R e s p i r a t o r y Di s t res s i n

Neonates
Underlying Causes and Current Imaging
Assessment
Mark C. Liszewski, MDa,*, A. Luana Stanescu, MDb,
Grace S. Phillips, MDb, Edward Y. Lee, MD, MPHc,d

KEYWORDS
 Neonatal  Respiratory distress  Pulmonary  Preterm  Full-term  Congenital lung malformations

KEY POINTS
 Respiratory distress in the newborn can be caused by a variety of underlying conditions, and appro-
priate management depends on accurate and timely imaging and diagnosis.
 Imaging and pathologic features of congenital lung malformations often overlap and lesions are
best considered on a spectrum, with each lesion demonstrating various degrees of parenchymal,
airway, and vascular involvement.
 The leading cause of morbidity and mortality among premature infants remains surfactant defi-
ciency disorder (previously known as hyaline membrane disease or respiratory distress syndrome)
but advances in treatment, including prenatal glucocorticoids and exogenous surfactant, have
altered the classic radiographic findings of surfactant deficiency disorder.
 Advances in treatment have resulted in a change in the radiographic features of chronic lung dis-
ease of prematurity (previously known as bronchopulmonary dysplasia). Though certain radio-
graphic features are typical for chronic lung disease of prematurity, current diagnostic criteria for
chronic lung disease of prematurity are based solely on clinical criteria.
 The congenital surfactant dysfunction disorders are a rare group of genetic diseases that lead to
abnormal production and/or function of surfactant in the lungs and produce typical, though nonspe-
cific imaging findings.

INTRODUCTION the imaging appearance of each of these condi-

tions is essential to timely diagnosis and appro-
Respiratory distress is among the most common priate management. In this article, current
clinical indications for imaging the newborn. A va- imaging techniques and modalities are described
riety of underlying conditions can cause respira- and the most commonly encountered neonatal
tory distress in the neonate, and familiarity with lung diseases are discussed, including congenital

Disclosure Statement: The authors have nothing to disclose.

radiologic.theclinics.com

a
Division of Pediatric Radiology, Department of Radiology, Montefiore Medical Center, Albert Einstein Col-
lege of Medicine, 111 East, 210th Street, Bronx, NY 10467, USA; b Department of Radiology, Seattle Children’s
Hospital, University of Washington School of Medicine, 4800 Sand Point Way Northeast, Seattle, WA 98105,
USA; c Division of Thoracic Imaging, Department of Radiology, Boston Children’s Hospital, Harvard Medical
School, 300 Longwood Avenue, Boston, MA 02115, USA; d Pulmonary Division, Department of Medicine, Bos-
ton Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
* Corresponding author.
E-mail address: [email protected]

Radiol Clin N Am - (2017) -–-

http://dx.doi.org/10.1016/j.rcl.2017.02.006
0033-8389/17/Ó 2017 Elsevier Inc. All rights reserved.
2 Liszewski et al

lung malformations and lung abnormalities in pre- assess for anomalous vasculature in cases of sus-
term infants, as well as full-term infants. pected pulmonary sequestration.5 Real-time, cine,
and M-mode ultrasound imaging are the preferred
IMAGING MODALITIES AND TECHNIQUES methods for assessing diaphragmatic motion in
Radiography cases of suspected paralysis and eventration,
and can be helpful in the evaluation of congenital
Chest radiographs are the primary imaging modal- diaphragmatic hernia.3,6–9 The aerated lung can
ity used in the assessment of the newborn with even be assessed in selected scenarios through
respiratory distress. In many cases, the manage- analysis of B-lines, the comet-tail artifacts that
ment of neonates relies only on chest radiographs are produced when the sound beam interacts
without the use of other imaging modalities. Chest with the interlobular septa at the pleural surface.
radiographs are relatively inexpensive, easy to Increased B-lines have been reported in transient
obtain, and use a very low amount of radiation, tachypnea of the newborn (TTN) and surfactant
making them an ideal initial test to evaluate many deficiency,10,11 though these entities are more
neonatal lung diseases. Radiation doses can be commonly diagnosed and managed using chest
further minimized through shielding and proper radiography alone.
coning of images.1,2
Most chest radiographs performed in neonates Computed Tomography
are obtained portably and consist of a single
anterior-posterior (AP) view with the child in a su- CT has the ability to produce cross-sectional im-
pine position. In certain scenarios, a lateral view ages with excellent anatomic detail, making it a
may be useful to localize a finding. AP lateral decu- powerful tool in the evaluation of many thoracic
bitus views may be used in select cases, such as diseases. CT uses ionizing radiation to produce
to visualize layering pleural effusion or to better images, and every effort should be made to use
assess a suspected pneumothorax. Though chest low-dose pediatric protocols and limit unneces-
radiographs are an indispensable tool, they do not sary CT scans, particularly in neonates who are
provide the same anatomic detail as computed to- inherently more sensitive to the effects of radiation
mography (CT) or MR imaging, and these may be than adults.12–15 Alternative modalities that use
indicated to further evaluate a finding seen on less or no ionizing radiation, such as radiography,
chest radiograph. ultrasound, and MR imaging, should always be
considered before performing CT. After consid-
Fluoroscopy ering these factors, CT is often the best imaging
modality to assess many neonatal lung diseases
Fluoroscopy can be useful to evaluate dynamic given its excellent anatomic detail and is lower
disease processes that change throughout the susceptibility to artifacts. The addition of intrave-
respiratory cycle but its role in neonatal respiratory nous contrast is often indicated to better evaluate
distress is limited to a few scenarios. Fluoroscopy the mediastinal structures and vasculature.
may be used to evaluate diaphragmatic motion in
cases of suspected diaphragmatic paralysis or MR Imaging
eventration, though ultrasound is often preferred
due to its portability and lack of radiation.3 Airway MR imaging has received much attention due to its
fluoroscopy may be performed in cases of sus- ability to generate images without the use of
pected tracheobronchomalacia to evaluate for ionizing radiation, though its role in the evaluation
large airway collapse during expiration.4 of respiratory distress in the newborn is limited.
Cost, availability, and physical properties of the
lung, including low signal-to-noise ratio, respira-
Ultrasound
tory and cardiac motion, and signal dephasing at
In recent years, ultrasound has received air-tissue interphases, limit the routine use of chest
increasing attention as a tool in the evaluation of MR imaging in neonates. Despite these limitations,
lung disease, though inherent physical properties MR imaging with MR angiography (MRA) may be
of the chest, including acoustic shadowing from used as a first-line alternative to CT in several spe-
air-filled lung and ribs, often impede ultrasound’s cific conditions, including pulmonary sequestra-
diagnostic utility in the thorax. Despite these limi- tion, pulmonary artery hypoplasia, pulmonary
tations, ultrasound can be very useful in selected vascular anomalies, partial or total anomalous pul-
scenarios.5 When chest radiograph demonstrates monary venous return, and vascular rings and
a completely opacified hemithorax, ultrasound can sling.16,17 Small-bore and modified MR imaging
help differentiate pleural fluid from pulmonary scanners have been used in research settings to
parenchymal disease.5 Doppler ultrasound can evaluate changes of chronic lung disease of
 Respiratory Distress in Neonates 3

