[Downloaded free from http://www.jcnonweb.com on Monday, February 8, 2021, IP: 99.239.6.

196]

Original Article

Clinical Manifestation of Necrotizing Enterocolitis in Preterm Infants:

8 Years’ Expeience in a Tertiary Care Center
Sarrh Siddig Sobeir, Mustafa Qaraqei, Tariq Wani1, Abdulrahman AlMatary

Department of Neonatology, Background: Necrotizing enterocolitis (NEC) is the most common devastating

Abstract
King Fahad Medical City,
1
Research Center, King Fahad
acquired disease of the gastrointestinal tract in preterm infants. Objective: The study
Medical City, Riyadh, Saudi is aimed to evaluate maternal, infant risk factors, and radiological manifestation, in
Arabia addition to the outcome. Methodology: This was a retrospective cohort study, all
preterm infants born <32 weeks that were delivered in our tertiary care hospital
from January 2011 to December 2018 with a confirmed diagnosis of NEC.
Results: Forty‑nine infants full‑filled the inclusion criteria. The average weight
of infants with NEC was 970 g (1028 ± 401) with P = 0.05. The gestational
age of affected infants was 27.5 ± 2.9 weeks with P = 0.007, the average age
of NEC diagnosis was 14.8 ± 11.2 days and their average length of stay was
79.9 ± 57.5 days with valueP = 0.015. Bowel stricture occurred in 4 (8.2%) infants
with P < 0.001. Short bowel syndrome occurred in 1 (2%) infants with P < 0.001.
Bronchopulmonary hypoplasia occurred in 24 (49%) with P < 0.001. Retinopathy
of prematurity occurred in 9 (18.8%) with P < 0.001. Conclusion: Maternal parity
multigravida had increased risk by more than double. More than half of our babies
developed advanced NEC, which is double the reported figures found in other
studies, which indicate routine needs to use of probiotics.
Submitted: 02‑Jun‑2020
Revised: 10‑Sep‑2020
Keywords: Bronchopulmonary hypoplasia, necrotizing enterocolitis, retinopathy
Accepted: 17‑Sep‑2020
of prematurity, total parenteral nutrition, umbilical arterial catheter, very low
Published: 08-Feb-2021 birth weight

Background
N ecrotizing enterocolitis (NEC) reports appeared as
early as the first half of the 19th century. It was
named and described as a clinical, radiographic, and
pathologic entity in the 60s,[1] following an epidemic
that occurred in a Children’s Hospital in New York
City between 1955 and 1966. In 1978, Bell et  al.
defined a severity and staging system for NEC to
support therapeutic discussion, which is still in use. In
the 19th ed.ition of the International Classification of
Diseases (ICD 9) published in 1987, an ICD‑code for
NEC was specified.[2,3]
NEC is the most common, devastating acquired disease
of the gastrointestinal tract in very low birth weight
infants (VLBW).[2] NEC proved to be the second
most expensive morbidity after bronchopulmonary
dysplasia (BPD) in VLBW infants.[4] Prematurity and
low birth weights are the most critical risk factors. It
has been reported to affect 10%–12% of VLBW infants,
with a mortality rate of about 15%–30%.[5,6]
The pathogenesis of NEC has not been clearly
explained.[3] NEC most likely represents a complex
interaction of factors causing a mucosal injury that
occurs with the coincidence of the following pathologic
events: immaturity of the gastrointestinal tract, intestinal
ischemia, excess protein substrate in the intestinal
lumen,[3,7] and colonization of the intestine by pathologic
bacteria. Preterm infants primarily acquired their
colonizing gastrointestinal bacteria from the neonatal
intensive care environment, rather than their mother’s
Address for correspondence: Dr. Abdulrahman AlMatary,
Department of Neonatology, King Fahad Medical City,
P. O. Box 59046, Riyadh, Saudi Arabia.
E‑mail: aalmatary@kfmc.med.sa

This is an open access article distributed under the terms of the Creative Commons
Access this article online Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak,
Quick Response Code: and build upon the work non‑commercially, as long as the author is credited and the new
Website: creations are licensed under the identical terms.
www.jcnonweb.com
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

DOI: How to cite this article: Sobeir SS, Qaraqei M, Wani T, AlMatary A. Clinical
10.4103/jcn.JCN_24_20 manifestation of necrotizing enterocolitis in preterm infants: 8 years’
experience in a tertiary care center. J Clin Neonatol 2021;10:5-10.

