YJPSU-59564; No of Pages 4

Journal of Pediatric Surgery xxx (xxxx) xxx

Contents lists available at ScienceDirect

Journal of Pediatric Surgery

journal homepage: www.elsevier.com/locate/jpedsurg

Accuracy of prenatal and postnatal imaging for management of

congenital lung malformations
Candace C. Style, MD a,b, Amy R. Mehollin-Ray a,c, Mariatu A Verla, MD a,b, Oluyinka O. Olutoye, MD, PhD a,b,d,
Patricio E. Lau, MD b, Brittany L. Johnson, MD a,b, Alice King, MD a,b,
Sundeep G. Keswani, MD a,b, Timothy C. Lee, MD a,b,⁎
a
Texas Children's Fetal Center, Baylor College of Medicine, Houston, TX
b
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX
c
Department of Radiology, Baylor College of Medicine, Houston, TX
d
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX

a r t i c l e i n f o a b s t r a c t

Article history: Purpose: The purpose of this study was to compare the accuracy of prenatal and postnatal imaging modalities for
Received 20 January 2020 evaluation and management of congenital lung malformations (CLMs).
Accepted 25 January 2020 Methods: A retrospective review was performed of all fetuses evaluated for a CLM between December 2001 and
Available online xxxx January 2018. Pre and postnatal imaging findings, operative treatment, and patient outcomes were collected.
Patients were included in analysis if they had fetal imaging (US and/or fetal MRI), a postnatal chest CT, and sur-
Key words:
gical pathology.
CPAM
Congenital lung malformation
Results: Over the study period, we identified 157 patients with prenatal imaging that also had a follow-up with
Chest CT postnatal chest CT at a median age of 2.1 [1.4, 3.2] months. Of these, 75% (n = 117) had surgical resection. Diag-
Fetal MRI nostic accuracy (DA) for localization of unilobar lesions was 100% for pre- and postnatal imaging and 97% vs 98%
Fetal imaging for multilobar disease, respectively. On comparison for identification of aberrant vasculature and pathology pre-
diction, pre- and postnatal imaging DAs were similar. However, postnatal CT had the highest specificity for diag-
nosing lesions overall (p b 0.05).
Conclusion: Prenatal imaging provides valuable information for counseling and possible fetal intervention. How-
ever, this study suggests that postnatal CT scan continues to provide important information for preoperative
counseling and surgical management.
Type of study: Retrospective study.
Level of evidence: Level IV.
© 2020 Elsevier Inc. All rights reserved.

The diagnosis and imaging of congenital lung malformations
(CLMs), which represent a spectrum of developmental abnormalities
of the pulmonary vasculature, bronchial tree, or foregut [1,2], have
evolved since first reported by Ch'In and Tang in 1949 [3]. Historically,
these lesions were typically diagnosed postnatally and classified by ap-
pearance on chest x-ray; but with the advent of computed topography
(CT), chest CT scans quickly became the gold standard of imaging for
CLMs. Currently, prenatal imaging and diagnosis have evolved and the
use of fetal ultrasound (US) has increased the incidence of diagnosis of
thoracic fetal malformations, with CLMs now commonly diagnosed
between 18 and 20 weeks of gestation [4,5].
With the continued advances of maternal–fetal medicine, prenatal
imaging, including fetal magnetic resonance imaging (MRI), is now
⁎ Corresponding author at: Texas Children's Fetal Center, 6701 Fannin Street, Houston,
TX 77030. Tel.: +1 832 822 3147.
E-mail address: timlee@bcm.edu (T.C. Lee).
available at many institutions for evaluation of CLMs. Enhancement in
ultrasound imaging quality aided by MRI has improved the ability to
not only diagnose but to further characterize lung lesions [2,6]. Using
these modalities, specific features can be used to determine high risk
lesions and predict pathologic variants, including bronchopulmonary
sequestrations, bronchogenic cysts, bronchial atresia, and congenital
pulmonary airway malformations (CPAMs), with increasing accuracy
to aid in postnatal care and management [7,8]. In this patient popula-
tion, rarely is fetal or early neonatal intervention required; thus, the
vast majority will be reevaluated as infants with a CT scan to further de-
fine the lesion and assess for elective operative intervention.
Given the improvement in prenatal evaluation and imaging qual-
ity, particularly with the incorporation of fetal MRI, use of prenatal
imaging begs the question of whether CT remains necessary to accu-
rately diagnose and determine postnatal operative management of
CLMs. Specifically, with the current concerns of radiation dosage in
the pediatric population, the use of ionizing radiation should only

