Is Abdominal Sonography a Useful Adjunct

to Abdominal Radiography in Evaluating

Neonates with Suspected Necrotizing Enterocolitis?
Sarah A Tracy, MD, Stefanie P Lazow, MD, Ilse M Castro-Aragon, MD, Alan M Fujii, MD,
Judy A Estroff, MD, Richard B Parad, MD, MPH, Steven J Staffa, MS, David Zurakowski, PhD,
Catherine Chen, MD, MPH, FACS

BACKGROUND: Abdominal sonography (AUS) is emerging as a potentially valuable adjunct to conventional

abdominal radiography (AXR) in the setting of suspected necrotizing enterocolitis (NEC).
We sought to evaluate concordance between AUS and AXR for signs of NEC to better under-
stand the potential advantages and disadvantages of AUS. As a secondary aim, we characterized
AUS-specific findings and evaluated the association of imaging results with clinical outcomes.
STUDY DESIGN: Hospitalized infants with clinical concern for NEC from 2009 to 2018 were included in this
multicenter retrospective review. All infant patients had at least 1 paired AXR followed by an
AUS within 24 hours. Findings were abstracted from written radiology reports. Cohen’s k,
nonparametric Mann-Whitney U test, and quantile regression were used to evaluate chance-
corrected levels of agreement for concordance analyses and associations with clinical outcomes.
RESULTS: In total, 66 patients and 96 paired studies were evaluated. Agreement between the 2 imaging
modalities was 61 of 96 (63.5%) for pneumatosis (k ¼ 0.29; 95% CI, 0.10 to 0.48), 79 of 96
(82.3%) for portal venous gas (k ¼ 0.07; 95% CI, 0.00 to 0.47), and 91 of 96 (94.8%) for
pneumoperitoneum (k ¼ 0.52; 95% CI, 0.11 to 0.93). Each finding was present more
frequently on AUS than AXR. On AUS, pneumatosis and focal fluid collection were indepen-
dently associated with a longer antibiotic course (4.1 days longer; p ¼ 0.03 and 21.3 days
longer; p < 0.001, respectively).
CONCLUSIONS: AUS holds promise as a useful adjunct to radiography for neonates with possible NEC. It
might be more sensitive for the presence or absence of bowel ischemia and can reveal findings
not detectable by radiography, which can aid provider decision-making. (J Am Coll Surg
2020;230:903e911.
2020 by the American College of Surgeons. Published by Elsevier
Inc. All rights reserved.)

CME questions for this article available at
http://jacscme.facs.org
Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein,
Editor-in-Chief, has nothing to disclose. Ronald J Weigel, CME Editor, has
nothing to disclose.
Presented at the 100th Annual Meeting of the New England Surgical Soci-
ety, Montreal, Quebec, September 2019.
Received October 15, 2019; Revised January 28, 2020; Accepted January
29, 2020.
From the Department of Surgery, Boston Children’s Hospital (Tracy,
Lazow, Staffa, Zurakowski, Chen), Departments of Radiology (Castro[HY-
PHEN]Aragon, Estroff) and Pediatrics (Fujii), Boston Medical Center, and
Department of Newborn Medicine, Brigham and Women’s Hospital
(Parad), Boston, MA.
Correspondence address: Sarah A Tracy, MD, Department of Surgery, Bos-
ton Children’s Hospital, 300 Longwood Ave, Fegan 3, Boston, MA 02115.
email: stracy@bidmc.harvard.edu
For more than 75 years, abdominal radiography (AXR)
has been the standard imaging study to diagnose necro-
tizing enterocolitis (NEC) in infants. However, the sensi-
tivity of AXR is not known, even when read by
experienced pediatric radiologists. Assessment of the
neonatal abdomen with abdominal ultrasonography
(AUS) is emerging as a potential valuable adjunct to con-
ventional AXR to confirm the diagnosis of NEC, espe-
cially in cases where a newborn’s clinical status raises
concern for NEC, but AXR findings are indeterminate
or nonspecific.1 Nondiagnostic AXR studies are common,
and even patients with perforated NEC might not have
definitive findings on AXR.2 Although total radiation
exposure in neonates undergoing serial AXR for NEC is
relatively low, radiation doses have been found to be

ª 2020 by the American College of Surgeons. Published by Elsevier Inc. https://doi.org/10.1016/j.jamcollsurg.2020.01.027

