Pe d i a t r i c I m a g i n g • R ev i ew

Liszewski and Lee

Neonatal Lung Disorders

Pediatric Imaging
Review FOCUS ON:

Neonatal Lung Disorders: Pattern

Recognition Approach to Diagnosis
Mark C. Liszewski1 OBJECTIVE. Lung disease is a common indication for neonates to require medical at-
Edward Y. Lee2 tention, and neonatal chest radiographs are among the most common studies interpreted by
pediatric radiologists. Radiographic features of many neonatal lung disorders overlap, and it
Liszewski MC, Lee EY may be difficult to differentiate among conditions.
CONCLUSION. This review presents an up-to-date practical approach to the radiologic
diagnosis of neonatal lung disorders, with a focus on pattern recognition and consideration of
clinical history, patient age, and symptoms.
American Journal of Roentgenology 2018.210:964-975.

wide spectrum of disorders may The standard chest radiograph in the

A affect the lungs of the neonate.

Keywords: full-term, lung, neonatal, preterm
doi.org/10.2214/AJR.17.19231
Received November 1, 2017; accepted after revision
December 30, 2017.
M. C. Liszewski receives grant support from Carestream
Health for an unrelated study.
1
Division of Pediatric Radiology, Departments of
Radiology and Pediatrics, Montefiore Medical Center,
Albert Einstein College of Medicine, 111 East 210th St,
Bronx, NY 10467. Address correspondence to
M. C. Liszewski (mliszews@montefiore.org).
2
Division of Thoracic Imaging, Departments of Radiology
and Medicine, Pulmonary Division, Boston Children’s
Hospital and Harvard Medical School, Boston, MA.
This article is available for credit.
AJR 2018; 210:964–975
0361–803X/18/2105–964
© American Roentgen Ray Society
Although ultrasound, CT, and
MRI may play a role in the diag-
nosis and characterization of some neonatal
lung disorders, chest radiographs are the pri-
mary imaging modality used in most cases.
Interpretation of neonatal chest radiographs
can be challenging, because many diseases
produce similar imaging findings. However,
by using a systematic pattern-based approach
described here, one can narrow the differen-
tial diagnoses and provide essential informa-
tion critical to clinical decision making.
Imaging Techniques
Most neonatal lung disorders are diagnosed
and managed exclusively on the basis of ra-
diographs, and appropriate radiographic tech-
nique is vital to patient safety and diagnosis. It
is essential to use the ALARA (as low as rea-
sonably achievable) principle when imaging
with a modality that uses ionizing radiation,
keeping radiation exposure as low as reason-
ably achievable. This is accomplished through
appropriate collimation and shielding, using
standardized exposure indexes to reduce the
risk of dose creep that may occur when imag-
ing with modern digital radiography systems,
and limiting unnecessary examinations [1–4].
When using proper technique, estimated radi-
ation doses to neonates in the neonatal ICU
(NICU) are low, ranging from 24 to 32 μGy
per chest radiograph, and are associated with
a very low estimated risk of developing radia-
tion-induced malignancy [5–7].
NICU consists of a single portable radio-
graph obtained in the anteroposterior pro-
jection. Additional views may be used in se-
lect situations. For example, lateral decubitus
radiographs may be used to confirm a sus-
pected pneumothorax or to assess a layer-
ing pleural effusion, and oblique radiographs
may help localize a finding relative to other
thoracic structures [8].
Most neonatal lung disorders can be diag-
nosed and managed with radiographs alone.
In select scenarios, including congenital lung
malformations and cardiovascular abnormali-
ties, cross-sectional imaging may provide es-
sential additional clinical information, and CT
may be indicated [9]. Compared with radio-
graphs, CT requires a relatively high radiation
dose and should be considered only after care-
fully weighing the potential risks and bene-
fits [9]. Modern MDCT scanners are widely
available and are able to image the entire neo-
natal thorax in a few seconds. Examinations
can often be performed during sleeping, after
feeding, with gentle immobilization and with-
out sedation [9]. Because chest CT of the neo-
nate is generally limited to the evaluation of
congenital lung malformations and cardiovas-
cular abnormalities, IV contrast agent is most
often indicated. Technical parameters should
be optimized to reduce radiation dose on the
basis of patient weight and size, and examina-
tions can most often be performed at very low
tube voltage (80 kV) [9, 10].
Other imaging modalities may be used in
select scenarios. Ultrasound plays a limited

964 AJR:210, May 2018

 Neonatal Lung Disorders

Diffuse Neonatal Lung Disorders Focal Neonatal Lung Disorders Diffuse or Focal Neonatal Lung Disorders

Congenital lobar overinflation Neonatal pneumonia

Preterm Congenital pulmonary airway malformation Pulmonary interstitial emphysema
Surfactant deficiency Bronchopulmonary sequestration Aspiration due to congenital anomaly
disorder

Full term

Retained fetal fluid

(transient tachypnea of newborn)
Meconium aspiration syndrome
Diffuse developmental disorder
Congenital surfactant dysfunction disorder
Congenital pulmonary lymphangiectasia

Preterm and full term

Alveolar growth disorder
Vascular congestion (cardiac disease)

Fig. 1—Spectrum of neonatal lung disorders.

American Journal of Roentgenology 2018.210:964-975.

role in evaluation of neonatal lung disease, spiratory distress syndrome, is the most com- maturity is the most common risk factor for
because acoustic shadowing from the air- mon cause of death in preterm infants [14, 15]. SDD, with a frequency of 60–80% in children
filled lung provides a major limitation. How- Surfactant is a lipoprotein produced by type born before 28 weeks and 15–30% in children
ever, ultrasound may be used to evaluate a II pneumocytes that reduces the surface ten- born between 32 and 36 weeks [16–19]. SDD
pleural effusion or an aberrant vascular sup- sion of alveoli and allows normal expansion after 36 weeks’ gestation is rare but can occur
ply, as seen in pulmonary sequestration [11]. of the lungs during respiration. In SDD, sur- in the setting of maternal diabetes because of
In current practice, MRI is rarely used in the factant production is deficient and alveoli are high insulin levels, which interfere with surfac-
evaluation of neonatal lung disease, though unable to adequately expand. Decreased lung tant production maturation. Other risk factors
newly developed MRI techniques using ul- compliance leads to alveolar injury, resulting for SDD include multiple gestations, cesarean
trashort TE sequences may provide a poten- in accumulation of fibrin and cellular debris delivery, and perinatal asphyxia [16–19].
tial alternative to CT in the future [12, 13]. (called hyaline membranes) within the alveo- The radiographic findings of untreated
li. This debris, as well as atelectasis, leads to SDD depend on the severity of disease and
Diffuse Neonatal Lung Disorders poor oxygen exchange. may range from fine granular pulmonary
When approaching the interpretation of Surfactant production does not mature un- opacities to complete white-out of the lungs
an abnormal neonatal chest radiograph, the til approximately 35 weeks’ gestation, and pre- (Fig. 2). Low lung volumes are classically de-
first step is to determine whether the neonate
is preterm or full term and whether the find-
ings are diffuse or focal (Fig. 1).
The diffuse lung disorder that most com-
monly affects preterm neonates is SDD. Dif-
fuse lung disorders that affect full-term neo-
nates include retained fetal fluid (also known
as transient tachypnea of the newborn), MAS,
diffuse developmental disorders, congenital
SDD, and congenital pulmonary lymphangi-
ectasia. Diffuse lung disorders that may oc-
cur in either preterm or full-term neonates in-
clude alveolar growth disorder and vascular
congestion due to cardiac disease. The radio-
graphic findings in each of these disorders are
described, and pearls that help to differentiate
among these conditions are highlighted. A B
Fig. 2—Male neonate born at 26 weeks’ gestation with respiratory distress due to surfactant deficiency disorder.
Preterm A, Frontal chest radiograph obtained soon after birth shows extensive diffuse bilateral pulmonary opacity with
air bronchograms.
Surfactant deficiency disorder (SDD), also B, Frontal chest radiograph obtained at day 1 of life after administration of exogenous surfactant shows
known as hyaline membrane disease and re- improved aeration of lungs.

