DOI: 10.1542/peds.

2011-2022
; originally published online January 23, 2012; 2012;129;e298 Pediatrics
Yoon, Shoo K. Lee and the Canadian Neonatal Network
Wendy H. Yee, Amuchou Singh Soraisham, Vibhuti S. Shah, Khalid Aziz, Woojin
Infants
Incidence and Timing of Presentation of Necrotizing Enterocolitis in Preterm

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Incidence and Timing of Presentation of Necrotizing
Enterocolitis in Preterm Infants
WHATS KNOWN ON THIS SUBJECT: Necrotizing enterocolitis
(NEC) can present within the rst week of life in term infants. In
preterm infants, NEC usually appears after commencement of
feeds and can occur between 2 and 3 weeks of life.
WHAT THIS STUDY ADDS: Among infants ,33 weeks gestation,
NEC appears to occur at mean age of 7 days in more mature
infants, whereas onset of NEC is delayed to 32 days of age in
smaller, lower gestational age infants.
abstract
OBJECTIVES: To examine the variation in the incidence and to identify
the timing of the presentation of necrotizing enterocolitis (NEC) in a
cohort of preterm infants within the Canadian Neonatal Network
(CNN).
METHODS: This was a population-based cohort of 16 669 infants with
gestational age (GA) ,33 weeks, admitted to 25 NICUs participating in
the CNN between January 1, 2003, and December 31
,
2008. Variations
in NEC incidence among the participating NICUs for the study period
were examined. We categorized early-onset NEC as occurring at ,14
days of age and late-onset NEC occurring at $14 days. Multivariate
logistic regression analysis was performed to identify risk factors for
early-onset NEC.
RESULTS: The overall incidence of NEC was 5.1%, with signicant var-
iation in the risk adjusted incidence among the participating NICUs in
the CNN. Early-onset NEC occurred at a mean of 7 days compared with
32 days for late-onset NEC. Early-onset NEC infants had lower incidence
of respiratory distress syndrome, patent ductus treated with indomethacin,
less use of postnatal steroids, and shorter duration of ventilation days.
Multivariate logistic regression analysis identied that greater GA and
vaginal delivery were associated with increased risk of early-onset NEC.
CONCLUSIONS: Among infants ,33 weeks gestation, NEC appears to
present at mean age of 7 days in more mature infants, whereas onset
of NEC is delayed to 32 days of age in smaller, lower GA infants.
Further studies are required to understand the etiology of this dis-
ease process. Pediatrics 2012;129:e298e304
AUTHORS: Wendy H. Yee, MD, FRCPC, MSc,
a
Amuchou Singh
Soraisham, MD, DM, FRCPC, MSc,
a
Vibhuti S. Shah, MD,
MRCP, FRCPC,
b
Khalid Aziz, MBBS, FRCPC,
c
Woojin Yoon,
MSc,
b
Shoo K. Lee, MBBS, FRCPC, PhD,
b
and the Canadian
Neonatal Network
a
Department of Pediatrics, Alberta Childrens Hospital Research
Institute for Child and Maternal Health, University of Calgary,
Alberta, Canada;
b
Department of Pediatrics, Maternal-Infant
Care Center, Mount Sinai Hospital, University of Toronto, Toronto,
Canada; and
c
Department of Pediatrics, University of Alberta,
Alberta, Canada
KEY WORDS
necrotizing enterocolitis, preterm infant, incidence
ABBREVIATIONS
BWbirth weight
CNNCanadian Neonatal Network
GAgestational age
IVHintraventricular hemorrhage
NECnecrotizing enterocolitis
PDApatent ductus arteriosus
RDSrespiratory distress syndrome
SGAsmall for gestational age
SIPspontaneous intestinal perforation
SNAP-IIScore for Neonatal Acute Physiology, version II
VLBWvery low birth weight
Drs Yee and Soraisham were involved in the study conception,
design, interpretation of data, and drafting the article; Drs Shah
and Aziz contributed to the study conception, design,
interpretation of data, and critical review of the article; and Drs
Yoon and Lee were involved in acquisition of data, data analysis,
interpretation of data, and critical review of the article.
www.pediatrics.org/cgi/doi/10.1542/peds.2011-2022
doi:10.1542/peds.2011-2022
Accepted for publication Oct 11, 2011
Address correspondence to Wendy H. Yee, MD, FRCPC, MSc,
Rockyview General Hospital, 63-7007 14 St SW, Calgary, AB, Canada
T2V 1P9. E-mail: wendy.yee@albertahealthservices.ca
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2012 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no nancial relationships relevant to this article to disclose.
e298 YEE et al
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Necrotizing enterocolitis (NEC) is one of
the leading causes of morbidity and
mortality in preterm infants.