© 2021 Journal of Clinical Neonatology | Published by Wolters Kluwer - Medknow 5

[Downloaded free from http://www.jcnonweb.com on Monday, February 8, 2021, IP: 99.239.6.196]
Sobeir, et al.: Clinical manifestation of Necrotizing enterocolitis
genital tract flora, skin, or breast milk.[8] Considering that
most premature infants do not develop NEC, it has been
suggested that there may be a genetic predisposition with
fewer mucin‑producing goblet cell in some infants.[9]
Most infants with Stage 1 or 2 NEC are managed
nonoperatively; however, surgical intervention is
considered in the event of intestinal perforation or
clinical deterioration.[10] From the infants who survive,
about 50% will develop long‑term complications,
and nearly 10% of these infants will develop late
gastrointestinal problems. However, the remaining
50% do not have any long‑term sequels.[11] The most
common complications are intestinal stricture, short
bowel syndrome, total parenteral nutrition (TPN)‑related
cholestasis, neurodevelopmental delay, prolonged
hospital stay, and death.[2,12,13]
The incidence of NEC has gradually decreased over
the past 10 years, partly due to initiatives directed at
preventing the onset of NEC.[14] Currently available
strategies for primary prevention of NEC include
antenatal glucocorticosteroids, cautious feeding strategy,
fluid restriction, breastfeeding, and probiotics.[3]
Amniotic fluid stem cell therapy is one of the future
prevention interventions in the pipeline where stem cell
migrate and colonize the damaged intestinal villi and
enhance regeneration of the intestinal epithelium.[15]
Furthermore, identifying babies who are at a higher risk
of developing NEC by using noninvasive indicators,
for example, fecal microbiota and some inflammatory
protein tests from the buccal epithelium.[16]
Methodology
Our study is aimed to evaluate maternal and infant risk
factors of NEC. Also, to look at the outcome of all
infants that developed NEC during the study period.
In this retrospective cohort study, we used the Electronic
Neonatal Database, reviewed the medical charts and
radiology reports for all preterm infants admitted to
our tertiary hospital from January 2011 to December
2018. All cases diagnosed with NEC were collected and
classified based on the Modified Bell’s criteria, which
included suspected, proven, and complicated NEC.
The “bowel stricture” was defined based on clinical
assessment and barium study, while “short bowel” was
defined based on the length of the bowel removed.
All statistical analysis was performed using the
Statistical Package for he IBM SPSS 25.0, Armonk,
New York, USA.
Our inclusion criteria included all preterm infants
born  ≤32  weeks, delivered at our tertiary care hospital,
and admitted to the newborn intensive care unit (NICU)
6 Journal of Clinical Neonatology  ¦  Volume 10  ¦  Issue 1  ¦  January-March 2021
with a confirmed diagnosis of NEC from January 2011
to December 2018. Our exclusion criteria included
infants diagnosed as spontaneous intestinal perforation,
anorectal malformations, congenital gastrointestinal
surgical conditions (omphalocele and gastroschisis),
and other congenital gastrointestinal diseases like
Hirschsprung disease.
The number of admitted babies during the study periods
is 5393 babies, Number of babies developed NEC
51 babies. Number of babies with NEC full fill the
inclusion criteria, 49 babies.
Results
Out of a total of 1265 admitted infants, 51 infants who
met the inclusion criteria were enrolled in our study, 2
of them were excluded because one was born in another
hospital, and the second was diagnosed as a case of
haemophagocytic syndrome. Consequently, only 49
infants full‑filled the inclusion criteria [Figure 1].
Neonatal demographic data mentioned in Table 1 and
maternal demographic data mentioned in Table 2.
Other studied risk factors for NEC include the use of
surfactant in 30 (57%) and no surfactant in 21 (43%)
of cases, umbilical arterial line in 24 (49%), and
no umbilical arterial line in 25 (51%). Hypotension
requiring inotropic support appeared in 16 (32.7%) of
the cases while in 29 (59.2%) of the cases it did not
require inotropic support. Sepsis associated with NEC
developed in 30 (61.2%) of the cases, while sepsis was
not reported in 19 (38.8%) of the cases. Packed red
Number of Admitted Babies during
the study period 5,393 babies
Number of Admitted Preterm less than 32
weeks during the study period 1, 265
babies
Number of babies developed NEC
51 babies
2 babies were
excluded: One
outborn and other
one diagnosed as
hemophagocytic
Syndrome
Number of babies with NEC fulfill the inclusion
criteria 49 babies
Figure 1: Study population
[Downloaded free from http://www.jcnonweb.com on Monday, February 8, 2021, IP: 99.239.6.196]