AJR:210, May 2018 965


Fig. 3—Male neonate born at 32 weeks’ gestation
with respiratory distress due to surfactant deficiency
disorder. Frontal chest radiograph obtained after
administration of exogenous surfactant shows small
round bubbly lucencies (arrows) in lower lobes due to
distended alveoli; this finding may mimic pulmonary
interstitial emphysema.
scribed in untreated SDD and occur as a re-
sult of impaired alveolar expansion.
American Journal of Roentgenology 2018.210:964-975.
It is important to recognize that treatments
and interventions frequently alter the radio-
graphic findings in SDD, such that radio-
graphs often do not display the classic find-
ings of untreated SDD. For example, most
children with symptomatic SDD receive re-
spiratory support, which expands the lung
volumes, and low lung volumes are not a reli-
able feature of SDD in modern practice [14,
18]. Exogenous surfactant is often admin-
istered via endotracheal tube to treat SDD,
which may result in normalization of lung
volumes (Fig. 2). Occasionally, acini receiv-
ing exogenous surfactant can become over-
distended, causing imaging findings of small
bubbly lucencies that mimic PIE [18] (Fig. 3).
Uneven distribution of exogenous surfactant
within the lungs can alter the radiographic
findings, such that the classic uniform granu-
lar opacity of SDD becomes more heteroge-
neous as the treated areas of the lung expand
and untreated areas display granular opacity
or atelectasis [20]. This may mimic the ap-
pearance of other conditions, such as MAS
and neonatal pneumonia. Therapeutic hypo-
thermia has emerged as a technique to treat
neonates with hypoxic ischemic encephalop-
athy, and this treatment has been associated
with a greater frequency of pulmonary com-
plications, including alveolar hemorrhage,
pneumonia, and air leak [21–23]. Because
these treatments can dramatically alter the
findings of SDD, communication with the
NICU staff and understanding of the clinical
scenario are essential for accurate interpreta-
tion of preterm neonatal chest radiographs.
966 AJR:210, May 2018
Liszewski and Lee
chanical ventilator settings. Pulmonary ede-
ma may occur as a result of increased left-
to-right shunting through a patent ductus
arteriosus (PDA) or may be neurogenic, as in
cases of severe germinal matrix hemorrhage
[14] (Fig. 4). Pulmonary hemorrhage may be
due to multiple factors, including immature
capillaries, coagulopathy, shunting across a
PDA, and therapeutic hypothermia [24–26]
(Fig. 5). Barotrauma sustained by the imma-
ture lung during mechanical ventilation may
result in air leak phenomena, including pneu-
mothorax, pneumomediastinum, pneumo-
peritoneum, and PIE, as described in a subse-
Fig. 4—4-week-old boy born at 25 weeks’ gestation quent section in greater detail.
with large patent ductus arteriosus. Frontal chest
radiograph shows increased bilateral pulmonary Full Term
vascular markings due to shunt vascularity and
cardiomegaly. Retained fetal fluid (transient tachypnea
of the newborn)—Retained fetal fluid, also
known as transient tachypnea of the new-
The imaging findings of SDD evolve dur- born, is a diffuse lung disorder that occurs
ing the first days of life. Findings are usually because of delayed clearance of fetal lung
most severe at birth, but can sometimes peak fluid after birth, typically in full-term neo-
at 12–24 hours of life, reflecting the fact that nates born via cesarean delivery. Delayed
macrophages begin to remove fibrin and cel- clearance of fetal lung fluid causes transient
lular debris from the lungs and type II pneu- respiratory distress that improves within
mocytes increase surfactant production at 48–72 hours after birth. In utero, the lungs
around 36–48 hours of life [18]. Radiographs are filled with fluid, and after birth this fluid
may normalize or evolve to findings of chron- clears via the airway, lymphatics, and capil-
ic lung disease of prematurity (previously laries [18]. The clearance of fetal lung fluid
known as bronchopulmonary dysplasia), de- is aided by adrenergic activation of sodium
scribed in a subsequent section in greater channels that help transport fluid out of the
detail. Acute increased opacification of the alveoli [27–30]. Cesarean delivery and pre-
lungs may occur because of atelectasis, pul- cipitous labor are risk factors for retained fe-
monary edema, or pulmonary hemorrhage. tal fluid, because adrenergic stimulation that
Atelectasis is usually the result of altered me- normally accompanies labor is reduced. The
A B
Fig. 5—1-day-old boy born at 25 weeks’ gestation with surfactant deficiency disorder (SDD) complicated by
pulmonary hemorrhage.
A, Frontal chest radiograph obtained at day 1 of life shows diffuse bilateral fine granular opacities
characteristic of SDD.
B, Frontal chest radiograph obtained 5 hours later when blood was seen coming from endotracheal tube shows
acute increased diffuse bilateral pulmonary opacity, compatible with pulmonary hemorrhage.

Fig. 6—2-hour-old boy born at full term via cesarean
section with retained fetal fluid. Frontal chest
radiograph shows bilateral pulmonary interstitial
opacities and fluid within minor fissure (arrow).
incidence of retained fetal fluid is approxi-
mately 35.5 cases/1000 infants delivered via
American Journal of Roentgenology 2018.210:964-975.
cesarean delivery before the onset of labor,
12.2 cases/1000 infants born by cesarean de-
livery after the onset of labor, and 5.3 cas-
es/1000 infants born by vaginal delivery [31].
Chest radiographs of neonates with re-
tained fetal fluid typically show diffuse
pulmonary interstitial opacities (Fig. 6).
Small pleural effusions are common, typi-
cally manifesting as trace fluid within the
fissures. Lung volumes may be normal or
increased. In some cases, imaging findings
may be similar to those of SDD, showing
diffuse granular opacities [18]. In other cas-
es, findings may mimic those of MAS or
neonatal pneumonia, showing irregular bi-
lateral opacities [18]. The most specific im-
A B
Fig. 8—13-month-old girl born at full term with respiratory distress due to ABCA3 genetic mutation.
A, Frontal chest radiograph shows diffuse bilateral hazy and interstitial pulmonary opacities.
B, Coronal CT image in lung window shows diffuse bilateral ground-glass opacities, interlobular septal
thickening, and bilateral pulmonary cysts.
AJR:210, May 2018 967
Neonatal Lung Disorders
Fig. 7—Newborn boy born at full term with meconium
aspiration syndrome. Frontal chest radiograph shows
irregular bilateral pulmonary opacities, hyperinflated
lungs, and small right pneumothorax (arrow).
aging feature of retained fetal fluid is in-
terval improvement within 48–72 hours. In
cases where the initial radiographic appear-
ance is atypical, consideration of birth his-
tory and follow-up radiographs are key to
establishing the diagnosis.
Meconium aspiration syndrome—MAS
is a diffuse lung disorder that is the result
of fetal aspiration of meconium and is the
most common cause of significant morbidity
and mortality among full-term and postterm
­neonates [32, 33]. Meconium staining of the
amniotic fluid occurs in 10–15% of births,
but MAS occurs in only approximately 5%
of these cases [18, 32, 33]. Aspirated me-
conium causes a chemical pneumonitis and
inactivates surfactant, resulting in hypoxia
and respiratory distress. MAS predisposes
to infection, and superimposed pneumonia
may occur [14]. Hypoxia in MAS may lead
to persistent pulmonary hypertension of the
neonate. Aspirated meconium often causes
areas of atelectasis and air trapping within
the lung. Deep suctioning of the airway and
mechanical ventilation are often required.
Pneumothorax and pneumomediastinum are
frequently seen, and PIE can occur. In severe
cases, extracorporeal membranous oxygen-
ation may be required. Exogenous surfactant
may be administered to replace endogenous
surfactant that was inactivated by meconi-
um. Inhaled nitric oxide may be adminis-
tered to treat pulmonary hypertension.
Radiographic findings of MAS depend on
the severity of disease. Findings can range
from clear lungs with hyperinflation to
coarse irregular bilateral pulmonary opaci-
ties with segmental areas of atelectasis and
hyperinflation. Pneumothorax is frequent
in MAS, occurring in 10–40% of cases [18,
33, 34] (Fig. 7). Therefore, when a neonatal
chest radiograph shows a pneumothorax and
diffuse lung disease, MAS should be strong-
ly considered. PIE is a rare complication and
should be suspected when small bubbly lu-
cencies develop within the lungs in a patient
with MAS.
Diffuse developmental disorder—The dif-
fuse developmental disorders are a rare group
of lung diseases that typically affect full-
term neonates. These disorders are caused
by abnormal development of the lung, lead-
ing to severe progressive respiratory failure
with a mortality rate of nearly 100% by age
2 months [35–37]. The three main diffuse
developmental disorders are acinar dyspla-
sia, congenital alveolar dysplasia, and alveo-
lar capillary dysplasia with misalignment of
pulmonary veins. Acinar dysplasia occurs be-
cause of arrest of lung development between
6 and 16 weeks’ gestation [38], congenital al-
veolar dysplasia occurs because of arrest of
lung development between 16 and 26 weeks’
gestation [39], and alveolar capillary dyspla-
sia with misalignment of pulmonary veins is
caused by abnormal development of the lung
architecture in which the pulmonary veins
develop adjacent to the pulmonary arteries,
rather than within the interlobular septa.
Acinar dysplasia is the most severe of
these conditions, because the lung is most
underdeveloped at the time of birth, con-
taining only airway structures and no alve-
oli. Patients with acinar dysplasia are typi-
cally born at full term with small lungs and
severe respiratory failure. Radiographs typ-
ically show low lung volumes with diffuse
opacity [40].

