surgery for congenital anomalies: a systematic review of potential risk factors
S
ome of the text of this chapter has been published previously as Tregay et al., 2015.20Reproduced with permission. © Cambridge University Press 2014.Introduction
In order to achieve optimal outcomes post discharge in infants going home after intervention, and to offer targeted support to vulnerable infants and their families at home in the community, it is also important to understand the risk factors for these late outcomes. We therefore undertook a systematic review of the published literature with the intent of capturing all studies of infants with congenital anomalies, to identify the key risk factors, identifiable at the time of discharge home after surgery, that are associated with unexpected death in the community or unplanned readmission to hospital. In setting up the systematic review, we aimed to capture studies from other specialist areas of practice, including but not exclusive to CHD, as we sought transferable knowledge as well as information regarding our specific population of interest.
Methods
Protocol and registration
The protocol and search strategy is registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42013003483.21
Search strategy
To ensure a comprehensive review of the evidence, and to capture any pertinent risk factors that may not yet have been identified in studies with CHD patients, we used a broad search strategy that included other life-threatening congenital malformations requiring major surgery in the first year of life, for example gastroschisis or diaphragmatic hernia. We used key terms relating to children, congenital abnormalities, surgical procedures, hospital discharge and adverse outcomes to electronically search MEDLINE (1980 to 1 February 2013), EMBASE (1980 to 1 February 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1981 to 1 February 2013), The Cochrane Library (1999 to 1 February 2013), Web of Knowledge (1980 to 1 February 2013) and PsycINFO (1980 to 1 February 2013). Conference abstracts from the Association for European Paediatric Cardiology, the American Heart Association and the European Surveillance of Congenital Anomalies symposia were searched for the period 2008 to 2012.
A forward citation search was carried out on the reference lists of all selected studies to identify additional published studies for review.
Selection of studies
Studies were eligible for inclusion only if they separately reported outcomes for children discharged from hospital and in-hospital surgical mortality. To ensure relevance to infant survival, only studies involving children up to the age of 5 years were included in the review and major surgery was defined as requiring intensive or high-dependency care in the postoperative period. Inclusion criteria for the studies included in the review are summarised in Box 1.
The titles and abstracts for all studies were independently reviewed by two reviewers (J Tregay and J Wray) then full-text papers of selected studies assessed by three reviewers (J Tregay, K Brown and R Knowles) to determine whether or not they met the inclusion criteria. Any discrepancies between reviewers were resolved through discussion with a fourth reviewer (J Wray) (see Figure 1).
Data extraction
Data extraction was independently completed by two reviewers (J Tregay and R Knowles) using a standard pro forma that included information on study design, population, diagnosis, comparison groups, outcomes and risk factors.
Quality assessment
Studies were assessed for methodological quality of study design using levels of evidence rated from one (most rigorous, e.g. randomised controlled trial) to four (least rigorous, e.g. retrospective uncontrolled case series).22Within each evidence level, studies were assessed as A (high quality) to C (lowest quality), using predetermined criteria such as confounding, completeness of follow-up and objective measurement of outcomes (see Appendix 2).
BOX 1 Summary of the eligibility criteria for inclusion in the review. Reproduced with permission from Tregay et al., 2015.20© Cambridge University Press 2014
Inclusion criteria
Studies that include children:
l aged from birth up to and including 5 years of age
l with a life-threatening congenital abnormality
l who have undergone major surgery (involving intensive care) for potentially life-threatening congenital disease
l who were discharged home from hospital following their successful surgery.
Exclusion criteria
Studies that:
l refer exclusively to adults, children over the age of 5 years old or where the age group of interest is not clearly defined
l include previously healthy children who had major surgery as a consequence of traumatic injury
l do not refer to specified adverse outcomes (e.g. death, unplanned hospital readmission)
l do not present postdischarge events and risk factors separately from in-hospital events
l included children discharged home for palliative medical care
l were case series of fewer than 20 cases, personal communications, letters and commentaries
l have no available English-language abstract.
