8 Original Article

Advanced Necrotizing Enterocolitis Part 1:

Mortality
M. Thyoka 1 P. de Coppi 1 S. Eaton 1 K. Khoo 1 N.J. Hall 1 J. Curry 1 E. Kiely 1 D. Drake 1
K. Cross 1 A. Pierro 1

1 Department of Surgery, Great Ormond Street Hospital and UCL Address for correspondence and reprint requests Agostino Pierro, M.D.,
Institute of Child Health, London, United Kingdom F.R.C.S., F.A.A.P., Department of Paediatric Surgery, UCL Institute of
Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom
Eur J Pediatr Surg 2012;22:8–12. (e-mail: [email protected]).

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Abstract Aim of the Study The aim of this study was to investigate the factors associated with
mortality in infants referred for the surgical treatment of advanced necrotizing
enterocolitis (NEC).
Methods Retrospective review of all infants with confirmed (Bell stage II or III) NEC
treated in our unit during the past 8 years (January 2002 to December 2010). Data for
survivors and nonsurvivors were compared using Mann-Whitney test and Fisher's exact
test and are reported as median (range).
Results Of the 205 infants with NEC, 35 (17%) were medically managed; 170 (83%) had
surgery; 66 (32%) infants died; all had received surgery. Survivors and nonsurvivors were
comparable for gestational age, birth weight, and gender distribution. Overall mortality
Keywords was 32%, the highest mortality was in infants with pan-intestinal disease (86%) but
► necrotizing remained significant in those with less severe disease (multifocal 39%; focal disease
enterocolitis 21%). The commonest cause of mortality was multiple organ dysfunction syndrome and
► mortality nearly half of the nonsurvivors had care withdrawn.
► multiple organ Conclusion Despite improvement in neonatal care, overall mortality (32%) for ad-
dysfunction vanced NEC has not changed in 10 years. Mortality is significant even with minimal
syndrome bowel involvement.

Introduction both medical and surgical treatment.5,6 The aim of this study
was to characterize the factors associated with mortality in
Necrotizing enterocolitis (NEC) remains a devastating disease
infants with NEC referred to our unit.
affecting newborn infants and is often associated with signif-
icant mortality and morbidity, especially in the very preterm
Materials and Methods
and extremely low birth weight (ELBW) infants.1,2 The
mortality rates are high particularly in those infants requiring With institutional ethical approval, we reviewed case notes
surgical intervention.3 At laparotomy, the extent of disease of all infants with confirmed (Bell stage II or III) NEC
varies from focal disease to multifocal or pan-intestinal treated in our unit during the past 8 years (January 2002 to
disease, affecting varying lengths of bowel.3,4 Previous December 2010). NEC was defined by Bell's criteria, as
reports have shown mortality rates increasing with more modified by Kliegman and Walsh.7,8 Data retrieved included
advanced and extensive disease.4 While advances in perinatal demographic, clinical, radiological, and operative details.
care have contributed to an improvement in survival of Using mortality as our main outcome, we compared two
extremely premature and ELBW infants, the mortality in groups (survivors and nonsurvivors) for factors predicting
infants with NEC has remained high despite advances in mortality. Data were compared using Mann-Whitney test,

received Copyright © 2012 by Thieme Medical DOI http://dx.doi.org/

May 15, 2011 Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0032-1306263.
accepted after revision New York, NY 10001, USA. ISSN 0939-7248.
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 Advanced Necrotizing Enterocolitis Part 1 Thyoka et al. 9

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Figure 1 Cohort of NEC infants.

Fisher's exact test, and chi-square test as appropriate. Binary gestational age, or gender distribution (►Table 1, ►Fig. 2). Of
logistic regression analysis was also performed to determine the 170 infants receiving surgery, there was a significant
the effect of predictors of mortality. Data reported as median difference in the extent of intestinal involvement between
(range), and the level of significance was set at p < 0.05. those who died and those who survived (►Table 2). Those
who died had a significantly higher incidence of more exten-
sive intestinal involvement (p < 0.0001) as indicated by a
Results
higher proportion of patients of pan-intestinal involvement
During the study period (2002 to 2010), 205 infants with (29% in the on-survivors vs. 3% in the survivors) and a lower
confirmed NEC (Bell stage II or III) were admitted to our unit proportion with focal disease (►Fig. 3A). The majority of
for further surgical evaluation. Of these, 35 (17%) were infants undergoing surgery had a primary laparotomy
managed medically and 170 (83%) required operative (n ¼ 161; 95%); nine infants (5%) had peritoneal drain (PD)
intervention. insertion as the first procedure as part of a previously
The overall mortality rate was 32%. All deaths (n ¼ 66) reported randomized controlled trial.9 All those receiving
occurred in infants who had surgery for NEC, giving a PD required a subsequent laparotomy for clinical deteriora-
mortality following surgery for NEC of 39%. Mortality was tion (►Table 3).
significantly higher in infants receiving surgery compared Cause of death is summarized in ►Table 4. Among non-
with those receiving medical treatment (p < 0.0001, ►Fig. 1). survivors, 32/66 (48%) of the deaths followed a decision to
There was no significant difference, using Mann-Whitney withhold or withdraw intensive care. In the infants who had
test, Fisher's exact test, or binary logistic regression analysis, care withdrawn, most (15 [47%]) had care withdrawn due to
between survivors and nonsurvivors in terms of birth weight, multiple organ dysfunction syndrome (MODS) refractory to