Congenital alveolar dysplasia also causes
severe progressive respiratory failure, al-
though affected patients typically survive
longer than patients with acinar dysplasia.
Underdeveloped alveoli are present in con-
genital alveolar dysplasia, although they have
thick alveolar septa, resulting in poor gas ex-
change. Affected neonates typically present
with progressive respiratory failure in the
first hours of life and frequently develop pul-
monary hypertension. Radiographs typically
show low lung volumes with diffuse opacity
and may show an enlarged main pulmonary
artery due to pulmonary hypertension [40].
Neonates with alveolar capillary dysplasia
with misalignment of pulmonary veins are
typically born at full term and develop severe
pulmonary hypertension and respiratory fail-
ure. Symptoms usually begin within the first
few days of life [40]. Radiographs typically
show low lung volumes with diffuse opacity
and enlarged main pulmonary artery due to
American Journal of Roentgenology 2018.210:964-975.
pulmonary hypertension [40].
Congenital surfactant dysfunction disor-
ders—The congenital surfactant dysfunction
disorders are caused by mutations in genes
involved in the production and metabolism
of surfactant. These include mutations in
the SFTPB gene, which normally produc-
es surfactant protein B; the SFTPC gene,
which normally produces surfactant protein
C; and the adenosine triphosphate–binding
cassette subfamily A member 3 (ABCA3)
gene, which normally produces the ABCA3
protein. Other rare congenital causes of sur-
factant dysfunction include thyroid tran-
scription factor–1 mutations, granulocyte-
macrophage colony-stimulating factor–Rα
mutations, and lysinuric protein intolerance
[41–44]. These mutations lead to impaired
clearance of surfactant, causing reduced
oxygen exchange. Bronchoalveolar lavage
shows periodic acid Schiff–positive materi-
al due to excessive surfactant and surfactant
metabolites within the alveoli. This is simi-
lar to acquired causes of pulmonary alveolar
proteinosis seen in older children and adults.
However, in these conditions, impaired sur-
factant clearance occurs because of an ac-
quired condition, such as production of anti–
granulocyte-macrophage colony-stimulating
factor autoantibodies, rather than because of
a genetic mutation, as in the congenital sur-
factant dysfunction disorders.
Neonates with congenital surfactant dys-
function disorders are usually born at full
term and have unexplained respiratory dis-
tress soon after birth. Chest radiographs typ-
968 AJR:210, May 2018
Liszewski and Lee
ically show diffuse hazy pulmonary opaci-
ties, similar to those seen in preterm patients
with SDD (Fig. 8). Unlike neonates with
SDD, children with these conditions are typ-
ically born at full term and their symptoms
do not improve. CT may be performed dur-
ing the workup for unexplained respiratory
distress and typically shows diffuse ground-
glass opacities and may also show inter-
lobular septal thickening in a crazy-paving
pattern (Fig. 8). These CT findings may be
similar to findings seen in older patients with
acquired pulmonary alveolar proteinosis.
Definitive diagnosis is based on genet-
ic testing and biopsy [40]. Mutations impair
pulmonary macrophages’ ability to clear sur-
factant, and biopsy in early infancy typically
shows pulmonary alveolar proteinosis with
diffuse alveolar hyperplasia and foamy mac-
rophages but no hyaline membranes [45, 46].
Congenital pulmonary lymphangiecta-
sia—Congenital pulmonary lymphangiecta-
sia is a rare cause of severe respiratory com-
promise in neonates characterized by dilated
pulmonary lymphatic channels and chylous
pleural effusions [47, 48]. Lymphangiecta-
sia may occur in neonates with genetic syn-
dromes, such as trisomy 21 and Noonan syn-
drome, or those with congenital heart disease
[49]. Historically, the condition has been de-
scribed as universally fatal, but improve-
ments in neonatal care have resulted in im-
proved outcomes, and patients with late-onset
disease have better outcomes [14, 48, 49].
Chest radiographs in congenital pulmonary
lymphangiectasia typically show diffuse inter-
Fig. 9—3-month-old girl born at 25 weeks’ gestation
with chronic lung disease of prematurity. Frontal
chest radiograph shows coarse bilateral pulmonary
opacities with hyperinflation and atelectasis within
right upper (arrow) and right middle (arrowhead)
lobes.
stitial opacity, pleural effusion, and hyperinfla-
tion in the neonatal period [14, 50]. CT findings
include interlobular septal thickening, ground-
glass opacity, and pleural effusions [14]. MRI
findings include T2-hyperintense interlobular
septal thickening and pleural effusions [51].
Among patients who survive beyond infancy,
interstitial opacities tend to decrease and hy-
perinflation increases [50]. The radiographic
findings of pulmonary lymphangiectasia are
somewhat nonspecific, and diagnosis can be es-
tablished by sampling the pleural effusion af-
ter a fatty meal, which shows chylous fluid [14].
Preterm and Full Term
The two main conditions that may cause
diffuse lung findings in both preterm and
full-term neonates are the alveolar growth
disorders and vascular congestion from car-
diac disease.
Alveolar growth disorders—Alveolar
growth disorders are different from the dif-
fuse developmental disorders because they
are not the result of a genetic defect in lung
development but are due to a superimposed
process [52]. This superimposed process may
occur during the prenatal or postnatal peri-
od and may affect neonates born preterm or
full term. This process can occur in utero;
in the neonatal period, because of a genetic
Fig. 10—2-day-old boy born at full term with
secondary pulmonary hypoplasia due to autosomal
recessive polycystic kidney disease. Frontal
radiograph of chest and abdomen shows protuberant
abdomen due to markedly enlarged kidneys and small
diffusely opacified lungs. (Courtesy of Taragin BH,
Soroka Hospital International, Beersheba, Israel)
 Neonatal Lung Disorders

or chromosomal defect that does not specifi-
cally cause a programmed lung disorder; or
because of congenital heart disease. The un-
derlying lung abnormality differs for each of
these conditions, although, in general, all con-
ditions result in decreased formation of alveo-
lar septa and enlarged alveoli and acini [40].
The most common alveolar growth disor-
der encountered in clinical practice is chron-
ic lung disease of prematurity (also known
as bronchopulmonary dysplasia). This condi-
tion first emerged in the 1960s when surviv-
al rates among premature infants with SDD
dramatically increased because of advances
in mechanical ventilation and oxygen thera-
py, but a subset of patients were noted to de-
velop a chronic pulmonary syndrome due to
traumatic effects of these therapies on the
immature lung. In 1967, Northway et al. [53]
first described this condition, defining four
stages of bronchopulmonary dysplasia. In
this original description, the diffuse granu-
American Journal of Roentgenology 2018.210:964-975.
Genetic or chromosomal defects that may
cause alveolar growth disorders include tri-
somy 21 and X-linked filamin-A mutation
[40]. Thirty-six percent of patients with tri-
somy 21 have underlying lung abnormali-
ties with characteristic imaging findings of
subpleural and peribronchial cysts, although
these are usually not evident until later in
childhood [55]. X-linked filamin-A gene mu-
tations cause diffuse pulmonary hyperinfla-
tion and enlarged main pulmonary arteries,
which may be identified at chest radiograph,
CT, or MRI.
Vascular congestion (cardiac disease)—Al-
though not truly a disorder of the lung, pulmo-
nary vascular congestion due to cardiac disease
is a common cause of diffuse lung findings on
chest radiographs. It is important to differenti-
ate pulmonary vascular congestion from a lung
disorder because the treatment differs. Pulmo-
nary vascular congestion may occur in preterm
or full-term neonates. For example, vascular
congestion due to a PDA is a frequent cause of
respiratory distress in preterm neonates. Neo-
nates with other congenital heart diseases may
be born at full term and develop pulmonary
vascular congestion in the first days of life.
A detailed description of the various con-
genital heart defects that may cause vascular
congestion is beyond the scope of this article. In

