Original Article

Alternative strategies in newborns and infants with majorco-morbidities to improve congenital heart surgery outcomesat 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

1Department of Pediatrics; 2Pediatric and Congenital Heart Surgery, The Children’s Heart Center; 3Pediatric and FetalCardiology, The Children’s Heart Center; 4Center of Biostatistics and Bioinformatics; 5Division of Pediatric CriticalCare, 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 andinfants generally considered in-operable, in an attempt to make them surgical candidates and achieve excellentoutcomes.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 pulmonaryartery 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 oralternative surgical strategy, prematurity (50%), gestational age, low birth weight, genetic syndromes (23%), andmajor non-cardiac co-morbidity requiring same admission surgery (27%) was analysed on the need for extracorporealmembrane oxygenation, mortality, length of intubation, as well as ICU and hospital length of stays. Results: The needfor extracorporeal membrane oxygenation (8%) and hospital survival (94%) varied significantly between surgicalstrategy groups (p=0.0083 and 0.028, respectively). In high-risk patients, alternative bi- and uni-ventricularstrategies minimised mortality, but were associated with prolonged intubation and ICU stay. Major pre-operativerisk 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-riskneonates and infants with complex CHDs and significant non-cardiac co-morbidity, in order to buffer risk andachieve 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

OUTCOMES FOR NEONATES AND INFANTS WITH

CHD have improved dramatically in the lastfew decades. With increased sophistication in

prenatal diagnostics, foetal–maternal medicine, andneonatal care, survival of even the most prematureand fragile babies is expected, but it brings about awhole new set of challenges as well. Not only ismanagement of a given CHD at stake, but also that ofmultiple non-cardiac malformations, prematurity,low birth weight, malnutrition, and geneticsyndromes, further complicating the picture.1,2 Assuch, patient-related co-morbidity may increase therisk of already complex congenital heart repairsto nearly prohibitive levels, making some babies

*Meeting Presentation: some contents of the abstract were presented at the 10thInternational 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 ofMississippi Medical Center, 2500 North State Street, Room S345, Jackson MS39216, 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, 2015doi:10.1017/S1047951115000463

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 ruralpopulation of approximately three million. SinceApril, 2010, an emerging comprehensive and multi-disciplinary Children’s Heart Center has been laun-ched, with the goal of treating all-comers regardlessof disease complexity and avoiding transfer ofpatients outside the State as had been the practice fordecades. We report our experience in all consecutiveneonates and infants since the inception of the pro-gramme, with a focus on flexible alternative strategiesin the highest-risk patients in an attempt to makethem reasonable surgical candidates. The impact ofnon-cardiac co-morbidity on the outcomes and theway co-morbidity influenced surgical and interven-tional cardiologic decision-making algorithms for bothcardiac and non-cardiac conditions were evaluated.

Materials and methods

From April, 2010 to November, 2013, 442 con-secutive primary cardiac operations were performedon 142 neonates and 300 infants at the Children’sHeart Center of the University of Mississippi MedicalCenter in Jackson, Mississippi. Our InstitutionalReview Board granted permission to proceed withretrospective chart review, and parental consentwas waived.Patients with heart defects underwent palliation or

complete repair for bi-ventricular physiology(n= 312) or staged palliations for uni-ventricularphysiology (n= 130). A distinction was madebetween 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 forbi-ventricular physiology included systemic-to-pulmonary artery shunts in case of cyanotic lesionsand main pulmonary artery banding for defects withpulmonary over-circulation. Alternative palliative/hybrid strategies included bilateral pulmonary arterybanding for truncus arteriosus with severe truncalvalve insufficiency, patent ductus arteriosus stentingin severely cyanotic patients with right ventricularoutflow obstruction, or right ventricular outflowresection with patching in cyanotic patients withdiminutive pulmonary arteries deemed unfavourablefor a standard systemic-to-pulmonary shunt. For thestaged care of single ventricle lesions, standard pal-liations included either a systemic-to-pulmonaryartery shunt, pulmonary artery banding, or aNorwood-type operation in the neonatal period, anda cavo-pulmonary anastomosis (Glenn operation) in

