Early mortality after neonatal surgery: Analysis of risk factors in an optimized health care system for the surgical newborn

Abstract

Objective:
Anesthetic and operative interventions in neonates remain hazardous procedures, given the vulnerability of the patients in this pediatric population. The aim was to determine the preoperative and intraoperative factors associated with 30-day post-operative mortality and describe mortality outcomes following neonatal surgery under general anesthesia in our center.

Methods:
Infants less than 28 days of age who underwent general anesthesia for surgery during an 11-year period (2000 - 2010) in our tertiary care pediatric center were retrospectively identified using the pediatric intensive care unit database. Multiple logistic regression was used to identify independent preoperative and intraoperative factors associated with 30-day post-operative mortality.

Results:
Of the 437 infants in the study (median gestational age at birth 37 weeks, median birth weight 2,760 grams), 28 (6.4%) patients died before hospital discharge. Of these, 22 patients died within the first post-operative month. Logistic regression analysis showed increased odds of 30-day post-operative mortality among patients who presented American Society of Anesthesiologists physical status (ASA) score 3 or above (odds ratio 19.268; 95%CI 2.523 - 147.132) and surgery for necrotizing enterocolitis/gastrointestinal perforation (OR 5.291; 95%CI 1.962 - 14.266), compared to those who did not.

Conclusion:
The overall in-hospital mortality of 6.4% is within the prevalence reported for developed countries. Establishing ASA score 3 or above and necrotizing enterocolitis/gastrointestinal perforation as independent risk factors for early mortality in neonatal surgery may help clinicians to more adequately manage this high risk population.

Full text

Rev Bras Epidemiol
2013; 16(4): 943-52
943
Early mortality after neonatal
surgery: analysis of risk factors
in an optimized health care
system for the surgical newborn
Mortalidade precoce após cirurgia
neonatal: análise de fatores de
risco em um sistema otimizado de
prestação de cuidados de saúde ao
recém-nascido cirúrgico
Dora CatréI,II,III
Maria Francelina LopesI,II,IV
Angel MadrigalV
Bárbara OliveirosVI
Joaquim Silva VianaVII
António Silvério CabritaII
ICentro de Formação e Investigação Clínica, Centro Hospitalar e Universitário de
Coimbra – Coimbra, Portugal.
IISchool of Medicine, Universidade de Coimbra – Coimbra, Portugal.
IIIDepartment of Anesthesiology, Centro Hospitalar Tondela-Viseu – Viseu, Portugal.
IVDepartment of Pediatric Surgery, Pediatric Hospital, Centro Hospitalar e
Universitário de Coimbra – Coimbra, Portugal.
VDepartment of Pediatric Anesthesiology, Pediatric Hospital, Centro Hospitalar
e Universitário de Coimbra – Coimbra, Portugal.
VIDepartment of Biostatistics and Medical Informatics, School of Medicine,
Universidade de Coimbra – Coimbra, Portugal.
VIISchool of Health Sciences, Universidade da Beira Interior – Covilhã, Portugal.
Corresponding author: Dora Catré. Centro de Formação e Investigação Clínica, Hospital
Pediátrico de Coimbra. Avenida Afonso Romão, Santo António dos Olivais, CEP: 3000-602,
Coimbra, Portugal. E-mail: doracatre@gmail.com
Conict of interests: nothing to declare.
Abstract
Objective: Anesthetic and operative interven-
tions in neonates remain hazardous proce-
dures, given the vulnerability of the patients in
this pediatric population. e aim was to deter-
mine the preoperative and intraoperative factors
associated with 30-day post-operative mortal-
ity and describe mortality outcomes following
neonatal surgery under general anesthesia in
our center. Methods: Infants less than 28 days
of age who underwent general anesthesia for
surge ry dur ing an 11-year period (2000 – 2010)
in our tertiary care pediatric center were retro-
spectively identied using the pediatric intensive
care unit database. Multiple logistic regression
was used to identify independent preoperative
and intraoperative factors associated with
30 -day po st-operative mortality. Results: Of the
437 infants in the study (median gestational age
at birth 37 weeks, median birth weight 2,760
gra ms), 28 (6.4%) patients died before hospital
discharge. Of these, 22 patients died within the
rst post-operative month. Logistic regression
analysis showed increased odds of 30-day post-
operative mortality among patients who pre-
sented American Society of Anesthesiologists
physical status (ASA) score 3 or above (odds ratio
19.268; 95%CI 2.523 – 147.132) and surgery for
necrotizing enterocolitis/gastrointestinal per-
foration (OR 5.291; 95%CI 1.962 – 14.266), com-
pared to those who did not. Conclusion: e
overall in-hospital mortality of 6.4% is within
the prevalence reported for developed countries.
Establishing ASA score 3 or above and necrotiz-
ing enterocolitis/gastrointestinal perforation as
independent risk factors for early mortality in
neonatal surgery may help clinicians to more
adequately manage this high risk population.
Keywords: Mortality. Surgery. Anesthesia,
general. Risk factors. Outcomes assessment.
Infant, newborn.

