This document describes a study conducted at a children's heart center examining alternative surgical strategies for high-risk neonates and infants with congenital heart defects and significant co-morbidities. The study analyzed 442 cardiac surgeries performed between 2010-2013. It found that alternative bi-ventricular and uni-ventricular strategies minimized mortality but were associated with prolonged intubation, ICU stay, and hospitalization compared to standard strategies. Major pre-operative risk factors and lower weight significantly correlated with worse outcomes. The study concludes that flexible surgical approaches allowed survival of high-risk patients, though at the cost of increased resource utilization.

1. Original Article
Alternative strategies in newborns and infants with major
co-morbidities to improve congenital heart surgery outcomes
at an emerging programme*
Jannika Dodge-Khatami,1
Ali Dodge-Khatami,2
Jarrod D. Knudson,3,5
Samantha R. Seals,4
Avichal Aggarwal,3
Mary B. Taylor,3,5
Jorge D. Salazar2
1
Department of Pediatrics; 2
Pediatric and Congenital Heart Surgery, The Children’s Heart Center; 3
Pediatric and Fetal
Cardiology, The Children’s Heart Center; 4
Center of Biostatistics and Bioinformatics; 5
Division of Pediatric Critical
Care, The Children’s Heart Center, University of Mississippi Medical Center, Jackson, Mississippi, United States of America
Abstract Introduction: Debilitating patient-related non-cardiac co-morbidity cumulatively increases risk for con-
genital heart surgery. At our emerging programme, flexible surgical strategies were used in high-risk neonates and
infants generally considered in-operable, in an attempt to make them surgical candidates and achieve excellent
outcomes. Materials and methods: Between April, 2010 and November, 2013, all referred neonates (142) and infants
(300) (average scores: RACHS 2.8 and STAT 3.0) underwent 442 primary cardiac operations: patients with bi-
ventricular lesions underwent standard (n = 294) or alternative (n= 19) repair/staging strategies, such as pulmonary
artery banding(s), ductal stenting, right outflow patching, etc. Patients with uni-ventricular hearts followed standard
(n =96) or alternative hybrid (n =34) staging. The impact of major pre-operative risk factors (37%), standard or
alternative surgical strategy, prematurity (50%), gestational age, low birth weight, genetic syndromes (23%), and
major non-cardiac co-morbidity requiring same admission surgery (27%) was analysed on the need for extracorporeal
membrane oxygenation, mortality, length of intubation, as well as ICU and hospital length of stays. Results: The need
for extracorporeal membrane oxygenation (8%) and hospital survival (94%) varied significantly between surgical
strategy groups (p =0.0083 and 0.028, respectively). In high-risk patients, alternative bi- and uni-ventricular
strategies minimised mortality, but were associated with prolonged intubation and ICU stay. Major pre-operative
risk factors and lower weight at surgery significantly correlated with prolonged intubation, hospital length of stay,
and mortality. Discussion: In our emerging programme, flexible surgical strategies were offered to 53/442 high-risk
neonates and infants with complex CHDs and significant non-cardiac co-morbidity, in order to buffer risk and
achieve patient survival, although at the cost of increased resource utilisation.
Keywords: CHD; outcomes; neonates; intensive care
Received: 4 March 2015; Accepted: 6 March 2015; First published online: 2 June 2015
O
UTCOMES FOR NEONATES AND INFANTS WITH
CHD have improved dramatically in the last
few decades. With increased sophistication in
prenatal diagnostics, foetal–maternal medicine, and
neonatal care, survival of even the most premature
and fragile babies is expected, but it brings about a
whole new set of challenges as well. Not only is
management of a given CHD at stake, but also that of
multiple non-cardiac malformations, prematurity,
low birth weight, malnutrition, and genetic
syndromes, further complicating the picture.1,2
As
such, patient-related co-morbidity may increase the
risk of already complex congenital heart repairs
to nearly prohibitive levels, making some babies
*Meeting Presentation: some contents of the abstract were presented at the 10th
International Conference of the Pediatric Cardiac Intensive Care Society, Miami,
Florida, USA, 11–14 December, 2014.
