-ductal pulse oximetry

         • Central venous and arterial access

         • Plain films of chest and abdomen

         • Maintain quiet environment, consider sedation and paralysis

      2. Ventilation

         • Goal: Use lowest possible peak pressure to allow adequate gas exchange while avoiding hypoxemia and acidemia (strategy of permissive hypercapnia).

         • Consider early use of high-frequency jet or oscillatory ventilation, ECMO for rescue.

      3. Oxygenation

         • Administer supplemental oxygen.

         • Trial of inhaled nitric oxide to relax pulmonary vasculature.

         • Consider surfactant administration.

      4. Other considerations

         • Support blood pressure using fluids and vasopressors.

           • Crucial to maintain adequate mean arterial pressure and minimize right-to-left shunt across ductus arteriosus

         • Echocardiography to evaluate for heart defects, assess function, determine presence of pulmonary hypertension.

         • Consider cranial, renal ultrasound.

         • Extracorporeal membrane oxygenation (ECMO)

           • Often used as rescue strategy in severe cases when medical management fails

           • Temporary strategy, selection criteria vary by center

   4. Surgical

      1. Ideal time for diaphragmatic repair remains unknown, usually delayed up to 7 to 10 days to allow maximal relaxation of pulmonary vasculature

      2. May be achieved via primary closure or use of prosthetic patch or muscle flap

8. Early developmental/therapeutic interventions

   1. Vary according to center, some place nasogastric tube at time of diaphragmatic repair to allow early introduction of feedings

   2. Occupational/speech therapy: To minimize development of oral aversion

   3. Physical therapy: To enhance mobility

   4. Weaning of sedation and paralysis as quickly as possible: To avoid iatrogenic neonatal abstinence syndrome (see Chapter 37)

9. Prognosis

   1. Predictors

      1. Determination of liver position and estimation of lung-to-head ratio may be useful in predicting outcome

   2. Patch repair, ECMO, days on ECMO, days of mechanical ventilation, and postoperative use of inhaled nitric oxide associated with neurocognitive delay at early school age

   3. Possible outcomes

      1. Respiratory: Chronic lung disease, reactive airway disease

      2. Cardiac: Pulmonary hypertension

      3. Growth and nutrition: Gastroesophageal reflux, feeding difficulties, failure to thrive

      4. Neurodevelopmental impairment

Chronic lung disease (associated with CDH)

(see also Chapter 7)

1. Definition (variable): Oxygen dependency at 30 days of age

2. Incidence Occurs in 40% to 60% of CDH survivors

3. Pathophysiology

   1. Lung structure fundamentally altered in CDH due to fewer bronchi and alveoli

   2. Postnatal exposure to mechanical ventilation and supplemental oxygen results in pulmonary edema and protein leak, causing surfactant denaturation and lung injury

4. Risk factors: Treatment with ECMO, patch repair of diaphragm, prolonged duration of mechanical ventilation

5. Clinical presentation

   1. Signs and symptoms: Oxygen dependency, increased work of breathing, failure to thrive

   2. Condition variability: Dependent on degree of underlying pulmonary hypoplasia as well as severity of iatrogenic injury to lungs in neonatal period

6. Diagnosis: Chest radiography may be useful.

7. Management

   1. Supportive care with supplemental oxygen, diuretics, aerosols

   2. Palivizumab for RSV prevention

   3. Annual influenza immunization (for infant and caregivers)

   4. Avoidance of exposure to environmental tobacco

8. Ongoing developmental/therapeutic interventions

   1. Maximize growth and nutrition to promote lung growth and healing

   2. Use of bronchodilators may be beneficial

9. Prognosis

   1. Early predictors: Treatment with ECMO, patch repair of diaphragm, prolonged duration of mechanical ventilation

   2. Outcomes: Chronic lung disease known to adversely affect neurodevelopmental outcome

   Reactive airway disease

1. Definition: Asthma-like respiratory condition in infants characterized by wheezing and bronchial reactivity

2. Incidence: ∼25% of CDH survivors show evidence of obstructive airway disease; up to 45% with asthma-like symptoms during childhood and adolescence

3. Pathophysiology

   1. Alveoli continue to form in CDH survivors, but remain reduced in number

   2. Hyperinflation from increased lung volume in absence of increased alveoli

   3. Hyperinflation decreases pulmonary compliance, may increase vascular resistance

4. Risk factors: Prolonged duration of mechanical ventilation, family history of asthma and/or atopic conditions, African American or Hispanic race

5. Clinical presentation

   1. Signs and symptoms: Wheezing, persistent coughing, respiratory distress

   2. Condition variability: Likely dependent on degree of underlying pulmonary hypoplasia as well as severity of iatrogenic injury to lungs in neonatal period

6. Diagnosis: Chest radiography demonstrating hyperinflation, evidence of obstructive or restrictive disease on spirometry (gold standard)

7. Management

   1. Supportive care with inhaled bronchodilators, inhaled corticosteroids, systemic steroids

   2. Palivizumab for RSV prevention (if eligible)

   3. Annual influenza immunization (for infant and caregivers)

   4. Avoidance of exposure to environmental tobacco and allergens

8. Ongoing developmental/therapeutic interventions

   1. Maximize growth and nutrition to promote lung growth and healing

   2. Encourage breast-feeding (breast milk might protect infants younger than 24 months of age against recurrent wheezing)

9. Prognosis

   1. Early predictors: Prolonged duration of supplemental oxygen

   2. Outcomes: Higher rates of asthma, increased airflow obstruction, and reduced diffusion capacity in adulthood compared to childhood

   Pulmonary hypertension (PHTN)

   (see also Chapter 30)