https://doi.org/10.1016/j.jpedsurg.2020.01.020
0022-3468/© 2020 Elsevier Inc. All rights reserved.

Please cite this article as: C.C. Style, A.R. Mehollin-Ray, M.A. Verla, et al., Accuracy of prenatal and postnatal imaging for management of congenital
lung malformations, Journal of Pediatric Surgery, https://doi.org/10.1016/j.jpedsurg.2020.01.020
2 C.C. Style et al. / Journal of Pediatric Surgery xxx (xxxx) xxx
be performed when absolutely necessary to provide clinical informa-
tion to aid in medical decision making. There have been a number of
studies that have demonstrated the increased incidence of leukemia
and central nervous system tumors when associated with ionizing
radiation in the pediatric population [9,10]. The hypothesis for this
study was that CT scan in the postnatal period continues to be neces-
sary to provide imaging information for surgical decision making.
Therefore, the purpose of this study was to assess the accuracy of
prenatal and postnatal imaging modalities for evaluation and man-
agement of CLMs.
1. Methods
1.1. Data collection
Permission for this study was obtained from the Baylor College of
Medicine Institutional Review Board (H-40178). A retrospective re-
view was performed of a prospectively collected dataset of all fetuses
evaluated for a congenital lung malformation between July 2001 and
January 2018 at our institution. Prenatal imaging findings, postnatal
imaging findings, operative treatment, and lung lesion pathology
were collected. Prenatal data included maternal and fetal demo-
graphics, gestational age at diagnosis, gestational age at birth, and
birth weight. Imaging features from ultrasound and ultrafast fetal
magnetic resonance imaging included lesion location, lesion size in-
cluding the congenital pulmonary airway malformation (CPAM)–
volume ratio (CVR) measurements, sonographic appearance (solid
vs cystic), presence of an anomalous systemic blood supply, medias-
tinal shift, findings of other anomalies, and fetal symptoms including
polyhydramnios, fetal hydrops, or cardiac failure. CVR was calculated
as previously described [11].
1.2. Inclusion criteria
The clinical data of neonates with a diagnosis of a left- or right-sided
lung lesion were reviewed. Patient data were included in this study if
they were evaluated and found to have a lung lesion in the fetal period,
and inborn at our institution with at least one year of postnatal follow-
up. Patients that did not undergo a postnatal chest CT and have surgical
pathology were tallied but excluded from statistical analysis.
1.3. Prenatal imaging data
All infants were diagnosed via ultrasonography and underwent a
subsequent fetal MRI. Ultrasound and fetal MRIs were interpreted by
pediatric radiologists trained in fetal imaging at the time of the study.
Ultrasound and ultrafast fetal MRI techniques were performed as previ-
ously described [8]. The data were retrieved from the final imaging re-
port. Data from US and fetal MRI were combined for prediction of final
pathology and management.
1.4. Postnatal imaging and management
For infants with CLM, a postnatal chest CT scan is routinely obtained
within the two months of life at an outpatient follow-up visit. All CT
scan data used were interpreted by a trained pediatric radiologist. Re-
section was offered to all children who were symptomatic owing to
the lung malformation. For the children with an asymptomatic lesion,
indications for resection were the presence of an anomalous arterial
blood supply (leading to aortopulmonary shunt), a lesion that involved
a significant portion of a lung lobe (generally N 40%), and lesions that
showed increasing size or imaging characteristics concerning for possi-
ble malignancy. If the lesion appeared to be a segmental bronchial atre-
sia and occupied less than 20% of the lobe, families were counseled with
the option of observation. All children represented in this cohort
underwent elective resection with surgical pathology.
Please cite this article as: C.C. Style, A.R. Mehollin-Ray, M.A. Verla, et al., Accuracy of prenatal and postnatal imaging for management of congenital
lung malformations, Journal of Pediatric Surgery, https://doi.org/10.1016/j.jpedsurg.2020.01.020
1.5. Statistical analyses
Diagnostic imaging accuracy of lesion location, type, and presence of
a blood supply was tested between the prenatal imaging, postnatal im-
aging and surgical pathology. The postnatal surgical findings and