Rev Bras Epidemiol
2013; 16(4): 943-52 944 Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn
Catré, D. et al.
Resumo
Objetivo: As intervenções anestésicas/cirúr-
gicas em recém-nascidos permanecem pro-
cedimentos perigosos, dada a vulnerabilidade
dos pacientes nesta população pediátrica.
O objetivo foi determinar os fatores pré e
intraoperatórios associados com a mortali-
dade aos 30 dias de pós-operatório e descre-
ver os resultados de mortalidade hospitalar
após cirurgia neonatal sob anestesia geral
no nosso centro. Métodos: Os recém-nascidos
submetidos à anestesia geral para cirurgia
durante um período de 11 anos (2000 – 2010)
no nosso centro de atendimento pediátrico
terciário foram identificados retrospectiva-
mente utilizando a base de dados da uni-
dade de terapia intensiva pediátrica. Foi
utilizado o método de regressão logística
múltipla para identificar os fatores de risco
independentes pré e intraoperatórios asso-
ciados com a mortalidade aos 30 dias de
pós-operatório. Resultados: Das 437 crian-
ças do estudo (mediana de 37 semanas de
idade gestacional e de 2.760 gramas de peso
ao nascer), 28 (6,4%) pacientes morreram
antes da alta hospitalar. Destes, 22 pacien-
tes morreram no primeiro mês de pós-ope-
ratório. Na regressão logística múltipla, a
mortalidade aos 30 dias de pós-operatório
foi associada a escore deestado físico da
Associação Americana de Anestesiologia
(ASA) 3 ou superior (odds ratio 19,268,
IC95% 2,523 – 147,132) e a cirurgia para ente-
rocolite necrosante/perfuração gastroin-
testinal (OR 5,291, IC95% 1,962 – 14,266).
Conclusão: Ataxa de mortalidade intra-hos-
pitalar de 6,4% está dentro da prevalên-
cia encontrada em países desenvolvidos.
O estabelecimento de classificação ASA 3
ou superior e de enterocolite necrosante/
perfuração gastrointestinal como fatores
de risco independentes para mortalidade
precoce em cirurgia neonatal pode ajudar
os médicos a gerir mais adequadamente
essa população de alto risco.
Palavras-chave: Mortalidade. Cirurgia.
Anestesia geral. Fatores de risco. Avaliação
de resultados. Recém-Nascido.
Introduction
The surgical neonate, i.e. the newborn
submitted to surgery between birth and
28 days of life, requires care in specialized
centers offering high-risk neonatal support,
with neonatology and pediatric surgical
specialties. ese patients are often imma-
ture and very ill1, presenting associations of
several risk factors such as preterm birth, low
birth weight, chromosomal defects, genetic
syndromes or serious illness with multiple
organ dysfunction, and thus require manage-
ment in highly dedicated neonatal intensive
care units.
In the context of gestational age at birth,
birth weight and neonatal pathological condi-
tions, certain adverse early variables — such
as decreasing gestational age, decreasing birth
weight and critically compromised neonatal
health status, specically in the presence of
surgical life-threatening conditions mainly
related to immaturity and low birth weight—
have been recognized for increasing risk of
poorer health outcomes for neonatal and infant
morbidity and mortality2,3. Assessing clinical
risk factors that can potentially inuence post-
operative course is therefore appropriate to
better understand and improve outcomes.
However, in literature these aspects have
not yet been addressed, except for some
studies limited to a single pathology or
surgery. Specifically, no data are available
on predictors of post-operative mortality
in neonates undergoing general anesthesia
for a broad range of surgical pathologies.
In an era of decrease in maternal/child
mortality among United Nation member
countries, namely Portugal3-7 and Brazil3,4,7,8,
the aim of this study was to determine clinical
pre and intraoperative risk factors associ-
ated with 30-day postoperative mortality
and describe in-hospital mortality following
neonatal surgery under general anesthesia
in a tertiary Portuguese care center.
Methods
Permission to review patient’s data was
obtained from the Hospital´s Institutional