All rights reserved. 903 ISSN 1072-7515/20

Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
904 Tracy et al Abdominal Sonography for Necrotizing Enterocolitis
CONTINUING MEDICAL EDUCATION
CREDIT INFORMATION
Accreditation: The American College of Surgeons
is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to pro-
vide continuing medical education for physicians.
AMA PRA Category 1 CreditsTM: The American
College of Surgeons designates this journal-based
CME activity for a maximum of 1 AMA PRA Cate-
gory 1 Credit. Physicians should claim only the
credit commensurate with the extent of their partic-
ipation in the activity.
Of the AMA PRA Category 1 Credits listed above,
a maximum of 1 credits meet the requirement for
Self-Assessment.
Abbreviations and Acronyms
AUS ¼ abdominal ultrasonography
AXR ¼ abdominal radiography
IQR ¼ interquartile range
NEC ¼ necrotizing enterocolitis
PDA ¼ patent ductus arteriosus
PI ¼ pneumatosis
PVG ¼ portal venous gas
significant and to exceed preferred lowest limits for in-
fants in intensive care.3-5
In addition to evaluating pneumatosis (PI), portal
venous gas (PVG), and pneumoperitoneum, AUS allows
for more detailed assessment of the bowel, with measure-
ment of bowel wall thickness, perfusion (with color
Doppler), and peristalsis.6,7 The presence and character
of intra-abdominal free fluid and fluid collections can
also be investigated. However, AUS is user-dependent
and can be influenced by the level of experience of the
imager.
Given a lack of expertise, reproducibility, and availabil-
ity of AUS for NEC, many institutions have yet to adopt
this imaging modality as part of their standardized prac-
tice regimens. For those that have, we have yet to see
many direct comparisons between AUS and the current
practice standard (AXR). We sought to assess the use of
AUS as an adjunct to AXR in the evaluation of infants
with a concern for NEC. Our primary aim was to evaluate
the radiographic concordance between AUS and AXR
Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
J Am Coll Surg
findings of PI, PVG, and pneumoperitoneum in an effort
to better understand the possible risks and benefits of add-
ing AUS to the diagnostic algorithm. Secondary outcomes
included the reported frequency of other potentially clin-
ically valuable AUS findings that could not be evaluated
by AXR and an assessment of imaging findings as poten-
tial predictors of NEC disease severity.
METHODS
This IRB-approved multicenter retrospective review was
performed at 3 level III to IV newborn ICUs in Boston,
MA, with consultation provided by pediatric surgeons
at Boston Children’s Hospital. One center is a major free-
standing children’s hospital (Boston Children’s Hospital)
and the others are academic hospitals (Brigham and
Women’s Hospital and Boston Medical Center) with
large nonfreestanding newborn ICUs. Charts of patients
evaluated for NEC from 2009 to 2018 were reviewed
for imaging and clinical data. Study data were collected
and managed using REDCap (Research Electronic Data
Capture) tools, a secure, web-based software platform
designed to support data capture for research studies.8,9
Reports from AXR and AUS studies were reviewed if in-
dications for the studies included signs or symptoms con-
cerning for NEC or surveillance after previous abnormal
radiographic studies. Single- or 2-view AXR was per-
formed by radiology technologists and read by experi-
enced pediatric radiologists. Two-view AXR was
obtained most often in an effort to assess for free air using
supine and left lateral decubitus or supine and cross-table
views. AUS studies were performed by sonographers or
attending radiologists with varying levels of experience
and read by experienced pediatric or adult radiologists.
Radiology findings were abstracted from imaging reports.
AUS reports were finalized by attending pediatric radiol-
ogists at 2 of the 3 centers or an attending adult radiolo-
gist at the third center (Brigham and Women’s Hospital).
Concordance analysis
Concordance analysis of reported AXR and AUS findings
was performed for findings that could be seen with both
imaging modalities. This included PI, PVG, and pneu-
moperitoneum. Bowel wall thickening can also be seen
with both AXR and AUS, but comments on the presence
or absence of this finding were inconsistent. Therefore,
bowel wall thickening was excluded from the concordance
analysis. Only study pairs in which AUS was performed
within 24 hours of AXR were included. If multiple
AXRs were performed within 24 hours before an AUS,
only the last AXR done before the AUS was included in
the pairing. Multiple paired studies could be reviewed
Vol. 230, No. 6, June 2020
per patient if meeting the aforementioned criteria. Find-
ings of interest for the concordance analysis between
AXR and AUS study pairs included PI, PVG, and pneu-
moperitoneum. Suspicious AXR findings for PI, such as
“bubbly lucencies concerning for NEC,” were considered
positive for all concordance analyses.
Patient characteristics and clinical outcomes
Demographic and clinical characteristics were abstracted
by medical chart review. Data elements included sex, birth
weight, gestational age, risk factors for NEC (including
formula feeding before NEC concern), presence of a pat-
ent ductus arteriosus (PDA), and need for medical treat-
ment and/or surgical intervention for NEC. Select clinical
outcomes were chosen as surrogates of disease severity to
correlate with concordance groupings, including need for
surgical intervention, mortality during initial hospitaliza-
tion, duration of antibiotic treatment for NEC, and time
to full feeds. Only the antibiotic course associated with
each paired study was considered, and time to full feeds
was defined as days from initial concern for NEC until
the infant reached full enteral feeds. Concordance for PI
and/or PVG was considered in patients without evidence
of bowel perforation (n ¼ 59). Seven patients with bowel
perforation (defined as a rush of air, feculent material,
succus, or a visible hole in the bowel at the time of surgical
intervention) were analyzed separately, as they were at
increased risk for operation and mortality. For the pur-
pose of this clinical analysis, if an infant had multiple
study pairs, only the first study pair with a positive result
was included. If the infant had no positive paired studies,
then their first paired study was included. Any patients
that died were excluded from antibiotic and feeding ana-
lyses, as treatment courses and feeding advancements were
often cut short.
Statistical analysis
Cohen’s k was used to evaluate chance-corrected agree-
ment between AXR and AUS for prespecified findings
and reported using 95% CIs. A Cohen’s k value of 1 rep-
resents perfect agreement and, in clinical practice, a value
of 0.81 to 1.00 represents good agreement; 0.61 to 0.80
represents substantial agreement; 0.41 to 0.60 represents
moderate agreement; 0.21 to 0.40 represents fair agree-
ment; and anything 0.20 represents poor agreement.10
The nonparametric Mann-Whitney U test was used to
compare antibiotic course duration and time to reach full
feeds between groups of patients with different sonographic
and radiographic findings. Quantile regression models were
used to investigate univariate associations between AXR and
AUS findings and each of the following outcomes of inter-
est: antibiotic course duration, days to full enteral feeding,
Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
Tracy et al Abdominal Sonography for Necrotizing Enterocolitis 905
and need for surgical intervention. Imaging findings that
were not reported consistently (bowel wall thickening by
AXR and bowel wall thinning, reduced peristalsis, and
reduced or absent mural flow by AUS) were excluded
from this analysis. For outcomes of interest that were found
to have a potential association with any imaging finding (p
< 0.2), either nonparametric multivariable quantile regres-
sion (ie median regression) or multivariable binary logistic
regression was performed, controlling for all other imaging
findings and select clinical risk factors for NEC. Risk factors
included birth weight, gestational age, formula feeding
before NEC concern, presence of a PDA, and hospital cen-
ter. Boston Children’s Hospital was used as the reference
hospital center and birth weight and gestational age were
modeled as continuous variables. Statistical analyses were
performed using STATA Software, version 15.0 (Stata
Corp) and IBM SPSS Software, version 24.0 (IBM Corp).
A 2-sided p value <0.05 was considered statistically
significant.
RESULTS
A total of 66 infants and 96 paired studies were evaluated.
Of the 66 infants, 35 (53.0%) were male, 13 infants
(19.7%) required surgical intervention for NEC, and 65
(98.5%) were treated with antibiotics and bowel rest.
Overall mortality was 4 of 66 (6.1%). Three infants
died from surgical NEC and 1 died before operation in
the setting of suspected fulminant NEC. Median gesta-
tional age was 27.6 weeks (interquartile range [IQR]
25.5 to 30.8 weeks) and median birth weight was 1.0
kg (IQR 0.7 to 1.4 kg). Considering risk factors for
NEC, 13 of 66 patients (19.7%) were fed some amount
of formula before NEC concern and 30 of 66 patients
(45.5%) had a PDA. Overall, 52 patients (78.8%) had
at least 1 positive paired study for PI and/or PVG. The
remaining 14 patients had concordant negative paired
studies for PI and/or PVG.
When evaluating the 96 paired studies, there was a me-
dian of 1 paired study per patient (IQR 1 to 2) and 6
hours (IQR 3 to 10 hours) between performance of
each AXR and AUS. Two-view AXR were obtained in
24 of 96 patients (25.0%) to assess for the presence of
pneumoperitoneum. PI, PVG, pneumoperitoneum, and
bowel wall thickening were detected more frequently by
AUS than AXR (Table 1). AUS was able to detect addi-
tional findings concerning for bowel ischemia, such as
bowel wall thinning, reduced peristalsis, and reduced or
absent mural flow with Doppler (Table 1). Ultrasound
findings concerning for perforation (in addition to pneu-
moperitoneum) included echogenic free fluid and focal
fluid collections. At least 1 AUS finding concerning for
906 Tracy et al Abdominal Sonography for Necrotizing Enterocolitis J Am Coll Surg