pathology results were considered the definitive diagnosis. Estimates
of sensitivity, specificity, accuracy, positive predictive value (PPV), and
negative predictive value (NPV) were calculated and conducted accord-
ing to the standards for reporting diagnostic accuracy study guidelines
[12]. Confidence intervals were generated using receiver operator
characteristic (ROC) curve analysis. Student's t-test, chi-square and
Mann–Whitney U test were used for comparisons based on variable
type and distribution, and results are presented as the median value
and interquartile range or mean and standard deviation. A p-value of
b 0.05 and 95% CI were considered significant. All statistical analysis
was performed using IBM Statistical Package for Social Sciences (IBM
SPSS version 25, NY, USA).
2. Results
2.1. Clinical and demographic data
A total of 242 fetuses were evaluated prenatally. Of these, 157 neo-
nates were inborn, underwent a fetal center evaluation with additional
prenatal imaging and had at a postnatal follow-up. Left-sided CLMs
accounted for 59% (n = 93/157) of the population with 48% of the
male sex (n = 76/157, Table 1). Mean age at diagnosis and fetal center
referral was 21.4 ± 4.2 weeks of gestation. Of the 157 evaluated, the
majority (86%, n = 135) were classified as low risk lesions (defined as
CVR b 1.6) with a median CVR of 0.7 [0.25, 1.2]. On postnatal follow-
up, children had a chest CT scan at a median age of 2.1 [1.4, 3.2] months.
Based on the evaluation and surgeon recommendation, 117 went on to
have surgical resection with definitive pathology results. Seven lesions
were no longer visible on CT scan, and 33 are continuing to be observed.
Overall cohort survival was 100%.
2.2. Comparison of fetal and postnatal imaging in the CLM cohort
2.2.1. Prenatal imaging
All patients evaluated underwent fetal US and the majority
(90%, n = 141/157) underwent a subsequent fetal MRI to further char-
acterize the lesion. Mean age at fetal MRI was 26.4 ± 4.7 weeks, with
75% (n = 106/141) occurring in the second trimester and 25% (n =
35/141) occurring in the third trimester. Of the patients who had a sur-
gical resection and pathologic specimen, 46% (n = 54/117) of fetuses
were found to have a systemic blood supply on US, in comparison to
39% (n = 46/117) on MRI in which eight vessels were unable to be de-
finitively identified solely by MRI. Most (n = 80) were characterized as
a cystic lesion (macro and/or micro), while 32% were identified as solid
lesion. Based on prenatal imaging characteristics, pathology was varied
with 54% being either bronchial atresia or CPAM (n = 63), 39%
bronchopulmonary sequestrations (n = 46), 5% congenital lobar em-
physema (n = 6), and two bronchogenic cysts (1%).
Table 1
Cohort demographics characteristics.
Left lung CLM 59% (93/157)
Right lung CLM 41% (63/157)
Male 48% (76/157)
Female 52% (82/157)
Gestational Age at Diagnosis (weeks) 21.4 ± 4.2
Gestational age at MRI, weeks 26.4 ± 4.7
Median age at postnatal CT scan [interquartile range] 2.1 [1.4, 3.2]
Elective Resection 75% (117/157)
Survival 100%
 C.C. Style et al. / Journal of Pediatric Surgery xxx (xxxx) xxx
2.2.2. Postnatal imaging
In comparison, of those with a persistent lesion on postnatal CT scan,
50 (43%) were found to have a systemic arterial supply. Sequestrations
accounted for 45% of lesion (n = 53), followed by bronchial atresia or
CPAM at 55% (n = 65, Fig. 1). The primary location of the lesion (side
and lobe) was accurately diagnosed both prenatally and postnatally
(100% accuracy); however, in 7% (n = 8), CT scan delineated additional
lobar involvement, also noted with surgical pathology (98% diagnostic
accuracy for multilobar disease on CT scan).
2.2.3. Diagnostic accuracy
Diagnostic accuracy (DA) was evaluated for both fetal imaging and
postnatal CT compared to final pathology for the 117 patients that
underwent elective resection (See Table 2). US & fetal MRI had similar
accuracy for detecting the presence of a systemic vessel when compared
to postnatal CT. Using McNemar chi-square analysis to analyze the dif-
ference in diagnostic outcomes, postnatal CT had the highest sensitivity
compared to prenatal imaging for diagnosing lesions overall (93% vs
83%, p b 0.01). When looking at congenital lobar emphysema, CT scan
had a 100% PPV versus 60% with Fetal MRI/Fetal US.
3. Discussion
Imaging quality in both fetal ultrasound and MRI has drastically
improved in the past several decades, and several studies have shown