Correspondence to: Ali Dodge-Khatami, MD, PhD, Chief, Professor of Surgery,
Pediatric and Congenital Heart Surgery, Children’s Heart Center, University of
Mississippi Medical Center, 2500 North State Street, Room S345, Jackson MS
39216, United States of America. Tel: + 601 984 4693; Fax: + 601 984 5872;
E-mail: adodgekhatami@umc.edu
Cardiology in the Young (2016), 26, 485–492 © Cambridge University Press, 2015
doi:10.1017/S1047951115000463

2. poor surgical candidates and to a point of with-
drawing care.
Our Children’s Hospital is the only one in the
entire State of Mississippi, providing for a geo-
graphically stable, underserved, and poorer rural
population of approximately three million. Since
April, 2010, an emerging comprehensive and multi-
disciplinary Children’s Heart Center has been laun-
ched, with the goal of treating all-comers regardless
of disease complexity and avoiding transfer of
patients outside the State as had been the practice for
decades. We report our experience in all consecutive
neonates and infants since the inception of the pro-
gramme, with a focus on flexible alternative strategies
in the highest-risk patients in an attempt to make
them reasonable surgical candidates. The impact of
non-cardiac co-morbidity on the outcomes and the
way co-morbidity influenced surgical and interven-
tional cardiologic decision-making algorithms for both
cardiac and non-cardiac conditions were evaluated.
Materials and methods
From April, 2010 to November, 2013, 442 con-
secutive primary cardiac operations were performed
on 142 neonates and 300 infants at the Children’s
Heart Center of the University of Mississippi Medical
Center in Jackson, Mississippi. Our Institutional
Review Board granted permission to proceed with
retrospective chart review, and parental consent
was waived.
Patients with heart defects underwent palliation or
complete repair for bi-ventricular physiology
(n = 312) or staged palliations for uni-ventricular
physiology (n = 130). A distinction was made
between standard complete repair and staging for bi-
ventricular hearts (n = 293, SB = standard bi-ven-
tricular) or alternative palliative strategies (n = 19,
AB = alternative bi-ventricular). Standard staging for
bi-ventricular physiology included systemic-to-
pulmonary artery shunts in case of cyanotic lesions
and main pulmonary artery banding for defects with
pulmonary over-circulation. Alternative palliative/
hybrid strategies included bilateral pulmonary artery
banding for truncus arteriosus with severe truncal
valve insufficiency, patent ductus arteriosus stenting
in severely cyanotic patients with right ventricular
outflow obstruction, or right ventricular outflow
resection with patching in cyanotic patients with
diminutive pulmonary arteries deemed unfavourable
for a standard systemic-to-pulmonary shunt. For the
staged care of single ventricle lesions, standard pal-
liations included either a systemic-to-pulmonary
artery shunt, pulmonary artery banding, or a
Norwood-type operation in the neonatal period, and
a cavo-pulmonary anastomosis (Glenn operation) in
infancy (n = 96, SU = standard uni-ventricular). On
the other hand, alternative palliations using hybrid
techniques – combined surgical and interven-
tional catheter procedures – were preferred for babies
considered very poor surgical candidates, either due
to the patient’s general condition or specific anato-
mical findings precluding the use of standard
palliative operations (n = 34, AU = alternative uni-
ventricular). The decision-making for standard or
alternative strategies was discussed prospectively on a
case-by-case basis at a weekly combined surgical,
cardiology, intensive care, and anaesthesiology con-
ference: the presence of superimposed complicating
cardiac anomalies or major patient-related non-
cardiac co-morbidity placed the patients in the high-
risk category. In those situations, flexible/alternative
strategies were attempted with the goal of making
the neonates and infants reasonable surgical candi-
dates and avoiding withdrawal of care. Procedures
were classified according to RACHS-1 and STAT
Scores.1,2
Patient demographic data included gender, race,
gestational age, birth weight and weight at surgery,
the presence or absence of genetic syndromes, sig-
nificant non-cardiac co-morbidity, or malformations,
which in turn required same-admission surgery
for other major organ systems, surgical strategy
according to treatment group as defined above, such
as standard bi-ventricular, alternative bi-ventricular,
standard uni-ventricular, or alternative uni-ventricular –
and, finally, pre-operative risk factors including sepsis,
immune deficiency, necrotising enterocolitis, seizures,
intracranial haemorrhage, need for cardiopulmonary
resuscitation, pre-operative extracorporeal membrane
oxygenation, and pre-operative mechanical ventilation.