prematurity (previously known as bronchopulmo- Congenital pulmonary airway malformation

nary dysplasia [BPD]) in neonates,18,19 though CPAMs, previously known as cystic adenomatoid
these techniques are not yet widely available in malformations, are congenital macrocystic or
the clinical setting. Chest MR imaging using hyper- microcystic lung lesions that are associated with
polarized gas (3He or 129Xe) as an inhaled contrast an abnormal bronchial tree and bronchiolar over-
agent has the potential to quantify changes in lung growth.32,33 Typically, CPAMs are associated
microstructure, and has been studied in older chil- with normal pulmonary vascular anatomy (Fig. 1),
dren with a past history of chronic lung disease of though pathologic features of CPAM are seen in
prematurity20 but has not been studied in the 29% to 33% of pulmonary lesions with abnormal
neonatal period.21 systemic arterial supply (Figs. 2 and 3) and up
to 50% of lobar emphysemas.31,34,35 Several
Nuclear Medicine different classification systems have been pro-
posed to categorize CPAM lesions. Though no
Nuclear medicine does not play a major role in the classification scheme is universally accepted, the
routine evaluation of most causes of neonatal res- system proposed by Stocker and colleagues
piratory distress. Pulmonary ventilation-perfusion in 197736 and updated in 200137 is often used. In
(V/Q) scans, in which the pulmonary distribution this classification system, type 1 lesions are
of an inhaled radiotracer (eg, 99mTc-labeled dieth- composed of 1 or more cysts measuring greater
ylenetriamine penta-acetic acid [DTPA], 133Xe, or than 2 cm, type 2 lesions are composed of 1 or
Technegas) and an injected radiotracer (eg, more cysts measuring less than 2 cm, and type 3
99mTc-labeled macroaggregated albumin) are lesions appear as solid masses macroscopically
imaged can be useful in certain diseases. For but contain microcysts on pathologic analysis.
example, V/Q scans have been used to assess Stocker also describes type 0 lesions (acinar
pulmonary hypoplasia in patients with history of dysplasia, which is incompatible with life) and
congenital diaphragmatic hernia.22–24 V/Q scans type 4 lesions (large peripherally located lung
can provide information about severity and abnor- cysts sometimes associated with pneumothorax),
malities in regional lung function in chronic lung though these lesions are controversial.38–43
disease of prematurity.25,26 Perfusion scintigraphy The clinical presentation of CPAM varies. With
can also be useful to determine differential pulmo- increased prenatal imaging, an increasing number
nary perfusion in cases of congenital heart of lesions are currently detected incidentally dur-
disease, pulmonary hypoplasia, and scimitar syn- ing routine fetal ultrasound (see Fig. 2). Some le-
drome,27,28 and can be used to quantify right-to- sions cause no symptoms, whereas others cause
left shunts.27 varying degrees of respiratory distress soon after
birth, particularly when large.43–45 Lesions may
present later in life due to superinfection or rarely
SPECTRUM OF UNDERLYING PULMONARY
due to development of associated malignancy.43
CAUSES OF NEONATAL RESPIRATORY
Approximately half of type 2 lesions are associated
DISTRESS
with additional congenital anomalies, including
Congenital Lung Malformations
cardiovascular malformations, extralobar pulmo-
Congenital lung malformations are a group of nary sequestration, tracheoesophageal fistula,
developmental lesions involving the lung paren- renal agenesis, intestinal atresia, and congenital
chyma, airway, and/or pulmonary vasculature. diaphragmatic hernia.43,46
Symptoms are variable and can range from no The imaging appearance of CPAM depends on
symptoms to progressive respiratory distress the type. Lesions with macroscopic cystic compo-
requiring surgical intervention. The 3 most com- nents (types 1 and 2) are typically filled with fetal
mon congenital lung malformations detected in lung fluid at birth and fluid partially or completely
the neonate are congenital pulmonary airway mal- clears from the cysts in the first few days of
formation (CPAM), pulmonary sequestration, and life.32 Initial chest radiographs typically demon-
congenital lobar overinflation (CLO). There is strate a dense lung lesion that becomes less
considerable overlap between these entities and dense as fetal lung fluid clears. CT and MR imag-
they can be best considered as lesions on a spec- ing demonstrate a cyst or cysts within the lung pa-
trum with each lesion demonstrating various de- renchyma, containing air and/or fluid.29,32 Lesions
grees of parenchymal, airway, and vascular composed of microscopic cysts (type 3) appear as
involvement.29–31 The classic radiographic and solid masses macroscopically and, therefore, will
pathologic features of these lesions are discussed appear as dense lung lesions on radiographs and
in the following sections and imaging findings are as solid enhancing masses on CT and MR imag-
summarized in Table 1. ing.29,32 When CPAMs present later in life with
4 Liszewski et al