Table 1. Summary of Radiographic and Sonographic Findings

Paired study (n ¼ 96) Infant with finding* (n ¼ 66)
AXR AUS AXR AUS
Variable n % n % n % n %
Finding concerning for ischemic bowel
Pneumatosisy 35 36.5 52 54.2 32 48.5 45 68.2
Portal venous gasy 2 2.1 17 17.7 2 3.0 17 25.8
Bowel wall thickening 9 9.4 18 18.8 8 12.1 16 24.2
Bowel wall thinning d d 9 9.4 d d 8 12.1
Reduced peristalsis d d 26 27.1 d d 23 34.8
Reduced or absent mural flow d d 15 15.6 d d 13 19.7
Finding concerning for perforation
Pneumoperitoneumy 2 2.1 7 7.3 2 3.0 6 9.1
Echogenic free fluid d d 12 12.5 d d 9 13.6
Focal fluid collection d d 8 8.3 d d 6 9.1
*Infant with imaging finding on any paired study.
y
Imaging finding included in the concordance analysis.
AUS, abdominal ultrasonography; AXR, abdominal radiography.

ischemia or perforation was present in 10 of 13 (76.9%)
and 8 of 13 (61.5%) infants with surgical NEC, respec-
tively (eTable 1).
Concordance analysis
For 19 of 66 infants (28.8%) with multiple paired AUS
and AXR studies, repeated measures were included in
the concordance analysis, with each paired study repre-
senting a different point in each infant’s treatment course
for NEC. Based on the total of 96 paired assessments,
AXR and AUS agreement was 63.5% (61 of 96) for PI,
82.3% (79 of 96) for PVG, and 94.8% (91 of 96) for
pneumoperitoneum. Focusing on discordant pairings,
most were cases where a negative AXR was followed by
a positive AUS for PI (26 of 35 [74.3%]), PVG (16 of
17 [94.1%]), and pneumoperitoneum (4 of 5 [80.0%])
(Fig. 1). This could reflect 2 potential clinical scenarios:
one in which the ultrasound finding is a false positive,
putting a patient at risk for unnecessary treatment, and
the other where it is a true positive that might have other-
wise been missed, putting the patient at risk for under-
treatment (Fig. 1). Chance-corrected agreement
(Cohen’s k) ranged from 0.29 for PI (95% CI, 0.10 to
0.48) and 0.07 for PVG (95% CI, 0.00 to 0.47) to
0.52 for pneumoperitoneum (95% CI, 0.11 to 0.93).
These values are interpreted as fair and poor chance-
corrected agreement between AXR and AUS for PI and
PVG, respectively. Pneumoperitoneum was a rare finding
with moderate chance-corrected agreement between AXR
and AUS.10 When the same concordance analysis was
repeated for 66 infants (including only the first paired
study or the first paired study with evidence of PI and/
or PVG), AXR and AUS agreement was 54.5% (36 of
66) for PI, 78.8% (52 of 66) for PVG, and 95.5% (63
of 66) for pneumoperitoneum.