Values are expressed as median and range (mini-
mum, maximum) or mean ± standard deviations for
continuous variables and N (%) for categorical vari-
ables. Continuous variables were compared using
one-way analysis of variance, and categorical variables
were compared using the χ2
or Fisher’s exact tests,
where appropriate. Total intubation time, ICU
length of stay, and overall hospital length of stay were
transformed using the natural log transformation and
modelled using linear regression, whereas extra-
corporeal membrane oxygenation and mortality were
modelled using logistic regression. Data were ana-
lysed using SAS software, version 9.4 (SAS Institute,
Cary, North Carolina, United States of America).
Results
Mean age at surgery was 113.1 ± 99.6 days, with
significant variability between the four treatment
groups, the youngest being in the hybrid uni-
ventricular AU group (73.4 ± 96.4 days;
486 Cardiology in the Young March 2016

3. p = 0.0014). Gender (53% male) and race (59%
African-American) were similar among all treatment
groups, as was weight at surgery (4.5 ± 2.1 kg).
There were significant differences among groups
with regard to the presence or absence of genetic
syndromes (23%), with the highest finding in
those who underwent alternative hybrid palliation
for bi-ventricular physiology (42%; p = 0.0003).
Furthermore, gestational age (mean 35.7 ±4.5
weeks), prematurity (defined as a gestational age
<37 weeks, 50% of all patients), and low birth weight
(mean 2.6 ± 0.9 kg) were significantly different among
treatment groups. The most premature (34.5 weeks of
gestation, 61% prematurity) and smallest at birth
(2.3 ± 1 kg) were in the SB group. The smallest at the
time of surgery were premature neonates with single
ventricle physiology requiring hybrid strategies for
palliation 4.1 ± 1.8 kg. Major pre-operative risk factors
including sepsis, immune deficiency, necrotising
enterocolitis, malnourishment (n =35; 7.8%), seizures,
intracranial haemorrhage, need for cardio-pulmonary
resuscitation, pre-operative extracorporeal membrane
oxygenation, and pre-operative mechanical ventilation
were present in 36% of all patients and did not sig-
nificantly differ among treatment groups. Major non-
cardiac abnormalities (24% of all patients) requiring
same-admission surgeries on other organ systems
(27%) were similar among treatment groups and are
listed in Table 1. Complete characterisation of patients
can be seen in Table 2.
The unadjusted association of variables with end
points is depicted in Table 3. End points included
intubation time (median 75.3 hours (2.2, 4767.5)),
ICU stay (5 days (1, 183)), hospital length of stay
(11 days (1, 241)), need for extracorporeal membrane
oxygenation (8%, n = 35), and mortality (6%,
n = 27). Intubation, ICU stay, and hospital stay were
significantly different between treatment
groups, whereas no difference was detected for
extracorporeal membrane oxygenation and mortality
(Table 3; Fig 1). Not surprisingly, alternative pal-
liative strategies for both bi-ventricular and uni-
ventricular hearts resulted in significantly longer
mechanical ventilation times (AB 172.4 hours (27.5,
3473.4) and AU 218.5 hours (19.6, 4767.5) com-
pared with standard repairs or palliations (SB
50.5 hours (2.2, 4345.5) and SU 78.6 hours (11.2,
1242.0)) (p = 0.0001 and 0.0005, respectively).
Accordingly, with alternative strategies, significantly
longer ICU stays were required for patients with both
bi-ventricular and uni-ventricular hearts (AB 10 days
(3, 146) and AU 17 days (1,125)) compared with
standard care (SB 4 days (1,183) and SU 6.5 days
(1,104)) (p = 0.0003 and 0.0004, respectively).
Longer length of hospital stay was required when
alternative surgical strategies were attempted (AB
21 days (5, 146) and AU 20 days (6,145)) compared
with standard care length of stay (SB 9 days (1,241)
and SU 13 days (4, 104)) (p = 0.007 and 0.0028,
respectively).
The adjusted association of variables with end
points is depicted in Table 4. All models were
adjusted for race, sex, genetic syndromes, birth
weight, gestational age, weight at operation, other
risk factors, other operations, and other cardiac
abnormalities. When comparing patients with bi-
ventricular and uni-ventricular hearts, surgical
strategy affected the length of intubation
(p = 0.0039 and 0.0035, respectively), length of
ICU stay (p = 0.0090 and p = 0.0062, respectively),
Table 1. Major non-cardiac abnormalities and same-admission non-cardiac surgery.