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2013; 16(4): 943-52
945
Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn
Catré, D. et al.
Review Board, according to the institutional
policy for protected health information.
A retrospective study was carried out of all
newborn patients subject to general anes-
thesia for surgical procedures admitted to the
Intensive Care Unit (PICU) of the Coimbra’s
Pediatric Hospital (CPH) between January 1st
2000 and December 31st 2010.
Study participants were identied from
clinical records of all neonates admitted
to the PICU. Eligible cases were dened as
those that met the following criteria: newborn
patients submitted to surgical procedures
under general anesthesia during the neo-
natal period (0 – 28 days of life), admitted to
the PICU either preoperatively or in the rst
post-operative hours and whose surgery was
completed at CPH.
Our hospital’s PICU is a regional tertiary
care unit for approximately 100 newborn
patients per year, including all surgical cases.
e central region of Portugal is served by
two other tertiary aliated perinatal hospi-
tals clustered with our tertiary medical and
surgical PICU and by a specialized neonatal
and pediatric emergency transport service to
transfer newborn infants at risk from other
health units within our wide area of referrals.
CPH has a combined pediatric and neonatal
intensive care unit with a team of health care
providers highly specialized in the manage-
ment of neonatal life-threatening conditions,
including pediatric anesthesiologists. All sub-
specialties of neonatal surgery are available
in this hospital except for open-heart cardiac
surgery that is performed in one aliated
adult hospital. All professionals who work in
the PICU and in the operating room, including
surgeons and anesthesiologists, are specialized,
highly skilled and exclusively dedicated to
the pediatric eld.
Patient demographics, pre, intra and post-
operative details and outcome were collected.
Outcomes were predictors of death within
30 days of surgery and in-hospital mortality,
dened as death occurring after surgery during
hospital stay.
Some continuous data (gestational age, birth
weight, Apgar score) were dichotomized into
categorical data according to break-points of
severity used in literature9,10, for statistical analy-
sis. Analysis of birth weight was performed using
gender- and gestation-specic charts previously
described11. Acquired surgical indication was
dened as surgical conditions that evolved after
birth. A V grade post-operative complication in
the Clavien-Dindo classication was dened as
resulting in death of the patient12. e variable
of days in PICU was dened as number of days
spent in our PICU system.
Statistical analysis
Statistical analyses were performed using
SPSS Software Version 19.0® for Windows (SPSS
Inc., Chicago, IL, USA). Categorical data are
summarized as absolute values (percentage).
Continuous data are presented as median and
range.
Initially, all factors potentially associated
with 30-day post-operative mortality (listed
in results Table 4) were analyzed (presence
vs. absence) using c2 or Fisher’s exact tests as
appropriate. Factors signicant on this analysis
(p < 0.05), and which were not clinically related
to other significant variables, were entered
into a logistic regression model using back-
ward stepwise (conditional) method in SPSS®
statistical software. Hosmer-Lemeshow and
omnibus tests were performed to determine
the goodness of fit and performance of the
model, respectively. Variables with odds ratio
95% condence intervals (CI) that did not cross
1 were considered to have an independent and
signicant association with mortality.
Evidence of association was set at p < 0.05.
Results
Patient and Operative Characteristics
Overall, of 1,055 newborns admitted to the
PICU between January 1st 2000 and December
31st 2010, 437 (41%) patients met inclusion
criteria. In these neonates, 558 interventions
were performed under general anesthesia, for
a total of 636 surgical procedures.
Table 1 refers to information regarding
characteristics at birth. From the wide list of
procedures performed, some interventions