lar opacities of SDD are seen through day 3

of life (stage I) and are subsequently replaced
by nearly complete opacification of the lungs
due to necrosis and repair of alveolar and
bronchiolar epithelial cells during days 4–10
of life (stage II), followed by the development
of interstitial edema and fibrosis producing
small cystlike lucencies and hyperinflation at
days 10–20 of life (stage III), which continue
to increase through age 1 month (stage IV) A B
[53]. Changes in treatment strategies result-
ing from this original description, including
use of antenatal glucocorticoids, exogenous
surfactant, less-traumatic mechanical venti-
lation strategies, and lower concentrations of
supplemental oxygen, have reduced the fre-
quency of chronic lung disease of prematu-
rity and altered the radiographic features.
In modern practice, the classic progression
through the four stages of bronchopulmona-
ry dysplasia originally described by North-
way et al. is often not seen, though the final
radiographic appearance is often similar,
with chest radiographs showing coarse bi-
lateral pulmonary opacities with areas of at-
electasis, hyperinflation, and small cystlike
bubbly lucencies [54] (Fig. 9).
The most common alveolar growth dis- C D
order to occur in the prenatal period is sec- Fig. 11—Male neonate born at full term with respiratory distress due to right middle lobe congenital lobar
ondary pulmonary hypoplasia due to ol- overinflation.
A, Frontal chest radiograph obtained soon after birth shows opacification and overinflation of right middle lobe
igohydramnios, skeletal dysplasia, or a (asterisk).
space-occupying lesion. Imaging findings B, Frontal chest radiograph obtained at day 3 of life shows increased lucency and persistent overinflation of
in secondary pulmonary hypoplasia include right middle lobe (asterisk).
small lungs and may reveal the underlying C, Axial CT image in lung window shows right middle lobe overinflation (O) causing mass effect with bilateral
lower lobe compressive atelectasis (A) and leftward mediastinal shift.
cause (i.e., findings of skeletal dysplasia or D, Sagittal CT image in lung window shows right middle lobe overinflation (O) causing mass effect with right
underlying space-occupying lesion) (Fig. 10). upper and right lower lobe compressive atelectasis (A).

AJR:210, May 2018 969


general, vascular congestion due to cardiac dis-
ease appears on chest radiographs as increased
pulmonary vascular markings, often with an
enlarged cardiac silhouette. When interstitial
edema is present, chest radiographs may show
Kerley B lines, and CT may show smooth in-
terlobular septal thickening. Diffuse ground-
glass opacities and air bronchograms are char-
acteristic of alveolar edema. The most common
cause of vascular congestion in the preterm ne-
onate is a PDA, which often causes findings of
pulmonary vascular congestion after the first
few days of life when pulmonary vascular re-
sistance decreases, resulting in increased left-
to-right shunting [14] (Fig. 4). One of the most
common causes of increased pulmonary vas-
cular markings and enlarged cardiac silhouette
in a full-term neonate is a ventriculoseptal de-
fect, which causes pulmonary vascular conges-
tion due to a left-to-right shunt [56].
Focal Neonatal Lung Disorders
American Journal of Roentgenology 2018.210:964-975.
Several conditions affecting the lungs of
neonates can cause focal imaging findings.
In general, these conditions have more-spe-
cific radiographic findings than do the dif-
fuse disorders, and imaging plays a central
role in their diagnosis. Conditions in this cat-
egory include congenital lobar overinflation,
congenital pulmonary airway malformation,
and bronchopulmonary sequestration.
Congenital Lobar Overinflation
Congenital lobar overinflation, also known
as congenital lobar emphysema, is a condition
in which there is hyperexpansion of a lobe of
the lung, often resulting in mass effect on ad-
jacent structures. The cause of congenital lo-
bar overinflation is not completely under-
stood, although narrowing or weakness of a
lobar bronchus causing a check-valve mecha-
nism is often cited as a likely cause [57, 58]. In
this scenario, air enters the lobe during inspi-
ration but is unable to exit the lobe during ex-
piration, and there is progressive hyperexpan-
sion of the affected lobe. Histologic analysis
may show decreased or increased numbers of
alveoli (hypoalveolar and polyalveolar types,
respectively) [35]. Symptoms largely depend
on the degree of lobar hyperexpansion. A
mildly hyperexpanded lobe may be asymp-
tomatic and decrease in size with time; close
follow-up is warranted in these cases. How-
ever, progressive hyperexpansion of a lobe
can occur and cause significant, sometimes
life-threatening, symptoms. The treatment of
choice for symptomatic lesions is lobectomy.
Given the potential for progressive hyperex-
970 AJR:210, May 2018
Liszewski and Lee
pansion, close monitoring of imaging studies
and symptoms is essential.
Congenital lobar overinflation may be first
diagnosed at antenatal imaging or on chest ra-
diographs obtained in a neonate with symp-
toms. Findings at antenatal imaging reflect
fluid-trapping, akin to air-trapping, within the
affected lobe, because the fetus breathes fetal
fluid while in utero. Findings at prenatal ul-
trasound may include a hyperexpanded hy-
poechoic lobe, and prenatal MRI may show
a hyperexpanded hyperintense lobe [59, 60].
­Neonates with congenital lobar overinflation
often have chest radiographs showing retention
of fetal fluid within the affected lobe, because
there is delayed clearance of fluid from the af-
fected lobe in the immediate postnatal period
[58, 61] (Fig. 11). In the first hours after birth,
the fetal fluid eventually clears from the affect-
ed lobe and is replaced by air. The affected lobe
then shows progressive lucency and hyperex-
pansion, the severity of which is correlated
with the severity of symptoms (Fig. 11).
Congenital Pulmonary Airway Malformation
Congenital pulmonary airway malforma-
tions, previously known as congenital cystic
TABLE 1: Stocker Classification System of Congenital Pulmonary Airway
Malformations
Type General Characteristics
Type 0 Bilateral acinar dysgenesis or
­tracheobronchial dysplasia involving all
lobes
Incompatible with life and not typically
encountered in clinical practice
Type 1 One or more large cysts measuring > 2 cm
Type 2 One or more cysts < 2 cm
Type 3 Appear as solid at gross inspection
Composed of microcysts measuring < 5 mm
and visible only on microscopy
Type 4 Multiple large peripheral cysts
May be associated with pneumothorax and
lobar hyperexpansion
Often indistinguishable from type 1 lesions at Pneumothorax or lobar hyperexpansion may
gross inspection
Note—Table was created using the updated classification system described by Stocker et al. [92].
adenomatoid malformations, are congenital
lung lesions composed of abnormally formed
lung tissue with bronchial overgrowth and ar-
rested alveolar development [62, 63]. On gross
inspection, congenital pulmonary airway mal-
formations may appear as a cyst or cysts of var-
ious sizes or as a solid mass. Most congenital
pulmonary airway malformations have con-
ventional arterial supply from the pulmonary
artery and drainage to the pulmonary vein [64].
Communication with the bronchial tree may be
normal or abnormal [62, 63]. Most congenital
pulmonary airway malformations are confined
to one lobe of the lung [65].
In recent years, it has become clear that there
is overlap between congenital pulmonary air-
way malformations and other congenital lung
lesions [62, 63, 66–68]. This has resulted in
some controversy surrounding the classifica-
tion of congenital pulmonary airway malfor-
mations, although the modified Stocker classifi-
cation system remains the most widely used by
radiologists. First proposed in 1977 and modi-
fied in 2001, the modified Stocker classification
system [69, 70] describes five types of congeni-
tal pulmonary airway malformation (type 0 to
type 4), which are described in Table 1.
Neonatal Imaging Findings
Not typically imaged, because incompatible
with life
Chest radiograph: cystic structures in the
lung may initially be filled with fetal fluid and
subsequently become lucent
CT and MRI: thin-walled cyst or cysts that are
usually air-filled
Type 1: cysts > 2 cm
Type 2: cysts < 2 cm
Chest radiograph: solid focal opacity
CT and MRI: solid enhancing mass
Chest radiograph: large peripheral cystic
structures in the lung may initially be filled
with fetal fluid and subsequently become
lucent
CT and MRI: peripheral cysts which are
usually air-filled
be seen
Often indistinguishable from type 1 lesions
 Neonatal Lung Disorders