Table 1
Imaging findings of congenital lung malformations

Congenital Lung
Malformation Imaging Findings Pearls and Pitfalls
Congenital pulmonary airway malformation (CPAM)
Stocker type 0a Atretic large airways and lungs Type 0 CPAM lesions can be only seen in
Stocker type 1a 1 or more cysts measuring >2 cm prenatal ultrasound or MR imaging
Stocker type 2a 2 or more cysts <2 cm In type 1 and 2 CPAM lesions initial CXR
Stocker type 3a Both imaging-wise and macroscopically typically demonstrates a dense lung
solid mass composed of microcysts on lesion that becomes less dense as fetal
pathologic analysis lung fluid clears
Stocker type 4a Large peripherally located lung cysts Type 3 CPAM lesions remain dense
sometimes associated with because they are macroscopically
pneumothorax solid masses
On imaging studies, pleuropulmonary
blastoma type 1 (pure cystic lesion)
has similar imaging appearance to
type 1, 2, and 4 CPAM lesions
When CT or MR imaging is performed,
contrast-enhanced CTA or MRA
technique should always be used to
evaluate for systemic arterial supply,
seen in so-called hybrid lesions
Pulmonary Cystic or solid lung mass Frequently detected during prenatal
sequestration Systemic arterial supply seen on US, CT ultrasound
or MR imaging Contrast-enhanced CTA or MRA are
Intralobar: venous drainage to recommended in cases of suspected
pulmonary veins sequestration
Extralobar: venous drainage to systemic Most often occur in the lower lobes,
pulmonary vein left>right
Extralobar sequestration may be
intrathoracic or extrathoracic
3D volume rendered CT images can
increase the diagnostic accuracy and
confidence level for correctly
identifying small anomalous vessels
in patients with pulmonary
sequestration
Congenital lobar Serial CXRs after birth first show an AKA congenital lobar emphysema
overinflation opacified lobe that becomes lucent Hyperexpansion often causes
(CLO) and then hyperexpands significant mass effect that may result
LUL>RML>RUL>RLL & LLL in significant respiratory distress and
necessitate lobectomy

Abbreviations: 3D, 3-dimensional; AKA, also known as; CTA, CT angiography; CXR, chest radiograph; LLL, left lower lobe;
LUL, left upper lobe; MRA, MR Angiography; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe.
a
Per the classification system described in: Stocker J. The respiratory tract. In: Stocker JT, Dejner LP, editors. Pediatric
pathology. 2nd edition. Philadelphia: Lippincott, Williams & Wilkins; 2001. p. 466–73.

superinfection, chest radiographs typically Figs. 2 and 3).34,35 Therefore, CT or MR imaging

demonstrate consolidation with air-fluid levels, should be performed with contrast and CT angiog-
and CT or MR imaging demonstrate cystic lung le- raphy (CTA) or MRA techniques should be used.
sions containing air-fluid levels and a thick
enhancing irregular wall.29,32,33 Typically, CPAMs Pulmonary sequestration
have a conventional pulmonary vascular anatomy Pulmonary sequestration is typically defined as a
but attention to vascular supply is essential disconnected bronchopulmonary mass or cyst
because a proportion of CPAMs have a systemic with an anomalous arterial supply.47 There are 2
arterial supply (so-called hybrid lesions; see types of sequestration that are commonly
 Respiratory Distress in Neonates 5