Anatomic anomalies Surgical procedures
Gastrointestinal
system
Hirsprung, anal atresia, intestinal malformation, diaphragmatic
hernia, umbilical hernia, duodenal atresia, inguinal hernia,
gastrocutanous fistula, ectopic anus, pylorostenosis
Gastrostomy, enterostomy, duodenal atresia repair,
anoplasty, Ladd procedure, jejunostomy, colostomy,
bowel resection, colectomy, abdominal exploration,
laparoscopy, diaphragmatic hernia repair, hernia
repair, liver resection, pyloromyotomy
Urinary tract Bilateral cryptorchism, hydronephrosis, polycycstic kidney
disease, multi-cystic kidney disease, nephrocalcinosis,
hypospadias, fused pelvic kidney, hydrocele, bicornate uterus,
cloacal malformation
Hypospadia repair, scrotal surgery, vesicotomy
Neuro Myelomeningocele, partial agnesis of corpus collosum, absent
corpus collosum, caudal regression, spinal fusion, vertebral
anomaly Dandy Walker malformation, hydrocephalus,
microcephaly
Cerebral aneurysm repair, ventriculo-peritoneal
shunt,
ENT/upper
respiratory tract
Trachea-oesophageal fistula, cleft palate, difficult airway,
choanal atresia,
Lobectomy, cleft palate repair, supraglottoplasty,
tracheoplasty, tracheal surgery, TEF repair
Others Clubfoot deformity, fused fingers, polydactyly, torticollis,
thoracogenic scoliosis, duane’s syndrome left eye, VACTERL
association, polysplenia, asplenia, adrenal insufficiency
Eye operation
Vol. 26, No. 3 Dodge-Khatami et al: Alternative strategies in newborns and infants 487

4. and length of hospital stay. With respect to length
of hospital stay, surgical strategy affected only
patients with uni-ventricular hearts (p = 0.0261).
Despite the prolonged need for respiratory, inten-
sive, and hospital care, as well as a positive trend in
the need for extracorporeal membrane oxygenation
and mortality, statistical significance was not
reached. The impact of same-admission surgery for
other major organ systems translated into a sig-
nificantly longer hospital length of stay in the 27%
of patients who needed it compared with those who
did not (p = 0.0025) (Table 4; Fig 1).
Discussion
Alternative palliative surgical and hybrid techniques
were used to manage high-risk neonates and infants
with complex CHD in our emerging programme,
which helped buffer mortality and improve survival,
although at the cost of prolonged need for mechanical
ventilation, longer length of hospital stay, and
increased trend in the need for extracorporeal mem-
brane oxygenation. The primary reason to use
unconventional palliative strategies involved a
patient-tailored approach for babies with severe co-
morbidities including prematurity, poor nutritional
status, low birth weight and low weight at operation,
and major non-cardiac congenital and genetic
abnormalities in an effort to make them reasonable
surgical candidates and avoid withdrawal of support.
Practically, this often meant breaking down a more
straightforward/standard but more aggressive proce-
dure into two or more smaller procedures, judged to
be potentially less traumatic. The second reason
involved practical considerations pertaining to our
newly assembled care team, sometimes with man-
power leanness at all levels and particularly during
night shifts with junior physicians and nursing
Table 2. Patient characteristics and outcomes.