Data analysis
The outcomes of interest were unexpected death or unplanned readmission to hospital in the first year of life after discharge following cardiac surgery. Factors associated with increased mortality or readmission risk are presented in a narrative synthesis.
Results
Study selection
There were 17 studies identified through systematic searches and a further six studies through forward citations. Of the 23 full-text papers reviewed, eight studies failed to meet inclusion criteria resulting in 15 studies eligible for review (Figure 1). Despite our inclusive search strategy, no studies of post-surgical outcomes for children with non-cardiac congenital anomalies met the inclusion criteria.
The review included eight retrospective reviews of surgical cases,23–30four retrospective cohort studies,31–34 two case–control studies35,36and one randomised controlled trial that was reported in two papers.26,37 Only three studies29,36,37included a prospective element. Although study designs differed, all studies were rated as good quality (Table 1); studies that were assigned a lower rating failed to address some
potential confounding factors. Ten reports were of patients with a functional single-ventricle (SV)
diagnosis,23,24,26–28,30,33,35–37which was most often HLHS. Fourteen papers involved patients who underwent cardiac surgery during the first year of life and the remaining study31included cardiac patients operated up to the age of 18 years with results provided separately for each age group. Only two studies were not conducted in the USA.23,27In total, 29,019 patients were followed up for mortality outcomes, of whom
Records identified
• No differentiation of in- and out-of-hospital deaths, n = 4
• No data (literature review), n = 1
• No differentiation of patients who had surgery and those who did not, n = 1
• No reference to risk factors, n = 1
• Not life-threatening (cleft lip), n = 1
FIGURE 1 The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) flow chart showing study selection process. Reproduced with permission from Tregay et al., 2015.20© Cambridge University Press 2014.
1113 (4%) died. Of the 3672 children who underwent SV surgery, 452 (12%) died, compared with 661 (3%) of 25,347 children who underwent other types of cardiac surgery. Of the 1639 children who were observed in three studies of unplanned readmission, 173 (11%) were readmitted to hospital during the study follow-up period. Table 2 summarises the included papers.
Adverse outcomes
Reported mortality rates varied markedly and were influenced by the study population at risk as well as the duration of follow-up. Five studies23,26,30,33,35involved children with SV diagnoses undergoing staged palliative surgery and reported‘interstage’ mortality between first- and second-stage surgery that ranged from 8% to 16%, with follow-up ending at around 1 year after surgery in most studies. Two further studies focused on‘unexpected’ interstage deaths, defined as acute events or sudden cardiovascular collapse, and reported 4–5% unexpected deaths in neonates discharged home between stages 1 and 2.28,37 Carlo et al.24and Hansen et al.27reported interstage mortality of 9% for children discharged home between second (superior cavopulmonary anastomosis or bidirectional Glenn) and third stage (Fontan) surgery.
Two studies investigated postdischarge mortality after all types of cardiac surgery: Chang et al.31reported a low mortality rate of 0.62% at 1 year after any cardiac surgery undertaken in children up to age 18 years, whereas Pinto et al.29found a higher mortality rate of 8% in the 2 years following discharge after neonatal congenital heart surgery. Mortality rates over 10% were reported in studies focusing on specific higher-risk cardiac defect subgroups32or patients discharged home on mechanical ventilation.25
TABLE 1 Summary of study quality by levels of evidence.aReproduced with permission from Tregay et al., 2015.20
© Cambridge University Press 2014 Study quality Study quality Study quality Study quality
A B C A B C A B C A B C
LOE, level of evidence; RCT, randomised controlled trial.
a Rated A (high quality) to C (low quality).