13
The
incidence of NEC has remained rela-
tively stable over recent epochs in the
very low birth weight (VLBW) infant po-
pulations. The Eunice Kennedy Shriver
National Institute of Child Health and
Human Development Neonatal Research
Network reported gestational age (GA)
specic mean incidence of NEC of 3% to
11% between 1997 and 2000
4
and 5% to
15% between 2003 and 2007.
5
Other
single centers and neonatal networks
have reported similar incidence of NEC.
6
8
One group
9
from Australia has repor-
ted a decrease in the incidence in NEC
from 12% between 1992 and 1993 com-
pared with 6% between 1998 and 1999
for infants 24 to 28 weeks gestation.
9
Traditionally, NEC in the preterm infant
is described in enterally fed infants
occurring at several days, if not weeks
of age.
2,10
Lin and Stoll,
1
in their review,
state that the disease [NEC] is espe-
cially poignant because it mainly
affects premature infants who have
survived the early neonatal period and
subsequently face a disease with high
morbidity and mortality. The mortality
for NEC can be as high as 50% and
surgical treatment is necessary in
almost 20% to 40%. The inverse re-
lationship between GA and age of onset
of NEC has been well documented,
11,12
with term infants presenting with NEC
in the rst week of life. Based on recent
clinical experience, we raise the ques-
tion of whether there is an earlier on-
set of NEC emerging in the VLBW infant
population as some infants appear to
be presenting with NEC in the rst week
of life.
Sankaran et al
13
reported that there
was no signicant variation in the risk
adjusted incidence of NEC among Ca-
nadian NICUs. Since that publication,
the number of participating NICUs in
the Canadian Neonatal Network (CNN)
has increased from 17 to 25. By using
this expanded network cohort we un-
dertook this study (1) to examine the
variation in the incidence and (2) to
identify the timing of the presentation of
NEC in a national population-based co-
hort of infants ,33 weeks GA admitted
to participating NICUs of the CNN.
METHODS
Study Population
This population-based cohort included
16 669 infants with GA ,33 weeks ad-
mitted to 25 NICUs participating in the
CNN between January 1, 2003, and De-
cember 31, 2008.
Data Collection
The CNN maintains an established na-
tional database for the purposes of
outcomes evaluation, benchmarking,
and quality improvement. Data for CNN
are collected from patient charts by
trained data abstractors at each of the
participating NICUs in accordance to
the manual of standardized operational
denitions for variables and outcomes
dened by the CNN. Details of data
collection and data management have
been published elsewhere.
14
Ethical
approval was obtained from the in-
stitutional review board of all partici-
pating institutions.
Denitions
Indices of neonatal outcome were de-
ned according to the CNN Data Ab-
stractor Manual.
14
GA was calculated
from the best obstetric estimate based
on early prenatal ultrasound exami-
nation, obstetric examination, and ob-
stetric history, if the postnatal pediatric
estimate of gestation differed from the
obstetric estimate by more than 2
weeks, the pediatric estimate was
used. NEC was dened according to
modied Bells criteria ($ stage 2),
15
and patent ductus arteriosus (PDA)
was dened as clinical diagnosis plus
treatment with indomethacin, surgical
ligation, or both. Bronchopulmonary
dysplasia was dened as requirement
for oxygen at 36 weeks corrected GA
16
or at discharge from the participating
unit. Retinopathy of prematurity was di-
agnosed according to the international
classication of retinopathy of pre-
maturity.
17
Diagnosis and severity of
intraventricular hemorrhage (IVH) was
based on the criteria of Papile.
18
Se-
verity of illness was measured by the
Score for Neonatal Acute Physiology,
version II (SNAP-II) as described by
Richardson et al.