tions have revealed mutations in the DICER1

gene in up to 66% of pleuropulmonary blas-
tomas, and genetic testing is likely to play
an increasing role in the management of pa-
tients with these lesions in the future.

Bronchopulmonary Sequestration
Bronchopulmonary sequestration is a fo-
cal lung lesion composed of nonfunction-
ing lung tissue that is disconnected from
the bronchial tree and has a systemic arte-
rial supply [78]. Bronchopulmonary seques-
trations are traditionally subdivided into in-
tralobar and extralobar types. Intralobar
bronchopulmonary sequestrations share a
A B
visceral pleural covering with adjacent nor-
Fig. 12—Female neonate without symptoms born at full term. Congenital pulmonary airway malformation was
detected at prenatal ultrasound. mal lung, and most often have venous drain-
A, Frontal chest radiograph obtained at day 1 of life shows left upper lobe round opacity (arrow) with central age to the pulmonary vein [62–64]. Extralo-
cystic lucency (arrowhead). bar bronchopulmonary sequestrations have
B, Axial contrast-enhanced CT image in lung window shows left upper lobe lesion composed of multiple small
cysts, compatible with Stocker type 2 congenital pulmonary airway malformation. their own pleural covering, and venous drain-
age is most often to a systemic vein [62–64].
The nonfunctioning lung tissue within in-
American Journal of Roentgenology 2018.210:964-975.

Congenital pulmonary airway malforma-
tions are often first detected at fetal ultrasound
as heterogeneous hyperechoic lesions, which
may contain cysts of various sizes, depending
on the type [59]. Lesions may be further char-
acterized with fetal MRI, which shows the
pulmonary lesions as hyperintense to adjacent
lung on T2-weighted imaging, and cysts may
be seen [59]. After birth, chest radiographs
typically show a focal lesion within the lung
(Fig. 12), and imaging findings for each type
of congenital pulmonary airway malforma-
tion are described in Table 1. It is important to
recognize that cystic pleuropulmonary blasto-
ma, which is a rare primary neoplasm, can be
indistinguishable from types 1, 2, and 4 con-
genital pulmonary airway malformation on
imaging studies [65, 71].
Symptomatic congenital pulmonary air-
way malformations are currently treated
with resection. Management of asymptom-
atic congenital pulmonary airway malforma-
tions is more controversial. Some advocate
resection because of the risk of superinfec-
tion and small risk of associated malignan-
cy [72–76]. Others recommend conserva-
tive management given the low frequency of
these complications [77]. Recent investiga-
tralobar and extralobar bronchopulmonary
sequestrations often contains cystic regions
similar to congenital pulmonary airway mal-
formations, and the term “hybrid lesion” has
been used to describe this phenomenon [68].
Both types of bronchopulmonary sequestra-
tion typically occur in the lower thorax. Less
common locations for extralobar broncho-
pulmonary sequestration include below the
diaphragm or within the mediastinum.
Bronchopulmonary sequestration is of-
ten first detected at prenatal ultrasound as a
homogeneous hyperechoic mass, with Dop-
pler imaging showing an anomalous arteri-

A B C
Fig. 13—3-day-old girl with prenatal diagnosis of right lower lobe mass, found to have intrapulmonary bronchopulmonary sequestration.
A, Lateral radiograph shows opacity (asterisk) in right lower lobe.
B, Axial contrast-enhanced CT image shows anomalous artery (arrow) arising from descending aorta (A) and extending to right lower lobe sequestration.
C, Frontal 3D volume-rendered CT image shows anomalous artery (arrow) arising from descending aorta (A) and extending to right lower lobe sequestration. Three-
dimensional volume-rendered CT image better shows entire course and size of anomalous artery than does axial CT image.

AJR:210, May 2018 971


Fig. 14—3-day-old girl born at 27 weeks’ gestation
with surfactant deficiency disorder and worsening
respiratory failure due to bilateral pulmonary
interstitial emphysema. Frontal chest radiograph
shows hyperinflated lungs containing numerous
American Journal of Roentgenology 2018.210:964-975.
round lucencies that do not conform to shape of
alveoli and extend to periphery of lung.
al supply from the aorta [79]. Prenatal MRI
may be performed and typically shows a le-
sion that is hyperintense to the adjacent lung
on T2-weighted imaging, and anomalous ar-
terial supply from the aorta can sometimes
be visualized as a flow void arising from the
aorta [80]. The most common appearance of
bronchopulmonary sequestration on neona-
tal chest radiographs is a lower lobe opaci-
ty or mass, which is often indistinguishable
from congenital pulmonary airway malfor-
mation (Fig. 13). Intralobar bronchopulmo-
nary sequestrations often become lucent
as fetal lung fluid clears and air enters the
bronchopulmonary sequestration via pores
of Kohn and canals of Lambert. Extralobar
bronchopulmonary sequestrations remain
dense, because there is no communication
with the normal lung. Ultrasound may show
a systemic arterial supply from the descend-
ing thoracic or abdominal aorta, although
aerated lung may obscure this finding at ul-
trasound. Contrast-enhanced CT angiogra-
phy or MR angiography is often indicated to
better define the arterial and venous supply
and can be especially helpful for presurgical
planning [51, 64]. Intralobar bronchopulmo-
nary sequestration typically appears as a cys-
tic lung lesion with systemic arterial supply
and venous drainage to the left atrium (Fig.
13). Extralobar bronchopulmonary seques-
tration typically appears as a solid enhanc-
ing mass with systemic arterial supply and
systemic venous drainage [79].
972 AJR:210, May 2018
Liszewski and Lee
Bronchopulmonary sequestrations can ratory distress, temperature instability, and
lead to symptoms if superinfected. Symp- hypothermia [85]. There are several reports
tomatic bronchopulmonary sequestrations of group B streptococcal pneumonia associ-
are treated with resection. Treatment of ated with delayed presentation of right-sided
asymptomatic bronchopulmonary sequestra- congenital diaphragmatic hernia, although
tion is more controversial. Many recommend the cause of this association is not clear [86].
resection for intralobar bronchopulmona- The radiographic findings for neonatal
ry sequestration given the risk for superin- pneumonia are variable. Pulmonary opacities
fection [81, 82]. Arterial embolization is an can be focal but are more often diffuse and bi-
alternative to surgery that has been used in lateral [85]. Chest radiographs can show hazy
both intralobar and extralobar bronchopul- opacities similar to those associated with SDD,
monary sequestration [83, 84]. coarse irregular opacities similar to those as-
sociated with MAS, or reticular opacities simi-
Diffuse or Focal Neonatal Lung lar to those associated with transient tachypnea
Disorders of the newborn [85]. Pleural effusions are more
Some lung disorders affecting neonates often seen in neonatal pneumonia and can be a
can present as either diffuse or focal find- clue to the diagnosis. Because the clinical signs
ings on imaging studies. Conditions in this and symptoms and the radiographic findings
category include neonatal pneumonia, PIE, are nonspecific, the key to diagnosis is a high
and aspiration in the setting of a congenital index of suspicion. Affected patients are often
anomaly, such as a trachea-esophageal fistula treated empirically with antibiotics. Definitive
or esophageal bronchus. diagnosis is based on blood or respiratory cul-
ture, though cultures are often negative [87].
Neonatal Pneumonia
Neonatal pneumonia is defined as pulmo- Pulmonary Interstitial Emphysema
nary infection occurring within the first 28 PIE is an air leak phenomenon that occurs
days of life. Transmission of infection may because of rupture of the respiratory epitheli-
occur in utero, during birth, or after birth um, allowing air to dissect through the pulmo-
[14]. The most common pathogen is group nary interstitium [17]. PIE is most often bilat-
B Streptococcus species, which is transmit- eral, although it can be unilateral or confined
ted during vaginal delivery from colonized to one lobe. PIE most often occurs in neonates
mothers, although a variety of other bacteria with SDD undergoing mechanical ventilation,
and viruses may be the cause. Risk factors but can occasionally be seen in neonates with
for neonatal pneumonia include prolonged other conditions, including congenital dia-
rupture of membranes, prematurity, MAS, phragmatic hernia, MAS, and neonatal pneu-
and therapeutic cooling [14, 21–23]. The monia. Other air leak phenomena may occur
signs and symptoms of neonatal pneumonia with PIE, including pneumothorax, pneumo-
are often nonspecific and may include respi- mediastinum, and pneumoperitoneum.
A B
Fig. 15—Female neonate with acute respiratory distress on first feeding.
A, Frontal chest radiograph shows patchy bilateral pulmonary opacities due to aspiration.
B, Esophagram shows connection (asterisk) between trachea (T) and esophagus (E) consistent with H-type
tracheoesophageal fistula. Aspirated contrast material is also noted in right and left lungs.