Fig. 1. A 2-year-old-boy with type 1 congenital pulmonary airway malformation (CPAM). Frontal (A) and lateral
(B) chest radiographs demonstrate an air-filled multicystic lesion (arrows) in the right lower lobe. Axial (C) and
coronal (D) lung window CT images show the lesion (arrows) is composed of multiple large air-filled cysts.

described: intralobar and extralobar. Intralobar characterized by abnormal lung tissue that does
sequestration is typically characterized by abnormal not communicate with the tracheobronchial tree
lung tissue that does not communicate with the and has an arterial supply from the aorta or one of
tracheobronchial tree, has an arterial supply from its branches. Extralobar sequestration differs from
the aorta or one of its branches, has venous intralobar sequestration in that its venous drainage
drainage to the pulmonary vein, and shares a 1 is to a systemic vein and its pleural covering is sepa-
visceral pleural covering with the adjacent normal rate from the adjacent lung.29,32,33 Extralobar
lung.29,32,33 Extralobar sequestration is also sequestration is most often located within the lower

Fig. 2. A 22-week-old fetus with congenital pulmonary airway malformation (CPAM) and bronchopulmonary
sequestration (hybrid lesion). (A) Grayscale prenatal ultrasound shows a multicystic mass (white arrow) in the
left lung displacing the heart (black arrow) to the right. (B) Color Doppler ultrasound image demonstrates a
feeding systemic artery (arrow) arising from the aorta.
6 Liszewski et al

Fig. 3. A 5-month-old boy with congenital pulmonary airway malformation (CPAM) and bronchopulmonary
sequestration (hybrid lesion) (same patient as Fig. 2). (A) Coronal image from contrast-enhanced CT angiography
(CTA) demonstrates an air-filled multicystic lesion within the left lung (black arrow) with a large feeding systemic
artery (white arrow). (B) Three-dimensional (3D) volume-rendered CT image shows the systemic feeding artery
(arrow) arising from the aorta.

lung but can occur below the diaphragm or within ultrasound with Doppler imaging may demonstrate
the mediastinum. The traditional description of a lung mass with an anomalous systemic arterial
pulmonary sequestration has shortcomings and vascular supply.5 Contrast-enhanced CTA or
many lesions do not fit the strict definition. For MRA are recommended in cases of suspected
example, lesions may have an abnormal arterial sup- sequestration.17,29 Extralobar sequestration typi-
ply but normal tracheobronchial connection.48 cally appears as a solid enhancing mass with sys-
These issues have led some to propose alternative temic arterial and venous circulation that may be
classification systems34,38,49 but the terms intralo- intrathoracic or extrathoracic. Intralobar seques-
bar and extralobar sequestration seem deep- tration typically appears as a cystic lung lesion
rooted despite their inherent limitations. with variable aeration (due to collateral air drift),
Pulmonary sequestration is frequently detected arterial supply from the aorta or one of its
incidentally during prenatal ultrasound as a pulmo- branches, and venous drainage to a pulmonary
nary mass with anomalous systemic arterial sup- vein (see Fig. 3; Fig. 4).32 Intralobar sequestration
ply (see Fig. 2).44 At birth, most pulmonary can present later in life with superinfection and
sequestrations are asymptomatic and appear as chest radiograph and CT may demonstrate
a lung mass within a lower lobe, on the left side increased consolidation and air-fluid levels within
more often than the right side.29 Postnatal chest a pre-existing lesion.29,32

Fig. 4. A 21-month-old boy with intralobar bronchopulmonary sequestration. (A) Axial contrast-enhanced CT
demonstrates a heterogeneous lesion in the right lower lobe containing large abnormal vessels (arrow). (B, C)
3D volume-rendered CT images show systemic feeding artery (white arrows) arising from the aorta and venous
drainage (black arrows) to the pulmonary veins and left atrium.
 Respiratory Distress in Neonates 7

