eMedicine Specialties > Radiology > Pediatrics

Pulmonary Hypoplasia

Prabhakar Rajiah, MD, MBBS, FRCR, Registrar, Department of Radiology, Central Manchester and Manchester Children's University Hospitals, UK

Updated: Sep 26, 2008

Introduction

Background

Pulmonary hypoplasia is a developmental abnormality of the lung characterized by a decrease in the number of alveoli, cells, and airways, eventually resulting in decreased size and weight of the lungs. Although pulmonary hypoplasia is occasionally a primary condition, most cases are secondary to other abnormalities that prevent complete pulmonary development. Pulmonary hypoplasia is frequently associated with malformations of the cardiac, genitourinary, gastrointestinal, and musculoskeletal systems. Bronchopulmonary malformations are also associated with this disease.^{1,2,3,4,5,6,7,8,9}

Related eMedicine topics:
Pulmonary Hypoplasia (Pediatrics)
Bronchopulmonary Dysplasia

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CME  Late-Preterm Infants Have Higher Mortality Rates Through Infancy vs Term Infants

Pathophysiology

FACTORS REQUIRED FOR NORMAL LUNG DEVELOPMENT 

Several factors are required for normal development of the lung:

• First, a normal volume and pressure relationship between the lung and amniotic fluid is needed. The lung fluid volume depends on the balance between fluid secreted by the lungs and fluid exiting into amniotic fluid. Tracheal pressure is normally higher than that of the amniotic fluid.
• Second, lung fluid factors or growth factors, such as peptide growth factors and thyroid transcription factor-1, are essential for proper lung development.
• Third, renal factors are needed. Proline secreted by the renal tubules is essential for the development of collagen and the mesenchyme of the lung. Hence, fetal urine is essential for pulmonary development.

Pulmonary hypoplasia is pathologically characterized by a decreased number of acini due to a decreased number of branching generations or decreased size of the alveoli. Unlike agenesis or aplasia, pulmonary hypoplasia results in bronchi and alveoli that are intact. The pulmonary artery is usually small or, sometimes, absent. Surfactant deficiency and delayed or absent epithelial differentiation are seen.¹⁰

CAUSES OF PULMONARY HYPOPLASIA

Primary pulmonary hypoplasia can occur without any clear cause.

Pressure effect on the developing lung

• (Any condition that restricts lung expansion during fetal life is a cause of pulmonary hypoplasia.)
• Cystic adenomatoid malformation
• Diaphragmatic hernia
• Eventration of diaphragm
• Sequestration of lung
• Pleural effusion
• Chylothorax
• Hydrops fetalis
• Ascites
• Cardiac mass
• Mediastinal mass
• Cystic hygroma
• Abdominal mass

Restricted thoracic expansion

• Jeune syndrome (asphyxiating thoracic dystrophy)
• Achondroplasia
• Thanatophoric dwarfism
• Osteogenesis imperfecta
• Chondroectodermal dysplasia

Impaired fetal breathing

• CNS lesions (brainstem or spinal cord)
• Arnold-Chiari malformations
• Anencephaly
• Hypoxic lesions
• Bulbar palsy
• Respiratory depressants
• Phrenic nerve lesions
• Neuromuscular disorders
• Arthrogryposis congenita multiplex
• Congenital myotonic dystrophy
• Pena Shokeir syndrome

Decreased pulmonary flow

• Tetralogy of Fallot
• Ebstein anomaly
• Aplasia/hypoplasia of the pulmonary artery
• Pulmonary stenosis
• Hypoplastic right heart
• Scimitar syndrome

Oligohydramnios

• Renal agenesis
• Renal dysplasia
• Renal cystic disease/hydronephrosis
• Bladder outlet obstruction
• Amniotic fluid leak
• Prolonged rupture of the membranes

Acquired causes

• Infection (Swyer-James syndrome)
• Aspiration
• Radiation
• Surgery
• Scoliosis

Primary/idiopathic causes

• Trisomy 18, 13, or 21
• Familial

Scimitar syndrome

Pulmonary hypoplasia is also a component of the Scimitar syndrome (congenital venolobar syndrome, hypogenetic lung syndrome), the components of which are the following: 

• An aberrant vein draining the right lower lobe into the subdiaphragmatic inferior vena cava
• Pulmonary hypoplasia
• An aberrant vascular supply from the aorta
• Dextrocardia

OTHER ASSOCIATIONS OF PULMONARY HYPOPLASIA

• Abdominal wall defects
• Hemolytic disease of the newborn
• Down syndrome
• Neonatal hypophosphatasia
• Glutaric acidemia (type II)
• Laryngotracheoesophageal cleft
• Cloacal dysgenesis
• Spinal deformities
• Deformed thumb
• Ventricular inversion

PATHOLOGY

The hypoplastic lung has decreased airway generations and acini and decreased alveolar size. A combination of the 2 can also be seen.