TABLE2Studiesmeetingcriteriaforthereview(n=15)examiningriskfactorsforpostdischargemortalityand/orunplannedhospitalreadmission.Reproducedwithpermission fromTregayetal.,2015.20 ©CambridgeUniversityPress2014 First author, yearParticipantsSettingandstudy designQuality ratingFollow-upperiodPrimaryoutcome measure
Mortalityrate (post-hospital discharge)Factorsassociatedwithmortality/hospital readmission Ashburn, 200323710HLHSwith criticalaortic stenosisoraortic valveatresiawho underwent Norwoodstage1 procedure (512infants dischargedalive afterstage1 surgery)
Canadian multicentrestudy; retrospectiverecords reviewofsurgical cases;riskanalysis foroutcomes includingdeath, furthersurgery 4AFollow-upat 1month,6months, 1yearand5years afterstage1 procedure Timetotransitionto death,furtherplanned surgery,transplantation orotheroutcome
12%of512infants diedbetweenstage1 andstage2surgery. Survivalafterstage1 surgeryforwhole cohort:72%at 1month;62%at 6months;60%at 1year;and54%at 5years
Patient-specificfactorslinkedtomortality:low birthweight,smallerascendingaorta,olderageat Norwood Institutionalfactorslinkedtomortality:institutions enrolling≤10neonateshigherriskthan institutionsenrolling≥40neonates Proceduralfactorslinkedtomortality:shunt originatingfromtheaorta,longercirculatory arresttime,managementofascendingaorta Carlo, 20112485HLHS(65% male)who underwent Norwoodstage1 followedbyBDG stage2procedure
SingleUScentre; retrospectiverecords reviewofsurgical cases;comparison betweensurvivors anddeceased 4AFromBDG(stage2) untilFontan (stage3)procedure, cardiactransplant ordeath.Follow-up formean3.4years (range1.6–5.8 years)afterstage2 procedure Interstageattrition (deathorcardiac transplantation) afterhospital dischargefromBDG (stage2procedure) andbeforeFontan (stage3procedure) Eightdied unexpectedlyat home(9.4% mortalityrate)and threeunderwent cardiac transplantation (13%overall attrition)
Factorsassociatedwithinter-stagemortality: longerintubationtimes(median2daysvs.1day, p<0.01),hospitallengthofstay(median19days vs.6days;p<0.01) Highermortalityriskonmultivariableanalysis: lowerweightz-scoreatBDGandmoderateto severetricuspidregurgitation Interstagemortalitynotassociatedwith:sex, anatomicsubtypeinHLHS,useofantegrade cerebralperfusion,restrictiveatrialseptumat birth,ageorweightatstage1palliation, stage1operativecharacteristics,ageatBDG, haemodynamicdataobtainedatcardiac catheterisation,aorticarchobstruction,right ventriculardysfunction continued
TABLE2Studiesmeetingcriteriaforthereview(n=15)examiningriskfactorsforpostdischargemortalityand/orunplannedhospitalreadmission.Reproducedwithpermission fromTregayetal.,2015.20©CambridgeUniversityPress2014(continued) First author, yearParticipantsSettingandstudy designQuality ratingFollow-upperiodPrimaryoutcome measure
Mortalityrate (post-hospital discharge)Factorsassociatedwithmortality/hospital readmission Chang, 20063123,897children <18years(55% male)withICD-9- CMprocedure codesindicating anycardiac surgery;includes cardiacsurgeryfor non-congenital diagnoses
AllUSCalifornian statehospitals; retrospectivecohort follow-upusing state-widedatabase; multivariateanalysis ofriskfactors 3AUpto365days postdischargePostoperativedeaths within1yearof surgery(included in-hospitaldeath). Latedeaths(occurring 31–365daysafter hospitaldischarge) werereported separately 23,987‘alive’ hospitaldischarges, 148deaths(0.62%) occurredwithin365 daysafterdischarge (37deathswithin 30days;44deaths at31–90days; 67deathsat 91–365days)