infancy (n= 96, SU= standard uni-ventricular). Onthe other hand, alternative palliations using hybridtechniques – combined surgical and interven-tional catheter procedures – were preferred for babiesconsidered very poor surgical candidates, either dueto the patient’s general condition or specific anato-mical findings precluding the use of standardpalliative operations (n= 34, AU= alternative uni-ventricular). The decision-making for standard oralternative strategies was discussed prospectively on acase-by-case basis at a weekly combined surgical,cardiology, intensive care, and anaesthesiology con-ference: the presence of superimposed complicatingcardiac anomalies or major patient-related non-cardiac co-morbidity placed the patients in the high-risk category. In those situations, flexible/alternativestrategies were attempted with the goal of makingthe neonates and infants reasonable surgical candi-dates and avoiding withdrawal of care. Procedureswere classified according to RACHS-1 and STATScores.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 surgeryfor other major organ systems, surgical strategyaccording to treatment group as defined above, suchas 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 cardiopulmonaryresuscitation, pre-operative extracorporeal membraneoxygenation, and pre-operative mechanical ventilation.Values are expressed as median and range (mini-

mum, maximum) or mean± standard deviations forcontinuous variables and N (%) for categorical vari-ables. Continuous variables were compared usingone-way analysis of variance, and categorical variableswere compared using the χ2 or Fisher’s exact tests,where appropriate. Total intubation time, ICUlength of stay, and overall hospital length of stay weretransformed using the natural log transformation andmodelled using linear regression, whereas extra-corporeal membrane oxygenation and mortality weremodelled 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, withsignificant variability between the four treatmentgroups, the youngest being in the hybrid uni-ventricular AU group (73.4± 96.4 days;

486 Cardiology in the Young March 2016

p= 0.0014). Gender (53% male) and race (59%African-American) were similar among all treatmentgroups, as was weight at surgery (4.5± 2.1 kg).There were significant differences among groupswith regard to the presence or absence of geneticsyndromes (23%), with the highest finding inthose who underwent alternative hybrid palliationfor bi-ventricular physiology (42%; p= 0.0003).Furthermore, gestational age (mean 35.7±4.5weeks), 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 amongtreatment groups. The most premature (34.5 weeks ofgestation, 61% prematurity) and smallest at birth(2.3± 1 kg) were in the SB group. The smallest at thetime of surgery were premature neonates with singleventricle physiology requiring hybrid strategies forpalliation 4.1± 1.8 kg. Major pre-operative risk factorsincluding sepsis, immune deficiency, necrotisingenterocolitis, malnourishment (n=35; 7.8%), seizures,intracranial haemorrhage, need for cardio-pulmonaryresuscitation, pre-operative extracorporeal membraneoxygenation, and pre-operative mechanical ventilationwere present in 36% of all patients and did not sig-nificantly differ among treatment groups. Major non-cardiac abnormalities (24% of all patients) requiringsame-admission surgeries on other organ systems(27%) were similar among treatment groups and arelisted in Table 1. Complete characterisation of patientscan be seen in Table 2.The unadjusted association of variables with end

points is depicted in Table 3. End points includedintubation 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 weresignificantly different between treatmentgroups, whereas no difference was detected forextracorporeal 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 longermechanical 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 (SB50.5 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, significantlylonger ICU stays were required for patients with bothbi-ventricular and uni-ventricular hearts (AB 10 days(3, 146) and AU 17 days (1,125)) compared withstandard 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 whenalternative surgical strategies were attempted (AB21 days (5, 146) and AU 20 days (6,145)) comparedwith 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 wereadjusted for race, sex, genetic syndromes, birthweight, gestational age, weight at operation, otherrisk factors, other operations, and other cardiacabnormalities. When comparing patients with bi-ventricular and uni-ventricular hearts, surgicalstrategy affected the length of intubation(p= 0.0039 and 0.0035, respectively), length ofICU 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