Congenital lobar overinflation Surfactant deficiency disorder, hyaline

CLO, also known as congenital lobar emphysema, membrane disease, or respiratory distress
is a lung lesion characterized by hyperexpansion syndrome
of a lobe of the lung. The primary defect in CLO Surfactant deficiency disorder, also known as hya-
is bronchial obstruction due to compression from line membrane disease or respiratory distress syn-
an external structure or intrinsic narrowing. The drome (RDS), is primarily a disease of premature
lung distal to the obstruction becomes hyperinflat- infants. Surfactant deficiency disorder occurs
ed. Mass effect from the hyperinflated lobe can when immature type II pneumocytes are unable to
result in significant symptoms, typically presenting produce sufficient surfactant to support normal
within the first 6 hours of life. CLO affects certain lung function. In the healthy state, surfactant re-
lobes more frequently; from most to least: left up- duces surface tension within alveoli and is essential
per lobe, right middle lobe, right upper lobe, right to normal alveolar expansion. Hyaline membranes,
or left lower lobes.50 which contain necrotic cells, fibrin, and plasma
CLO produces a classic appearance on serial transudate, form within the alveoli of the
chest radiographs. The initial radiograph per- surfactant-deficient lung and further impair
formed immediately after birth typically shows an oxygenation. Antenatal corticosteroids (which
opacified lobe due to entrapped fetal lung fluid. accelerate surfactant production) and exogenous
As the fluid clears, the lobe becomes more lucent surfactant have improved survival among prema-
and demonstrates progressive hyperinflation. ture children.51 Mechanical ventilation is often
Hyperinflation often continues to increase and required to treat patients with surfactant deficiency
causes mass effect on the mediastinum and dia- disorder but efforts are focused on reducing baro-
phragm (Fig. 5A). Mass effect is frequently accom- trauma because this is a major cause of morbidity
panied by worsening respiratory distress, requiring through air-leak phenomena and increased risk of
lobectomy. If clinically stable, preoperative CT is chronic lung disease of prematurity.
generally indicated to define the lobar anatomy Chest radiographs in untreated surfactant defi-
before lobectomy (Fig. 5B, C).29 Classically, CLO ciency disorder typically demonstrate low lung vol-
is associated with conventional vascular anatomy. umes with diffuse homogenous granular opacities
(Fig. 6). This classic appearance is altered by the
Lung Abnormalities in Preterm Infants administration of exogenous surfactant. After sur-
Advances in neonatal intensive care over the past factant, granular opacities and lung hypoinflation
50 years have led to greatly improved survival may uniformly improve, asymmetrically decrease,
rates for infants born before term. The leading or show no change.52 Surfactant is often adminis-
cause of morbidity and mortality among premature tered before the first radiograph, so even initial
infants is respiratory distress due to insufficient chest radiographs may not demonstrate the
surfactant production. Complications of surfactant classic pattern of surfactant deficiency disorder.
deficiency disorder, including pulmonary intersti- Asymmetric improvement can produce radio-
tial emphysema (PIE) and chronic lung disease of graphic findings similar to neonatal pneumonia or
prematurity, can further contribute to morbidity meconium aspiration, and correlation with clinical
and mortality in this patient group. The radio- history is essential in these cases.51 Surfactant
graphic and pathologic features of these entities deficiency disorder is typically managed using ra-
are discussed in the following sections and imag- diographs alone, and other imaging modalities are
ing findings are summarized in Table 2. rarely used.

Fig. 5. A 9-month-old girl with left upper lobe congenial lobar overinflation (CLO). (A) Frontal chest radiograph
demonstrates hyperlucent left upper lobe with mild mass effect on the mediastinum. Axial (B) and coronal (C)
contrast-enhanced CT images show hyperlucent left upper lobe.
8 Liszewski et al

Table 2
Imaging findings of the most common lung abnormalities in preterm infants

Lung Abnormality Imaging Findings Pearls and Pitfalls

Surfactant deficiency Low lung volumes with diffuse Initial CXR may not demonstrate the
disorder, hyaline homogenous granular opacities classic pattern of surfactant
membrane disease, After surfactant granular opacities deficiency disorder because
or respiratory may uniformly improve, surfactant is often administered
distress syndrome asymmetrically decrease, or show before the first radiograph is
(RDS) no change obtained
CXR may show asymmetric
improvement after surfactant is
administered and can appear similar
to neonatal pneumonia or
meconium aspiration
Pulmonary interstitial CXR: bubbly and/or linear lucencies Most common in mechanically
emphysema (PIE) CT: line-and-dot pattern due to ventilated patients with surfactant
interstitial air surrounding the deficiency disorder
bronchovascular bundles Surfactant given to treat surfactant
deficiency disorder can cause
localized acinar overdistention that
may mimic PIE
Chronic lung disease Coarse reticular opacities, cystic New diagnostic criteria for BPD are
of prematurity or lucencies and hyperexpansion based solely on clinical features, and
bronchopulmonary do not include radiographic
dysplasia (BPD) features

Pulmonary interstitial emphysema also occur in meconium aspiration syndrome

PIE is a condition that occurs when air ruptures (MAS) or neonatal pneumonia. PIE may be
through the bronchoalveolar junctions and dis- accompanied by additional air-leak phenomena,
sects into the pulmonary interstitium.53 PIE occurs including pneumothorax, pneumomediastinum,
most commonly in mechanically ventilated pa- pneumopericardium, and pneumoperitoneum.
tients with surfactant deficiency disorder but can Chest radiographs in PIE typically demonstrate
bubbly or linear lucencies with morphology
different from air-bronchograms or normal air
within alveoli (Fig. 7).54,55 PIE may be focal,
diffuse, unilateral or bilateral.55 If PIE persists for
longer than 1 week, it is termed persistent PIE
(PPIE) (see Fig. 7C). The involved lung can enlarge
and cause mass effect.
Other entities can occasionally mimic the
appearance of PIE on chest radiographs. Exoge-
nous surfactant given to treat surfactant defi-
ciency disorder can cause localized acinar
overdistention that produces an appearance of
bubbly lucencies that may mimic PIE.51 In this
scenario, consideration of the child’s clinical con-
dition is essential: patients with PIE tend to
decompensate and patients with acinar distention
from exogenous surfactant tend to improve.51
Localized PPIE can mimic CPAM and CLO on
chest radiographs but prior imaging studies typi-
Fig. 6. Newborn girl born premature at 28 weeks cally demonstrate a characteristic pattern of PIE
gestation with surfactant deficiency disorder. Frontal in the same region.53 If the diagnosis of PPIE is
chest radiograph demonstrates diffuse bilateral hazy unclear, CT may be performed and demonstrate
pulmonary opacities and low lung volumes. interstitial air surrounding the bronchovascular
 Respiratory Distress in Neonates 9

