Laboratory Studies
If the cause of the pulmonary hypoplasia is renal pathology, serum creatinine, blood urea, and electrolytes levels should be measured to assess renal function.
Imaging Studies
There is no gold standard for the prenatal prediction of pulmonary hypoplasia or for postnatal diagnosis.
Radiographs
Chest radiographic findings vary. The ribs may appear crowded with a low thoracic-to-abdominal ratio, and the chest wall is classically bell-shaped; however, lung fields are clear unless there is also coexisting respiratory distress syndrome. Pneumothorax or other forms of air leak are frequently present. Films may also show features of the neonate's underlying condition. In severe cases, there may be mediastinal shift with a homogenous density on the involved hypoplastic side and compensatory herniation of the contralateral lung across the mediastinum. Rib deformities may be observed. See the images below.
Two and three dimensional ultrasonography
Thoracic circumference (TC), thoracic circumference to abdominal circumference (TC:AC) ratio and lung area (LA) are frequently used measurements to assess prenatal risk for pulmonary hypoplasia. [1] TC and LA are gestational-age dependent whereas TC:AC ratio is not affected by gestational age. All of these measurements have a high specificity (between 40-100%) but none have a high enough sensitivity to be used reliably in clinical practice. However, in fetuses with CDH, the observed to expected lung-to-head ratio (LHR) measured by two-dimensional ultrasound remains the best predictor of pulmonary hypoplasia. [38]
Three-dimensional ultrasound techniques, which include pulmonary volume measurement, appears to have a high sensitivity 92% and specific 84% and appears to be a reliable technique to predict pulmonary hypoplasia. [39, 40] Barros and Colleagues found that lung volumes measurements using 3D ultrasound has a high sensitivity (83.3%) and specificity (100%) for predicting lethal pulmonary hypoplasia in infant with skeletal anomalies. [41]
Targeted fetal ultrasonography may demonstrate renal malformations, oligohydramnios, and decreased fetal movements in fetal neuromuscular diseases. While this is readily available at most centers, diagnosing disease requires expertise and can be limited by the presence of maternal obesity, low AFI and fetal malposition. [42]
Autopsy studies have shown that pulmonary hypoplasia is associated with a reduction in a number of pulmonary vessels and with increased arterial smooth muscle thickness, which may lead to increased pulmonary vascular resistance and decreased pulmonary arterial compliance. Pulmonary vasculature remodeling and pulmonary hypertension is particularly common in CDH and results in high mortality. [43] Given abnormalities in the vasculature, Doppler ultrasonography has been studied as way to predict pulmonary hypoplasia. Determination of pulmonary artery blood velocity waveforms is one tool used to diagnose pulmonary hypoplasia, however as a single test is unreliable. Pulsatile index of the ductus arteriosus for predicting PH had a sensitivity of only 37% and specificity of 2% which is again, not clinically reliable. [44]
.
Chest radiograph of a newborn with primary pulmonary hypoplasia of the right lung showing shift of the mediastinum to the right hemithorax.
A posteroanterior radiograph of a 3-month-old infant with primary pulmonary hypoplasia of the right lung.
Lateral view of the same patient (a 3-month-old infant with primary pulmonary hypoplasia of the right lung) showing one dome of the diaphragm.
A chest radiograph of a 14-year-old child with primary pulmonary hypoplasia of the right side causing secondary scoliosis.
Diaphragmatic hernia (see first 3 images below), associated skeletal anomalies (see fourth image below), scimitar syndrome, and sequestration may be identified.
A chest radiograph of a newborn with diaphragmatic hernia in the right hemithorax shortly after birth.
CT scan of the same child (a newborn with diaphragmatic hernia in the right hemithorax shortly after birth) showing the presence of abdominal contents in the right hemithorax. Note the presence of the left lower bronchus and its main branches (horizontal arrow) and absence of the right lower lobe bronchus. The liver in the right hemithorax is indicated by the upper arrow.
A chest radiograph of a 10-month-old child after repair of a right diaphragmatic hernia showing loss of lung volume in the right hemithorax.
A chest radiograph of a newborn with achondroplasia and small chest causing hypoplasia of both lungs.
Chest CT scanning may show loss of lung volume and abnormal or absent normal airway branching to the affected lung (see images below).
CT scan of the same patient (a newborn with primary pulmonary hypoplasia of the right lung) showing absence of the right lung. Note branching of the left lower lobe bronchus (horizontal arrow) and absence of airways in the right side (vertical arrow).
