Abstract
Progress in our understanding of the pathophysiology, prevention and treatment of necrotizing enterocolitis (NEC) has been hampered for many reasons. Included among these is the fact that what we are calling “NEC” is likely to represent different disease processes, which need to be delineated before evaluating individual pathogenic mechanisms and attempting to develop predictive and diagnostic biomarkers. Treatment is also likely to be hampered because not all of the different entities called “NEC” will respond to the same regimen. In this review, some of these entities will be discussed in more detail, with suggestions for refining our approach toward improving methods for their diagnosis, prevention and treatment.
References
1.
Neu
J
, Walker
WA
. Necrotizing enterocolitis
. N Engl J Med
. 2011
Jan
;364
(3
):255
–64
.
[PubMed]
0028-47932.
Bazacliu
C
, Neu
J
. Necrotizing enterocolitis: long term complications
. Curr Pediatr Rev
. 2019
;15
(2
):115
–24
.
[PubMed]
1573-39633.
Neu
J
. Necrotizing enterocolitis: the mystery goes on
. Neonatology
. 2014
;106
(4
):289
–95
.
[PubMed]
1661-78004.
Neu
J
, Modi
N
, Caplan
M
. Necrotizing enterocolitis comes in different forms: historical perspectives and defining the disease
. Semin Fetal Neonatal Med
. 2018
Dec
;23
(6
):370
–3
.
[PubMed]
1744-165X5.
Obladen
M
. Necrotizing enterocolitis—150 years of fruitless search for the cause
. Neonatology
. 2009
;96
(4
):203
–10
.
[PubMed]
1661-78006.
Fitzgibbons
SC
, Ching
Y
, Yu
D
, Carpenter
J
, Kenny
M
, Weldon
C
, et al. Mortality of necrotizing enterocolitis expressed by birth weight categories
. J Pediatr Surg
. 2009
Jun
;44
(6
):1072
–5
.
[PubMed]
0022-34687.
Soni
R
, Katana
A
, Curry
JI
, Humphries
PD
, Huertas-Ceballos
A
. How to use abdominal X-rays in preterm infants suspected of developing necrotising enterocolitis
. Arch Dis Child Educ Pract Ed
. 2020
Feb
;105
(1
):50
–7
.
[PubMed]
1743-05938.
Kim
WY
, Kim
WS
, Kim
IO
, Kwon
TH
, Chang
W
, Lee
EK
. Sonographic evaluation of neonates with early-stage necrotizing enterocolitis
. Pediatr Radiol
. 2005
Nov
;35
(11
):1056
–61
.
[PubMed]
0301-04499.
Kim
JH
. Role of abdominal US in diagnosis of NEC
. Clin Perinatol
. 2019
Mar
;46
(1
):119
–27
.
[PubMed]
0095-510810.
Cuna
AC
, Lee
JC
, Robinson
AL
, Allen
NH
, Foley
JE
, Chan
SS
. Bowel ultrasound for the diagnosis of necrotizing enterocolitis: a meta-analysis
. Ultrasound Q
. 2018
Sep
;34
(3
):113
–8
.
[PubMed]
1536-025311.
Janssen Lok
M
, Miyake
H
, Hock
A
, Daneman
A
, Pierro
A
, Offringa
M
. Value of abdominal ultrasound in management of necrotizing enterocolitis: a systematic review and meta-analysis
. Pediatr Surg Int
. 2018
Jun
;34
(6
):589
–612
.
[PubMed]
0179-035812.
Gordon
PV
, Swanson
JR
. Necrotizing enterocolitis is one disease with many origins and potential means of prevention
. Pathophysiology
. 2014
Feb
;21
(1
):13
–9
.
[PubMed]
0928-468013.
Battaglia
M
, Ahmed
S
, Anderson
MS
, Atkinson
MA
, Becker
D
, Bingley
PJ
, et al. Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes
. Diabetes Care
. 2020
Jan
;43
(1
):5
–12
.
[PubMed]
0149-599214.
Aldana-Valenzuela
C
, Mannino
FL
. [Spontaneous intestinal perforation in newborn infants. A form of necrotizing enterocolitis]
. Bol Méd Hosp Infant México
. 1989
;46
:30
–4
.0539-611515.
Zamir
O
, Goldberg
M
, Udassin
R
, Peleg
O
, Nissan
S
, Eyal
F
. Idiopathic gastrointestinal perforation in the neonate
. J Pediatr Surg
. 1988
Apr
;23
(4
):335
–7
.
[PubMed]
0022-346816.
Adderson
EE
, Pappin
A
, Pavia
AT
. Spontaneous intestinal perforation in premature infants: a distinct clinical entity associated with systemic candidiasis
. J Pediatr Surg
. 1998
Oct
;33
(10
):1463
–7
.
[PubMed]
0022-346817.
Mintz
AC
, Applebaum
H
. Focal gastrointestinal perforations not associated with necrotizing enterocolitis in very low birth weight neonates
. J Pediatr Surg
. 1993
Jun
;28
(6
):857
–60
.
[PubMed]
0022-346818.
Pumberger
W
, Mayr
M
, Kohlhauser
C
, Weninger
M
. Spontaneous localized intestinal perforation in very-low-birth-weight infants: a distinct clinical entity different from necrotizing enterocolitis
. J Am Coll Surg
. 2002
Dec
;195
(6
):796
–803
.
[PubMed]
1072-751519.