Frequency

United States

The incidence of pulmonary hypoplasia is approximately 13%, with a range of 9-28%.

International

The worldwide incidence of pulmonary hypoplasia is 3-28% in cases of premature rupture of membranes at 15-28 weeks.

Mortality/Morbidity

Mortality rates of pulmonary hypoplasia are high during the neonatal period, and 71-95% of deaths are due to severe respiratory compromise. The mortality rate is higher in cases involving premature deliveries, marked oligohydramnios, or premature rupture of the membranes.

Pneumothorax and respiratory distress are common in these infants.

A lethal type of pulmonary hypoplasia is acinar aplasia, where the alveolar ducts are not developed, resulting in the absence of gas exchange and early death.

Age

The majority of cases of pulmonary hypoplasia occur during the perinatal period, with respiratory distress.

Anatomy

NORMAL DEVELOPMENT OF THE TRACHEOBRONCHIAL TREE AND LUNG

The development of lung proceeds in many stages from the third week of intrauterine life until 2 years after birth. The lung bud divides into right and left branches by 28 days, and segmental bronchi are formed by 30 days. Progressive branching takes place from this stage. The right lung divides faster than the left and has more branches.

STAGES IN LUNG DEVELOPMENT

The 5 stages in the development of the lung are the embryonic period, the pseudoglandular period, the canalicular period, the saccular period, and the alveolar period.

Embryonic period (first 7 weeks)

The lung bud originates from the ventral aspect of the primitive foregut, at the level of the pharynx, as a small medial bulge during days 24 through 36 of development. The mesoderm proliferates in the primitive mesentery, which contributes to the muscles, connective tissues, and cartilage of the tracheobronchial tree and the lung, while the epithelium originates from the endoderm. The vascular supply of lung, which until 30 days is from the splenic plexus, shifts to the pulmonary arteries. The pulmonary venous system forms from the capillary plexus in the mesenchyme, which eventually fuses with the pulmonary arterial system. This venous system anastomoses with the central pulmonary veins arising from the sinoatrial region and eventually drains into the left atrium.

Pseudoglandular period (weeks 5-17)

The lung looks like a gland during this stage, extending into the surrounding mesenchyme, which is solid. All future nonrespiratory airways are formed toward the end of this period. Cartilage is formed in the trachea and proximal bronchi at around 10 weeks and in the segmental bronchi at 16 weeks. The bronchi have no lumina at this stage.

Canalicular period (weeks 17-26)

During the canalicular stage, the peripheral tubules open and widen. The cuboidal epithelium differentiates into type I and type II epithelial cells; type II epithelial cells produce the surfactant. Thin air-blood barriers are formed at this stage, and the number of generations of distal airways is gradually reduced, as some of the terminal bronchioles become converted into respiratory bronchioles, with conversion of the lining epithelium. Preacinar vessels and intra-acinar vessels develop to supply the acini; they arise from the pulmonary artery, which in turn is derived from the sixth aortic arch.

Saccular period (week 26 until birth)

This stage is characterized by progressive development of pulmonary parenchyma and a decrease in the amount of connective tissue. The saccules continue to divide and become smaller, with thinner walls. The surfactant system further matures. At birth, the alveoli are not completely formed, and the lungs are immature. Gas exchange takes place through transitory ducts and saccules. The septa are thick, with a double layer of capillaries, and gas exchange is limited. Alveoli appear from 32 weeks onward.

Alveolar period (birth to 3 years of age)

The alveoli progressively develop by means of septal formation. The septa are thin and have a single layer of capillaries. The gas-exchange area of the lung progressively increases, and the alveoli are continually formed and become bigger until about 300 million are formed at 8 years of age. Continuous development of the intra-acinar arteries also occurs.

Presentation

The clinical features of pulmonary hypoplasia are variable depending on the age of presentation, the severity of the disease, and the presence of associated malformations.

In the neonatal period, the disease is usually severe and presents as respiratory failure. Occasionally, the onset is delayed, and patients present with difficulty in breathing, cyanosis, frequent respiratory infections, and growth retardation.