Sobeir, et al.: Clinical manifestation of Necrotizing enterocolitis

blood cell transfusion was observed in 21 (42.9%) of bowel syndrome occurred in 1 (2%) of our cases.
NEC cases. Recurrent NEC was observed in 1 (2%) of our cases.
Over half (53%) of our NEC cases needed surgical Neonatal morbidity such as BPD was regarded as
intervention, such as penrose or laparotomy, while about an association of NEC in 24 (49%) of the cases with
(47%) required only medical treatment and observation. P < 0.001 while retinopathy of prematurity was observed
in 9 (18.8%) of our cases with P < 0.001.
A significant number of patients 7  (14.3%) showed
cholestasis on TPN.
Discussion
Post‑NEC recovery complications such as bowel To our knowledge, this is one of the largest local studies
stricture occurred in 4 (8.2%) of our cases and short evaluating babies that developed NEC. Forty‑nine
preterm VLBW neonates had definite or advanced NEC;
Table 1: Neonatal demographic data the prevalence of NEC was 3.9%, which is less than
Variables Percentage P the internationally reported data. Neonatal Research
Gender
Network has mentioned that the mean prevalence of
Male 61.2 0.8
NEC in VLBW infants was about 7%.[9] Approximately
Female 38.8
35% of babies with NEC died in our hospital. Which
Birth weight 970 (1028±401 g) 0.05
Gestational age (27.5±2.9 weeks) 0.007
is similar to the international mortality rate data for
Mode of delivery NEC (20%–40%).[3,9,17,18]
Vaginal delivery 36.7 0.638 In our study group around 31 (63.3%) of the affected
Cesarean section 63.3 neonates were born via cesarean section which is; a
Abnormal Doppler US known risk factor for NEC.[2,3] In our study, we found
Yes 6.3 0.41
preterm infants born to multigravida mothers had more
No 87.5
than a 2‑fold (71.4%) increased risk to develop NEC
Unknown 6.3
Time of enteral feeding initiation 5.1±3.5 days 0.920
when compared to a preterm infant born to a primigravida
Age of NEC diagnosis - 14.8±11.2 days 0.260 mother  (28.4%) with significant  (P = 0.037) which is
Length of stay - 79.9±57.5 days 0.015 significant; although maternal parity is not a known risk
NEC – Necrotizing enterocolitis; US – Ultrasound factor for NEC.
Maternal comorbidities (hypertension, diabetes mellitus,
Table 2: Maternal demographic data and chorioamnionitis), the use of intrapartum antibiotics,
Risk factors Percentage P and prolonged rupture of the membrane  (˃18 h) did
Maternal age (20–47 years) 0.495 not increase the risk of NEC in our study because of
Maternal parity under‑reporting. The negative association with NEC
Primigravida 28.6 0.037 included maternal preeclampsia, premature rupture of
Multipara 71.4 membrane, and urinary tract infection [Table 2].[2]
Maternal morbidities
Diabetes Babies born to mothers who did not receive antenatal
Yes 8.2 0.128 steroids had higher rates of NEC (79.6%) in comparison
No 91.8 to (20.4%) in the group that received antenatal steroids
Preeclampsia as P value is not significant  (0.274). This is contrary to
Yes 22.4 0.557 expectations as antenatal steroids have a protective effect
No 77.6 against NEC.[3] Antenatal glucocorticoid therapy could
Chorioamnionitis reduce the mucosal uptake of macromolecules, decrease
Yes 8.7 0.126 colonization with aerobic bacteria, reduce translocation
No 91.3 and increase the activity of enzymes such as lactase,
Premature rupture of membrane
maltase, sucrase, and Na\K‑ATPase, which have been
Yes 14.3 0.22
correlated with a reduction in NEC.[3]
No 85.7
Ante partum antibiotics Prematurity has adverse relation on NEC [Figure 2],
Yes 8.2 0.128 the more preterm the infant, the more likely the
No 91.8 infant will develop NEC; (P = 0.007), which is a
Antenatal glucocorticoids well‑known risk factor.[1‑3] More than half, 28 (57.2%)
Yes 79.6 0.274 of the affected babies in our study weighed <1000 g,
No 20.4 14 (28.5%) weighed 1000–1499 g and only 7 (14.2%)

