Pulmonary hypoplasia

Pulmonary hypoplasia refers to underdevelopment of one or both lungs. This can be rapidly fatal at birth or mild, escaping detection for decades. It is most often secondary to congenital abnormalities that either restrict intrathoracic space or alter pulmonary fluid dynamics.

Epidemiology

Pulmonary hypoplasia has been reported to affect 1.4% of all live births ¹³; however, the true prevalence is difficult to establish, as some die in utero and mild cases may go undetected. In cases of premature rupture of membranes at 15-28 weeks gestation, the reported prevalence of pulmonary hypoplasia is 9-28%, the variation being due to the lack of strict diagnostic criteria ².

Pathology

Pulmonary hypoplasia is characterized by disproportionately low lung volume and weight with consequent reduced gas-exchange. However lung weight can be increased by edema and congestion and so histological features such as low alveolar count, reduced branching of airways, fewer, smaller vessels and low DNA content are helpful findings. Unilateral pulmonary hypoplasia can be associated with compensatory hypertrophy of the contralateral lung.

The lungs are derived from the primitive foregut and vascular development follows airway development. Disease that affects the earlier stages of fetal lung development are more severe. The stages of lung development are:

• embryonic: day 22-6 weeks: formation of the larynx, trachea, lung primordia, lobes, and bronchopulmonary segments

• pseudoglandular: 5-17 weeks: terminal bronchioles, arterial system, cartilage, smooth muscle, cilia, lung fluid production and movement

• canalicular: 16-25 weeks: respiratory units and capillary network

• saccular: 24 weeks - birth: increasing surface-area for efficient gas-exchange and increasing surfactant production

• alveolar: 36 weeks' gestation to 8 years: increasing alveolar maturity, number, and size

Etiology

Primary pulmonary hypoplasia is rare and congenital acinar dysplasia is typically lethal. Milder forms of hypoplasia accompany trisomy 21. The disease can be multifactorial:

• genetic mutations may affect any of the various growth factors ^1616. which promote cell proliferation and differentiation, bronchial branching, angiogenesis, alveolar cell proliferation, and alveolarisation

• environmental

• maternal

• nutritional

Secondary pulmonary hypoplasia has two main underlying causes: lack of space within the pleural cavity or abnormal fluid dynamics.

During the pseudoglandular phase of development, airway contractions and fetal breathing move fluid in and out of the lungs. Positive pressure (about 2.5 mm water) maintains patency of the distal airways, stimulating branching and development of terminal sacs. Excessive fluid drainage and oligohydramnios interfere with this development.

50-85% of cases of pulmonary hypoplasia are associated with other congenital anomalies. Causes include:

• congenital diaphragmatic hernia: most common intrathoracic cause

• congenital pulmonary airway malformation (CPAM)

• extralobar sequestration

• agenesis of the diaphragm

• mediastinal mass(es)/tumor(s)

  • mediastinal teratoma

• decreased pulmonary vascular (arterial) perfusion

  • congenital cardiovascular anomaly with poor pulmonary blood flow:

  • tetralogy of Fallot

  • hypoplastic right heart

  • unilateral absence of the pulmonary artery

  • hypoplastic pulmonary artery

  • scimitar syndrome

  • trisomy 18, 21

Extrathoracic causes include:

• oligohydramnios and its causes

  • Potter sequence: fetal renal anomalies

  • prolonged preterm premature rupture of membranes (PPROM); predictors of fatal pulmonary hypoplasia include gestational age < 25 weeks, long duration and low amniotic fluid index

• skeletal dysplasias, especially those causing a narrow fetal thorax

  • Jeune syndrome (asphyxiating thoracic dystrophy)

  • thanatophoric dysplasia

  • achondrogenesis

  • osteogenesis imperfecta

  • short rib polydactyly syndrome

  • campomelic dysplasia

• large intra-abdominal mass compressing the thorax

• neuromuscular conditions such as iniencephaly, spinal muscular atrophy, or congenital myotonic dystrophy are causes of ineffective foetal breathing movements and reduced foetal lung volume

Other associations include:

• Fryns syndrome

• Meckel Gruber syndrome

• Neu-Laxova syndrome

• Pena-Shokeir syndrome

Clinical presentation

Pulmonary hypoplasia is commonly lethal in the neonatal period. Milder forms present with neonatal respiratory insufficiency, pulmonary hypertension and persistent fetal circulation, bronchopulmonary dysplasia, pulmonary hemorrhage, recurrent infections, bronchiectasis, and hypoxemia exacerbated by exercise. Associated congenital abnormalities are often apparent. Occasionally, the first presentation maybe an abnormal chest radiograph in an adult.

Pulmonary function tests can demonstrate an obstructive or restrictive pattern and reduced diffusion capacity.

Imaging features

Radiograph

Possible findings include

• chest wall deformity

• small lung with mediastinal shift and herniation of contralateral lung

• clear lung unless respiratory distress syndrome

• features of underlying cause

Ultrasound

Antenatal ultrasound may show ancillary features such as the presence of oligohydramnios and/or also show any of the causative anomalies.

Several sonographic parameters may give indirect clues as to the presence and extent of pulmonary hypoplasia. Such include:

• fetal lung : head ratio: reduced (ratios <1 usually indicate a poor prognosis)

• fetal chest circumference (or thoracic circumference) 6: reduced

In the case of intrathoracic causes, both these parameters can be normal.

• thoracic : abdominal circumference ratio <0.6 15

• femur length : abdominal circumference ratio <0.16 15

Doppler

Peripheral pulmonary arterial resistance is often increased with pulmonary hypoplasia.

MRI

Fetal MRI may be useful to more accurately calculate lung volumes.

• T1: normal fetal lung is usually low signal on T1

• T2: normal fetal lung is usually high signal on T2; fetuses with pulmonary hypoplasia are thought to have low signal 1

Treatment and prognosis

Pulmonary hypoplasia is often a critical determinant of fetal survival, however underlying causes affect both prognosis and treatment. Perinatal mortality rate is typically between 70 - 95%. Right-sided lesions and genetic abnormalities carry a poor prognosis.

PPROM: corticosteroids promote lung maturation in fetuses over 24 weeks gestation. Amnioinfusions decrease the incidence of pulmonary hypoplasia.

Congenital diaphragmatic hernia: fetal tracheal occlusion by balloon causes distal fluid distension which promotes lung maturation.

Congenital pulmonary airway malformation and congenital diaphragmatic hernia: fetal surgery may be attempted.

Complications such as tracheomalacia, persistent pulmonary hypertension, and pneumothorax may require treatment. Growth restriction is common.

Differential diagnosis

In adult cases of unilateral pulmonary hypoplasia, consider conditions associated with a small hemithorax such as:

• Swyer-James syndrome

• Poland syndrome

• scimitar syndrome

• lung atelectasis