On examination, the affected thorax is usually small; the mediastinum is shifted to the same side; percussion is dull because of displacement of mediastinal structures or resonant due to pneumothorax; and breath sounds are reduced. Associated skeletal and cardiac malformations can be detected.

Other problems to consider are atelectasis, persistent pulmonary hypertension, pulmonary agenesis, and pulmonary aplasia. In pulmonary agenesis, the lung is absent, as are the bronchi, airways, and pulmonary vasculature. The right and left sides are affected equally. The prognosis is worse if the right side is involved because of associated severe congenital malformations. The affected side has reduced volume. Patients have homogeneous opacification of the entire lung, with a mediastinal shift to the same side. Compensatory overinflation of the opposite lung and herniation and congenital malformation are associated findings. In pulmonary aplasia, the lung is absent, but a rudimentary blind ending bronchus is present.^2,11

Preferred Examination

Antenatal ultrasonography provides early predictors of pulmonary hypoplasia.^12,13

MRI is used in some centers to assess fetal volume and predict the presence of pulmonary hypoplasia.¹⁴

After birth, chest radiography shows changes of pulmonary hypoplasia, which is better demonstrated on CT scans. Any vascular abnormality is also assessed with CT or contrast-enhanced magnetic resonance angiography.

Differential Diagnoses

Other Problems to Be Considered

Atelectasis
Persistent pulmonary hypertension
Pulmonary agenesis
Pulmonary aplasia
Proximal interruption of pulmonary artery.

Radiography

Findings

• Hypoplasia is usually unilateral but occasionally seen bilaterally
• The volume of the chest is reduced on the affected side
• Bell-shaped thorax and rib deformities are frequently observed
• The affected lung is small, and the mediastinum is shifted toward the side of the hypoplastic lung
• Increasing ipsilateral mediastinal shift during inspiration because of increased volume of the contralateral lung
• The lung is more lucent than normal; homogeneous opacification can also be seen
• The hilum is small because of hypoplastic or aplastic pulmonary artery
• Associated lung and vertebral anomalies are also noted¹⁵

Computed Tomography

Findings

CT scans show an abnormally shaped thorax, volume reduction on the affected side, compensatory overinflation of the opposite side, ipsilateral mediastinal shift, hypoplastic airways, and rib abnormalities.

With the advent of multisection CT scanners, CT angiography can be performed in a few minutes with intravenous contrast material and images reconstructed in multiple planes. This study is a noninvasive way of assessing pulmonary vasculature, as compared with conventional angiography. The pulmonary arteries are hypoplastic. Aberrant vasculature can be seen.

Associated cardiac abnormalities, scimitar syndrome, diaphragmatic abnormalities, and gastrointestinal and genitourinary abnormalities can be seen.

Magnetic Resonance Imaging

Findings

MRI of the fetus is being increasingly used to predict the presence of pulmonary hypoplasia.¹⁴

Factors used for prediction are (1) the fetal lung volume, (2) the relative lung volume, and (3) the ratio of lung volume to body weight (which is the most widely used ratio).^16,17

Fetal lung volume is measured by obtaining thin sections of the lung. The cross-sectional area is calculated by drawing an outline of the lung and estimating the area within it. Volume of each section is obtained by multiplying the area by the section thickness.

To determine the relative lung volume, the percentage of lung volume is calculated relative to the expected lung volume for the patient's gestational age. This parameter is not applicable when the fetus is macrosomic or has retardation.

A combination of MRI and ultrasonography can also be used. Tanigaki et al used the ratio of fetal lung volume measured by means of MRI and fetal body weight estimated by means of ultrasonography to predict the development of pulmonary hypoplasia.¹⁸

Postnatally, MR angiography is a reliable method of assessing pulmonary vasculature, which can be hypoplastic and aberrant but not completely absent (unlike agenesis).

Ultrasonography

Findings

Antenatal ultrasonography can be used to predict development of pulmonary hypoplasia.^{12,13,19,20,21}

Features that are useful in predicting pulmonary hypoplasia are (1) the lung area; (2) the ratio of lung area to thoracic area; (3) the ratio of thoracic to abdominal circumference; and (4) lung volume, which can be measured by using many techniques, including 3-dimensional sonography.

Sonography can be used to assess factors contributing to pulmonary hypoplasia, such as oligohydramnios, renal agenesis, renal obstruction, renal cysts, renal dysplasia, diaphragmatic hernia, thoracic and abdominal masses, and pleural effusion.

Associated congenital malformations can also be seen.