Factorsassociatedwithpostdischargedeath: youngerageandproceduretypeintermsof neonatesandinfantsundergoingNorwood procedure,aortopulmonaryshuntwithatrial septostomy,totalanomalouspulmonaryveinsor truncusarteriosusrepair,thoracicvesselprocedures andopenvalvotomy Factorsnotassociatedwithpostdischargedeath: ethnicity,sex,income,hospitalcarevolume Edwards, 20102535CHD(various) (46%male)who underwentany CHDsurgeryand wereinahome mechanical ventilation programme
SingleUScentre; retrospectivereview usinghospital records;survival analysis 4A2–168monthsafter startinghome mechanical ventilation
Mortality12(34%)diedHighermortalityriskonunivariableanalysis: bronchopulmonarydysplasia,neurological disorder Highermortalityriskonmultivariableanalysis: adjustedRACHSscoreof≥4 Fixler, 2012321213CHD diagnosis associatedwith >25%mortality
USstate(Texas) registry; observationalcohort follow-upusing linkedrecords; multivariateanalysis ofriskfactors
3AUpto1yearafter birthFirst-yearmortalityOverallfirst-year survivalwas59.9%Overallethnicitywasnotassociatedwithsurvival, butHispanicinfantswithHLHShaddecreased survival Factorsassociatedwithworsesurvivalafter adjustmentfordefecttype:livingonMexican border(proxyfordeprivation),lowbirthweight (<2500kg)andgestationalage,extracardiac defects Factorsnotassociatedwithfirstyearmortality: distancetocardiaccentre,parentalbirthplace, sex,maternaleducationandmaritalstatus
First author, yearParticipantsSettingandstudy designQuality ratingFollow-upperiodPrimaryoutcome measure
Mortalityrate (post-hospital discharge)Factorsassociatedwithmortality/hospital readmission Ghanayem, 201226426SVdiagnosis; survivedto hospitaldischarge afterNorwood stage1surgery
USmulticentre; retrospectivecase recordsanalysis withinacontrolled trial;multivariaterisk factoranalysis 3AUntilstage2 surgeryordeath (upto14months afterstage1 surgery)
Interstagemortality posthospitaldischarge50(12%)diedFactorsassociatedwithworsesurvival:preterm delivery,Hispanicethnicity,aortic/mitralatresia, highernumberofpostoperativecomplications, percentagebelowpovertyline(UScensus data),shunttype(MBTSlinkedtoworsesurvival thanRVPA) Hansen, 201127115HLHS(67% male);underwent superior cavopulmonary anastomosis (stage2)surgery
Singlecentre, Germany; retrospectivesurgical caseseries; multivariateanalysis ofriskfactors 4AFollow-upovera 14-yearperiod– minimumfollow-up of2years Death/cardiac transplant; postoperative complicationand adverseevents Lateadverse outcomein10 (8.7%)patients (deathn=8;cardiac transplantn=2)
Factorsassociatedwithdeath/cardiactransplant: longercardiopulmonarybypasstime,moderateor greatertricuspidregurgitationonpost-operative echocardiogram(OR16.5,95%CI4.4to62.6; p<0.001) Factorsnotassociatedwithdeath/cardiac transplant:aged<4monthsatsurgery(OR1.2, 95%CI0.4to3.6;p=0.78) Hebson, 201233334neonates aged<30daysat surgery;SV diagnosis(varied); underwent Norwoodstage1 (n=165), pulmonaryartery band(n=17),or MBTS(n=152) procedures
SingleUScentre; retrospectivecohort study;analysisof differentfeeding modalitiespost discharge 3AUntilstage2 surgery(follow-up rangedfrom1to 8yearsoverall,but wasnotspecified forindividual patients) Interstagemortality26(7.8%)interstage deaths.Ninedeaths withNForGT; 17withoutNF/GT. Sevendiedin hospitaland 19diedathome/ localfacilities
Higherriskofinterstagemortalityonmultivariate analysis(adjustedforage,weight,genetic syndromes,prematurity,heterotaxy,postoperative arrhythmia;andventricularfunctionatdischarge): feedingwithGTwith/withoutNF(relativerisk 2.38,95%CI1.05to5.40;p=0.04) continued