Gastrointestinalsystem

Hirsprung, anal atresia, intestinal malformation, diaphragmatichernia, 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, herniarepair, liver resection, pyloromyotomy

Urinary tract Bilateral cryptorchism, hydronephrosis, polycycstic kidneydisease, 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, absentcorpus collosum, caudal regression, spinal fusion, vertebralanomaly Dandy Walker malformation, hydrocephalus,microcephaly

Cerebral aneurysm repair, ventriculo-peritonealshunt,

ENT/upperrespiratory 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, VACTERLassociation, polysplenia, asplenia, adrenal insufficiency

Eye operation

Vol. 26, No. 3 Dodge-Khatami et al: Alternative strategies in newborns and infants 487

and length of hospital stay. With respect to lengthof hospital stay, surgical strategy affected onlypatients with uni-ventricular hearts (p= 0.0261).Despite the prolonged need for respiratory, inten-sive, and hospital care, as well as a positive trend inthe need for extracorporeal membrane oxygenationand mortality, statistical significance was notreached. The impact of same-admission surgery forother major organ systems translated into a sig-nificantly longer hospital length of stay in the 27%of patients who needed it compared with those whodid not (p= 0.0025) (Table 4; Fig 1).

Discussion

Alternative palliative surgical and hybrid techniqueswere used to manage high-risk neonates and infantswith complex CHD in our emerging programme,which helped buffer mortality and improve survival,

although at the cost of prolonged need for mechanicalventilation, longer length of hospital stay, andincreased trend in the need for extracorporeal mem-brane oxygenation. The primary reason to useunconventional palliative strategies involved apatient-tailored approach for babies with severe co-morbidities including prematurity, poor nutritionalstatus, low birth weight and low weight at operation,and major non-cardiac congenital and geneticabnormalities in an effort to make them reasonablesurgical candidates and avoid withdrawal of support.Practically, this often meant breaking down a morestraightforward/standard but more aggressive proce-dure into two or more smaller procedures, judged tobe potentially less traumatic. The second reasoninvolved practical considerations pertaining to ournewly assembled care team, sometimes with man-power leanness at all levels and particularly duringnight 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

SexMale 234 (52.9%) 8 (42.1%) 156 (53.2%) 19 (55.9%) 51 (53.1%) 0.7951Female 208 (47.1%) 11 (57.9%) 137 (46.8%) 15 (44.1%) 45 (46.9%)

RaceAA 261 (59%) 12 (63.2%) 174 (59.4%) 23 (67.6%) 52 (54.2%) 0.5454Non-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) 0.0014SyndromesYes 103 (23.3%) 8 (42.1%) 80 (27.3%) 6 (17.1%) 9 (9.4%) 0.0003No 339 (76.7%) 11 (57.9%) 213 (72.7%) 28 (82.4%) 87 (90.6%)

ECMOYes 35 (7.9%) 4 (21.1%) 16 (5.5%) 6 (17.6%) 9 (9.4%) 0.0083No 407 (92.1%) 15 (78.9%) 277 (94.5%) 28 (82.4%) 87 (90.6%)

Pre-operative risk factorsYes 160 (36.2%) 8 (42.1%) 107 (36.5%) 17 (50%) 28 (29.2%) 0.1605No 282 (63.8%) 11 (57.9%) 186 (63.5%) 17 (50%) 68 (70.8%)

Non-cardiac operationsYes 120 (27.1%) 8 (42.1%) 75 (25.6%) 11 (32.4%) 26 (27.1%) 0.3961No 322 (72.9%) 11 (57.9%) 218 (74.4%) 23 (67.6%) 70 (72.9%)

Non-cardiac abnormalitiesYes 106 (24%) 3 (15.8%) 71 (24.2%) 14 (41.2%) 18 (18.8%) 0.0535No 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) <0.0001Weight 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) 0.5987Gestational age 38 (22, 41) 39 (28, 41) 37 (22, 41) 38 (34, 39) 38 (27, 40) <0.0001PrematureYes 221 (50%) 3 (15.8%) 179 (61%) 11 (32.4%) 30 (31.3%) <0.0001No 221 (50%) 16 (84.2%) 114 (39%) 23 (67.6%) 62 (64.6%)