SB (n = 293) SU (n = 96)
Total (n = 442) AB (n = 19) (4%) (66%) AU (n = 34) (8%) (22%) p-value
Sex
Male 234 (52.9%) 8 (42.1%) 156 (53.2%) 19 (55.9%) 51 (53.1%) 0.7951
Female 208 (47.1%) 11 (57.9%) 137 (46.8%) 15 (44.1%) 45 (46.9%)
Race
AA 261 (59%) 12 (63.2%) 174 (59.4%) 23 (67.6%) 52 (54.2%) 0.5454
Non-AA 181 (41%) 7 (36.8%) 119 (40.6%) 11 (32.4%) 44 (45.8%)
Age 92.5 (0, 357) 21 (3, 348) 105 (0, 357) 8 (0, 328) 60.5 (0, 249) 0.0014
Syndromes
Yes 103 (23.3%) 8 (42.1%) 80 (27.3%) 6 (17.1%) 9 (9.4%) 0.0003
No 339 (76.7%) 11 (57.9%) 213 (72.7%) 28 (82.4%) 87 (90.6%)
ECMO
Yes 35 (7.9%) 4 (21.1%) 16 (5.5%) 6 (17.6%) 9 (9.4%) 0.0083
No 407 (92.1%) 15 (78.9%) 277 (94.5%) 28 (82.4%) 87 (90.6%)
Pre-operative risk factors
Yes 160 (36.2%) 8 (42.1%) 107 (36.5%) 17 (50%) 28 (29.2%) 0.1605
No 282 (63.8%) 11 (57.9%) 186 (63.5%) 17 (50%) 68 (70.8%)
Non-cardiac operations
Yes 120 (27.1%) 8 (42.1%) 75 (25.6%) 11 (32.4%) 26 (27.1%) 0.3961
No 322 (72.9%) 11 (57.9%) 218 (74.4%) 23 (67.6%) 70 (72.9%)
Non-cardiac abnormalities
Yes 106 (24%) 3 (15.8%) 71 (24.2%) 14 (41.2%) 18 (18.8%) 0.0535
No 336 (76%) 16 (84.2%) 222 (75.8%) 20 (58.8%) 78 (81.3%)
Birth weight 2.8 (0.5, 4.3) 3.4 (0.9, 4.2) 2.6 (0.5, 4.3) 3 (1.8, 3.8) 2.9 (0.7, 4.1) <0.0001
Weight at operation 4.1 (0.7, 11.3) 3.7 (1.5, 8.5) 4.5 (0.7, 11.3) 3.4 (1.8, 7.9) 4 (0.9, 9.1) 0.5987
Gestational age 38 (22, 41) 39 (28, 41) 37 (22, 41) 38 (34, 39) 38 (27, 40) <0.0001
Premature
Yes 221 (50%) 3 (15.8%) 179 (61%) 11 (32.4%) 30 (31.3%) <0.0001
No 221 (50%) 16 (84.2%) 114 (39%) 23 (67.6%) 62 (64.6%)
Mortality
Yes 27 (6.1%) 2 (10.5%) 12 (4.1%) 5 (14.7%) 8 (8.3%) 0.0280
No 415 (93.9%) 17 (89.5%) 281 (95.9%) 29 (85.3%) 88 (91.7%)
ICU LOS 5 (1, 183) 10 (3, 146) 4 (1, 183) 17 (1, 125) 6.5 (1, 104) <0.0001
Hospital LOS 11 (1, 241) 21 (5, 146) 9 (1, 241) 20.5 (6, 145) 13 (4, 104) <0.0001
Intubation time 75.1 (2.2, 4767.5) 172.4 (27.5, 3473.4) 50.5 (2.2, 4345.5) 218.5 (19.6, 4767.5) 78.6 (11.2, 1242) <0.0001
AA = African-American; AB = alternative bi-ventricular; AU = alternative uni-ventricular; ECMO = extracorporeal membrane oxygenation;
LOS = length of stay; SB = standard bi-ventricular; SU = standard uni-ventricular
488 Cardiology in the Young March 2016

5. staff. Combined with patient-related factors were
initial operational logistics, building, and materials
shortcomings, which led to flexibility in medical
decision-making to accommodate for potential high-
risk situations, even in standard-risk patients.
Lower weight at surgery influenced our treatment
strategy, making us withdraw from more established
surgical repairs and palliations and move towards
alternative hybrid pathways. The algorithm seemed
less aggressive for more fragile babies, involving less
Table 3. Univariable associations.
Intubation (hours) ICU (days) LOS (days) ECMO Mortality
Predictor Estimate p-value Estimate p-value Estimate p-value OR p-value OR p-value
Surgical group
AB 2.54 0.0001 2.14 0.0003 1.79 0.0028 2.17 0.2213 1.98 0.1476
SB – – – – – – – – – –
AU 2.77 0.0005 2.57 0.0004 1.84 0.0007 4.62 0.1280 4.62 0.1280
SU – – – – – – – – – –
African-American 1.12 0.3551 0.96 0.7387 1.15 0.1301 0.80 0.5389 0.85 0.698
Sex 1.02 0.8693 1 0.966 0.95 0.5454 1.35 0.3983 1.11 0.7952
Other syndromes 0.94 0.6941 1.1 0.4627 1.16 0.1798 0.99 0.9724 1.18 0.7189
Birth weight 0.87 0.0563 1 0.9569 0.83 0.0009 1.32 0.1992 1.04 0.8643
Gestational age 0.97 0.0307 0.99 0.6161 0.96 0.0004 1.07 0.1988 0.99 0.8239
Weight at operation 0.76 <0.0001 0.80 <0.0001 0.82 <0.0001 0.74 0.0025 0.68 0.0011
Pre-operative risk factors 2.2 <0.0001 1.79 <0.0001 1.94 <0.0001 1.53 0.2315 3.82 0.0015
Non-cardiac operations 2.07 <0.0001 1.96 <0.0001 2.11 <0.0001 0.94 0.8685 0.60 0.3153
Non-cardiac abnormalities 1.78 <0.0001 1.71 <0.0001 1.75 <0.0001 0.79 0.5864 0.38 0.1239
AB = alternative bi-ventricular; AU = alternative uni-ventricular; ECMO = extracorporeal membrane oxygenation; LOS = length of stay; OR = odds
ratio; SB = standard bi-ventricular; SU = standard uni-ventricular
Figure 1.