19
Small for GA (SGA)
was dened as birth weight (BW)
,10th percentile for the given GA, and
outborn status was dened if the infant
was born at a hospital different from
the one in which the participating NICU
was located. Congenital anomalies were
identied from a dened list within the
CNN database.
Data Analysis
We performed 2 separate analyses to
identify: (1) risk factors for NEC, and (2)
risk factors for early-onset NEC.
In the rst analysis, univariate analyses
were performed to describe the char-
acteristics of the study population and
to explore associations between pop-
ulation characteristics and NEC. Multi-
variate logistic regression model was
used to identify risk factors for NEC. The
variables shown to be signicantly
different (P ,.05) between the infants
diagnosed with NEC and those without
NEC in the univariate analyses were
selected as possible risk factors for
NEC and entered in the model.
Variations in NEC incidence among the
participatingNICUs for the study period
were examined by looking at crude and
risk adjusted odds ratios for the NEC
incidence, where the site with median
incidence rate was chosen as the ref-
erence site. Variables included in the
adjusted model were GA, Apgar score at
5 minutes, SNAP-II, girl, cesarean de-
livery, outborn infant, and SGA.
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Thehistogramof the time to onset of NEC
for the cohort suggested a bimodal
distributionwiththe rst peak aroundat
8 days of age and the second peak
around at 19 days of age. The least
overlap between the 2 distributions was
notedtobeat day14. Basedonthiscutoff,
we categorized early-onset NEC as oc-
curring at ,14 days of age and late-
onset NEC occurring at $14 days. A
second analysis was restricted to the
subset of infants with NEC. Inthis second
analysis, univariate analyses were per-
formed to explore the characteristics of
infants with early- and late-onset NEC.
Multivariate logistic regression analysis
was performed to identify risk factors
for early-onset NEC. Signicant variables
(P , .05) identied on univariate anal-
yses were entered into the regression
model. Statistical signicance was con-
sidered to be present at the level P ,
.05. Statistical analysis was performed
by using SAS version 9.2 (SAS Institute,
Inc, Cary, NC) software package.
RESULTS
NEC in the Cohort
Of the 16 669 preterm infants ,33
weeks admitted during the study pe-
riod, 858 (5.1%) infants had NEC $
stage 2. Baseline characteristics and
clinical outcomes of infants with and
without NEC are presented in Table 1.
The neonatal factors signicantly cor-
related with NEC were lower BW, GA,
and 5-minute Apgar score, higher ad-
mission SNAP-II, SGA infant, outborn
infant, use of narcotic in the rst 3 days
of life, and postnatal steroid use. Clinical
morbidities signicantly associated
with NEC were respiratory distress
syndrome (RDS), PDA treated with in-
domethacin after 24 hours of age,
nosocomial infection, IVH $ grade 3,
and more ventilation days. Mortality
was signicantly higher in infants with
NEC compared with those without NEC.
On multivariate logistic regression anal-
ysis, risk factors for NEC were lower GA,
SGA infant, outborn infant, narcotic use
during the rst 3 days of life, postnatal
steroid use, and presence of congenital
anomalies (Table 2).
Variations in the Incidence of NEC
The overall incidence of NEC was 858 of
16 669 (5.1%) with crude incidence
varying from 1.3% to 12.9% (median
4.6%). Figure 1 shows that there was
signicant variation in the risk ad-
justed incidences of NEC among the
participating NICUs. Six NICUs had sig-
nicantly increased incidence of NEC
compared with the reference site with
the median incidence rate, whereas 2
sites had lower incidence of NEC.