Vongbhavit
K
, Underwood
MA
. Intestinal perforation in the premature infant
. J Neonatal Perinatal Med
. 2017
;10
(3
):281
–9
.
[PubMed]
1934-579820.
Paquette
L
, Friedlich
P
, Ramanathan
R
, Seri
I
. Concurrent use of indomethacin and dexamethasone increases the risk of spontaneous intestinal perforation in very low birth weight neonates
. J Perinatol
. 2006
Aug
;26
(8
):486
–92
.
[PubMed]
0743-834621.
Shah
BA
, Migliori
A
, Kurihara
I
, Sharma
S
, Lim
YP
, Padbury
J
. Blood level of inter-alpha inhibitor proteins distinguishes necrotizing enterocolitis from spontaneous intestinal perforation
. J Pediatr
. 2017
Jan
;180
:135
–140.e1
.
[PubMed]
0022-347622.
Eicher
C
, Seitz
G
, Bevot
A
, Moll
M
, Goelz
R
, Arand
J
, et al. Surgical management of extremely low birth weight infants with neonatal bowel perforation: a single-center experience and a review of the literature
. Neonatology
. 2012
;101
(4
):285
–92
.
[PubMed]
1661-780023.
Ostlie
DJ
, Spilde
TL
, St Peter
SD
, Sexton
N
, Miller
KA
, Sharp
RJ
, et al. Necrotizing enterocolitis in full-term infants
. J Pediatr Surg
. 2003
Jul
;38
(7
):1039
–42
.
[PubMed]
0022-346824.
McElhinney
DB
, Hedrick
HL
, Bush
DM
, Pereira
GR
, Stafford
PW
, Gaynor
JW
, et al. Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes
. Pediatrics
. 2000
Nov
;106
(5
):1080
–7
.
[PubMed]
0031-400525.
Spinner
JA
, Morris
SA
, Nandi
D
, Costarino
AT
, Marino
BS
, Rossano
JW
, et al. Necrotizing enterocolitis and associated mortality in neonates with congenital heart disease: a multi-institutional study
. Pediatr Crit Care Med
. 2019
Sep
;1
.; Epub ahead of print
.
[PubMed]
1529-753526.
Caubet
JC
, Cianferoni
A
, Groetch
M
, Nowak-Wegrzyn
A
. Food protein-induced enterocolitis syndrome
. Clin Exp Allergy
. 2019
Sep
;49
(9
):1178
–90
.
[PubMed]
0954-789427.
Miceli Sopo
S
, Gelsomino
M
, Rivetti
S
, Del Vescovo
E
. Food protein-induced enterocolitis syndrome: proposals for new definitions
. Medicina (Kaunas)
. 2019
May
;55
(6
):55
.
[PubMed]
1648-914428.
Petrosino
MI
, Scaparrotta
A
, Di Filippo
P
, Attanasi
M
, Di Pillo
S
, Chiarelli
F
, et al. Food protein-induced enterocolitis syndrome in children: what’s known? What’s new?
Eur Ann Allergy Clin Immunol
. 2018
May
;50
(3
):99
–107
.
[PubMed]
1764-148929.
Lenfestey
MW
, de la Cruz
D
, Neu
J
. Food protein-induced enterocolitis instead of necrotizing enterocolitis? A Neonatal Intensive Care Unit case Series. J Pediatr. 2018
;200:270-3.s30.
Gosain
A
, Frykman
PK
, Cowles
RA
, Horton
J
, Levitt
M
, Rothstein
DH
, et al.; American Pediatric Surgical Association Hirschsprung Disease Interest Group
. Guidelines for the diagnosis and management of Hirschsprung-associated enterocolitis
. Pediatr Surg Int
. 2017
May
;33
(5
):517
–21
.
[PubMed]
0179-035831.
Weitkamp
JH
, Koyama
T
, Rock
MT
, Correa
H
, Goettel
JA
, Matta
P
, et al. Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratios
. Gut
. 2013
Jan
;62
(1
):73
–82
.
[PubMed]
0017-574932.
Van Belkum
M
, Mendoza Alvarez
L
, Neu
J
. Preterm neonatal immunology at the intestinal interface
. Cell Mol Life Sci
. 2019
Oct
; Epub ahead of print
.
[PubMed]
1420-682X33.
Benkoe
TM
, Mechtler
TP
, Weninger
M
, Pones
M
, Rebhandl
W
, Kasper
DC
. Serum levels of interleukin-8 and gut-associated biomarkers in diagnosing necrotizing enterocolitis in preterm infants
. J Pediatr Surg
. 2014
Oct
;49
(10
):1446
–51
.
[PubMed]
0022-346834.
Claud
EC
, Walker
WA
. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis
. FASEB J
. 2001
Jun
;15
(8
):1398
–403
.
[PubMed]
0892-663835.
Dorling
J
, Abbott
J
, Berrington
J
, Bosiak
B
, Bowler
U
, Boyle
E
, et al.; SIFT Investigators Group
. Controlled trial of two incremental milk-feeding rates in pretermiInfants
. N Engl J Med
. 2019
Oct
;381
(15
):1434
–43
.
[PubMed]
0028-479336.
Lenfestey
MW
, Neu
J
. Probiotics in newborns and children
. Pediatr Clin North Am
. 2017
Dec
;64
(6
):1271
–89
.
[PubMed]
0031-3955© 2020 S. Karger AG, Basel
2020
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