Additional abdominal ultrasonography findings

Figure 1. Abdominal radiography (AXR) and abdominal ultrasonog-
raphy (AUS) paired concordance results for pneumatosis, portal
venous gas, and pneumoperitoneum. N ¼ 96 paired studies. Most
discordant pairings were in infants where a negative x-ray was fol-
lowed by a positive ultrasound.
Twelve of 66 patients (18.2%) had at least 1 additional
AUS finding concerning for perforated bowel, including
echogenic free fluid (n ¼ 6), focal fluid collection (n ¼
5), and pneumoperitoneum (n ¼ 3). Of these patients,
4 had operations within 1 week of their paired study, 2
had confirmed bowel perforations, and 2 died. Of the 2

Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
Vol. 230, No. 6, June 2020 Tracy et al Abdominal Sonography for Necrotizing Enterocolitis 907

that did not have evidence of perforation, 1 had NEC

Time to full feeds,

*This infant underwent primary peritoneal drainage of clear ascites 5 days after the paired imaging studies for worsening abdominal distension and respiratory distress, then underwent laparotomy for

Two infants with negative paired studies underwent delayed laparotomy for necrotizing enterocolitis-related stricture resection. The third infant underwent a laparotomy with diffusely ischemic but
d, median (IQR)
(20e34)

(21e57)
(12e50)
totalis and 1 had ascites, diffusely ischemic bowel, and PI.

(4e38)
In the univariate logistic regression analysis, 3 of 13 pa-
tients (23.1%) with surgical NEC vs 0 of 53 patients

28
15
33
30
(0.0%) with medical NEC had pneumoperitoneum on
AUS (p ¼ 0.01). Bowel wall thickening on AUS was asso-

Table 2. Additional Ultrasonography Findings and Clinical Outcomes for 59 Infants Without Evidence of Perforation by Concordance Group
ciated with a significantly increased likelihood (odds ratio:

Antibiotic course,
d, median (IQR)
8.2; 95% CI, 2.0 to 34.3) for requiring surgical interven-

(14e15)

(13e15)
tion for NEC (p ¼ 0.01). We did not have enough out-

(1e10)

(3e15)
Clinical outcomes
comes for a meaningful analysis of either of these variables
in the multivariable analysis.

15
6
15
12
Clinical outcomes analyses
Seven infants had confirmed perforated viscus at the time

non-necrotic bowel 1 day after the paired imaging studies, followed by a second laparotomy for necrotizing enterocolitis-related stricture resection.
0.0
0.0
4.3
0.0
%
Mortality
of laparotomy or primary peritoneal drainage. Preopera-
tively, pneumoperitoneum was detected in 2 of 7 infants

0/18

1/23
0/12
n/N

0/6
by AUS and none by AXR. PI and/or PVG were detected

AUS, abdominal ultrasonography; AXR, abdominal radiography; IQR, interquartile range; PI, pneumatosis; PVG, portal venous gas.
in 3 by AXR and 5 by AUS. Additional concerning AUS

0.0
16.7
8.7
25.0
findings were present: 2 infants had echogenic free fluid, 1

%
Operation
had a focal fluid collection, and 4 had bowel wall thick-
ening. Two of 7 infants experienced mortality before fin-

3/12y
n/N
0/18

2/23
1/6*
ishing their treatment course and were excluded from
antibiotic and time to full feed analyses. Median anti-
biotic course duration in the remaining 5 patients was

0.0
0.0
4.3
0.0
Additional AUS finding concerning for perforation or ischemia

%
Free air
17.0 days (IQR 14.0 to 23.0 days) and time to full feeds
from time of the initial AXR for NEC was 51.4 days

0/18

1/23
0/12
n/N

0/6
(IQR 35.0 to 63.4 days).
Additional AUS findings and clinical outcomes asso-
ciated with each concordance group (for PI and/or
11.1
0.0
13.0
16.7
Bowel wall
thickening
%

PVG) are summarized in Table 2 for the remaining

59 infants, after exclusion of the 7 patients with perfo-
2/18

3/23
2/12
n/N

0/6

ration. Of the patients with discordant findings, 6 of 59

(10.2%) had a positive AXR and a negative AUS for PI
and/or PVG. None of these patients had additional
11.1
0.0
8.7
0.0
Focal fluid

%
collection

findings on AUS concerning for perforation or

ischemia, but 1 did undergo peritoneal drainage of clear
2/18

2/23
0/12
n/N

ascites and then a laparotomy 1 month later for a bowel

0/6

obstruction. None of these patients died. More than

one-third of the 59 patients (23 of 59 [39.0%]) had a
16.7
0.0
0.0
8.3
Echogenic

%
free fluid

negative AXR and a positive AUS for PI and/or PVG.

Several of the 23 patients had additional AUS findings
3/18

0/23
1/12
n/N

concerning for perforation or ischemia, such as focal

0/6

fluid collections, bowel wall thickening, and/or free

bowel obstruction 1 month later.

air, and 2 patients underwent surgical intervention for

30.5
10.2
39.0
20.3
Infants ( N

NEC and 1 died (Table 2).