Doppler ultrasonography of the fetal pulmonary arteries is a useful study in capable hands. In hypoplasia, the development of pulmonary vasculature is delayed and the vessels are hypoplastic, resulting in increased impedance. This results in increased pulsatility index and decreased peak systolic velocity.

Degree of Confidence

Direct visualization of hypoplasia is possible with proper technique and well-trained sonographers.

Associated anomalies, which contribute to development of pulmonary hypoplasia, can be detected with confidence.

Nuclear Imaging

Findings

Perfusion scans obtained by using albumin microspheres can show defects due to decreased pulmonary vascularity. This type of scanning is not an important investigation in pulmonary hypoplasia.

It can be used to differentiate Swyer-James syndrome (unilateral acquired hyperlucent lung due to obliterative/constrictive bronchiolitis) and proximal pulmonary arterial interruption, which can have similar radiographic appearances.

In Swyer-James syndrome, perfusion scan is normal, but there is expiratory obstruction seen as a filling defect in ventilatory scans. High-resolution CT scans, however, are usually sufficient to make the diagnosis.

In proximal pulmonary arterial interruption, there is complete absence of uptake in perfusion scans, but ventilatory scans are normal.

Angiography

Findings

In the past, angiography was commonly used to confirm the diagnosis of pulmonary hypoplasia.

The pulmonary artery is patent and hypoplastic (unlike in agenesis, in which it is absent)

Pulmonary hypoplasia can be associated with a proximally interrupted pulmonary artery with patent intraparenchymal branches that anastomose with systemic collateral vessels.

Aberrations and associated scimitar syndrome can be detected. With the advent of CT angiography and magnetic resonance angiography, conventional angiography is no longer required to confirm the diagnosis.

Degree of Confidence

Although angiography was once very useful in diagnosing the vascular status in pulmonary hypoplasia, it is now obsolete because CT and MR angiography are noninvasive and equally sensitive.

Intervention

Medicolegal Pitfalls

Multimedia

Media file 1: Radiograph showing left pulmonary hypoplasia.

Media file 2: CT scan showing pulmonary hypoplasia on the left side.

Media file 3: CT scan (mediastinal window) shows a hypoplastic left lung.

Media file 4: CT scan ( mediastinal window) shows left pulmonary hypoplasia.

References

1. Effmann EL. Anomalies of the Lung. Caffey's Pediatric Diagnostic Imaging. 10th ed, Vol 1. 2004: 899-901.

2. Lauria MR, Gonik B, Romero R. Pulmonary hypoplasia: pathogenesis, diagnosis, and antenatal prediction. Obstet Gynecol. Sep 1995;86(3):466-75. [Medline].

3. Nimrod C, Varela-Gittings F, Machin G, et al. The effect of very prolonged membrane rupture on fetal development. Am J Obstet Gynecol. Mar 1 1984;148(5):540-3.

4. Rotschild A, Ling EW, Puterman ML, Farquharson D. Neonatal outcome after prolonged preterm rupture of the membranes. Am J Obstet Gynecol. Jan 1990;162(1):46-52.

5. Totan M, Yildiz G, Baysal K. Pulmonary Hypoplasia Associated with Ventricular Inversion. International Pediatrics. 2003;18(1).

6. Vergani P, Ghidini A, Locatelli A, et al. Risk factors for pulmonary hypoplasia in second-trimester premature rupture of membranes. Am J Obstet Gynecol. May 1994;170(5 Pt 1):1359-64. [Medline].

7. Stark Z, Patel N, Clarnette T, Moody A. Triad of tracheoesophageal fistula-esophageal atresia, pulmonary hypoplasia, and duodenal atresia. J Pediatr Surg. Jun 2007;42(6):1146-8. [Medline].

8. Ackerman KG, Pober BR. Congenital diaphragmatic hernia and pulmonary hypoplasia: new insights from developmental biology and genetics. Am J Med Genet C Semin Med Genet. May 15 2007;145C(2):105-8. [Medline].

9. Abrams ME, Ackerman VL, Engle WA. Primary unilateral pulmonary hypoplasia: neonate through early childhood - case report, radiographic diagnosis and review of the literature. J Perinatol. Oct 2004;24(10):667-70. [Medline].

10. Berrocal T, Madrid C, Novo S, et al. Congenital anomalies of the tracheobronchial tree, lung, and mediastinum: embryology, radiology, and pathology. Radiographics. Jan-Feb 2004;24(1):e17. [Medline].