Journal of Clinical Neonatology  ¦  Volume 10  ¦  Issue 1  ¦  January-March 2021 7

[Downloaded free from http://www.jcnonweb.com on Monday, February 8, 2021, IP: 99.239.6.196]

Sobeir, et al.: Clinical manifestation of Necrotizing enterocolitis

weighed >1500 g with a P = 0.05. Decreased Gestational Age per week

birth weight is also known to be associated with 8
NEC [Figure 3].[6,17] 7
7
6 6
Positive blood culture was present in half of our 6
5 5 5
cases, with for [Figure 4] most being Gram‑positive, 5
4 4 4
while less than half were Gram‑negative cultures. In 4
3
the literature, studies have revealed the association 3

of sepsis with NEC.[9] Previous studies show that the 2

most common organism identified in NEC infants are 1

Gram‑negative (Escherichia coli, Klebsiella pneumonia, 0

˂24 24 25 26 27 28 29 30 31 32
Proteus, Staphylococcus aureus, Staphylococcus
epidermidis, Enterococcus spp, Clostridium perfringeous, Figure 2: Gestational age by weeks
and Pseudomonas aeruginous) while in the majority of
our cases has staphylococcus followed by Klebsiella.[10] Birthweight

Eighty‑five percent of the babies who developed 7

NEC were on enteral feeding which is similar to the cases
percentage (90%) reported by Huda et  al.[9,17] The weighted less than 1,000 grams
average age at which the infants commenced feeding
was 5 days and only 7 (14.3%) developed NEC while 14 28 weighted 1,000-1,499 grams
cases cases
they were on “nothing by mouth” (NPO). Most of the weighted more than 1,500 grams
feeding interventions that neonatologists adopt aim to
encourage the rapid achievement of full enteral feedings
to improve postnatal growth, but this approach may
potentially increase the risk of NEC. However, the Figure 3: Neonatal birthweight
provision of a full package of standardized feeding
regimens and practice may decrease the frequency Organisms
25
of NEC as adopted and followed in our hospital.[16] 21
20
Seventy‑eight percent reduction in the staging of NEC 14
15
was observed with the use of a standardized feeding
10
regimen.[13] When feeding was delayed beyond 4 days 5
5 2 1 1 1 1 1 1 1
after birth, it did not cause a reduction in the occurrence 0
of NEC.[12]
No growth