¼ 59)

On review of the patients with concordant studies for

18
6
23
12

PI and/or PVG, 18 of 59 (30.5%) had concordant posi-

N

tive studies and several had additional AUS findings con-

AUS

cerning for perforation or ischemia. However, no patients

þ

þ
e

e
PI and/or

in this group underwent operation for NEC or died.

Concordant negative studies were found in 12 of 59 pa-
AXR
PVG

tients (20.3%), but 1 had echogenic free fluid and 2

þ
þ
e
e

Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
908 Tracy et al Abdominal Sonography for Necrotizing Enterocolitis J Am Coll Surg

had bowel wall thickening seen on AUS. Three of 12
patients underwent operations for NEC, but none died.
The surgical interventions in this group were delayed
operations for NEC-related strictures (2 patients) and
an initial laparotomy for diffusely ischemic, but non-
necrotic bowel, with a second laparotomy for a
NEC-related stricture (1 patient) (Table 2).
Patients with a negative AUS for PI and/or PVG had
significantly shorter antibiotic courses than patients with
a positive AUS (p < 0.01), but there was no difference
in time to full enteral feeding between these groups
(p ¼ 0.11). For AXR, there was no difference in antibiotic
course duration (p ¼ 0.61) or time to full enteral feeding
(p ¼ 0.24) for patients with or without findings of PI
and/or PVG. The overall median antibiotic course dura-
tion was 14.5 days (IQR 10.0 to 15.0 days) and time to
full feeds was 28.4 days (IQR 19.6 to 38.4 days).
Imaging finding associations with clinical outcomes
were evaluated in the 59 patients without evidence of
perforation. Results from the univariate quantile
regression analysis with antibiotic course duration as the
end point of interest suggested that several AUS findings
were significantly associated with increased antibiotic
course duration, including PI (p < 0.01) and focal fluid
collection (p < 0.01). Presence of a PDA was also associ-
ated with increased antibiotic course duration (p ¼ 0.01).
Using multivariable quantile regression analysis when
controlling for all other imaging findings and select clin-
ical variables, AUS findings of focal fluid collection
(p < 0.01) and PI (p ¼ 0.03) were the only variables
significantly associated with a longer antibiotic course
duration (Table 3). Univariate quantile regression analysis
indicated possible associations between time to full enteral
feeding and PVG on AXR, as well as PI on AUS
(p < 0.20). However, when these variables were included
in the multivariable regression model, neither had a sig-
nificant association with time to full enteral feeding
(p > 0.05).
When comparing antibiotic course duration for NEC
using the freestanding children’s hospital newborn ICU

Table 3. Multivariable Quantile Median Regression Model Results of Antibiotic Duration in 59 Infants Without Evidence of
Perforation
Adjusted difference in median
Variable antibiotic course duration,* d 95% CIy p Value
Abdominal ultrasonography imaging finding
Portal venous gas 0.4 e3.7 to 4.5 0.85
Pneumatosis 4.1 0.4 to 7.7 0.03
Pneumoperitoneumz NA NA NA
Echogenic free fluid 3.7 e5.5 to 12.9 0.42
Focal fluid collection 21.3 13.8 to 28.8 <0.01
Bowel wall thickening 4.2 e1.7 to 10 0.16
Abdominal radiography imaging finding
Portal venous gas 5.4 e6.9 to 17.7 0.38
Pneumatosis 0.8 e3 to 4.6 0.66
Pneumoperitoneumz NA NA NA
Clinical variable
Birth weight, kg e2.6 e8.7 to 3.6 0.41
Gestational age, wk 0 e1.1 to 1.1 0.96
Persistent patent ductus arteriosus 2.7 e1.1 to 6.5 0.16
Formula feeding before necrotizing 4.4 e0.5 to 9.3 0.08
enterocolitis concern
Hospital center
Center 1 Reference d d
Center 2 3.6 e4.2 to 11.4 0.36
Center 3 2.4 e5.9 to 10.6 0.57
*Median antibiotic course duration for the 59 patients included in this analysis was 14.5 days (interquartile range 10.0 to 15.0 days).
y
95% CIs that exclude the value 0 were considered to be statistically significant for this analysis.
z
Unable to compute for abdominal ultrasonography and abdominal radiography findings of pneumoperitoneum due to the limited number of cases (n ¼ 1
for abdominal ultrasonography , n ¼ 0 for abdominal radiography).
NA, not applicable.

Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
Vol. 230, No. 6, June 2020
as a reference on univariate regression analysis, there
were no significant differences among the 3 institutions
(p > 0.24). However, there were differences when
comparing rates of surgical intervention for NEC and
time to full enteral feeds. In the univariate regression
analysis, rates of surgical intervention were significantly
lower at the other 2 hospitals compared with the free-
standing children’s hospital (odds ratio 0.03; 95% CI,
0.01 to 0.66; p ¼ 0.03 and odds ratio 0.02; 95% CI,
0.01 to 0.57; p ¼ 0.02). Infants from the freestanding
children’s hospital had a longer time to full feeds
compared with infants from Brigham and Women’s
Hospital (but not Boston Medical Center), with a me-
dian difference of 30.6 days (95% CI, 3.0 to 58.2
days; p ¼ 0.03).
DISCUSSION
AUS appears to be a useful diagnostic adjunct to serial
AXR for NEC. Major advantages of AUS include the
avoidance of exposure to ionizing radiation and its avail-
ability due to accepted widespread use for other pediatric
intestinal pathologies, including pyloric stenosis, appendi-
citis, and intussusception. Several studies have shown that
AUS can identify signs of ischemic and perforated bowel
earlier than AXR.2,11,12 However, the majority of pub-
lished studies are single-center reviews and case series
with outcomes influenced by institutional practice pat-
terns.13,14 Most of the literature focuses on radiologic
criteria for diagnosing NEC, rather than on criteria to
exclude the diagnosis of NEC to avoid overtreatment.
AUS can play an important role in this setting because
prolonged courses of empiric antibiotic therapy, bowel
rest, and parenteral nutrition are associated with compli-
cations and suboptimal outcomes in extremely low birth
weight infants.15,16
Important insights into the use of AUS as an adjunct to
serial AXR can be gained from this review of 3 Boston in-
stitutions where AUS for NEC was included in the
workup of patients with suspected NEC or for moni-
toring of known NEC. In this cohort, AUS identified
more cases of PI, PVG, and pneumoperitoneum than
AXR. As such, AUS might be more sensitive than AXR
for signs of ischemic bowel and perforation and might
be useful for “ruling out” NEC in cases where clinical
suspicion is low. Alternatively, AUS can introduce false-
positive information and put the patient at risk for over-
treatment with a long antibiotic course.
Notably, several AUS findings, but no AXR findings,
were significantly associated with a longer antibiotic
treatment course for NEC. Unfortunately, without a
standardized treatment protocol or the consideration
Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
Tracy et al Abdominal Sonography for Necrotizing Enterocolitis 909
of other variables that can alter a patient’s clinical
course, one cannot determine whether AUS has better
predictive value than AXR for cases of severe NEC.
Antibiotic courses are likely to be influenced by
institution-based practice patterns, the need for surgical
intervention, and NEC risk factors in addition to imag-
ing study results. No significant differences were seen
in antibiotic courses between the 3 institutions in this
study, but there did appear to be a difference in oper-
ative rates and time to full feeds, with a higher rate of
surgical NEC and longer time to full feeds at the free-
standing children’s hospital. This might be related to a
greater proportion of high-risk and more complex pa-
tients at the freestanding children’s hospital, where pa-
tients were often transferred from outside institutions
specifically for management of severe and/or perforated
NEC. Despite the fact that these were 3 different insti-
tutions, the same surgical service was responsible for
the care of the patients at all of them, which should
limit variability in practice patterns.
A prospective evaluation of the influence of imaging
findings on patient management and outcomes is needed
to better define the predictive capability of AUS findings
before suggestions can be made for clinical practice. In a
recent European web-based questionnaire, only 58% of
respondents claimed their institutions used AUS for
NEC and indications for AUS varied widely. Most centers
did not follow an imaging schedule or protocol.17 Despite
the fact that AUS for NEC is not considered standard of
care at most institutions, most providers would agree on
the use of abdominal ultrasound to confirm the diagnosis
of NEC when AXR is indeterminate, as AUS seems to be
more sensitive for signs of bowel ischemia. AUS can also
improve the negative predictive accuracy for NEC when
combined with serial AXR. In our cohort, patients with
a negative AUS (for PI and/or PVG) had significantly
shorter antibiotic courses than patients with a positive
study.
Using AUS as a tool to potentially limit overtreatment for
NEC in cases where the clinical suspicion for disease is low is
an intriguing concept. Although AUS has proved to be use-
ful in this regard, providers must keep in mind that false neg-
atives also occur. In our cohort, 3 of 13 surgical patients
(23.1%) without AUS findings concerning for ischemia or
perforation went on to have operations for NEC within
11 days, with confirmation of necrosis and/or perforation
(patient numbers 1, 2, and 11 in eTable 1). All 3 patients
had concerning symptoms, with a high clinical suspicion
for NEC that prompted surgical intervention and 1 infant
had a subsequent AXR with free air. Imaging findings
must always be interpreted in the context of the overall clin-
ical picture of the patient and the incidence of false-negative
910 Tracy et al Abdominal Sonography for Necrotizing Enterocolitis
studies can decrease over time as sonographers and radiolo-
gists gain more experience.
Several study limitations should be noted. As a retrospec-
tive chart-based review, the data are restricted to what is
available in reports and notes. In this cohort, symptoms con-
cerning for NEC were inconsistently documented, making
it difficult to stratify patients into categories of disease
severity. In addition, the majority of AXR studies were
single-view supine studies, which are less sensitive than
2-view AXR for pneumoperitoneum, and this likely contrib-
uted to the low rate of detection of pneumoperitoneum by
AXR. Additionally, with AUS, the presence of bowel gas
can make it challenging to obtain a viewable window, and
studies might need to be repeated. Repeat AXR and AUS
study pairs were evaluated in this study and included in
our concordance analysis.
It takes time and practice for sonographers and radi-
ologists to gain proficiency with AUS for NEC, and
the role of interobserver variability is not yet well un-
derstood. Although a single radiologist championed
the reading of AUS studies at each institution in this
study, there were times when additional radiologists
were asked to assist if the champion radiologist was un-
available, and this introduced a potential for a greater
degree of variability in terms of skill level, technique,
and reader bias. Future studies should focus on stan-
dardizing AUS training and reporting to improve com-
fort with the more challenging aspects of the study,
completeness and accuracy.
CONCLUSIONS
This multi-institutional review provides valuable insight
into the added value of AUS as an adjunct to serial