Rev Bras Epidemiol
2013; 16(4): 943-52 946 Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn
Catré, D. et al.
Surgical condition n
Congenital diaphragmatic defects 52
Esophageal atresia /tracheoesophageal stula 48
Necrotizing enterocolitis/gastrointestinal perforation 39
Small bowel obstruction or atresia 80
Anorectal malformations 31
Hirschsprung disease 18
Omphalocele 26
Gastroschisis 38
Bladder extrophy 8
Congenital cystic adenomatoid malformation of the lung 5
Hydrocephalus 68
Myelomeningocele 32
Choanal atresia 8
Congenital tumors 8
Patent ductus arteriosus 10
Table 2 - Most relevant surgical conditions among the 636 surgical procedures performed.
Tabela 2 - Situações cirúrgicas mais relevantes entre as 636 operações realizadas.
*indicates Lenz, Alagille, Beckwith Wiedemann and Goldenhar syndromes: 1 of each.
*indica síndromas de Lenz, Alagille, Beckwith Wiedemann e Goldenhar: 1 de cada.
Characteristic n %
Gender
Male 244 56
Female 193 44
Birth weight, grams (median 2.760, range 440 – 4350)
< 1.500 62 14
1.500 – 2.499 105 24
≥ 2.500 270 62
Gestational age, weeks (median 37, range 24–41)
< 32 66 15
32 – 36 112 26
≥ 37 259 59
Birth weight/gestational age
Percentile < 10 67 14
Percentile > 90 17 4
Percentile 10 – 90 353 82
Apgar
7 – 10 at 5 minutes 412 94
< 7 at 5 minutes 16 4
Missing 9 2
Congenital malformations 356 82
Syndromes, associations or genetic anomalies 49 11
Myelomeningocele and Chiari II 16 –
VATER/VACTERL 11 –
Trisomy 21 11 –
Trisomy 18 1 –
Charge 2 –
Treacher collins 2 –
Cystic brosis 2 –
Other* 4 –
Table 1 - Birth characteristics among the 437 infants.
Tabela 1 - Características ao nascer dos 437 pacientes.