Early- Versus Late-Onset NEC
The time of diagnosis of NEC (in days)
was documented in 841 of 858 (98%) of
infants. Of the 841 infants, 336 (40%)
infants had early-onset NEC, whereas
505 infants had late-onset NEC. The
mean (SD) age of diagnosis in the early-
onset NEC group was 7.6 (3.1) days as
compared with 32 (17.2) days among
the late-onset NEC group. The incidence
of surgical NEC was signicantly higher
in early-onset NEC group (40%) com-
pared with late-onset NEC group (28%;
P , .001). Figure 2 shows the distri-
bution of cases according to GA at birth
and the postmenstrual age at the time
of NEC diagnosis. The peak onset of NEC
TABLE 1 Characteristics of Infants With and Without NEC
NEC
N = 858
No NEC
N = 15 811
P
BW, g
a
1059 6 384 1324 6 457 ,.001
GA, wk
a
27.4 6 2.5 29 6 2.5 ,.001
Boy, n (%) 477 (55.5) 8519 (53.8) .28
Multiple births, n (%) 237 (27.6) 4821 (30.4) .07
Antenatal steroid, n (%) 688 (80) 12 390 (78.3) .18
Chorioamnionitis, n (%) 104 (12.1) 1758 (11.1) .24
Cesarean delivery, n (%) 500 (58.2) 9170 (58) .80
Apgar score at 5 min
b
8 (6.9) 8 (7.9) ,.001
SNAP-II
b
14 (5, 22) 9 (0, 14) ,.001
SGA, n (%) 107 (12.4) 1594 (10) .02
Outborn, n (%) 266 (31) 3062 (19.3) ,.001
Congenital anomalies, n (%) 310 (36) 3563 (23) ,.001
Narcotic use in rst 3 d, n (%) 332 (38.6) 2826 (17.8) ,.001
RDS, n (%) 651 (75.8) 9872 (62.4) ,.001
PDA, indomethacin .24 h, n (%) 283 (32.9) 3356 (21.2) ,.001
Early onset sepsis, n (%) 6 (0.6) 170 (1) .29
Nosocomial sepsis, n (%) 385 (44.8) 2450 (15.4) ,.001
IVH $ grade 3, n (%) 163 (19) 1561 (9.8) ,.001
Postnatal steroids, n (%) 296 (34.4) 2037 (12.8) ,.001
Duration of ventilation, d
b
14 (4, 37) 2 (0, 7) ,.001
Mortality, n (%) 215 (25) 1075 (6.7) ,.001
a
Mean 6 SD.
b
Median (interquartile range).
TABLE 2 Risk Factors for NEC From Multivariate Logistic Regression Analysis
Adjusted Odds Ratio (95% Condence Interval) P
GA 0.84 (0.810.87) ,.001
SGA 1.35 (1.081.69) .007
Narcotics in rst 3 d 1.97 (1.672.32) ,.001
Outborn 1.55 (1.311.83) ,.001
Postnatal steroids 1.71 (1.432.06) ,.001
PDA treated with indomethacin 0.98 (0.821.16) .84
Apgar at 5 min 1.03 (0.981.07) .16
SNAP-II 0.99 (0.991.003) .36
RDS 1.12 (0.931.36) .22
Congenital anomalies 1.41 (1.432.06) ,.001
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in this cohort was 32 weeks post-
menstrual age.
As shown in Table 3, early-onset NEC
infants were of greater BW and GA, had
higher 5-minute Apgar score, were
more likely to be delivered vaginally,
had lower SNAP-II, and had a lower rate
of congenital anomalies on univariate
analysis. Compared with late-onset NEC
infants, the early-onset NEC infants had
lower incidence of RDS, PDA treated
with indomethacin after 24 hours of
age, less use of postnatal steroids, and
shorter duration of ventilation days
(Table 4). Multivariate logistic regression
analysis identied that greater GA and
vaginal delivery were associated with
increased risk of early-onset NEC. Post-
natal steroid use was not associated
with early-onset NEC. There was a trend
toward reduction in risk of early-onset
NEC in infants with PDA treated with in-
domethacin (Table 5).
DISCUSSION
The overall incidence of NEC was 5.1%
in this national population cohort of
infants ,33 weeks GA, which is within
the range reported by other large
network databases and single cen-
ters.
4,5,7,8
There was a signicant vari-
ation in the risk adjusted incidence
of NEC among the 25 NICUs within
the CNN. Our ndings are consistent
with the Eunice Kennedy Shriver Na-
tional Institute of Child Health and
Human Development neonatal network
who report persistent variation across
sites in the incidence of NEC in VLBW
infants.
4,5
The authors of previous epidemiologic
studies
11,12,20
have described early- and
late-onset NEC with early-onset NEC
presenting in the rst week of life in
term infants. Studies of lower GA and
lower BW infants reveal mean or me-
dian age of occurrence of NEC ranging
from 13 to 23 days.
11,12,2022
In his re-
view, Neu
2
describes classic NEC oc-
curring in preterm infants after 8 to 10
days of age. The peak onset of NEC
at postmenstrual age of 32 weeks is
similar to that reported previously.