(a, top left): median ICU and hospital length of stay by treatment group. (b, top right): median intubation times by treatment group.
(c, bottom left): need for extracorporeal membrane oxygenation by treatment group. (d, bottom right): in-hospital mortality by treatment group.
AB = alternative bi-ventricular; AU = alternative uni-ventricular; SB = standard bi-ventricular; SU = standard uni-ventricular.
Vol. 26, No. 3 Dodge-Khatami et al: Alternative strategies in newborns and infants 489

6. or no exposure to cardio-pulmonary bypass and/or
potentially less post-operative haemodynamic
instability, as may occur with systemic-pulmonary
artery shunt-dependent palliations. In our study, the
mean weight at birth was 2.6 ± 0.9 kg and at surgery
it was 4.5 ± 2.1 kg among all groups, with the
lowest findings among the AB and AU groups.
Heavier weight was significantly associated with
decreased length of intubation (p <0.0001), ICU stay
(p <0.0001), and hospital length of stay (p < 0.0001),
as well as decreased mortality (p= 0.0011) and extra-
corporeal membrane oxygenation need (p= 0.0024).
This is in accordance with other studies showing
increased mortality in patients with low weight and
poor nutritional status at the time of surgical
repair.3,4
Curzon et al3
found significantly higher
mortality in infants weighing 1–2.5 kg compared
with those weighing 2.5–4 kg for several surgical
procedures. Lower weight remained strongly asso-
ciated with mortality after adjustment by the RACHS
categorisation and Aristotle complexity levels.4
Wei et al5
found an increased risk for post-operative
infections (p < 0.0001) in patients with low weight at
surgery, with a cut-off weight at 2.4 kg. Low weight at
surgery has been associated with higher morbidity not
only in neonates and infants but also in older children:
in a study by Anderson et al,6
weight-for-age Z score of
< − 2 at Fontan completion was associated with a
higher rate of serious post-operative infections and
longer length of hospital stay.
We found signs of malnourishment in 35 (7.8%)
of our patients, without a significant difference
among treatment strategies. The effect of pre-
operative nutritional status on post-operative out-
comes in children undergoing surgery for CHDs was
assessed by Radman et al,7
showing lower total body
fat mass and acute and chronic malnourishment to be
associated with worse clinical outcomes. They also
reported an inverse correlation between total body fat
and brain natriuretic peptide levels. The duration of
inotropic support and brain natriuretic peptide
increased concomitantly to decreasing nutritional
status in their patients, supporting the hypothesis
that malnourishment is associated with decreased
myocardial function.7
A clear association between
poor nutritional status and adverse outcome has
recently sparked efforts to streamline nutritional
practices in inter-stage single ventricle patients.
Keating et al8
examined the impact of early fundo-
plication or a gastrostomy tube on the mid-term
outcomes of patients with single ventricle physiol-
ogy. hypoplastic left heart syndrome anatomy
(p = 0.002) and those with a morphological right
ventricle (p = 0.003) were associated with the need
for fundoplication or gastrostomy. Although neither
of the cardiac morphology variables affected
mid-term survival, the need for fundoplication or
gastrostomy was significantly associated with poor
outcomes (hazard ratio of 4.3; p = 0.003).8
In addi-
tion, recent studies indicate that exclusive oral
feeding post-Norwood is associated with higher age-
for-weight Z-score at the time of stage II palliation,9
and gastrostomy/fundoplication is associated with
higher inter-stage mortality.10
Some surmise that the
need for inter-stage tube feeding is a marker of
unmeasured co-morbidities. As such, efforts by the
National Pediatric Cardiology Quality Improvement
Collaborative have resulted in improved inter-stage
growth in several programmes around the country.11
We hypothesise that the co-morbidities seen in our
Table 4. Multivariable associations.