Staphepidermis

Klebsilla pneumonia

Enterobactercoloace

Enterobacter fecalis

Staphaureus

Staph species

Ecoli

Candida

About half (47%) of the babies develop NEC while
they were on breast milk, about 29% on formula feed
and 14.3% were NPO. Breastfeeding has a well‑known
protective effect on NEC,[14,18,19] perhaps due to the
bioactive components in a mother’s milk that functions
synergistically to provide multiple levels of protection
from NEC, including immunomodulatory, anti‑infective,
antioxidant, growth‑promoting, and gut colonizing
effects. The concentration of bioactive components is
highest in colostrum and transitional milk.[14,17]
Our study showed that the presence of a umbilical artery
catheter (UAC) increased the risk of NEC. Fifty‑one
percent had no UAC and a lesser number of the cases
had UAC with a P = 0.027. However, some researchers
showed no association between developing NEC and
the insertion of UAC in contrast to our study. A study
conducted by Rand et  al. showed decreased mesenteric
blood flow with the use of UAC, and they recommended
it to be used carefully in hemodynamically unstable
Yeast
Pseudomonas
Figure 4: Organism
neonates.[20] Similarly, another study showed that the
umbilical artery or venous catheter did not seem to
increase the risk of NEC.[10]
Hypotension before the development of NEC requiring
treatment with inotropes was significant in our study.
The literature review showed that hypotension, which
required inotropic support is a well‑known risk factor
for NEC.[5] Surfactant administration was seen in more
than half of our NEC patients, which was not significant.
Data from studies that investigated the use of surfactant
as a risk factor showed huge conflict with some studies
showed no association between NEC and the use of
surfactant.[4]