On chest radiographs, PIE appears as mul-
tiple small round bubbly or nonbranching
linear lucencies that do not conform to the
shape of air bronchograms and extend to the
periphery of the lung [88, 89] (Fig. 14). Lu-
cencies represent air within the pulmonary
interstitium. Differentiating PIE from other
conditions on chest radiographs can some-
times be challenging. For example, chronic
lung disease of prematurity can have a simi-
lar radiographic appearance, because small
round areas of hyperexpanded lung may
mimic the appearance of interstitial air. PIE
and chronic lung disease can often be differ-
entiated by considering the time course and
reviewing prior imaging. PIE usually occurs
in the first week of life as an acute change
on radiographs accompanied by clinical de-
compensation, whereas chronic lung disease
tends to produce lucencies on radiographs
that slowly evolve over the first 3–4 weeks
of life. Occasionally, alveoli can rapidly ex-
American Journal of Roentgenology 2018.210:964-975.
pand after exogenous surfactant is adminis-
tered, producing an appearance that mimics
that of PIE [18] (Fig. 3). This can often be
differentiated from PIE by considering the
clinical scenario, because patients with PIE
typically experience worsening symptoms,
whereas patients typically improve with sur-
factant-mediated alveolar expansion [18].
Rarely, PIE may be localized to one lobe and
may mimic congenital lobar overinflation
or congenital pulmonary airway malforma-
tion. These conditions can most often be dif-
ferentiated by reviewing prior radiographs,
because PIE typically develops acutely dur-
ing the first week of life, whereas findings of
congenital lobar overinflation and congenital
pulmonary airway malformation are typical-
ly present at birth [17]. Though CT is almost
never necessary to diagnose PIE, pulmo-
nary interstitial air is easily identified on CT
images as lucencies surrounding the bron-
chovascular bundles, producing a line-and-
dot pattern [89–91]. When one detects PIE,
NICU staff should be notified immediately
so that they may modify the mechanical ven-
tilation to reduce barotrauma and mitigate
further air leak [89].
Aspiration Due to Congenital Anomaly
Aspiration is a rare cause of significant re-
spiratory symptoms in the neonate but can
occur in cases when an abnormal communi-
cation exists between the esophagus and the
airway. Three conditions where this may oc-
cur include H-type tracheoesophageal fistula
(TEF), proximal TEF with distal esophageal
AJR:210, May 2018 973
Neonatal Lung Disorders
atresia, and esophageal bronchus in which
an anomalous bronchus originates from the
esophagus. Patients with these rare condi-
tions typically present with acute respiratory
distress after the first feeding.
Radiographic findings in aspiration due
to one of these congenital anomalies in-
clude focal or diffuse pulmonary opacities
that acutely develop after feeding (Fig. 15).
In cases of proximal TEF with distal esopha-
geal atresia radiographs may show a malpo-
sitioned enteric tube with tip in high position
(above the fistula) or passing into the airway
(below the fistula). Definitive diagnosis of
TEF and esophageal bronchus is established
with esophagram (Fig. 15).
Conclusion
A variety of lung disorders commonly oc-
cur in neonates, and understanding the imag-
ing findings in in these conditions is essential
for optimal patient care. Although the imag-
ing findings in many neonatal lung diseases
overlap, one can use principles of pattern rec-
ognition described here to recommend ap-
propriate management strategies and arrive
at correct diagnoses.
References
1. Soboleski D, Theriault C, Acker A, Dagnone V,
Manson D. Unnecessary irradiation to non-tho-
racic structures during pediatric chest radiogra-
phy. Pediatr Radiol 2006; 36:22–25
2. Bader D, Datz H, Bartal G, et al. Unintentional
exposure of neonates to conventional radiography
in the neonatal intensive care units. J  Perinatol
2007; 27:579–585
3. Seibert JA, Morin RL. The standardized exposure
index for digital radiography: an opportunity for
optimization of radiation dose to the pediatric
population. Pediatr Radiol 2011; 41:573–581
4. Don S, Whiting BR, Rutz LJ, Apgar BK. New ex-
posure indicators for digital radiography simpli-
fied for radiologists and technologists. AJR 2012;
199:1337–1341
5. Puch-Kapst K, Juran R, Stoever B, Wauer RR. Radia-
tion exposure in 212 very low and extremely low birth
weight infants. Pediatrics 2009; 124:1556–1564
6. Smans K, Struelens L, Smet M, Bosmans H,
­Vanhavere F. Patient dose in neonatal units. Ra-
diat Prot Dosimetry 2008; 131:143–147
7. Makri T, Yakoumakis E, Papadopoulou D, et al.
Radiation risk assessment in neonatal radiograph-
ic examinations of the chest and abdomen: a clini-
cal and Monte Carlo dosimetry study. Phys Med
Biol 2006; 51:5023–5033
8. Goo HW, Drubach LA, Lee EY. Imaging techniques.
In: Coley BD, ed. Caffey’s pediatric diagnostic
­imaging. Philadelphia, PA: Elsevier, 2013:506–518
9. Lobo L, Antunes D. Chest CT in infants and chil-
dren. Eur J Radiol 2013; 82:1108–1117
10. Yu L, Bruesewitz MR, Thomas KB, Fletcher JG,
Kofler JM, McCollough CH. Optimal tube poten-
tial for radiation dose reduction in pediatric CT:
principles, clinical implementations, and pitfalls.
RadioGraphics 2011; 31:835–848
11. Coley BD. Chest sonography in children: current
indications, techniques, and imaging findings.
­Radiol Clin North Am 2011; 49:825–846
12. Higano NS, Fleck RJ, Spielberg DR, et al. Quanti-
fication of neonatal lung parenchymal density via
ultrashort echo time MRI with comparison to
CT. J Magn Reson Imaging 2017; 46:992–1000
13. Hahn AD, Higano NS, Walkup LL, et al. Pulmo-
nary MRI of neonates in the intensive care unit
using 3D ultrashort echo time and a small foot-
print MRI system. J Magn Reson Imaging 2017;
45:463–471
14. Cleveland RH, Rhein L. Newborn chest. In:
Cleveland RH, ed. Imaging in pediatric pulmon-
ology. New York, NY: Springer, 2012:81–97
15. Rodriguez R, Martin R, Fanaroff A. Respiratory
distress syndrome and its management. In: Fan-
aroff A, Martin R, eds. Fanaroff and Martin’s
neonatal-perinatal medicine: diseases of the fetus
and infant. St. Louis, MO: Mosby, 2002:1001–1011
16. Ueda T, Ikegami M, Jobe AH. Developmental
changes of sheep surfactant: in vivo function and
in vitro subtype conversion. J Appl Physiol 1985;
76:2701–2706
17. Agrons GA, Courtney SE, Stocker JT, Markowitz
RI. From the archives of the AFIP: lung disease in
premature neonates—radiologic-pathologic cor-
relation. RadioGraphics 2005; 25:1047–1073
18. Cleveland RH. A radiologic update on medical
diseases of the newborn chest. Pediatr Radiol
1995; 25:631–637
19. Arthur R. The neonatal chest X-ray. Paediatr
Respir Rev 2001; 2:311–323
20. Dinger J, Schwarze R, Rupprecht E. Radiological
changes after therapeutic use of surfactant in in-
fants with respiratory distress syndrome. Pediatr
Radiol 1997; 27:26–31
21. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO,
Inder TE, Davis PG. Cooling for newborns with
hypoxic ischaemic encephalopathy. Cochrane
Database Syst Rev 2013; CD003311
22. Eicher DJ, Wagner CL, Katikaneni LP, et al. Mod-
erate hypothermia in neonatal encephalopathy:
safety outcomes. Pediatr Neurol 2005; 32:18–24
23. Azzopardi D, Brocklehurst P, Edwards D, et al.
The TOBY Study: whole body hypothermia for
the treatment of perinatal asphyxial encephalopa-
thy—a randomised controlled trial. BMC Pediatr
2008; 8:17
24. van Houten J, Long W, Mullett M, et al. Pulmo-