Fig. 7. Newborn girl born premature at 29 weeks gestation with surfactant deficiency disorder and persistent pul-
monary interstitial emphysema (PIE) (PPIE). (A) Chest radiograph at day 1 of life shows diffuse bilateral hazy pul-
monary opacities of surfactant deficiency disorder. (B) Chest radiograph at day 2 of life demonstrates new
bilateral bubbly and linear lucencies that do not conform to the shape of air-bronchograms, compatible with
PIE. (C) Chest radiograph at day 9 of life shows persistent bubbly and linear lucencies of PIE, compatible with PPIE.

bundles, producing a line-and-dot pattern.55–57 Chronic lung disease of prematurity or

Bubbly lucencies in PIE can also mimic lucencies bronchopulmonary dysplasia
seen in chronic lung disease of prematurity, and Though many patients with surfactant deficiency
consideration of the time course and patient age disorder completely recover, a subset of patients
are essential to differentiate these entities. PIE develops persistent pulmonary disease called
generally occurs as an acute event during the first chronic lung disease of prematurity, also
week of life, whereas imaging findings of chronic known as BPD. Northway and colleagues59 first
lung disease of prematurity tend to appear grad- described this condition in 1967, describing 4
ually around the second and third week.58 stages of BPD occurring in a subset of patients
Presence of PIE should be reported to neonatal with surfactant deficiency disorder and treated
intensive care unit (NICU) staff immediately with mechanical ventilation. In the classic BPD
because patients will often be changed from con- described by the investigators, chest radio-
ventional mechanical ventilation to high-frequency graphs evolve from findings of surfactant defi-
oscillatory ventilation.56 Most PIE responds to ciency disorder in the first days of life to diffuse
conservative management and resolves sponta- bilateral opacities that are slowly replaced by
neously. A minority of cases persist, leading to coarse reticular opacities, cystic lucencies, and
PPIE. Most PPIE is managed conservatively. A hyperexpansion beginning around day 10 and
small number of cases of PPIE require surgical progressing beyond 1 month of age (Fig. 8).
resection due to mass effect.56 CT is often indi- Pathologically, chronic lung disease of prematu-
cated in these cases to aid surgical planning.55–57 rity is characterized by emphysema, atelectasis,

Fig. 8. A 3-month-old girl born premature at 26 weeks gestation with chronic lung disease of prematurity. (A)
Chest radiograph shows bilateral coarse interstitial opacities, atelectasis, and right hemidiaphragm elevation
due to right lung volume loss. (B) Coronal lung window CT image demonstrates bilateral ground glass opacities,
septal thickening, and atelectasis that are greater on the right with right hemidiaphragm elevation.
10 Liszewski et al