11. Newman B. Imaging of medical disease of the newborn lung. Radiol Clin North Am. Nov 1999;37(6):1049-65. [Medline].

12. Osada H, Iitsuka Y, Masuda K, et al. Application of lung volume measurement by three-dimensional ultrasonography for clinical assessment of fetal lung development. J Ultrasound Med. Aug 2002;21(8):841-7.

13. Vintzileos AM, Campbell WA, Rodis JF, et al. Comparison of six different ultrasonographic methods for predicting lethal fetal pulmonary hypoplasia. Am J Obstet Gynecol. Sep 1989;161(3):606-12. [Medline].

14. Duncan KR, Gowland PA, Moore RJ, et al. Assessment of fetal lung growth in utero with echo-planar MR imaging. Radiology. Jan 1999;210(1):197-200. [Medline].

15. Alford BA, McIlhenny J. An approach to the asymmetric neonatal chest radiograph. Radiol Clin North Am. Nov 1999;37(6):1079-92. [Medline].

16. Ruano R, Martinovic J, Aubry MC, Dumez Y, Benachi A. Predicting pulmonary hypoplasia using the sonographic fetal lung volume to body weight ratio--how precise and accurate is it?. Ultrasound Obstet Gynecol. Dec 2006;28(7):958-62. [Medline].

17. Cannie M, Jani JC, De Keyzer F, Devlieger R, Van Schoubroeck D, Witters I, et al. Fetal body volume: use at MR imaging to quantify relative lung volume in fetuses suspected of having pulmonary hypoplasia. Radiology. Dec 2006;241(3):847-53. [Medline].

18. Tanigaki S, Miyakoshi K, Tanaka M, et al. Pulmonary hypoplasia: prediction with use of ratio of MR imaging-measured fetal lung volume to US-estimated fetal body weight. Radiology. Sep 2004;232(3):767-72.

19. Gerards FA, Twisk JW, Fetter WP, Wijnaendts LC, van Vugt JM. Predicting pulmonary hypoplasia with 2- or 3-dimensional ultrasonography in complicated pregnancies. Am J Obstet Gynecol. Jan 2008;198(1):140.e1-6. [Medline].

20. Gorincour G, Eurin D, Avni FE. Prenatal prediction of pulmonary hypoplasia: US and MR imaging working together. Radiology. Nov 2007;245(2):608-9; author reply 609. [Medline].

21. Gerards FA, Twisk JW, Fetter WP, Wijnaendts LC, Van Vugt JM. Two- or three-dimensional ultrasonography to predict pulmonary hypoplasia in pregnancies complicated by preterm premature rupture of the membranes. Prenat Diagn. Mar 2007;27(3):216-21. [Medline].

Keywords

pulmonary hypoplasia, hypoplastic lung, underdeveloped lung, congenital venolobar syndrome, scimitar syndrome, hypogenetic lung syndrome

Contributor Information and Disclosures

Author

Prabhakar Rajiah, MD, MBBS, FRCR, Registrar, Department of Radiology, Central Manchester and Manchester Children's University Hospitals, UK
Prabhakar Rajiah, MD, MBBS, FRCR is a member of the following medical societies: American Roentgen Ray Society, North American Society for Cardiac Imaging, Radiological Society of North America, Royal College of Radiologists, Society for Cardiovascular Magnetic Resonance, and Society of Cardiovascular Computed Tomography
Disclosure: Nothing to disclose.

Medical Editor

S Bruce Greenberg, MD, Professor of Radiology, University of Arkansas for Medical Sciences; Consulting Staff, Department of Radiology, Arkansas Children's Hospital
S Bruce Greenberg, MD is a member of the following medical societies: Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

Kieran McHugh, MBBCh, Honorary Lecturer, The Institute of Child Health; Consultant Pediatric Radiologist, Department of Radiology, Great Ormond Street Hospital for Children, London, UK
Kieran McHugh, MBBCh is a member of the following medical societies: American Roentgen Ray Society and Royal College of Radiologists
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Kavita Garg, MD, Professor, Department of Radiology, University of Colorado Health Sciences Center
Kavita Garg, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Radiological Society of North America, and Society of Thoracic Radiology
Disclosure: Nothing to disclose.

The author and editors gratefully acknowledge Biswaranjan Banerjee, MD, for the contributions made to this article.

Preterm prelabour rupture of membranes.
Royal College of Obstetricians and Gynaecologists.  2006 Nov.  11 pages.  NGC:005920

Growth disturbances: risk of intrauterine growth restriction.
American College of Radiology.  1996 (revised 2007).  10 pages.  NGC:006006

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