nary hemorrhage in premature infants after treat-
ment with synthetic surfactant: an autopsy evalua-
tion. The American Exosurf Neonatal Study
Group I, and the Canadian Exosurf Neonatal
Study Group. J Pediatr 1992; 120:S40–S44
25. Garland J, Buck R, Weinberg M. Pulmonary hem-
orrhage risk in infants with a clinically diagnosed
patent ductus arteriosus: a retrospective cohort
study. Pediatrics 1994; 94:719–723
26. Alfaleh K, Smyth JA, Roberts RS, Solimano A,
Asztalos EV, Schmidt B. Prevention and 18-month
outcomes of serious pulmonary hemorrhage in
extremely low birth weight infants: results from
the trial of indomethacin prophylaxis in preterms.
Pediatrics 2008; 121:e233–e238
27. Olver RE, Ramsden CA, Strang LB, Walters DV.
The role of amiloride-blockable sodium transport
in adrenaline-induced lung liquid reabsorption in
the fetal lamb. J Physiol 1986; 376:321–340
28. Niisato N, Ito Y, Marunaka Y. cAMP stimulates
Na+ transport in rat fetal pneumocyte: involve-
ment of a PTK- but not a PKA-dependent path-
American Journal of Roentgenology 2018.210:964-975.
way. Am J Physiol 1999; 277:L727–L736
29. Norlin A, Folkesson HG. Ca2+-dependent stimula-
tion of alveolar fluid clearance in near-term fetal
guinea pigs. Am J Physiol Lung Cell Mol Physiol
2002; 282:L642–L649
30. O’Brodovich H, Hannam V, Seear M, Mullen JB.
Amiloride impairs lung water clearance in new-
born guinea pigs. J Appl Physiol (1985) 1990;
68:1758–1762
31. Morrison JJ, Rennie JM, Milton PJ. Neonatal re-
spiratory morbidity and mode of delivery at term:
influence of timing of elective caesarean section.
Br J Obstet Gynaecol 1995; 102:101–106
32. Lee J, Romero R, Lee KA, et al. Meconium
aspiration syndrome: a role for fetal systemic in-
flammation. Am J Obstet Gynecol 2016; 214:366.
e1–366.e9
33. Dargaville PA, Copnell B. The epidemiology of
meconium aspiration syndrome: incidence, risk
factors, therapies, and outcome. Pediatrics 2006;
117:1712–1721
34. Yeh TF, Harris V, Srinivasan G, Lilien L, Pyati S,
Pildes RS. Roentgenographic findings in infants
with meconium aspiration syndrome. JAMA
1979; 242:60–63
35. Al-Hathlol K, Phillips S, Seshia MK, Casiro O,
­Alvaro RE, Rigatto H. Alveolar capillary dysplasia:
report of a case of prolonged life without extracor-
poreal membrane oxygenation (ECMO) and review
of the literature. Early Hum Dev 2000; 57:85–94
36. Michalsky MP, Arca MJ, Groenman F, Hammond
S, Tibboel D, Caniano DA. Alveolar capillary dys-
plasia: a logical approach to a fatal dis-
ease. J Pediatr Surg 2005; 40:1100–1105
37. Hugosson CO, Salama HM, Al-Dayel F, ­K houmais
N, Kattan AH. Primary alveolar capillary dyspla-
974 AJR:210, May 2018
Liszewski and Lee
sia (acinar dysplasia) and surfactant protein B de-
ficiency: a clinical, radiological and pathological
study. Pediatr Radiol 2005; 35:311–316
38. Davidson LA, Batman P, Fagan DG. Congenital
acinar dysplasia: a rare cause of pulmonary hypo-
plasia. Histopathology 1998; 32:57–59
39. Hegde S, Pomplun S, Hannam S, Greenough A.
Nonfatal congenital alveolar dysplasia due to abnor-
malities of NO synthase isoforms. Acta P­aediatr
2007; 96:1248–1250
40. Lee EY, Cleveland RH, Langston C. Interstitial
lung disease in infants and children: new classifi-
cation system with emphasis on clinical, imaging,
and pathologic correlation. In: Cleveland RH, ed.
Imaging in pediatric pulmonology. New York,
NY: Springer, 2011:99–154
41. Yonker LM, Kinane TB. Pediatric interstitial lung
disease: thyroid transcription factor-1 mutations and
their phenotype potpourri. Chest 2013; 144:728–730
42. Greenhill SR, Kotton DN. Pulmonary alveolar
proteinosis: a bench-to-bedside story of granulo-
cyte-macrophage colony-stimulating factor dys-
function. Chest 2009; 136:571–577
43. Parto K, Svedstrom E, Majurin ML, Harkonen R,
Simell O. Pulmonary manifestations in lysinuric
protein intolerance. Chest 1993; 104:1176–1182
44. Valimahamed-Mitha S, Berteloot L, Ducoin H,
Ottolenghi C, de Lonlay P, de Blic J. Lung in-
volvement in children with lysinuric protein intol-
erance. J Inherit Metab Dis 2015; 38:257–263
45. Guillerman RP, Brody AS. Contemporary per-
spectives on pediatric diffuse lung disease. Radiol
Clin North Am 2011; 49:847–868
46. Wang T, Lazar CA, Fishbein MC, Lynch JP 3rd.
Pulmonary alveolar proteinosis. Semin Respir
Crit Care Med 2012; 33:498–508
47. Esther CR Jr, Barker PM. Pulmonary lymphangi-
ectasia: diagnosis and clinical course. Pediatr
Pulmonol 2004; 38:308–313
48. Malone LJ, Fenton LZ, Weinman JP, Anagnost MR,
Browne LP. Pediatric lymphangiectasia: an imaging
spectrum. Pediatr Radiol 2015; 45:562–569
49. Yao LC, Testini C, Tvorogov D, et al. Pulmonary
lymphangiectasia resulting from vascular endo-
thelial growth factor-C overexpression during a
critical period. Circ Res 2014; 114:806–822
50. Chung CJ, Fordham LA, Barker P, Cooper LL.
Children with congenital pulmonary lymphangi-
ectasia: after infancy. AJR 1999; 173:1583–1588
51. Liszewski MC, Hersman FW, Altes TA, et al.
Magnetic resonance imaging of pediatric lung pa-
renchyma, airways, vasculature, ventilation, and
perfusion: state of the art. Radiol Clin North Am
2013; 51:555–582
52. Lee EY. Interstitial lung disease in infants: new
classification system, imaging technique, clinical
presentation and imaging findings. Pediatr Radiol
2013; 43:3–13; quiz, 128–129
53. Northway WH Jr, Rosan RC, Porter DY. Pulmo-
nary disease following respirator therapy of hya-
line-membrane disease: bronchopulmonary dys-
plasia. N Engl J Med 1967; 276:357–368
54. Swischuk LE, Shetty BP, John SD. The lungs in
immature infants: how important is surfactant
therapy in preventing chronic lung problems?
­Pediatr Radiol 1996; 26:508–511
55. Biko DM, Schwartz M, Anupindi SA, Altes TA.
Subpleural lung cysts in Down syndrome: preva-
lence and association with coexisting diagnoses.
Pediatr Radiol 2008; 38:280–284
56. CulhAm J, Mawson J. Chest radiography in pedi-
atric cardiovascular disease. In: Coley B, ed.
Caffey’s pediatric diagnostic imaging. Philadel-
phia, PA: Elsevier, 2013:684–688
57. Chow J, Chung E, Colin A, Cleveland R, Sawicki
G. Focal lung disease. In: Cleveland R, ed. Imag-
ing in pediatric pulmonology. New York, NY:
Springer, 2012:193–248
58. Lee E. Congenital lung masses. In: Cleveland R,
ed. Imaging in pediatric pulmonology. New York,
NY: Springer, 2012:31–38
59. Alamo L, Gudinchet F, Reinberg O, et al. Prenatal
diagnosis of congenital lung malformations.
P­ediatr Radiol 2012; 42:273–283
60. Pacharn P, Kline-Fath B, Calvo-Garcia M, et al.
Congenital lung lesions: prenatal MRI and post-
natal findings. Pediatr Radiol 2013; 43:1136–1143
61. Cleveland RH, Weber B. Retained fetal lung liq-
uid in congenital lobar emphysema: a possible
predictor of polyalveolar lobe. Pediatr Radiol
1993; 23:291–295
62. Epelman M, Daltro P, Soto G, Ferrari CM, Lee
EY. Congenital lung anomalies. In: Coley B, ed.
Caffey’s pediatric diagnostic imaging. Philadel-
phia, PA: Elsevier, 2013:550–566
63. Lee EY, Dorkin H, Vargas SO. Congenital pulmo-
nary malformations in pediatric patients: review
and update on etiology, classification, and imaging
findings. Radiol Clin North Am 2011; 49:921–948
64. Lee EY, Boiselle PM, Cleveland RH. Multidetec-
tor CT evaluation of congenital lung anomalies.
Radiology 2008; 247:632–648
65. Stocker JT. Cystic lung disease in infants and chil-
dren. Fetal Pediatr Pathol 2009; 28:155–184
66. Langston C. New concepts in the pathology of
congenital lung malformations. Semin Pediatr
Surg 2003; 12:17–37
67. Holder PD, Langston C. Intralobar pulmonary se-
questration (a nonentity?). Pediatr Pulmonol
1986; 2:147–153
68. Riedlinger WF, Vargas SO, Jennings RW, et al.
Bronchial atresia is common to extralobar seques-
tration, intralobar sequestration, congenital cystic
adenomatoid malformation, and lobar emphyse-
ma. Pediatr Dev Pathol 2006; 9:361–373
69. Stocker JT, Madewell JE, Drake RM. Congenital