Rev Bras Epidemiol
2013; 16(4): 943-52
947
Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn
Catré, D. et al.
stand out given their prevalence or severity,
namely those for conditions listed in Table 2.
Most interventions (85%) were performed
in the operating room using balanced anes-
thesia, intravenous anesthesia or inhalational
anesthesia, however, in selected cases, new-
born infants underwent operative procedures
in the PICU under intravenous anesthesia.
ese cases included newborns subject to
special techniques (namely high-frequency
oscillatory ventilation in the case of some dia-
phragmatic hernias), critically ill newborns too
unstable to transport to the operating room
or those receiving simple interventions such
as central vascular access placement, bal-
loon atrial septostomy for congenital heart
disease or chest tube placement for pleural
eusions. Intravenous anesthesia was usually
achieved using a combination of midazolam
and fentanyl and inhalational anesthesia with
sevourane.
Over the study period, while always
following the state of the art, surgical neo-
nates handling techniques did not change
significantly and in-hospital mortality
remained stable.
Median PICU stay was 7 days (range 1 –
204). Ten patients suered from a Clavien-
Dindo grade V post-operative complication
within 30 days of surgery, with death occur-
ring outside this time period in only one
case (p < 0.001).
In-hospital mortality
Twenty-eight of the 437 patients (6.4%)
died in-hospital. Of those, 22 patients died
within the rst post-operative month (30-day
mortality), including 9 patients who died up
to the second post-operative day. Causes of
in-hospital death are presented in Table 3;
almost two-thirds (61%) of all in-hospital
deaths were preterm related.
Initial screening of factors associated
with 30-day mortality
Within 30 days of surgery, there were 22
deaths (5%). Signicant dierences between
these patients and patients who survived were
detected (Table 4).
Screening analysis of adverse outcome
showed that the presence of preterm birth
(under 37 weeks gestation), low birth weight
(under 2,500 g), very low birth weight (< 1500 g) in
very preterm (under 32 weeks gestation), large
for gestational age, acquired surgical indica-
tion, American Society of Anesthesiologists
physical status (ASA) score 3 or above in at
least one procedure, balanced or intravenous
anesthesia, abdominal surgery, necrotizing
enterocolitis and need for intraoperative car-
diopulmonary resuscitation maneuvers were
each signicantly associated with a higher
risk of mortality (Table 4), compared with
its absence. On the other hand, several other
clinical characteristics, presented in Table 4,
also tested in the initial screening analysis,
were not signicantly associated with 30-day
postoperative mortality.
Logistic regression analysis
Characteristics not significantly associ-
ated with mortality or showing strong clinical
relation to other more representative variables
were excluded from our model of logistic
regression analysis to avoid reducing statistical
Table 3 - Causes of in-hospital postoperative death.
Tabela 3 - Causas de morte pós-operatória intrahospitalar.
Cause of death All (n = 28) 30-day mortality (n = 22)
Peritonitis/Abdominal sepsis 12 10
Central nervous system hemorrhage 5 4
Respiratory insuciency 4 2
Cardiac insuciency 2 2
Neonatal sepsis 2 2
Hypoventilation of central cause 1 –
Acute renal insuciency 1 1
Abdominal compartment syndrome 1 1