11
Our data suggest that a different prole
andpresentationof NEChas emergedin
this population of preterm infants ,33
weeks gestation. There remains an in-
verse relationship between GA/BW and
onset of NEC, but the timeline has shifted
such that the preterm infants with BW
.1000 g present withNEC at a mean of 7
days (early onset) and NEC is delayed
until a mean of 32 days (late onset) in
lower GA infants with BW ,1000 g.
Grosfeld et al
23
reported on a 25-year
cohort of infants with surgical NEC and
identied average age at diagnosis of 13
days for infants with BW.1000 g and 21
days for infants with BW ,1000 g.
In the late 1980s and early 1990s, reports
of focal intestinal perforation began
emerging.
2427
The authors of sub-
sequent studies began to make the as-
sociation between this entity and use of
indomethacin and postnatal steroids.
28,29
The term spontaneous intestinal perfo-
ration (SIP) has also been used to de-
scribe this lesion, which occurs in
preterm infants, receiving minimal en-
teral feeds or before receiving any en-
teral feeds and occurring in the rst
week of life. The incidence of SIP has been
difcult to ascertain because it can only
be conrmed histologically with laparot-
omy.
30
Surgical management of intestinal
perforation with intraperitoneal drain
cannot reliably conrm the diagnosis.
FIGURE 1
Risk adjusted incidence of NEC by hospital for neonates ,33 weeks GA. (Adjusted for GA, Apgar score at
5 minutes, SNAP-II, girl, cesarean delivery, and SGA.) Hospital sites are on the x-axis, and the odds ratio
(95% condence interval) is on the y-axis.
FIGURE 2
Distribution of cases of NEC according to GA and postmenstrual age (PMA) in the study cohort.
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Because most neonatal networks and
single centers,
48
including CNN, have
not reported an overall increase in NEC
$ stage 2 and 1 group reported a de-
crease,
9
this suggests that if SIP is
misclassied and disproportionately
contributing to the incidence of stage 3
surgical NEC, the incidence of stage 2
nonsurgical NEC must be decreasing
globally. Alternatively, if SIP contributes
marginally to the overall incidence of
NEC, we should consider the possibility
of existence of an early-onset NEC that
occurs in VLBW preterm infants pre-
senting in the rst 2 weeks of life at
a mean of 7 days postnatal.
In our study, early-onset NEC occurred
in 40% of the cohort. From multivariate
analysis, the independent risk factors
for early-onset NECwere greater GAand
vaginal delivery. There was a trend to
lower risk of NEC in infants with PDA
treated with indomethacin. This as-
sociation of decreased NEC with PDA
treatment was described previously by
Sharma et al.
31
In our study, postnatal
steroid use and SGA infant were not
independently associated with early-
onset NEC. Therefore, even if early-
onset NEC represented misclassied
SIP, the described risk factors of in-
domethacin and postnatal steroids
treatment were not signicantly asso-
ciated with early-onset NEC in our co-
hort. Our data do not permit us to
distinguish between early postnatal
steroid use for treatment of hypoten-
sion compared with later treatment of
bronchopulmonary dysplasia and this
may explain the lack of association
between postnatal steroids and early-
onset NEC.
We do not know why vaginal delivery is
a risk factor for early onset NEC. We
speculate that the early-onset NEC
group were more mature, larger BW
infants and probably more likely to
be delivered vaginally. The apparent
paradox of these vaginally delivered
infants developing early-onset NEC may
be related to feeding practices. Enteral
feeding has been associated with NEC
as most infants developing NEC have
been fed. We speculate that more ma-
ture and potentially more stable
infants could have been given enteral
feeds earlier with more aggressive
volume advancement. There is con-
icting evidence as to whether these
are risk factors associated with NEC.
Recent meta-analyses
32,33
do not con-
rm that early trophic feeds or rate of
feeding advancements are associated
with NEC. Exclusive breast milk feeds
have been identied as protective for
development of NEC compared with
mixed feeds or formula feeds.
34,35
More
aggressive advancement of feeds with
suboptimal breast milk volumes may
have resulted in supplementation with
formula feeds.