Intubation (hours) ICU (days) LOS (days) ECMO Mortality
Predictor Estimate p-value Estimate p-value Estimate p-value OR p-value OR p-value
Surgical group
AB 2.50 0.0039 2.12 0.0090 1.49 0.0981 3.66 0.2492 1.30 0.6367
SB – – – – – – – – – –
AU 1.99 0.0035 1.77 0.0062 1.52 0.0261 1.87 0.4914 1.79 0.1217
SU – – – – – – – – – –
African-American 1.10 0.4645 0.94 0.5869 1.14 0.1988 0.77 0.5473 0.61 0.3231
Sex 1.14 0.2995 1.04 0.7285 1.04 0.7299 1.98 0.1324 1.71 0.2990
Other syndromes 0.98 0.9269 1.14 0.3773 1.25 0.0847 0.87 0.8283 1.88 0.3744
Birth weight 1.07 0.6535 1.18 0.2025 1.07 0.5111 0.95 0.9157 0.94 0.9113
Gestational age 1.01 0.7593 1.00 0.9084 0.98 0.4898 1.18 0.0781 1.10 0.3828
Weight at operation 0.78 <0.0001 0.81 <0.0001 0.84 <0.0001 0.57 0.0024 0.55 0.0011
Pre-operative risk factors 1.50 <0.0001 1.26 0.0844 1.32 0.0158 1.79 0.2029 4.59 0.0014
Non-cardiac operations 1.35 0.0857 1.27 0.1310 1.51 0.0002 0.77 0.6224 0.45 0.2113
Non-cardiac abnormalities 1.18 0.3786 1.19 0.2910 1.05 0.7150 0.71 0.5836 0.21 0.0536
AB = alternative bi-ventricular; AU = alternative uni-ventricular; ECMO = extracorporeal membrane oxygenation; LOS = length of stay; SB = standard
bi-ventricular; SU = standard uni-ventricular
490 Cardiology in the Young March 2016

7. population likely represent some of the “unmea-
sured”. Despite these challenges, our hospital survival
is satisfactory; however, as previously mentioned,
expectations are changing and inter-stage and mid-
term survival are increasingly important.
Prematurity was present in 50% of our patient
population, known to adversely impact on clinical
outcomes in newborns requiring congenital heart
surgery.5,12
Wei at al5
found lower gestational age at
birth to be associated with home oxygen use, higher
tracheostomy rates, and discharge with a gastrostomy
tube, without influencing survival to discharge. Azakie
et al12
found a slightly lower survival trend among
patients born at <37 weeks of gestation at 83 versus
97% among patients born at 37 weeks of gestation or
greater, without achieving statistical significance.
Necrotising enterocolitis, seizures, need for supple-
mental oxygen, and gavage feeds at discharge were all
more frequent among their late preterm infants.12
The
correlation between prematurity and outcomes was also
examined by Costello et al,13
comparing neonates who
were delivered at 39–40 completed weeks of gestation
with those born at 37–38 weeks, who had increased
mortality (6.9 versus 2.6%; adjusted p= 0.049), mor-
bidity (49.7 versus 39.7%; adjusted p = 0.02), and
longer duration of mechanical ventilation (adjusted
p =0.05). Patients born after 40 or before 37 weeks of
gestation had increased morbidity rates and required
more days of mechanical ventilation and intensive care.
Based on their findings, they suggest that morbidity
and mortality rates are lowest when delivery occurs or
may safely be delayed to 39–40 weeks of gestation.13
Based on these findings and in concert with our own
experience, we have reached an understanding with our
own and other referring foetal–maternal medical teams
to allow a gestational age of at least 38 weeks, when it is
safe for the expecting mother and the foetus.