TABLE2Studiesmeetingcriteriaforthereview(n=15)examiningriskfactorsforpostdischargemortalityand/orunplannedhospitalreadmission.Reproducedwithpermission fromTregayetal.,2015.20©CambridgeUniversityPress2014(continued) First author, yearParticipantsSettingandstudy designQuality ratingFollow-upperiodPrimaryoutcome measure
Mortalityrate (post-hospital discharge)Factorsassociatedwithmortality/hospital readmission Hehir, 200835313‘hospital survivors’with HLHS(and variants); underwent Norwoodstage1 procedure
SingleUScentre; retrospective, nested,case–control study;multivariate analysisofrisk factors 3AFollow-upwasfor 1yearafterstage1 surgeryoruntil stage2surgeryor deathifearlier Interstagemortality (postdischargeand beforestage2 procedure)
33interstagedeaths (10.5%)Higherriskofdeathonunivariateanalyses: restrictiveatrialseptum,olderageatoperation, postoperativearrhythmiasandrespiratory complications Higherriskofdeathonmultivariateanalyses: highlyrestrictiveatrialseptum(OR7.6,95%CI 1.9to29.6),ageatoperation>7days(OR3.8, 95%CI1.3to11.2) Factorsnotassociatedwithinterstagedeath: intra-operativefactors,cardiacstatusatdischarge, sex,birthweight,gestation,prenataldiagnosis, distancefromcentre,feedingatdischarge, non-cardiacanomalies,oxygenatdischarge, reoperation,dischargeon>threemedications, seizures,postoperativeECMOorcardiacarrest Higherriskofreadmissiononunivariateanalysis: youngerage;lowerweightatsurgery;Hispanic; geneticsyndrome;failuretothrive;pre-operative ventilation;higherRACHS-1score;nasogastric feedingatdischarge;palliativesurgery;longer lengthofstayinICU/hospital Higherriskofreadmissiononmultivariate analysis:Hispanicethnicity;failuretothrive; hospitallengthofstay>10days Factorsnotassociatedwithunplanned readmission:arrhythmia,gastro-oesophageal refluxanddevelopmentaldelay
First author, yearParticipantsSettingandstudy designQuality ratingFollow-upperiodPrimaryoutcome measure
Mortalityrate (post-hospital discharge)Factorsassociatedwithmortality/hospital readmission Kogon, 201234685anyCHD diagnosisrequiring surgery (57%male)
SingleUScentre; retrospective observationalcohort study;multivariate analysisofrisk factors 3BUntil30daysafter hospitaldischargeUnplanned readmissionswithin 30daysofhospital discharge 70patients(10.2%) werereadmitted (total74 readmissionsin 70patients)
Riskfactorsforunplannedreadmissionon univariableanalysis:youngerage;lowerweightat surgery;Hispanic;geneticsyndrome;failureto thrive;pre-operativeventilation;higherRACHS-1 score;nasogastricfeedingatdischarge;palliative surgery;longerlengthofstayinICU/hospital Riskfactorsforunplannedreadmissionon multivariableanalysis:Hispanicethnicity;failureto thrive;hospitallengthofstay>10days Factorsnotassociatedwithunplanned readmission:arrhythmia,gastro-oesophageal refluxanddevelopmentaldelay Mackie, 200436162(54cases;108 controlpatients) HLHS,otherSV diagnosisor transpositionof thegreatarteries; underwent Norwoodstage1 orarterialswitch procedure
SingleUScentre; case–controlstudy; multivariateanalysis ofriskfactors 2BUntil30daysafter hospitaldischargeUnplanned readmissionordeath (combinedoutcome usedtoexplorerisk factors) 54cases(from 752operated children)included: 48readmissions (29.6%of752); sixdeaths(3.7% of752)
Factorsassociatedwithdeathorreadmission: residualhaemodynamicproblems(OR4.10),ICU stay>7days(OR5.17),establishmentoffulloral intake<2daysbefore.Combiningwiththe controlgroup,livinginalowincomeareaswas associatedwithalowerlikelihoodofreadmission (OR0.25,95%CI0.07to0.85;p=0.027) Mahle, 200128536HLHSand variants; underwentstage1 surgeryforSV reconstruction
SingleUScentre; retrospective records-based identificationof cohortwith prospective confirmationof outcomes; multivariateanalysis ofrisk 3BDeathswithinthe firstyearafter stage1(range 25–227days postsurgery)