36
In a recent study, only
30% of mothers were able to provide
sufcient breast milk to their extremely
premature infants.
37
TABLE 3 Demographic Characteristics of Early-Onset NEC and Late-Onset NEC Groups
Early-onset NEC
N = 336
Late-onset NEC
N = 505
P
BW, g
a
1160 6 435 992 6 328 ,.001
GA, wk
a
28 6 2.7 27 6 2.3 ,.001
Boy, n (%) 197 (58.6) 272 (53.8) .18
SGA, n (%) 36 (10.7) 70 (13.8) .17
Multiple gestations, n (%) 99 (29.4) 130 (25.7) .24
Cesarean delivery, n (%) 179 (53.2) 316 (62.5) .005
Antenatal steroid, n (%) 270 (80.3) 407 (80.5) .81
Chorioamnionitis, n (%) 34 (10.1) 69 (13.6) .12
Apgar score at 5 min
b
8 (7, 9) 7 (6, 8) ,.001
SNAP-II
b
10 (0, 21) 14 (7, 24) .01
Outborn, n (%) 109 (32.4) 151 (29.9) .40
Congenital anomalies, n (%) 106 (31.5) 200 (39.6) .01
a
Mean 6 SD.
b
Median (interquartile range).
TABLE 4 Comparison of Clinical Outcomes Between Early and Late NEC Group
Early-Onset NEC
N = 336
Late-Onset NEC
N = 505
P
RDS, n (%) 235 (69.9) 400 (79.2) .004
PDA, indomethacin .24 h, n (%) 89 (26.4) 186 (36.8) .001
Early onset sepsis, n (%) 1 (0.3) 5 (1) .41
Nosocomial sepsis, n (%) 145 (43) 233 (46) .39
Narcotic use in rst 3 d, n (%) 133 (39.5) 194 (38.4) .73
IVH $ grade 3, n (%) 62 (18.4) 98 (19.4) .78
Postnatal steroids, n (%) 100 (29.7) 193 (38.2) .01
Duration of ventilation, d
a
9 (3, 27) 20 (5, 42) ,.001
Mortality, n (%) 92 (27.3) 121 (23.9) .26
a
Median (interquartile range).
TABLE 5 Risk Factors for Early NEC From Multivariable Logistic Regression Analysis
Adjusted Odds Ratio
(95% Condence Interval)
P
GA 1.14 (1.051.23) ,.001
Apgar at 5 min 1.08 (0.981.19) .09
Cesarean delivery 0.56 (0.410.76) ,.001
SNAP-II 1.00 (0.981.01) .79
RDS 0.98 (0.661.45) .93
PDA treated with indomethacin 0.73 (0.511.04) .08
Postnatal steroids 1.08 (0.751.54) .66
Congenital anomalies 0.81 (0.591.54) .19
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The authors of recent reviews
13,10
dis-
cuss the multifactorial pathogenesis of
NEC and suggest the complex interplay
between immature gastrointestinal
tract with associated immature muco-
sal barrier, immune defense, circulatory
regulation, altered microbiota, inam-
matory response, and genetics along
with the more traditional putative fac-
tors of hypoxic-ischemic injury and en-
teral feeding in the host preterm infant.
This raises the possibility that NEC is a
developmental phenomenon with GA
interacting with perinatal events, such
as bacterial colonization and use of
perinatal antibiotics that may inuence
the microbiota of the immature gut.
It is possible that NEC represents 2 or
more different conditions, in differing
patient populations, with differing eti-
ologies. Gordon et al
30
has suggested
that NEC represents a disease entity
within a spectrum of conditions affecting
the neonatal gut, which they have termed
acquired neonatal intestinal disease.
SIP may be part of this spectrum of con-
ditions. The association between surgical
NEC and poorer neurodevelopmental
outcome as compared with no NEC has
been reported.
38
Others have reported
poorer neurodevelopmental outcome in
patients with surgical NEC as compared
with SIP.
39
The expression of NEC and the
long-term outcomes may depend on the
underlying etiology in the population af-
fected.
Strengths of this study include the large
size cohort, the standardization of
denitions of neonatal morbidities, and
the quality of the CNN database in
a regionalized healthcare system.