We showed that pre-operative risk factors, present
in more than a third of our patients, including
necrotising enterocolitis, sepsis, seizures, immune
deficiency, cardio-pulmonary resuscitation, intracra-
nial haemorrhage, pre-operative extracorporeal
membrane oxygenation, and need for mechanical
ventilation, were associated with significant higher
lengths of intubation (p = 0.0001) and hospital stay
(p = 0.0158, respectively), as well as a higher mor-
tality rate (p = 0.0014). We found major non-cardiac
abnormalities requiring same-admission surgeries,
present in 27.1% of our patients, to be associated
with significantly longer length of hospital stay
(p = 0.0025) among our treatment groups. Patel et al
evaluated the impact of non-cardiac congenital and
genetic abnormalities on outcomes in patient with
hypoplastic left heart syndrome, based on two large
multi-institutional data sets. They suggested that the
presence of co-existing non-cardiac anomalies or
genetic abnormalities confer an additional risk of
death for infants undergoing staged palliation for
hypoplastic left heart syndrome.14
Stage 1 in-hospital
mortality (26 versus 20%, p = 0.04) and mean post-
operative length of stay (42 versus 31 days,
p < 0.0001) were greater, and post-operative com-
plications were significantly more prevalent in infants
with non-cardiac genetic defects. Chromosomal
defects (n = 14) were highly unfavourable: the early
risk of death was doubled (10 year survival 25 ± 9
versus 54 ± 2%, p = 0.005). The presence of non-
cardiac abnormalities and genetic syndromes was
associated with significantly delayed post-operative
recovery (post-operative length of hospital stay
>14 days) at both stage 1 (76 versus 67%, p = 0.02)
and stage 2 (31 versus 18%, p = 0.007), as well as
reduced survival.14
Aortic atresia (versus stenosis),
low birth weight, and presence of a non-cardiac
abnormality or genetic syndrome were all indepen-
dent risk factors for increased early risk of death after
Norwood stage I operation.14
Prematurity and genetic co-morbidity are com-
monplace in our programme. In our study, genetic
syndromes (n = 23.3%), with the highest incidence
among patients who underwent bi-ventricular alter-
native palliation (n = 42.1%, p <0.0002), were not
significantly associated with longer intubation time,
length of ICU and hospital stay, extracorporeal
membrane oxygenation need, or mortality. With the
exception of 22q11.2 deletion syndrome, morbidity
data on large a number of patients with specific
genetic syndromes/chromosomal anomalies are
scarce. Simsic et al15
studied the effect of genetic
abnormalities on short-term outcomes following
neonatal cardiac surgery, finding a higher risk of
post-operative complications, longer hospital length
of stay, but no increase in hospital mortality.
McDonald et al16
showed that children with 22q11.2
deletion have a higher risk of post-operative compli-
cations after cardiac surgery, such as prolonged
infections, need for dialysis, and unplanned non-cardiac
surgeries such as gastrostomy and gastrostomy with
fundoplication, with no difference in length of
mechanical ventilation, ICU length of stay, hospital
length of stay, or mortality.
Study limitations
The limitations of the manuscript are inherent to those
of any retrospective database study. The analysis
focusses on outcomes of the immediate initial hospital
stay during which the first surgery was performed
and does not address follow-up issues pertaining to the
need for unplanned re-operations or interventional
catheter procedures. In patients with single ventricle
physiology, inter-stage mortality, suitability for stage
Vol. 26, No. 3 Dodge-Khatami et al: Alternative strategies in newborns and infants 491

8. II, the results of either cavo-pulmonary anastomosis or
comprehensive stage I + II palliation, or further down
the single ventricle pathway, are also not addressed and
judged beyond the scope of the manuscript.
In conclusion, the initial 4 years of our experience
as the sole emerging congenital heart programme in a
State treating neonates and infants with complex
cardiac disease with a higher than expected incidence
of accompanying non-cardiac co-morbidity has been
encouraging. Alternative surgical and hybrid pallia-
tive pathways for bi-ventricular and single ventricle
physiology in our highest-risk patients buffered risk,
allowed us to expand the number of reasonable sur-
gical candidates who may have otherwise been denied
care, and achieved excellent outcomes. The flexible
algorithms were tailored not only according to
patient-related cardiac and non-cardiac co-morbidity,
but also took into consideration the manpower and
logistical limitations during a team-building phase.
As the programme matures with more established
protocols in a current phase of sustainability, we shall
re-assess the necessity of less conventional palliations
in our continued quest of providing quality care and
achieving excellent benchmark outcomes.
Acknowledgement
None.
Financial Support
This research received no specific grant from any
funding agency, commercial, or not-for-profit sectors.
Conflicts of Interest
None.
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492 Cardiology in the Young March 2016