Table 1 Characteristics of Infants with NEC: Survivors and Nonsurvivors

Survivors Nonsurvivors p Value

n ¼ 139 n ¼ 66
Birth gestational age (wk) 27 (22–42) 27 (23–42) 0.62
Corrected gestational age (wk) 32 (24–137) 32 (23–47) 0.63
Birth weight (kg) 0.92 (0.40–4.72) 0.96 (0.48–3.43) 0.50
Admission weight (kg) 1.28 (0.58–4.40) 1.30 (0.52–3.45) 0.95
Gender, male [n (%)] 80 (58) 42 (65) 0.45

Data reported as median (range) or number (percentage); p < 0.05.

European Journal of Pediatric Surgery Vol. 22 No. 1/2012

10 Advanced Necrotizing Enterocolitis Part 1 Thyoka et al.

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Figure 2 Mortality by birth weight.

maximal medical treatment with presumed poor outcome

and 4 (13%) because of NEC totalis and the decision not to
perform surgical resection of the entire gastrointestinal tract
(►Table 4). A total of 34 infants died without care being
actively withdrawn, predominantly from MODS or sepsis.

Discussion
Mortality rates among infants treated for NEC remains high,
especially among ELBW infants, those requiring surgery and Figure 3 (A) Extent of disease and mortality. (B) Mortality by extent of
disease in 1986 to 1996. Data redrawn from Fasoli et al.4
those with multiorgan failure.1,3 As more extremely prema-
ture and low birth weight infants survive with improved
perinatal care, the population of infants with risk factors for
development of NEC increases. In parallel with these trends, treme prematurity as a contraindication for laparotomy. This
advances in preventive, medical, and surgical treatment of is reflected in our series in which there is preponderance for
NEC have failed to appreciably reduce the mortality rates in surgery in infants with NEC in contrast to other series.
infants with NEC.10,11 In this study, we have shown that overall mortality in
Fitzgibbons et al, using data from Vermont Oxford Net- infants with confirmed NEC remains high, and these rates
work showed a trend of increasing mortality from NEC with mirror the extent of disease found at laparotomy, with highest
decreasing birth weight categories; the highest mortality rates among infants with pan-intestinal disease.13 This con-
(42%) observed in infants weighing 500 to 750 g.12 In our curs with our unit's published previous experience where
study patients there was no significant association between Fasoli et al4 showed overall mortality rate of 30%, the highest
birth weight, admission weight, birth gestational age or mortality (67%) occurring in the infants with pan-intestinal
corrected gestational age, and mortality. This apparent con- disease (►Fig. 3B). This may be because either (1) there has
tradiction may be due to the following reasons: (1) exclusion been no improvement in the treatment of infants with NEC or
of suspected NEC (Bell stage I) in our study; (2) the inclusion (2) we are now referred sicker infants with NEC. It is notable
in our study of only infants referred for surgical assessment that there remains a significant mortality rate (21%) in the
rather than all infants with NEC; and (3) in our institution, we infants with less extensive, focal NEC. This may signify that
use the same criteria for surgical treatment in extremely extent of disease alone may not be the only factor affecting
premature infants, whereas other centers may consider ex- mortality.

Table 2 Extent of Disease at Laparotomy

Survivors Nonsurvivors p Value

n ¼ 105 n ¼ 65
Focal, n (%) 68 (65) 21 (32) <0.0001
Multifocal, n (%) 34 (32) 22 (34)
Pan intestinal, n (%) 3 (3) 22 (34)

Data reported as number (percentage); p < 0.05.

European Journal of Pediatric Surgery Vol. 22 No. 1/2012

 Advanced Necrotizing Enterocolitis Part 1 Thyoka et al. 11

Table 3 Infants Who Underwent Surgery (n ¼ 170) improve survival through preventive remedies such as breast
milk promotion, judicious introduction and advancement of
Procedure Survivors Nonsurvivors enteral feeds, probiotic therapy,14,15 as well as novel thera-
(n ¼ 104) (n ¼ 66) peutic interventions such as therapeutic hypothermia16 and
Laparotomy (n ¼ 99) (n ¼ 62) stem cell therapy17 in vulnerable, at-risk groups.
Stoma (  bowel resection) 59 31
Anastomosis 42 20 Conclusion
Open and close 1 11
Despite improvement in neonatal care, overall mortality
Clip and drop 2 2 (32%) for advanced NEC has not changed in the past 10 years.
Peritoneal drain (n ¼ 5) (n ¼ 4) Mortality, while highest in infants with extensive NEC, is
Drain alone 0 0 significant even with minimal bowel involvement. In those
infants with definite NEC, mortality does not appear to be
Drain followed by laparotomy
related to low birth weight or prematurity. The commonest

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Stoma 4 3 cause for mortality due to NEC is MODS. Further attempts at
Anastomosis 1 0 prevention of NEC and treatment of established disease are
Open and close 0 1 desperately needed.

Conflict of Interest
Table 4 Cause of Death None

Reason n
Following withdrawal of care 32
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European Journal of Pediatric Surgery Vol. 22 No. 1/2012