Thedenitionof early- versus late-onset
NEC derived from dichotomizing the
cohort at 14 days is not based on
any physiologic principle but on an
inspection of our data. The distinction
between stage 3 surgical NEC with in-
testinal perforation and SIP requiring
surgical intervention cannot be de-
lineated in our network population co-
hort. Data are not available to describe
the relationship between type, timing,
and rate of advancement of feeds and
development of NEC. These are signi-
cant limitations of this study. Our study
data do not allow for reporting of long-
term neurodevelopmental outcomes in
infants with NEC. Network databases,
including the CNN, may have to consider
stratication of these disease entities to
better identify risk factors and predict
long-term outcomes.
CONCLUSIONS
The overall incidence of NEC within the
CNN is similar to other centers and
networks. Within a cohort of preterm
infants ,33 weeks GA, NEC appears to
present at a mean of 7 days (early on-
set) in more mature preterm infants
and is delayed to 32 days (late onset) in
lower BW, lower GA preterminfants. This
early-onset NEC represents a shift in the
timing of traditional preterm NEC. Fur-
ther studies are required to understand
the etiology of this disease process.
ACKNOWLEDGMENTS
The Maternal-Infant Care Research Cen-
ter issupportedby theMinistry of Health
and Long-term Care, Ontario, Canada.
Site Investigators of the Canadian Neo-
natal Network were as follows: Shoo K.
Lee (Director, Canadian Neonatal Net-
work); Prakesh S. Shah (Associate Di-
rector, Canadian Neonatal Network);
Wayne Andrews (Janeway Childrens
Health and Rehabilitation Centre, St
Johns, NF, Canada); Francine Lefebvre
(Sainte Justine Hospital, Montreal, QC,
Canada); Nalini Singhal (Foothills Medi-
cal Centre, Calgary, AB, Canada); Barbara
Bullied (Everett Chalmers Hospital,
Fredericton, NB, Canada); Rody Canning
(MonctonHospital, Moncton, NB, Canada);
Gerarda Cronin (St Boniface General
Hospital, Winnipeg, MB, Canada); Kim-
berly Dow (Kingston General Hospital,
Kingston, ON, Canada); Michael Dunn
(Sunnybrook Health Sciences Centre,
Toronto, ON, Canada); Adele Harrison
(Victoria General Hospital, Victoria,
BC, Canada); Andrew James (Hospital
for Sick Children, Toronto, ON, Canada);
Zarin Kalapesi (Regina General Hospi-
tal, Regina, SK, Canada); Lajos Kovacs
(Jewish General Hospital, Montreal, QC,
Canada); David Lee (St Josephs Health
Centre, London, ON, Canada); Douglas
D. McMillan (Izaak Walton Killam Health
Centre, Halifax, NS, Canada); Prakesh
Shah (Mount Sinai Hospital, Toronto,
ON, Canada); Cecil Ojah (St John Re-
gional Hospital, St John, NB, Canada);
Khalid Aziz (Royal Alexandra Hospital,
Edmonton, AB, Canada); Bruno Pied-
boeuf (Centre Hospitalier Universitaire
de Qubec, Sainte Foy, QC, Canada); Pat-
ricia Riley (Montreal Childrens Hospital,
Montreal, QC, Canada); Daniel Faucher
(Royal Victoria Hospital, Montreal, QC,
Canada); Nicole Rouvinez-Bouali (Child-
rens Hospital of Eastern Ontario, Ottawa,
ON, Canada); Koravangattu Sankaran
(Royal University Hospital, Saskatoon,
SK, Canada); Mary Seshia (Health Sci-
ences Centre, Winnipeg, MB, Canada);
Sandesh Shivananda (Hamilton Health
Sciences Centre, Hamilton, ON, Canada);
Todd Sorokan (Royal Columbian Hospi-
tal, New Westminster, BC, Canada); and
Anne Synnes (Childrens and Womens
Health Centre of British Columbia, Van-
couver, BC, Canada).
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DOI: 10.1542/peds.2011-2022
; originally published online January 23, 2012; 2012;129;e298 Pediatrics
Yoon, Shoo K. Lee and the Canadian Neonatal Network
Wendy H. Yee, Amuchou Singh Soraisham, Vibhuti S. Shah, Khalid Aziz, Woojin
Infants
Incidence and Timing of Presentation of Necrotizing Enterocolitis in Preterm

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