AXR in the workup and surveillance of a neonate with
suspected NEC. Specifically, AUS might be more sensi-
tive than radiography for PI and PVG, as most of the
disagreement between paired studies came from cases
where findings were seen with AUS only. In addition to
PI, PVG, and pneumoperitoneum, other findings, such
as focal fluid collections, echogenic free fluid, reduced
peristalsis, reduced or absent mural flow, bowel wall
thickening, and bowel wall thinning, can be characterized
by AUS and might provide helpful information for med-
ical and surgical decision-making.
Author Contributions
Study conception and design: Tracy, Castro-Aragon,
Fujii, Estroff, Parad, Chen
Acquisition of data: Tracy, Lazow
Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
J Am Coll Surg
Analysis and interpretation of data: Tracy, Lazow, Staffa,
Zurakowski, Chen
Drafting of manuscript: Tracy, Lazow
Critical revision: Tracy, Lazow, Castro-Aragon, Fujii,
Estroff, Parad, Staffa, Zurakowski, Chen
Acknowledgment: The authors would like to thank Dr Jen-
nifer Perez for her assistance with data collection.
REFERENCES
1. Kim WY, Kim WS, Kim IO, et al. Sonographic evaluation of
neonates with early-stage necrotizing enterocolitis. Pediatr
Radiol 2005;35:1056e1061.
2. Miller SF, Seibert JJ, Kinder DL, et al. Use of ultrasound in
the detection of occult bowel perforation in neonates.
J Ultrasound Med 1993;12:531e535.
3. Puch-Kapst K, Juran R, Stoever B, et al. Radiation exposure in
212 very low and extremely low birth weight infants. Pediatrics
2009;124:1556e1564.
4. Scott MV, Fujii AM, Behrman RH, Dillon JE. Diagnostic
ionizing radiation exposure in premature patients. J Perinatol
2014;34:392e395.
5. Thierry-Chef I, Maccia C, Laurier D, et al. Radiation doses
received by premature babies in the neonatal intensive care
unit. J Radiol 2005;86:143e149.
6. Faingold R, Daneman A, Tomlinson G, et al. Necrotizing
enterocolitis: assessment of bowel viability with color Doppler
US. Radiology 2005;235:587e594.
7. Richburg DA, Kim JH. Real-time bowel ultrasound to charac-
terize intestinal motility in the preterm neonate. J Perinatol
2013;33:605e608.
8. Harris PA, Taylor R, Thielke R, et al. Research electronic data
capture (REDCap)da metadata-driven methodology and
workflow process for providing translational research infor-
matics support. J Biomed Inform 2009;42:377e381.
9. Harris PA, Taylor R, Minor BL, et al. The REDCap con-
sortium: building an international community of software
partners. J Biomed Inform 2019;95:103208.
10. Petrie A, Sabin C. Assessing agreement. In: Medical Statistics at a
Glance. 2nd ed. Malden: Blackwell Publishing Ltd; 2005:105e107.
11. Bonhorst B, Kuebler JF, Rau G, et al. Portal venous gas detected
by ultrasound differentiates surgical NEC from other acquired
neonatal intestinal diseases. Eur J Pediatr Surg 2011;21:12e17.
12. McBride WJ, Roy S, Brudnicki A, Stringel G. Correlation of com-
plex ascites with intestinal gangrene and perforation in neonates
with necrotizing enterocolitis. J Pediatr Surg 2010;45:887e889.
13. Cuna AC, Reddy N, Robinson AL, Chan SS. Bowel ultra-
sound for predicting surgical management of necrotizing
enterocolitis: a systematic review and meta-analysis. Pediatr
Radiol 2018;48:658e666.
14. Muchantef K, Epelman M, Darge K, et al. Sonographic and
radiographic imaging features of the neonate with necrotizing
enterocolitis: correlating findings with outcomes. Pediatr
Radiol 2013;43:1444e1452.
15. Cotten CM, Taylor S, Stoll B, et al. Prolonged duration of initial
empirical antibiotic treatment is associated with increased rates
Vol. 230, No. 6, June 2020
of necrotizing enterocolitis and death for extremely low birth
weight infants. Pediatrics 2009;123:58e66.
16. Kuppala VS, Meinzen-Derr J, Morrow AL, Schibler KR. Prolonged
initial empirical antibiotic treatment is associated with adverse out-
comes in premature infants. J Pediatr 2011;159:720e725.
17. Ahle M, Ringertz HG, Rubesova E. The role of imaging in the
management of necrotising enterocolitis: a multispecialist survey
and a review of the literature. Eur Radiol 2018:3621e3631.
Invited Commentary
Baird Mallory, MD
Portland, ME
This case series of 66 patients with 96 paired studies presents
compelling evidence that abdominal ultrasound (US), in the right
hands, provides more information about the intestinal and liver
health of a neonate than plain abdominal film in the evaluation
of necrotizing enterocolitis (NEC).1 Ultrasound seems to better
detect pneumatosis intestinalis (PI), free air (FA), and portal venous
gas (PVG). Additional information about bowel wall thickness,
motility, perfusion, and the presence of extra-intestinal fluid collec-
tion (not evident on plain film) is captured.
The idea that ultrasound might be useful for this purposedcon-
sidered discrete from clinical and laboratory metricseis chal-
lenging, but not new; this article is one in a series progressively
delineating findings and proving this point.2,3 However, the salient
question is, does this increased knowledge improve our ability to
make 1 of the following 3 critical decisions (a fourth decisiondcan
we predict a stricture of operative severitydcan probably be post-
poned, allowing the bowel to recover until the answer becomes
obvious in about 6 weeks)?
Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.
Mallory Invited Commentary 911
1. The bowel is normal and does not require treatment.
2. The abdominal process is amenable to bowel rest, total
parenteral nutrition, and IV antibiotics.
3. The abdominal process requires operation.
This study does not define number 1, as just 1 patient did not
receive antibiotics. This paper does not define number 3, as in
the 7 patients with operatively confirmed perforation (of whom 2
died) free air was observed only twice on US and not seen on
abdominal plain film. This study is largely concerned with the
group 2 patients without clarity as to how this group was defined.
No patients required immediate operation; 6 patients subsequently
did, and it would seem this need was largely determined by clinical
criteria. Retrospective attempts at univariate and multivariate anal-
ysis have not yielded a convincing algorithm.
I think the authors are to be lauded for advancing the role of US,
defining metrics and their association with clinical outcomes in a
blended prospective study of moderate size across 3 institutions.
But we have more to do. Future studies prospectively using the in-
formation US adds may help define an algorithm optimizing the
care of these NEC patients prone to under- or overtreatment.
REFERENCES
1. Tracy SA, Lazow SP, Castro-Aragon IM, et al. Is abdominal
sonography a useful adjunct to abdominal radiography in
evaluating neonates with suspected necrotizing enterocolitis?
J Am Coll Surg 2020;230:903e911.
2. Faingold R, Daneman A, Tomlinson G, et al. Necrotizing
enterocolitis: assessment of bowel viability with color Doppler
US. Pediatr Imaging 2005;235:587e594.
3. Yikilmaz A, Hall NJ, Daneman A, et al. Prospective evaluation
of the impact of sonography on the management and surgical
intervention of neonates with necrotizing enterocolitis. Pediatr
Surg Int 2014;30:1231e1240.
 eTable 1. Ultrasonography and Radiography Findings of 13 Patients with Surgical Necrotizing Enterocolitis (n ¼ 23 Paired Abdominal Radiography and