increasing diagnostic accuracy utilizing either modality for prediction
of postnatal outcomes and pathology [6,8,13]. In spite of this, there is a
paucity of data evaluating a comparison of prenatal imaging versus
postnatal imaging, particularly in comparison to the gold standard of
imaging for lung lesions, CT scans. This question is of particular rele-
vance with the data concerning CT scan ionizing radiation and develop-
ment of leukemia and central nervous system tumors in the pediatric
population. In a perfect world, it would be desirable to limit any postna-
tal CT imaging if the information from the prenatal imaging was accu-
rate and sufficient. In this study, we sought to evaluate the diagnostic
accuracy of prenatal imaging (US/MRI) and a postnatal CT using final
pathology as the gold standard to determine if prenatal imaging alone
can or should be used for operative planning/counseling in the early
infant setting. We found that although the diagnostic accuracy is indeed
high when evaluating prenatal imaging and similar to postnatal
Distribution of Pathology Prediction by Imaging Type
70
65
63
60
Number of histologic variant
50
40
30
20
10
0
BA/CPAM
Fig. 1. Comparison of imaging of cystic vs solid lesions predicted pathology to final pathology. BA/CPAM=Bronchial Atresia/Congenital Pulmonary Airway Malformation; CLE=Congenital
Lobar Emphysema.
Please cite this article as: C.C. Style, A.R. Mehollin-Ray, M.A. Verla, et al., Accuracy of prenatal and postnatal imaging for management of congenital
lung malformations, Journal of Pediatric Surgery, https://doi.org/10.1016/j.jpedsurg.2020.01.020
3
imaging, CT scan continues to have a slightly higher concordance to
post-surgical pathology.
Our study highlights the increasing accuracy of prenatal ultrasound
and MRI particularly when combined to accurately predict both the
size and pathology of the lesion. In the initial diagnostic period prena-
tally, size is arguably the more important feature given that larger
lesions often cause lung compression, severe cardiomediastinal shift,
and fetal hydrops which may result in fetal or early postnatal interven-
tion. The routine use of advanced imaging is controversial with CLMs;
and while not all lung lesions will necessitate additional imaging, it is
often difficult to correlate final pathology and outcome prediction by
ultrasound alone [14]. For this reason, magnetic resonance imaging
(MRI) is used as adjunct imaging. MRI enables quantification of the
congenital lesion size, total fetal lung volumes (to assess pulmonary hy-
poplasia), and cardiomediastinal shift [15–17]. This can be very advan-
tageous when paired with a US providing exquisite anatomic and
pathologic detail. Of particular importance in lung masses, compressed
lung can still be viewed on MRI allowing for visualization of distinct
the lobar anatomy.
Although the diagnostic accuracy is indeed high when evaluating pre-
natal imaging, in this study CT scan had a slightly higher concordance to
post-surgical pathology. Data are limited comparing imaging techniques;
however, recently a similar study from Mon et al. was the first to evaluate
the diagnostic accuracy of prenatal imaging and postnatal CT in compari-
son to final pathology [18]. Their study evaluated ultrasound and MRI sep-
arately, and found that CT was superior in predicting histology and the
presence of aberrant vasculature to both US and MRI alone. We also
found that, while detecting the presence of a systemic vessel was similar,
CT scan had a slightly higher sensitivity and positive predictive value for
histologic type than prenatal imaging. Furthermore, we know that the
natural history of a lung lesion is varied and may change over time. Le-
sions tend to grow rapidly between 18 and 26 weeks of gestation, but
will often shrink in mid-to-late gestation resulting in the disappearance
of lesions [4,19] . In this study, there were 7 patients who had regression
of their lung lesion, thereby necessitating no further surgical manage-
ment. Additionally, lesions may also continue to grow postnatally and,
while rare, there is the b1% of malignancy for all CLMs [20,21]. Taking
these into consideration, we would continue to recommend use of post-
natal CT for patient counseling and operative planning, as limited use
can be safe and continues to be an effective method of evaluation.
62
50 49
46
6
3 4
Sequestration CLE
US/MRI CT Scan Final Pathology
4 C.C. Style et al. / Journal of Pediatric Surgery xxx (xxxx) xxx