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2013; 16(4): 943-52 948 Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn
Catré, D. et al.
Table 4 - Characteristics of infants who died within 30 days of surgery and patients who did not and their association
with 30-day mortality in the initial screening statistical analysis.
Tabela 4 - Características dos recém-nascidos que morreram nos primeiros 30 dias de pós-operatório e dos que não morreram
e sua associação com morte na análise estatística inicial.
OR: odds ratio; CI: condence interval; *association of presence vs. absence of each factor with 30-day mortality; **in at least 1 intervention; GA: gestation
age; BW: birth weight; SGA: small for gestation age; LGA: large for gestation age; ASA score: physical status by the American Society of Anesthesiologists
classication system; CPR: cardiopulmonary resuscitation maneuvers; NS: not signicant; ***statistically signicant.
OR: odds ratio; CI: intervalo de conança; *associação da presença vs. ausência de cada fator com a mortalidade aos 30 dias; **em pelo menos uma intervenção;
GA: idade de gestação; SGA: pequeno para a idade de gestação; LGA: grande para a idade de gestação; ASA score: estado físico pelo sistema de classicação da
Sociedade Americana de Anestesiologia; CPR: manobras de ressuscitação cardiorrespiratória; NS: sem signicado estatístico; ***estatisticamente signicativo.
Factors
30-day mortality OR
(95%CI)* p-value
Yes (n = 22)
n
No (n = 415)
n
Patient characteristics at birth
Male gender (n = 244) 15 229 1.7 (0.7 – 4.4) NS
GA < 37 weeks (n = 178) 14 164 2.7 (1.1 – 6.5) 0.025***
BW < 2,500 g (n = 167) 15 152 3.7 (1.5 – 9.3) 0.003***
BW < 1,500g and GA < 32 weeks (n = 56) 9 47 5.4 (2.2 – 13) < 0.001***
SGA (< 10th percentile) (n = 67) 6 61 2.2 (0.8 – 5.8) NS
LGA (> 90th percentile) (n = 17) 3 14 4.5 (1.2 – 17) 0.048***
More than 1 congenital malformation (n = 91) 3 88 0.6 (0.17 – 2) NS
Patient characteristics at surgery
1st operation at < 8 days of life (n = 309) 12 297 0.48 (0.2 – 1) NS
More than 1 anesthetic/surgical intervention (n = 95) 4 91 0.8 (2.6 – 2.4) NS
Acquired surgical indication (n = 99) 12 87 4.5 (1.9 – 11) < 0.001***
ASA score ≥ 3 (n = 207) 21 186 25.8 (3 – 194) < 0.001***
Anesthesia** (each vs. others)
Balanced (n = 372) 15 357 0.35 (0.14 – 0.9) 0.022***
Intravenous (n = 75) 8 57 3 (1.2 – 7.3) 0.014***
Inhalational (n = 8) 1 7 2.8 (0.3 – 23.6) NS
Surgery for (each vs. others)
Esophageal atresia (n = 42) 1 41 0.4 (0.06 – 3) NS
Abdominal wall defects (n = 49) 3 46 1.3 (0.4 – 4.4) NS
Diaphragmatic hernia (n = 42) 2 40 0.9 (0.2 – 4) NS
Necrotizing enterocolitis (n = 31) 8 23 9.7 (3.7 – 26) < 0.001***
Duodenal obstruction (n = 25) 0 25 0.94 (0.92 – 0.96) NS
Small bowel atresia (n = 16) 0 16 0.96 (0.94 – 0.98) NS
Anorectal malformations (n = 30) 1 29 0.6 (0.08 – 5) NS
Hirschsprung disease (n = 6) 0 6 0.99 (0.97 – 1) NS
Hydronephrosis (n = 4) 1 3 6.5 (0.65 – 66) NS
Cardiac malformations (n = 31) 1 30 0.6 (0.08 – 4.7) NS
Acquired hydrocephalus (n = 30) 1 29 0.6 (0.08 – 5) NS
Myelomeningocele (n = 27) 0 27 0.93 (0.91 – 0.96) NS
Abdominal surgery (n = 225) 19 206 6.4 (1.9 – 22) 0.001***
Thoracic surgery (n = 62) 0 62 0.85 (0.82 – 0.9) NS
Duration of surgery > 2h (n = 177) 7 170 0.67 (0.27 – 1.7) NS
Intraoperative CPR (n = 2) 2 0 1.1 (0.96 – 1) 0.002***
relevance. Specically, the confounders preterm
birth, balanced anesthesia, abdominal surgery
and cardiopulmonary resuscitation were not
included, since they were clinically related
to one or more of the selected characteristics
(respectively to very preterm birth, intravenous
anesthesia, necrotizing enterocolitis/gastroin-
testinal perforation and ASA score 3 or above).
Our model, composed by very low birth
weight in very preterm, ASA score 3 or above,
acquired surgical indication, intravenous
anesthesia and necrotizing enterocolitis/
gastrointestinal perforation, was nalized in
four steps by the backward stepwise method,
and showed good performance, and was
deemed reliable respectively by omnibus
(X2
(2) = 35.187; p < 0.001) and Hosmer-
Lemeshow (X2
(2) = 0.096; p = 0.953) tests.
Table 5 summarizes the two independent
risk factors (ASA score ≥ 3 and necrotizing