MortalityYes 27 (6.1%) 2 (10.5%) 12 (4.1%) 5 (14.7%) 8 (8.3%) 0.0280No 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) <0.0001Hospital LOS 11 (1, 241) 21 (5, 146) 9 (1, 241) 20.5 (6, 145) 13 (4, 104) <0.0001Intubation 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

staff. Combined with patient-related factors wereinitial operational logistics, building, and materialsshortcomings, which led to flexibility in medicaldecision-making to accommodate for potential high-risk situations, even in standard-risk patients.

Lower weight at surgery influenced our treatmentstrategy, making us withdraw from more establishedsurgical repairs and palliations and move towardsalternative hybrid pathways. The algorithm seemedless 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 groupAB 2.54 0.0001 2.14 0.0003 1.79 0.0028 2.17 0.2213 1.98 0.1476SB – – – – – – – – – –AU 2.77 0.0005 2.57 0.0004 1.84 0.0007 4.62 0.1280 4.62 0.1280SU – – – – – – – – – –

African-American 1.12 0.3551 0.96 0.7387 1.15 0.1301 0.80 0.5389 0.85 0.698Sex 1.02 0.8693 1 0.966 0.95 0.5454 1.35 0.3983 1.11 0.7952Other syndromes 0.94 0.6941 1.1 0.4627 1.16 0.1798 0.99 0.9724 1.18 0.7189Birth weight 0.87 0.0563 1 0.9569 0.83 0.0009 1.32 0.1992 1.04 0.8643Gestational age 0.97 0.0307 0.99 0.6161 0.96 0.0004 1.07 0.1988 0.99 0.8239Weight at operation 0.76 <0.0001 0.80 <0.0001 0.82 <0.0001 0.74 0.0025 0.68 0.0011Pre-operative risk factors 2.2 <0.0001 1.79 <0.0001 1.94 <0.0001 1.53 0.2315 3.82 0.0015Non-cardiac operations 2.07 <0.0001 1.96 <0.0001 2.11 <0.0001 0.94 0.8685 0.60 0.3153Non-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= oddsratio; 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

or no exposure to cardio-pulmonary bypass and/orpotentially less post-operative haemodynamicinstability, as may occur with systemic-pulmonaryartery shunt-dependent palliations. In our study, themean weight at birth was 2.6± 0.9 kg and at surgeryit was 4.5± 2.1 kg among all groups, with thelowest findings among the AB and AU groups.Heavier weight was significantly associated withdecreased 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 showingincreased mortality in patients with low weight andpoor nutritional status at the time of surgicalrepair.3,4 Curzon et al3 found significantly highermortality in infants weighing 1–2.5 kg comparedwith those weighing 2.5–4 kg for several surgicalprocedures. Lower weight remained strongly asso-ciated with mortality after adjustment by the RACHScategorisation and Aristotle complexity levels.4

Wei et al5 found an increased risk for post-operativeinfections (p< 0.0001) in patients with low weight atsurgery, with a cut-off weight at 2.4 kg. Low weight atsurgery has been associated with higher morbidity notonly 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 ahigher rate of serious post-operative infections andlonger length of hospital stay.We found signs of malnourishment in 35 (7.8%)

of our patients, without a significant differenceamong 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 bodyfat mass and acute and chronic malnourishment to beassociated with worse clinical outcomes. They alsoreported an inverse correlation between total body fatand brain natriuretic peptide levels. The duration ofinotropic support and brain natriuretic peptideincreased concomitantly to decreasing nutritionalstatus in their patients, supporting the hypothesisthat malnourishment is associated with decreasedmyocardial function.7 A clear association betweenpoor nutritional status and adverse outcome hasrecently sparked efforts to streamline nutritionalpractices in inter-stage single ventricle patients.Keating et al8 examined the impact of early fundo-plication or a gastrostomy tube on the mid-termoutcomes of patients with single ventricle physiol-ogy. hypoplastic left heart syndrome anatomy(p= 0.002) and those with a morphological rightventricle (p= 0.003) were associated with the needfor fundoplication or gastrostomy. Although neitherof the cardiac morphology variables affectedmid-term survival, the need for fundoplication orgastrostomy was significantly associated with pooroutcomes (hazard ratio of 4.3; p= 0.003).8 In addi-tion, recent studies indicate that exclusive oralfeeding post-Norwood is associated with higher age-for-weight Z-score at the time of stage II palliation,9