8 Journal of Clinical Neonatology  ¦  Volume 10  ¦  Issue 1  ¦  January-March 2021

[Downloaded free from http://www.jcnonweb.com on Monday, February 8, 2021, IP: 99.239.6.196]
Sobeir, et al.: Clinical manifestation of Necrotizing enterocolitis
Theoretically, red blood cell transfusion is possibly one
predisposing factor of NEC; from our research, half
of NEC babies had received red blood cell transfusion
48 h before developing NEC. Transfusion‑associated
NEC (TANEC) is the recently described entity that
refers to preterm babies who developed NEC within 48
h of receiving a blood transfusion. TANEC is associated
with NEC in over one‑fourth of the babies.[3,7] The
risk of TANEC was higher with lower pretransfusion
hematocrit.[12] Etiology may relate to an increase
proinflammatory cytokine seen after transfusion in
neonates, alteration in vascular adaptability after
transfusion as well as altered blood flow velocity and
reperfusion injury related to the sudden correction of
anemia in poorly perfused and oxygenated intestinal
tissue.[12] Garg and Sinha performed a meta‑analysis of
17 observational studies and did not find an independent
association between blood transfusion and NEC.[12]
Abdominal radiographs confirm the diagnosis of NEC
and allow following the progression of the disease.[7]
All cases with pneumoperitoneum were diagnosed as
Stage 3, which around 59.2%, Stage 2 occurred in 26.5%
of total cases, and Stage 1 in 14.3%. Stage 1 is the most
challenging stage to be diagnosed because it had a lot of
differential diagnoses, for example, viral gastroenteritis,
sepsis, and feeding intolerance of prematurity.[2]
Pneumoperitoneum is high in our study group may be
explained partially by we are not using probiotics yet in
our unit. Studies showed probiotics decrease the rate of
NEC by around 50%.[8]
Recurrent NEC was not common in our study group,
which occurred in only one case during the study
period, which is less than the reported percentage[5,11]
Moreover, some literature review also reveals that up
to 10% of NEC cases can develop recurrent NEC.[11]
Fortunately, the majority of patients with recurrent NEC
are successfully treated nonoperatively.[4] Prolong use of
TPN increases the chances of TPN‑cholestasis, which
was significant in our babies, and is known to be an
associated complication.[1] In our study group, 7 cases
developed TPN complications. One study showed that
42% of surgical NEC developed cholestasis, but this
cholestasis does not increase the mortality.[21]
Bowel stricture significantly occurred in a few of our
cases. Bowel strictures are known to occur mainly in
the left colon in one‑third of the cases when an area of
the intestine heals with scarring after both operative and
nonoperative management.[4,7] An insignificant number of
babies also developed short bowel syndrome. However,
from the literature review, short bowel syndrome is
the most severe postoperative complication of NEC,
Journal of Clinical Neonatology  ¦  Volume 10  ¦  Issue 1  ¦  January-March 2021
occurring in as many as 22%–35% after resection
of more than 20 cm.[22] These infants go through a
prolonged period of intestinal rehabilitation, depending
on the size of the remaining viable gut. The neonatal gut
typically grows and adapts over time, but this growth
may take up to 2 years. Most infants have a normal gut
function at 1–10 years of age.[11] Therefore, 12 of our
cases subsequently developed complications because of
NEC.
Babies that need surgical intervention including primary
peritoneal drainage, laparotomy with resection and
enterostomy, resection with primary anastomosis, or
proximal diverting jejunostomy. Surgical indications of
NEC include pneumoperitoneum, deteriorating infant
despite maximum medical treatment, abdominal mass,
and signs of persistent intestinal obstruction. Relative
indications include increased abdominal tenderness,
distention, or persistence portal vein gas.[9] Researchers
are still attempting to determine the optimal time for
surgical intervention and appropriate techniques to
be used.[23] Approximately 46.9% of our study group
required surgical intervention while 53.1% were treated
by conservative management, which is almost similar
to the study results of AlFaleh et  al., 27%–63%.[7]
Compared to age‑matched controls without NEC, infants
with medically managed NEC had 22 days longer
length of stay and those with surgically managed NEC
had 60 days longer length of stay.[4] Among VLBW
infants, surgical NEC was associated with significant
growth delay and adverse neurodevelopmental outcomes
at 18–22 months corrected age compared with no
NEC. However, medical NEC does not seem to confer
additional risk. Surgical NEC is likely associated
with greater severity of the disease.[13] Approximately
50% of neonates who developed NEC have a
neurodevelopmental effect, mainly motor developmental
delay that seems to be mediated by white matter
abnormalities on brain imaging.[4,10]
Conclusion
From our study, the prevalence of NEC in our NICU
was lower, but our mortality rate was similar to those
reported. Multigravida mothers have an increased risk