cystic adenomatoid malformation of the lung:
classification and morphologic spectrum. Hum
Pathol 1977; 8:155–171
70. Stocker J. The respiratory tract. In: Stocker JT,
Dehner LP, Husain AN, eds. Stocker & Dehner’s
pediatric pathology. Philadelphia, PA: Lippin-
cott, Williams & Wilkins, 2001:466–473
71. Priest JR, Williams GM, Hill DA, Dehner LP, Jaffe
A. Pulmonary cysts in early childhood and the risk
of malignancy. Pediatr Pulmonol 2009; 44:14–30
72. MacSweeney F, Papagiannopoulos K, Goldstraw
P, Sheppard MN, Corrin B, Nicholson AG. An
assessment of the expanded classification of con-
genital cystic adenomatoid malformations and
their relationship to malignant transformation.
Am J Surg Pathol 2003; 27:1139–1146
73. d’Agostino S, Bonoldi E, Dante S, Meli S,
­Cappellari F, Musi L. Embryonal rhabdomyosar-
coma of the lung arising in cystic adenomatoid
malformation: case report and review of the litera-
ture. J Pediatr Surg 1997; 32:1381–1383
74. Domizio P, Liesner RJ, Dicks-Mireaux C, Risdon
American Journal of Roentgenology 2018.210:964-975.
RA. Malignant mesenchymoma associated with a
congenital lung cyst in a child: case report and review
of the literature. Pediatr Pathol 1990; 10:785–797
75. Özcan C, Çelik A, Ural Z, Veral A, Kandiloğlu G,
Balik E. Primary pulmonary rhabdomyosarcoma
arising within cystic adenomatoid malformation:
a case report and review of the literature. J Pediatr
Surg 2001; 36:1062–1065
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Neonatal Lung Disorders
76. Federici S, Domenichelli V, Tani G, et al. Pleuro-
pulmonary blastoma in congenital cystic adeno-
matoid malformation: report of a case. Eur  J
­Pediatr Surg 2001; 11:196–199
77. Burge D, Wheeler R. Increasing incidence of de-
tection of congenital lung lesions. (letter) Pediatr
Pulmonol 2010; 45:103; author reply, 104
78. Pryce DM. Lower accessory pulmonary artery
with intralobar sequestration of lung; a report of
seven cases. J Pathol Bacteriol 1946; 58:457–467
79. Epelman M, Kreiger PA, Servaes S, Victoria T,
Hellinger JC. Current imaging of prenatally diag-
nosed congenital lung lesions. Semin Ultrasound
CT MR 2010; 31:141–157
80. Cannie M, Jani J, De Keyzer F, et al. Magnetic
resonance imaging of the fetal lung: a pictorial es-
say. Eur Radiol 2008; 18:1364–1374
81. Eber E. Antenatal diagnosis of congenital thoracic
malformations: early surgery, late surgery, or no sur-
gery? Semin Respir Crit Care Med 2007; 28:355–366
82. Laje P, Liechty KW. Postnatal management and
outcome of prenatally diagnosed lung lesions.
Prenat Diagn 2008; 28:612–618
83. Lee BS, Kim JT, Kim EA, et al. Neonatal pulmo-
nary sequestration: clinical experience with tran-
sumbilical arterial embolization. Pediatr ­Pulmonol
2008; 43:404–413
84. Yeh CN, Wang JN, Tsai YC, Yao CT, Lin CS, Wu
JM. Coil embolization of pulmonary sequestra-
tion in two infants: a safe alternative management.
Acta Paediatr Taiwan 2006; 47:88–91
85. Haney PJ, Bohlman M, Sun CC. Radiographic
findings in neonatal pneumonia. AJR 1984;
143:23–26
86. Strunk T, Simmer K, Kikiros C, Patole S. Late-
onset right-sided diaphragmatic hernia in neo-
nates: case report and review of the literature.
Eur J Pediatr 2007; 166:521–526
87. Webber S, Wilkinson AR, Lindsell D, Hope PL,
Dobson SR, Isaacs D. Neonatal pneumonia. Arch
Dis Child 1990; 65:207–211
88. Boothroyd AE, Barson AJ. Pulmonary interstitial
emphysema: a radiological and pathological cor-
relation. Pediatr Radiol 1988; 18:194–199
89. Donnelly LF, Frush DP. Localized radiolucent
chest lesions in neonates: causes and differentia-
tion. AJR 1999; 172:1651–1658
90. Donnelly LF, Lucaya J, Ozelame V, et al. CT find-
ings and temporal course of persistent pulmonary
interstitial emphysema in neonates: a multiinstitu-
tional study. AJR 2003; 180:1129–1133
91. Jabra AA, Fishman EK, Shehata BM, Perlman EJ.
Localized persistent pulmonary interstitial em-
physema: CT findings with radiographic-patho-
logic correlation. AJR 1997; 169:1381–1384
92. Stocker J, Mani H, Husain AN. The respiratory
tract. In: Stocker JT, Dehner LP, Husain AN, eds.
Stocker & Dehner’s pediatric pathology, 3rd edi-
tion. Philadelphia, PA: Lippincott, Williams &
Wilkins, 2011:441–515