smooth muscle hypertrophy, and pulmonary Lung Abnormalities in Full-Term Infants

fibrosis. Patients with chronic lung disease of
A variety of conditions may lead to respiratory
prematurity have persistent respiratory distress
distress in full-term newborns, often leading to
requiring continued respiratory treatment ranging
NICU admission. Conditions range from rare ge-
from supplemental oxygen to long-term mechan-
netic diseases, such as congenital surfactant
ical ventilation.
dysfunction disorders, to more common condi-
There have been many changes in the treat-
tions, including TTN, MAS, and infection. The
ment of surfactant deficiency disorder and
radiographic and pathologic features of these en-
chronic lung disease of prematurity since the orig-
tities are discussed in the following sections and
inal 1967 description by Northway and col-
imaging findings are summarized in Table 3.
leagues.59 These changes include antenatal
glucocorticoid therapy, exogenous surfactant,
use of lower oxygen concentrations, and less Congenital surfactant dysfunction disorders
harmful ventilation techniques. This has resulted The surfactant dysfunction disorders are a rare
in survival of larger numbers of infants who have group of genetic diseases that lead to abnormal
low and extremely low birth weight, many of production and/or function of surfactant in the
whom go on to develop chronic lung disease lungs, and can cause respiratory distress in the
requiring long-term respiratory support. The im- newborn. Several mutations have been identified,
aging features of chronic lung disease in this including mutations in genes for surfactant protein
group often differ from the original findings B (Fig. 9), surfactant protein C, adenosine triphos-
described by Northway and colleagues,59 leading phate (ATP)-binding cassette transporter protein,
to the term the new BPD. For example, early thyroid transcription factor-1, and granulocyte-
chest radiographs in extremely premature infants macrophage colony-stimulating factor–Ra.68–72
may only demonstrate mild perihilar opacities and Patients affected with surfactant dysfunction
fine granularity in a pattern termed immature disorder are typically born at term with respiratory
lung60 but subsequent radiographs often demon- distress. Symptoms may range from mild to se-
strate typical features of BPD, including coarse vere. Chest radiograph typically shows bilateral
interstitial opacities, cystic lucencies, and hyper- patchy or diffuse hazy opacities.73–75 Findings on
expansion.51,53 Because the radiographic fea- CT may include ground-glass opacities, consoli-
tures in these patients often differ from those dation, and interlobular septal thickening.73–76
originally described by Northway and col- Definitive diagnosis can be established with ge-
leagues,59 the National Institute of Child Health netic testing. Some cases are related to yet-
and Human Development’s National Heart, unknown genetic mutations and, in these cases,
Lung, and Blood Institute Workshop developed biopsy is required for diagnosis.
new diagnostic criteria for BPD that are based
solely on clinical features and do not include a Transient tachypnea of the newborn
consideration of the radiographic findings TTN is a condition caused by retained fetal fluid
because they did not increase the established within the lung after birth, resulting in respiratory
diagnostic sensitivity or specificity.61,62 This work- distress. Fetal lung liquid is cleared through the
shop recommended continued use of the term airway, lymphatic channels, and capillaries.51
BPD, though many now prefer the term chronic Clearance is promoted by adrenergic stimulation
lung disease of prematurity given the evolution that occurs during the normal vaginal birth pro-
of the disease since the original description by cess.77–80 Therefore, TTN is more common among
Northway and colleagues.59 infants born by cesarean section or precipitous
Treatment of chronic lung disease of prematu- vaginal delivery.81,82 Retained fluid in TTN is
rity is supportive. Oxygen toxicity and barotrauma located within the alveoli, pulmonary interstitium,
are major risk factors for developing chronic lung and enlarged lymphatics. This distribution is very
disease of prematurity63; therefore, high supple- similar to the distribution of fluid in pulmonary
mental oxygen concentrations and positive pres- edema; therefore, the imaging findings are similar.
sure ventilation are limited as much as possible. Chest radiographs obtained soon after birth
Inhaled bronchodilators may be used for tempo- typically show perihilar interstitial opacities, indis-
rary symptom relief, though they do not improve tinct pulmonary markings, and small pleural effu-
long-term outcomes.63,64 Systemic corticoste- sions (Fig. 10). Lung volumes may be normal or
roids can improve lung function but are reserved increased. Symptoms are usually mild and typi-
for only the most severe cases due to serious cally resolve by days 2 to 3 of life. Chest radio-
potential side effects, including neurologic graphs also typically normalize during this time
dysfunction.65–67 period.
 Respiratory Distress in Neonates 11

Table 3
Imaging findings of the most common lung abnormalities in full-term infants

Lung Abnormality Imaging Findings Pearls and Pitfalls

Surfactant CXR: bilateral patchy or diffuse hazy Entities include surfactant protein B
dysfunction opacities and C deficiency, ATP-binding
disorders CT: ground-glass opacities, cassette transporter protein
consolidation, and interlobular septal deficiency, thyroid transcription
thickening factor-1 deficiency, granulocyte-
macrophage colony-stimulating
factor–Ra deficiency
Definitive diagnosis is established with
genetic testing or biopsy
Transient CXR soon after birth: Perihilar Caused by retained fetal fluid within
tachypnea interstitial opacities, indistinct the lung after birth
of newborn (TTN) pulmonary markings, and small Clearance of fluid is promoted by
pleural effusions. Lung volumes may adrenergic stimulation that occurs
be normal or increased. during the normal vaginal birth
Aeration improves on CXR after 2–3 d process
Therefore, TTN is more common after
cesarean section or precipitous
vaginal delivery
Meconium Hyperinflation with asymmetric Exogenous surfactant may be given to
aspiration irregular opacities replace surfactant that has been
syndrome (MAS) Pneumothorax in 10%–40% chemically inactivated by meconium
Pleural effusion in 10%–20% Affected neonates are at higher risk for
pneumonia and imaging findings are
similar to neonatal pneumonia,
therefore patients are often treated
with antibiotics
Pulmonary infection Most commonly, bilateral alveolar Fever is not typical, temperature
opacities instability is more common
Findings may be identical to RDS or TTN May be difficult to differentiate
CXR can be normal neonatal pneumonia from other
entities based on imaging findings
alone, therefore patients are often
treated presumptively with
antibiotics
Abbreviation: ATP, adenosine triphosphate.

Fig. 9. A 26-day-old girl born at full term with congenital surfactant protein B deficiency. (A) Chest radiograph
demonstrates diffuse bilateral hazy pulmonary opacities. (B) Axial lung window CT image shows diffuse ground
glass opacity throughout bilateral lungs.
12 Liszewski et al