Rev Bras Epidemiol
2013; 16(4): 943-52
949
Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn
Catré, D. et al.
enterocolitis/gastrointestinal perforation in
operated newborns) for early mortality within
30 days of surgery. Very low birth weight in very
preterm, acquired surgical indication and intra-
venous anesthesia lost signicance (p ≥ 0.05).
Discussion
In a large cohort of critically ill neonates
undergoing anesthetic/surgical procedures at
our center, the present study was the rst to
demonstrate that both ASA score 3 or above
and necrotizing enterocolitis/gastrointestinal
perforation were independent risk factors for
30-day post-operative mortality in the specic
population of surgical neonates. Moreover, we
found that the overall in-hospital mortality
was 6.4%. e commonest cause of mortal-
ity was multiple organ dysfunction, usually
preterm related.
Compared with patients who survived the
rst post-operative month, deceased patients
within this time period were more premature,
lighter and sicker (with worse physical status)
and were more likely to have had abdominal
surgery for acquired illnesses associated with
preterm birth, such as necrotizing enterocoli-
tis/gastrointestinal perforation. Probably given
their worse physical status, intraoperative car-
diopulmonary resuscitation maneuvers were
more likely needed during their procedures.
More than one third of deaths occurred within
the rst post-operative month but mortality was
mostly due to complications related to the pre-
vious illness. Neonatal anesthesia and surgery
in this setting are likely to have by themselves
a negative impact on post-operative condition,
which in turn may inuence survival.
In our series, there was an overall discharge
mortality of 6.4% and a 30-day mortality of
5%. is overall mortality, relating to a sur-
gical PICU population of risk, is within the
prevalence reported for developed countries,
which is usually below 10%13. To place results
in context, nowadays, global neonatal surgical
mortality is variable, especially depending
on the level of development of the country.
Two large studies reported 6.714 and 7.5%13 in
South Korea and Japan, respectively, which
compares favorably to 35 and 45% in stud-
ies from India15 and Nigeria16,17, respectively.
In our cohort, despite the large num-
ber of patients with disabling illness (45.5%
classied as ASA 3 or higher), there were no
intraoperative deaths. is probably reects
the global improvement in healthcare in
Portugal recognized in the 2011 report of the
Organization for Economic Co-operation and
Development (OECD)3, which showed an
impressive decrease in neonatal mortality
rates despite the increase of preterm births3,5,18.
e achievements of successful outcomes in
this group of complicated patients seem to
be related to the availability of very special-
ized resources, namely those provided by
dedicated medical teams, including neo-
natologists and pediatric anesthesiologists,
and well-equipped hospital facilities, while
key indicators of progress. Thus, optimal
stabilization procedures and access to spe-
cialist care will probably improve outcome
for neonates undergoing neonatal surgery
in general19.
A number of factors were associated with
30-day post-operative mortality on the initial
statistical screening, but only two remained
CI: condence interval; ASA score: physical status by the American Society of Anesthesiologists classication system;
*the reference was the absence of the factor; NEC: necrotizing enterocolitis.
CI: intervalo de conança; ASA score: estado físico pelo sistema de classicação da Sociedade Americana de Anestesiologia;
*a referência usada foi a ausência do fator; NEC: enterocolite necrosante.
Table 5 - Independent risk factors for 30-day post-operative mortality among pediatric intensive
care unit surgical admissions.
Tabela 5 - Fatores de risco independentes para mortalidade aos 30 dias de pós-operatório entre as
admissões cirúrgicas na unidade de terapia intensiva pediátrica.
Risk factor 30-day mortality p-value
Odds ratio 95%CI
ASA score 3 or above* 19.268 2.523 – 147.132 0.004
NEC/Perforation* 5.291 1.962 – 14.266 < 0.001