911.e1
Abdominal Ultrasonography Studies)
Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.

Abdominal radiography finding Abdominal ultrasonography finding

Concerning for Concerning for Concerning for Concerning for
Patient no. Paired study* ischemia perforation Other finding ischemia perforation Other finding
1 A d d Paucity of bowel gas d d Simple FF

Tracy et al
2 A d d Dilated bowel d d Simple FF
3 A d d Dilated bowel BW thick FFC d
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.

3 B d d Dilated bowel PI FFC d

4 A PI d Dilated bowel Reduced peristalsis; EFF Dilated bowel
BW thick; PI;

Abdominal Sonography for Necrotizing Enterocolitis

reduced mural flow
4 B PI d Dilated bowel Reduced peristalsis; EFF Dilated bowel
BW thick; PI;
increased mural
flow
5 A d d Nonspecific bowel gas BW thick EFF d
pattern
5 B d d Nonspecific bowel gas d d d
pattern
5 C d Possible FA Dilated bowel d FA d
5 D d Possible FA Dilated bowel; fixed d FA Simple FF
loop
6 A Possible PI d Paucity of bowel gas Reduced peristalsis d Simple FF; dilated
bowel
6 B d d Dilated bowel Reduced peristalsis d Simple FF; dilated
bowel
6 C d FA d Reduced peristalsis; EFF; FFC Dilated bowel
BW thin; PI;
absent and reduced
mural flow
6 D Possible PI FA d BW thick; reduced EFF Dilated bowel
mural flow
6 E BW thick d Dilated bowel; AF Reduced peristalsis; FA; EFF; possible Dilated bowel
level BW thick; PVG; PI FFC
7 A d d Centralization of EFF Dilated bowel
bowel loop
8 A d d Dilated bowel BW thick; PI FA; EFF Incarcerated umbilical
hernia
9 A PI BW thick; PI Simple FF

J Am Coll Surg
d d d
10 A Possible PI d Dilated bowel; Reduced peristalsis; FA Simple FF; dilated
AF level BW thick; PVG; bowel
(Continued)
 eTable 1. Continued

Vol. 230, No. 6, June 2020

Downloaded for Anonymous User (n/a) at Far Eastern University Doctor Nicanor Reyes Medical Foundation from ClinicalKey.com by Elsevier on August 31, 2020.

Abdominal radiography finding Abdominal ultrasonography finding

Concerning for Concerning for Concerning for Concerning for
Patient no. Paired study* ischemia perforation Other finding ischemia perforation Other finding
PI; increased mural
flow
11 A d d Paucity of bowel gas d d Simple FF; possible
IVC thrombosis
12 A Nonspecific bowel gas Reduced peristalsis; FA; FFC
For personal use only. No other uses without permission. Copyright ©2020. Elsevier Inc. All rights reserved.

d d d
pattern PI; absent mural
flow
13 A d d Nonspecific bowel gas Reduced peristalsis; d Simple FF; GB wall
pattern BW thick; PI thick
13 B Possible PI d Dilated bowel d d Simple FF
*For patients with multiple paired studies, each paired study is assigned a letter in chronologic order: A, B, C, D, or E.
AF, air fluid; BW thick, bowel wall thickening; BW thin, bowel wall thinning; EFF, echogenic free fluid; FA, free air; FF, free fluid; FFC, focal fluid collection; GB, gallbladder; PI, pneumatosis; PVG,
portal venous gas.

Tracy et al
Abdominal Sonography for Necrotizing Enterocolitis
911.e2