relatively common, seen in 10% to 40% of

cases.51,83,85 Pleural effusion is seen in 10% to
20% of cases.51,85 Occasionally, the only finding
on chest radiograph is pneumothorax, with clear
lungs.51
Patients with MAS are managed supportively to
maintain oxygenation. Mechanical ventilation is
optimized to reduce risk of pneumothorax and
pneumomediastinum through use of low positive
airway pressures and high-frequency oscillatory
ventilation in select cases. Exogenous surfactant
may be given via endotracheal tube to replace sur-
factant that has been chemically inactivated by
meconium.83,86 Extracorporeal membrane
oxygenation may be required in severe cases to
maintain oxygenation. Because patients with
Fig. 10. A 3-hour-old full-term boy born via cesarean MAS are at higher risk for superimposed bacterial
section with transient tachypnea of newborn (TTN). infection and their imaging findings are similar to
Frontal chest radiograph demonstrates bilateral pul- neonatal pneumonia, patients with MAS are usu-
monary interstitial opacities and trace fluid (arrow) ally treated with antibiotics.51
in the minor fissure.
Infection
Meconium aspiration syndrome Pulmonary infection and sepsis can be acquired
MAS occurs when meconium is passed and aspi- via hematogenous transplacental spread in utero,
rated during birth. Meconium is a thick and tena- during labor and delivery, or in the period soon af-
cious chemical irritant. When aspirated, it causes ter birth. Possible causes of neonatal pneumonia
small and medium airway obstruction, chemical and sepsis include group A and B streptococcus,
pneumonitis, and inactivation of surfactant. MAS Escherichia coli, listeria, herpes simplex virus,
is more common in children born after 40 weeks and cytomegalovirus, among others. Signs and
gestation.83 Respiratory distress may range from symptoms typically include respiratory distress
mild to severe. MAS is the most common cause and temperature instability.87 Fever is not typical.
of mortality in term infants.84 Risk factors for neonatal pneumonia include
Chest radiographs in MAS typically show hyper- maternal infection and prolonged rupture of
inflation with asymmetric irregular opacities due to membranes.
combination of air-trapping, atelectasis, and The imaging findings in neonatal pneumonia are
chemical pneumonitis (Fig. 11). Pneumothorax is variable. In a series by Haney and colleagues,87

Fig. 11. A 1-day-old girl with meconium aspiration syn- Fig. 12. A 7-day-old girl with group B streptococcus
drome (MAS). Frontal chest radiograph demonstrates sepsis. Frontal chest radiograph shows bilateral
asymmetric bilateral irregular pulmonary opacities. diffuse hazy pulmonary opacities.
 Respiratory Distress in Neonates 13

the most common pattern was bilateral alveolar 7. Epelman M, Navarro OM, Daneman A, et al. M-
opacities seen in 77% (Fig. 12). Findings were mode sonography of diaphragmatic motion:
identical to RDS in 13% and identical to TTN in description of technique and. Pediatr Radiol 2005;
17%.87 Chest radiographs can be normal in up 35(7):661–7.
to 10%.87 Because of the crossover in imaging 8. Taylor GA, Atalabi OM, Estroff JA. Imaging of
findings with other entities, neonatal pneumonia congenital diaphragmatic hernias. Pediatr Radiol
may be difficult to differentiate from other causes 2009;39(1):1–16.
of neonatal respiratory distress based on imaging 9. Nason LK, Walker CM, McNeeley MF, et al. Imaging
findings alone. Blood or sputum culture are helpful of the diaphragm: anatomy and function. Radio-
when positive, though are often falsely negative. graphics 2012;32(2):E51–70.
Therefore, affected patients are often treated pre- 10. Copetti R, Cattarossi L. The ‘double lung point’: an
sumptively with antibiotics. ultrasound sign diagnostic of transient tachypnea
of the newborn. Neonatology 2007;91(3):203–9.
11. Avni EF, Braude P, Pardou A, et al. Hyaline mem-
SUMMARY
brane disease in the newborn: diagnosis by ultra-
Respiratory distress has a variety of causes in the sound. Pediatr Radiol 1990;20(3):143–6.
newborn. Conditions such as surfactant deficiency 12. Miglioretti DL, Johnson E, Williams A, et al. The use
disorder and chronic lung disease of prematurity of computed tomography in pediatrics and the asso-
have been described since the beginning of pedi- ciated radiation exposure and estimated cancer
atric radiology but advances in treatment have risk. JAMA Pediatr 2013;167(8):700–7.
changed the patient population with these condi- 13. Brenner DJ. Estimating cancer risks from pediatric
tions and altered the imaging findings. A greater CT: going from the qualitative to the quantitative. Pe-
understanding of congenital lung malformations diatr Radiol 2002;32(4):228–31 [discussion: 242–4].
has changed the way clinicians approach imaging 14. Kim JE, Newman B. Evaluation of a radiation dose
CPAM, pulmonary sequestration, and CLO. Newly reduction strategy for pediatric chest CT. AJR Am
characterized genetic causes of neonatal respira- J Roentgenol 2010;194(5):1188–93.
tory distress, including the congenital surfactant 15. Goo HW. Individualized volume CT dose index
dysfunction disorders, have advanced apprecia- determined by cross-sectional area and mean den-
tion of rare, previously unexplained cases of sity of the body to achieve uniform image noise of
neonatal lung disease. An up-to-date knowledge contrast-enhanced pediatric chest CT obtained at
of the imaging findings in the full range of neonatal variable kV levels and with combined tube current
lung diseases is essential for accurate diagnosis modulation. Pediatr Radiol 2011;41(7):839–47.
and optimal management. 16. Wielputz M, Kauczor HU. MRI of the lung: state of
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