Table 2
Diagnostic accuracy of prenatal US, fetal MRI, and postnatal CT in infants with CLMs.

Diagnostic accuracy Sensitivity Specificity PPV NPV

US/Fetal MRI⁎ Lesion Location (Left vs Right) 100% 100% 100% 100% 100%
Presence of Systemic Vessel 89% 88% 90% 87% 90%
Bronchial Atresia & CPAMs 88% 94% 82% 83% 94%
Bronchopulmonary Sequestration 90% 87% 92% 89% 91%
Congenital lobar emphysema 97% 75% 98% 60% 99%
Postnatal CT Lesion Location (Left vs Right) 100% 100% 100% 100% 100%
Presence of Systemic Vessel 89% 88% 91% 91% 85%
Bronchial Atresia & CPAMs 94% 96% 92% 92% 96%
Bronchopulmonary Sequestration 87% 90% 88% 90% 88%
Congenital lobar emphysema 99% 75% 100% 100% 99%
⁎ US/MRI were performed and interpreted as paired imaging; MRI=magnetic resonance imaging; CT=computed topography; BPS=bronchopulmonary sequestration (intra- and
extralobar), and CLE=congenital lobar emphysema; PPV: positive predictive value; NPV: negative predictive value.

This study is limited by the single-institution retrospective nature of
the review. Additionally, our radiologists paired the information from
the ultrasound and MRI for the vast majority of patients to provide a
more comprehensive radiologic interpretation. The limitation with
this technique is that that the radiologists are interpreting each individ-
ual study in combination, so it is difficult to analyze the studies within
an individual context. Another limitation of the study is that the data
were based on the initial radiologist read at the time of the study and
were not rereviewed by radiology for this study. Our radiologist has im-
proved in efficiency of diagnosis over the study time period and thus we
plan to prospectively evaluate future prenatal imaging accuracy and ex-
trapolate ultrasound and MRI data separately. Additionally, the use of
MRI for lung lesions in the prenatal period is not universally performed,
particularly for smaller lesions.
From this study, we can conclude that prenatal imaging provides
useful information that can be used to guide fetal intervention and for
perinatal planning, especially in the early neonatal period. Addressing
the specific question of this study on whether postnatal CT is necessary
when prenatal imaging has already been obtained, this study would
conclude that given the nature of lung lesion development with the ac-
curacy and positive predictive value of postnatal CT scan, it would seem
prudent to continue to use this imaging modality for parental counsel-
ing and operative planning.
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Please cite this article as: C.C. Style, A.R. Mehollin-Ray, M.A. Verla, et al., Accuracy of prenatal and postnatal imaging for management of congenital
lung malformations, Journal of Pediatric Surgery, https://doi.org/10.1016/j.jpedsurg.2020.01.020