of NEC by more than double, more than half of our
babies developed advanced NEC, which is double the
reported figures found in other studies. Measured to
decrease NEC with the use of mother own milk and
probiotics is strongly recommended. It is a single‑center
study; however, it is a sizeable local study identifying
maternal, neonatal risk factors and outcome of NEC.
The importance of the use of probiotics shown clearly
in our study increased advanced NEC but not the rate
9
[Downloaded free from http://www.jcnonweb.com on Monday, February 8, 2021, IP: 99.239.6.196]
Sobeir, et al.: Clinical manifestation of Necrotizing enterocolitis
of NEC. Further local and regional studies are needed
to evaluate such serious problems and associated risk
factors as well as explore possible preventive measures.
Acknowledgments
The authors would like to thanks the Research Centre,
King Fahad Medical City, Riyadh, Saudi Arabia, for
providing support in preparing this manuscript.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Magnusson A, Ahle M, Swolin‑Eide D, Elfvin A, Andersson RE.
Population‑based study showed that necrotising enterocolitis
occurred in space‑time clusters with a decreasing secular trend in
Sweden. Acta Paediatr 2017;106:1097‑102.
2. Ahle M. Necrotising Enterocolitis: Epidemiology and
Imaging. [PhD dissertation]. [Linköping]; 2017. (Linköping
University Medical Dissertations). Available from: http://urn.
kb.se/resolve?urn=urn:nbn:se:liu:diva‑142375. [Last accessed on
2019 Aug 31].
3. Lin HY, Chang JH, Chung MY, Lin HC. Prevention of
necrotizing enterocolitis in preterm very low birth weight infant:
Is it feasible? J Formos Med Assoc 2014;113:490‑7.
4. Raval MV, Moss RL. Surgical necrotizing enterocolitis: A primer
for the neonatologist. Neo Rev 2013;14:e393‑401.
5. Samuels N, van de Graaf RA, de Jonge RCJ, Reiss IKM,
Vermeulen MJ. Risk factors for necrotizing enterocolitis in
neonates: A systematic review of prognostic studies. BMC
Pediatr 2017;17:105.
6. Schanler RJ, Abrams SA, Kim MS. Clinical Features and
Diagnosis of Necrotizing Enterocolitis in Newborn; May,
2010. Available from: https://pdfs.semanticscholar.org/5411/
b72c1f6d4055745a6e634284a097bcd4a252.pdf. [Last accessed
on 2019 Aug 31].
7. Alfaleh K, Anabrees J, Bassler D. Probiotics reduce the risk of
necrotizing enterocolitis in preterm infants: A meta‑analysis.
Neonatology 2010;97:93‑9.
8. Jacobs SE, Tobin JM, Opie GF, Donath S, Tabrizi SN, Pirotta M,
et al. ProPrems study group. probiotic effect on late‑onset sepsis
in very preterm infant a randomized controlled trial. Pediatrics
2013;132:1055‑62.
10 Journal of Clinical Neonatology  ¦  Volume 10  ¦  Issue 1  ¦  January-March 2021
9. Huda S, Chaudhery S, Ibrahim H, Pramanik A. Neonatal
necrotizing enterocolitis: Clinical challenges, pathophysiology
and management. Pathophysiology 2014;21:3‑12.
10. Zani A, Pierro A. Necrotizing enterocolitis: Controversies and
challenges. F1000Res 2015;4:F1000.
11. Battersby C, Santhalingam T, Costeloe K, Modi N. Incidence
of neonatal necrotising enterocolitis in high‑income countries:
A systematic review. Arch Dis Child Fetal Neonatal Ed
2018;103:F182‑9.
12. Thompson‑Branch  AM, Havranek  T. Influences of feeding on
necrotizing enterocolitis. Neo Reviews 2018;19;e664.
13. Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA,
Donovan EF, et al. Neurodevelopmental and growth outcomes of
extremely low birth weight infants after necrotizing enterocolitis.
Pediatrics 2005;115:696‑703.
14. Patel AL, Kim JH. Human milk and necrotizing enterocolitis.
Semin Pediatr Surg 2018;27:34‑8.
15. Alganabi M, Lee C, Bindi E, Li B, Pierro A. Recent advances
in understanding necrotizing enterocolitis. F1000Res 2019;8:pii:
F1000.
16. Choi YY. Necrotizing enterocolitis in a newborn update in
pathophysiology and newly emerging therapeutic strategies.
Korean J Pediatr 2014:57:505‑13.
17. Boo NY, Cheah IG. Risk factors associated with
necrotising enterocolitis in very low birth weight infants in
Malaysian neonatal intensive care units. Singapore Med J
2012;53:826‑31.
18. Garg S, Sinha S. The rapidity of advancement of feedings in
premature infants: Evidence basis and current recommendations.
NeoReviews 2018;19;e675-e681.
19. Probiotics to Prevent Necrotizing Enterocolitis in Preterm Infants.
Cochrane Review, Eyes on Evidence Newsletter National Institute
for Health and Care Excellence; February, 2015. Available fro
m: https://www.nice.org.uk/Media/Default/newsletter/Eyes%20
on%20Evidence%20February%202015.pdf. [Last accessed on
2019 Aug 31].
20. Rand T, Weninger M, Kohlhauser C, Bischof S, Heinz‑Peer G,
Trattnig S, et al. Effects of umbilical arterial catheterization on
mesenteric hemodynamics. Pediatr Radiol 1996;26:435‑8.
21. Karila K, Anttila A, Iber T, Pakarinen M, Koivusalo A.
Intestinal failure associated cholestasis in surgical necrotizing
enterocolitis and spontaneous intestinal perforation. J Pediatr
Surg 2019;54:460‑4.
22. Hong CR, Fullerton BS, Modi BP. Neonatal short bowel
syndrome. NeoReviews 2017;18;e480.
23. Henry MC, Moss RL. Laparotomy versus peritoneal drainage for
perforated necrotizing enterocolitis. NeoReviews 2006;7;e456.