and gastrostomy/fundoplication is associated withhigher inter-stage mortality.10 Some surmise that theneed for inter-stage tube feeding is a marker ofunmeasured co-morbidities. As such, efforts by theNational Pediatric Cardiology Quality ImprovementCollaborative have resulted in improved inter-stagegrowth 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 groupAB 2.50 0.0039 2.12 0.0090 1.49 0.0981 3.66 0.2492 1.30 0.6367SB – – – – – – – – – –AU 1.99 0.0035 1.77 0.0062 1.52 0.0261 1.87 0.4914 1.79 0.1217SU – – – – – – – – – –

African-American 1.10 0.4645 0.94 0.5869 1.14 0.1988 0.77 0.5473 0.61 0.3231Sex 1.14 0.2995 1.04 0.7285 1.04 0.7299 1.98 0.1324 1.71 0.2990Other syndromes 0.98 0.9269 1.14 0.3773 1.25 0.0847 0.87 0.8283 1.88 0.3744Birth weight 1.07 0.6535 1.18 0.2025 1.07 0.5111 0.95 0.9157 0.94 0.9113Gestational age 1.01 0.7593 1.00 0.9084 0.98 0.4898 1.18 0.0781 1.10 0.3828Weight at operation 0.78 <0.0001 0.81 <0.0001 0.84 <0.0001 0.57 0.0024 0.55 0.0011Pre-operative risk factors 1.50 <0.0001 1.26 0.0844 1.32 0.0158 1.79 0.2029 4.59 0.0014Non-cardiac operations 1.35 0.0857 1.27 0.1310 1.51 0.0002 0.77 0.6224 0.45 0.2113Non-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= standardbi-ventricular; SU= standard uni-ventricular

490 Cardiology in the Young March 2016

population likely represent some of the “unmea-sured”. Despite these challenges, our hospital survivalis 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 clinicaloutcomes in newborns requiring congenital heartsurgery.5,12 Wei at al5 found lower gestational age atbirth to be associated with home oxygen use, highertracheostomy rates, and discharge with a gastrostomytube, without influencing survival to discharge. Azakieet al12 found a slightly lower survival trend amongpatients born at <37 weeks of gestation at 83 versus97% among patients born at 37 weeks of gestation orgreater, without achieving statistical significance.Necrotising enterocolitis, seizures, need for supple-mental oxygen, and gavage feeds at discharge were allmore frequent among their late preterm infants.12 Thecorrelation between prematurity and outcomes was alsoexamined by Costello et al,13 comparing neonates whowere delivered at 39–40 completed weeks of gestationwith those born at 37–38 weeks, who had increasedmortality (6.9 versus 2.6%; adjusted p= 0.049), mor-bidity (49.7 versus 39.7%; adjusted p= 0.02), andlonger duration of mechanical ventilation (adjustedp=0.05). Patients born after 40 or before 37 weeks ofgestation had increased morbidity rates and requiredmore days of mechanical ventilation and intensive care.Based on their findings, they suggest that morbidityand mortality rates are lowest when delivery occurs ormay safely be delayed to 39–40 weeks of gestation.13