‘Unexpected’death (definedas cardiovascularcollapse withoutregaining consciousness)
22unexpected deaths(4.1%)and 63non-surgery- relateddeaths (11.8%)from 536infants dischargedhome afterstage1 surgery.Medianage atunexpected deathwas 79(25–227)days Factorsassociatedwithlatemortality: perioperativearrhythmiaandearlieryearof surgery Factorsnotassociatedwithlatemortality:prenatal diagnosis,aorticatresia,ageatadmission,age ateachsurgicalstage,perioperativeseizure, ventricularfunctionmeasuresandfeeding difficulties continued
TABLE2Studiesmeetingcriteriaforthereview(n=15)examiningriskfactorsforpostdischargemortalityand/orunplannedhospitalreadmission.Reproducedwithpermission fromTregayetal.,2015.20©CambridgeUniversityPress2014(continued) First author, yearParticipantsSettingandstudy designQuality ratingFollow-upperiodPrimaryoutcome measure
Mortalityrate (post-hospital discharge)Factorsassociatedwithmortality/hospital readmission Ohye, 201237549SV; underwent Norwoodstage1 (randomisedto twoshunttypes)
USA;multicentre; prospectiveRCT comparingtwo typesofSVsurgery; multivariateanalysis ofriskfactors 1BUntil12months afterstage1 surgery Deaths(including ‘unexpected’death) inthe12months followingNorwood stage1surgery
164died:88 in-hospitalatstage1; 54betweenstages1 and2;16in-hospital atstage2;and6 within12monthsof stage2discharge.A totalof29deaths were‘unexpected’
Factorassociatedwithinter-stagemortality:shunt type,withMBTShigherriskthanRVPA.Twelve (41%)ofthe29‘unexpected’(postdischarge) deathshadprodromalillnessincludingpoor feeding/vomiting,fussiness,diarrhoea,cyanosis, feverandincreasedworkofbreathing Pinto, 201229202anyCHD requiringsurgery (51.5%male); underwent neonatal congenitalheart surgery(notminor surgery)
SingleUScentre; retrospectiverecords reviewand follow-upsurvey; multivariateanalysis ofriskfactors 4A23.9(±3.4)months postdischargeafter neonatalcongenital heartsurgery Mortality+‘adverse events’(unplanned readmissionsand cardiacreinterventions)
16deaths(8%). Postdischargeadverse eventswerereported forsurvivingpatients bytelephonesurvey (contactrate59%). Ofthose,49(45%) hadanunplanned readmission
Patientsresident90–300minutesfromthesurgical centrewerelesslikelytoexperienceanadverse eventthanthoseliving<90minutesawaybut therewasanon-significanttrendtowardhigher mortalityinthissamegroupwhencomparedwith thoseliving<90minutesand>30minutesaway. Residence>300minutesfromthehospitalnot associatedwithhigherriskofpostdischargedeath Simsic, 20053050HLHS/SV diagnosis; underwent Norwoodstage1 procedure
SingleUScentre; retrospectivereview ofsurgicalcasesand outcomes; multivariable analysisofrisk factors 4BFor1yearafter stage1surgery (untilstage2 surgeryordeath) Interstagemortality betweenNorwood stage1dischargeand stage2surgery Eightdeaths(16%) within1yearafter Norwoodprocedure
Factorsassociatedwithinterstagemortality: postoperativearrhythmias;decreasedventricular function.Factorsnotassociatedwithinterstage mortality:durationofcardiopulmonarybypass, crossclamporcirculatoryarrest;moderatevalve regurgitation;postoperativeepinephrine,length ofmechanicalventilation,lengthofhospitalstay anddischargemedication BDG,bidirectionalGlenn;CI,confidenceinterval;ECMO,extracorporealmembraneoxygenation;GT,gastrostomytube;ICD-9-CM,InternationalClassificationofDiseases,NinthEdition, ClinicalModification;ICU,intensivecareunit;LOS,lengthofstay;MBTS,modifiedBlalock–Taussigshunt;NF,Nissenfundoplication;OR,oddsratio;RACHS,RiskAdjustmentinCongenital HeartSurgery;RCT,randomisedcontrolledtrial;RVPA,rightventricle-to-pulmonaryarteryconduit.