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2013; 16(4): 943-52 950 Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn
Catré, D. et al.
signicant on our model of multiple logistic
regression: ASA score 3 or above and nec-
rotizing enterocolitis/gastrointestinal perfora-
tion. Regarding the rst factor, high ASA score
was the strongest predictor of mortality, as
wasexpected20, thus conrming the accuracy
of this physical status scoring system. irty-
day post-operative mortality was 19 times
greater among children with ASA scores 3 or
above. Regarding necrotizing enterocolitis,
which is known to be a life-threatening condi-
tion mainly related to immaturity and low birth
weight21-23, our results were largely consistent
with others that report post-operative high
morbidity and mortality following surgery
for this condition, given its progression to
abdominal sepsis with multiorgan failure24-26.
In the current study, necrotizing enterocolitis
was found to be the leading primary cause
of in-hospital mortality following neonatal
surgery, accounting for 41% of all causes of
30-day post-operative mortality. Additionally,
risk for 30-day post-operative death was found
to be 5 times greater.
Studies have also shown that other fac-
tors associated with mortality in infants
include low birth weight and preterm
birth3,27. These factors are known to act
by themselves as risk characteristics for
poor health outcomes, particularly at the
lower end of viability of gestational age
and birth weight28. However, the impact
of these demographics on neonatal sur-
gery mortality remains under-researched,
even though they are more commonly
found in critically ill patients than in other
newborns. Although the initial statistical
screening showed significant differences
in 30-day mortality in the presence of very
low birth weight in very preterm compared
with the absence of the factor, our results
do not support the hypothesis of an inde-
pendent causal association between these
variables, suggesting involvement of other
factors29. A possible explanation for the
lack of independent association of very low
birth weight in very preterm with 30-day
mort ality fo und in our series is the increased
healthcare infant support oered in Portugal
in the study period, recently addressed by the
2011 OECD indicators3, which may have
lowered the incidence of certain events
pertaining to the surgery experience, such
as perioperative hypothermia, dehydra-
tion, hypotension, electrolyte imbalances
and increased transfusion needs, to which
this group is more susceptible and that are
known to worsen outcomes.
ere were several strengths to the present
study. Firstly, very few studies can be found in
literature addressing specically the surgical
infant and neonatal populations14-17,30,31 and
none focuses on the impact of clinical risk
factors on outcomes or includes such a broad
range of surgical pathologies. e present study
aims to fulll this gap. Secondly, our work is
representative of the Portuguese neonatal
surgical population of tertiary PICUs, given
our wide area of inuence and the similarity
of demographic and clinical characteristics
provided in previous descriptive studies of a
southern Portugal tertiary PICU5,31. irdly, it
is based on a very complete data set that pro-
spectively registers numerous demographic
and clinical details of newborns admitted to
our PICU. is enabled collection of potential
risk factors of birth and clinical characteristics.
However, there were some limitations
to the present study. Although the infor-
mation in the PICU database was gathered
prospectively, the design of our study was
retros pective, so we relied on accurate record
keeping, which may have introduced misclas-
sication bias. Also, our study population is
limited to the patients admitted at our tertiary
intensive care unit, overlooking on one hand
the higher mortality expected in open-heart
procedures operated outside our pediatric
hospital and, on the other hand, the lower
mortality of operated newborns without criti-
cal disease or risk factors serious enough to
justify intensive care admission.
Conclusions
We have documented an incidence of in-
hospital overall mortality of 6.4% in infants
undergoing neonatal surgery which, although
found to be within the prevalence reported
for developed countries, may allow further

Rev Bras Epidemiol
2013; 16(4): 943-52
951
Early mortality after neonatal surgery: analysis of risk factors in an optimized health care system for the surgical newborn
Catré, D. et al.
improvement. In-hospital mortality was found to
be particularly associated with preterm related
illnesses, such as necrotizing enterocolitis, and
with ASA score 3 or above. Establishing these
conditions as independent risk factors for early
mortality in neonatal surgery may help clini-
cians to more adequately manage this high-risk
population and to diminish prognosis uncer-
tainty allowing better understanding of risk
and hence better communication to parents.
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