Based on these findings and in concert with our ownexperience, we have reached an understanding with ourown and other referring foetal–maternal medical teamsto allow a gestational age of at least 38 weeks, when it issafe for the expecting mother and the foetus.We showed that pre-operative risk factors, present

in more than a third of our patients, includingnecrotising enterocolitis, sepsis, seizures, immunedeficiency, cardio-pulmonary resuscitation, intracra-nial haemorrhage, pre-operative extracorporealmembrane oxygenation, and need for mechanicalventilation, were associated with significant higherlengths 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-cardiacabnormalities requiring same-admission surgeries,present in 27.1% of our patients, to be associatedwith significantly longer length of hospital stay(p= 0.0025) among our treatment groups. Patel et alevaluated the impact of non-cardiac congenital andgenetic abnormalities on outcomes in patient withhypoplastic left heart syndrome, based on two largemulti-institutional data sets. They suggested that thepresence of co-existing non-cardiac anomalies or

genetic abnormalities confer an additional risk ofdeath for infants undergoing staged palliation forhypoplastic left heart syndrome.14 Stage 1 in-hospitalmortality (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 infantswith non-cardiac genetic defects. Chromosomaldefects (n= 14) were highly unfavourable: the earlyrisk of death was doubled (10 year survival 25± 9versus 54± 2%, p= 0.005). The presence of non-cardiac abnormalities and genetic syndromes wasassociated with significantly delayed post-operativerecovery (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 asreduced survival.14 Aortic atresia (versus stenosis),low birth weight, and presence of a non-cardiacabnormality or genetic syndrome were all indepen-dent risk factors for increased early risk of death afterNorwood stage I operation.14

Prematurity and genetic co-morbidity are com-monplace in our programme. In our study, geneticsyndromes (n= 23.3%), with the highest incidenceamong patients who underwent bi-ventricular alter-native palliation (n= 42.1%, p<0.0002), were notsignificantly associated with longer intubation time,length of ICU and hospital stay, extracorporealmembrane oxygenation need, or mortality. With theexception of 22q11.2 deletion syndrome, morbiditydata on large a number of patients with specificgenetic syndromes/chromosomal anomalies arescarce. Simsic et al15 studied the effect of geneticabnormalities on short-term outcomes followingneonatal cardiac surgery, finding a higher risk ofpost-operative complications, longer hospital lengthof stay, but no increase in hospital mortality.McDonald et al16 showed that children with 22q11.2deletion have a higher risk of post-operative compli-cations after cardiac surgery, such as prolongedinfections, need for dialysis, and unplanned non-cardiacsurgeries such as gastrostomy and gastrostomy withfundoplication, with no difference in length ofmechanical ventilation, ICU length of stay, hospitallength of stay, or mortality.

Study limitationsThe limitations of the manuscript are inherent to thoseof any retrospective database study. The analysisfocusses on outcomes of the immediate initial hospitalstay during which the first surgery was performedand does not address follow-up issues pertaining to theneed for unplanned re-operations or interventionalcatheter procedures. In patients with single ventriclephysiology, inter-stage mortality, suitability for stage

Vol. 26, No. 3 Dodge-Khatami et al: Alternative strategies in newborns and infants 491

II, the results of either cavo-pulmonary anastomosis orcomprehensive stage I+ II palliation, or further downthe single ventricle pathway, are also not addressed andjudged beyond the scope of the manuscript.In conclusion, the initial 4 years of our experience

as the sole emerging congenital heart programme in aState treating neonates and infants with complexcardiac disease with a higher than expected incidenceof accompanying non-cardiac co-morbidity has beenencouraging. Alternative surgical and hybrid pallia-tive pathways for bi-ventricular and single ventriclephysiology in our highest-risk patients buffered risk,allowed us to expand the number of reasonable sur-gical candidates who may have otherwise been deniedcare, and achieved excellent outcomes. The flexiblealgorithms were tailored not only according topatient-related cardiac and non-cardiac co-morbidity,but also took into consideration the manpower andlogistical limitations during a team-building phase.As the programme matures with more establishedprotocols in a current phase of sustainability, we shallre-assess the necessity of less conventional palliationsin our continued quest of providing quality care andachieving excellent benchmark outcomes.

Acknowledgement

None.

Financial Support

This research received no specific grant from anyfunding agency, commercial, or not-for-profit sectors.

Conflicts of Interest

None.

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