CT scan of the same child (a newborn with diaphragmatic hernia in the right hemithorax shortly after birth) showing the presence of abdominal contents in the right hemithorax. Note the presence of the left lower bronchus and its main branches (horizontal arrow) and absence of the right lower lobe bronchus. The liver in the right hemithorax is indicated by the upper arrow.
Other imaging studies
Echocardiography may be used to identify associated cardiac anomalies. The frequency of cardiovascular malformations associated with isolated CDH is 11-15%. [45] The most common anomalies include atrial and ventricular septal defects, conotruncal defects, and left ventricular outflow tract obstructive defects.
Angiography is indicated to confirm the diagnosis of any aberrant pulmonary vessels, to rule out scimitar syndrome, and to confirm reduced pulmonary vascular bed.
MRI or magnetic resonance angiography (MRA) may also be used to identify the smaller pulmonary arterial supply to the affected lung and the presence of other abnormal vascular anatomy (see image below).
MRI of the same patient (a 10-month-old child after repair of a right diaphragmatic hernia) showing loss of right lung volume and smaller right pulmonary artery than the left pulmonary artery (arrow).
Fetal MRI during the second and third trimester has been attracting increasing attention; however, universally accepted standardized values for the prediction of pulmonary hypoplasia are not available. Different techniques, including MRI volumetry, assessment of signal intensities, and MRI spectroscopy of the fetal lung, have been used clinically to identify abnormal fetal lung growth. [46]
Both MRI and ultrasonography appear to be useful in determining the degree of pulmonary hypoplasia. [47] The American College of Radiology and Society of Pediatric Radiology joint guidance on the performance of MRI during pregnancy endorses the use of MRI at any stage of pregnancy for further evaluation of any anomaly found on ultrasonography. Specific indications include volumetric assessment of fetal lung parenchyma for secondary hypoplasia in at-risk fetuses. [48]
Particularly in CDH, MRI based total fetal lung volume (FLV) and fetal body volume (FBV) measurements are useful in predicting post-natal survival. More recent studies are also demonstrating that MRI based FLV:FBV ratio measurements are not only able to predict neonatal mortality but also able to predict ECMO requirement with high accuracy. [49] Additionally, the use of lung-to-liver signal intensity ratio on T2-weighted images to predict fetal pulmonary hypoplasia has been proposed. [50]
Lung scintigraphy has been used to evaluate the degree of pulmonary hypoplasia in infants with CDH. One study suggested that lung scintigraphy is useful to predict long-term pulmonary morbidity and poor nutritional status in survivors of CDH. [51]
Other Tests
Obtaining an ECG and/or echocardiogram is important to distinguish between dextrocardia and dextroposition caused by pulmonary hypoplasia. In dextrocardia, ECG findings include an inverted P wave and T in lead 1, with negative QRS deflection and a reverse pattern between aVR and aVL. A mirror image progression is observed from V1 to a right-sided V6 lead. A tall R in lead V1 or an RS ratio equal to or greater than 1 also suggests dextrocardia.
The frequency of cardiovascular malformations associated with isolated CDH is 11-15%. [45] The most anomalies include atrial and ventricular septal defects, conotruncal defects, and left ventricular outflow tract obstructive defects.
Bronchoscopy or bronchography is indicated because the reduced size of a bronchus and its branches confirms the diagnosis (see image below).
Bronchogram of the same patient (a 3-month-old infant with primary pulmonary hypoplasia of the right lung) showing absence of the airways in the right side and presence of the left main bronchus and its branches.
Pulmonary function testing is difficult to obtain in the young age, however it may a useful tool in monitoring the course of the disease to assess lung maturation and development. A recent study has demonstrated that lung function remains abnormal in the first three years of life in children with congenital diaphragmatic hernia. This study revealed normalization of total lung capacity, however with increasing residual volumes likely due to pulmonary overinflation. They hypothesized that the pulmonary hyperinflation was not due to normal alveolarization that occurs in the first three years of life, but is likely due to overdistended, simplified air spaces that was functionally different from those seen in normally grown lungs. [52] Another study reported normalization of all lung function parameters after surgery by age 24 months. [53] As expected, lung function significantly correlated with increase in age, height, and, especially, weight.
Histologic Findings
On autopsy, in pulmonary hypoplasia, the overall lung size is reduced, cell numbers are decreased, branches of airways may be narrower and fewer, alveolar differentiation may be reduced, and a surfactant deficiency may be present.
Histopathologic descriptions of pulmonary hypoplasia may have limited value since some may appear similar to normal lung. However, in other cases there may be a reduction in a number of pulmonary vessels (and smaller pulmonary arterioles) and increased arterial smooth muscle thickness, indicating the presence of pulmonary hypertension.
The diagnosis of pulmonary hypoplasia is made if the lung weight–to–body weight ratio is less than 0.015 in infants born before 28 weeks of gestation and less than 0.012 in infants born after 28 weeks of gestation, in conjunction with a mean radial alveolar count (RAC) of less than 4%. The RAC provides a simple objective measurement of the "relative paucity of alveoli" or "crowding of bronchial structures, which is unaffected by the state of expansion of the lungs.
In addition, in infants with severe risk factors (renal anomalies, diaphragmatic hernia), lung hypoplasia may be diagnosed by a lung volume–to–body weight ratio less than the 10th percentile when assessed on age-specific reference values. [54]
-
Chest radiograph of a newborn with primary pulmonary hypoplasia of the right lung showing shift of the mediastinum to the right hemithorax.
-
CT scan of the same patient (a newborn with primary pulmonary hypoplasia of the right lung) showing absence of the right lung. Note branching of the left lower lobe bronchus (horizontal arrow) and absence of airways in the right side (vertical arrow).
-
A posteroanterior radiograph of a 3-month-old infant with primary pulmonary hypoplasia of the right lung.
-
Lateral view of the same patient (a 3-month-old infant with primary pulmonary hypoplasia of the right lung) showing one dome of the diaphragm.
-
Bronchogram of the same patient (a 3-month-old infant with primary pulmonary hypoplasia of the right lung) showing absence of the airways in the right side and presence of the left main bronchus and its branches.
-
A chest radiograph of a 14-year-old child with primary pulmonary hypoplasia of the right side causing secondary scoliosis.
-
A chest radiograph of a newborn with achondroplasia and small chest causing hypoplasia of both lungs.
-
A chest radiograph of a newborn with diaphragmatic hernia in the right hemithorax shortly after birth.
-
CT scan of the same child (a newborn with diaphragmatic hernia in the right hemithorax shortly after birth) showing the presence of abdominal contents in the right hemithorax. Note the presence of the left lower bronchus and its main branches (horizontal arrow) and absence of the right lower lobe bronchus. The liver in the right hemithorax is indicated by the upper arrow.
-
A chest radiograph of a 10-month-old child after repair of a right diaphragmatic hernia showing loss of lung volume in the right hemithorax.
-
MRI of the same patient (a 10-month-old child after repair of a right diaphragmatic hernia) showing loss of right lung volume and smaller right pulmonary artery than the left pulmonary artery (arrow).
Tables
Transcription Factors |
Growth Factors |
Thyroid transcription factor-1 (TTF-1) [12] |
Vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) [15] |
GATA-4 [20] |
Insulinlike growth factors (IGF-1 and IGF-2) and their receptors (IGF-1R and IGF-2R) [18] |
FOG-2 [23] |
Epidermal growth factors and its receptor family (eg, ErbB receptors) [21] |
Hepatocyte nuclear factor (HNF3ß10) |
Mitogen-activated protein kinases |
|
Connective tissue growth factor [25] |
Small Fetal Thoracic Volume |
Prolonged Oligohydramnios |
Decreased Fetal Breathing Movements |
Congenital Heart Diseases With Poor Pulmonary Blood Flow |
CDH |
Fetal renal agenesis |
Central nervous system (CNS) lesions |
|
Cystic adenomatoid malformation (CAM) |
Urinary tract obstruction |
Lesions of the spinal cord, brain stem, and phrenic nerve |
Hypoplastic right heart |
Pulmonary sequestration |
Bilateral renal dysplasia |
Neuromuscular diseases (eg, myotonic dystrophy, spinal muscular atrophy) |
Pulmonary artery hypoplasia |
Pleural effusions with fetal hydrops, hydrothorax |
Bilateral cystic kidneys |
Arthrogryposis multiplex congenital secondary to fetal akinesia |
Scimitar syndrome causing a unilateral right-sided pulmonary hypoplasia |
Thoracic neuroblastomas |
Prolonged rupture of membranes (PROM) |
Maternal depressant drugs |
Trisomies 18 and 21 |
Malformations of the thorax (eg, asphyxiating thoracic dystrophy) |
Premature PROM |
|
|
Diaphragmatic anomalies (eg, abdominal wall defects, eventration of the diaphragm) |
Potter syndrome |
|
|
Musculoskeletal disorders (eg, achondroplasia, thanatophoric dysplasia, osteogenesis imperfecta) |
|
|
|
Abdominal masses causing compression |
|
|
|