Two studies evaluated unplanned hospital readmissions as distinct from mortality29,34and one further study36reported unplanned readmissions as part of a combined outcome measure of mortality and readmission. Readmission rates within 30 days of hospital discharge ranged from 10%34to 30%36and at 2 years post discharge were 45%;29variations were influenced by duration of follow-up and differences in data collection methods, which included hospital records review34,36and telephone survey.29
Risk factors associated with adverse outcomes
Although many different factors were investigated, the findings relating to individual factors were inconsistent; this may reflect the heterogeneity of participant characteristics and study designs. Figure 2 summarises the factors investigated by different studies and indicates whether or not these were found to increase mortality risk.
Individual and family factors
Ethnicity,26,29,32,34socioeconomic status26,32,36and non-cardiac malformations or genetic syndromes32,34,36were the most frequently evaluated individual factors. Hispanic ethnicity14,19,23and socioeconomic deprivation, as assessed through measures such as household income,36family income below the national poverty threshold26and deprivation index of the residential area32were highlighted as risk factors for mortality and unplanned hospital readmission in the US studies. Preterm birth26,32and low birthweight23,32were risk factors for mortality, but patient sex was not significantly associated with adverse outcomes.24,31,32,35Children living 90–300 minutes from the cardiac centre were at significantly lower risk of unplanned readmission29 compared with families living under 90 minutes away, but there was no association with mortality.29,32 Family factors, including maternal education, marital status and country of birth, were not associated with adverse outcomes.32
Cardiac diagnosis and procedural factors
Infants with more complex hypoplastic left heart variants23,24,26,27,35were at higher risk of mortality or readmission. Children undergoing more complex operations, based on the Risk Adjustment in Congenital Heart Surgery (RACHS)– 1 system,9,38were at greater risk.25,29,34Several studies reported that Norwood procedures,31specific shunt operations,23,26,31,37total anomalous pulmonary venous connection (TAPVC) repair31and truncus arteriosus repair31were associated with significantly higher mortality, whereas palliative operations34increased the risk of unplanned readmission. There was insufficient evidence to suggest that intraoperative characteristics, such as cardiopulmonary bypass or circulatory arrest time, had a negative impact on outcome.23,30,35
In children undergoing staged palliative operations, older age at first procedure was associated with higher mortality risk,23,35whereas younger age (under 4 months) at the second-stage Glenn procedure increased the risk of postoperative complications.27In two papers26,37reporting findings from the Single Ventricle Reconstruction (SVR) trial, in which patients with HLHS were randomised to receive different surgical interventions, higher mortality rates after hospital discharge were observed in the group receiving a modified Blalock–Taussig shunt (MBTS) than in the group undergoing a right ventricle-to-pulmonary artery conduit (RVPA); this difference was no longer significant after adjustment for severity of postoperative atrioventricular valvar regurgitation.
Postoperative symptoms/complications
Five studies explored postoperative feeding difficulties;28,33–36three of these identified feeding
difficulties,33,34,36including the need for gastrostomy tube placement,33as a risk factor for mortality or unplanned readmission. Peri- and postoperative arrhythmias were also a significant risk factor for mortality in two studies;28,30although airway complications, prolonged postoperative length of stay (LOS),
postoperative complications and medications at discharge were not found to influence outcomes post discharge.
Sex
Race/ethnicity SES/home income
Parent factor, for example maternal education Distance to cardiac centre
Prematurity/gestational age < 37 weeks Low birthweight
Failure to thrive
Extracardiac/genetic syndromes
Factors reported (by category) Reference numbers for studies reporting on each factor Studies reporting
Operative characteristics at stage 1 surgery Age at surgery
Operative complexity (RACHS score of > 4) Procedure typea
Moderate AV valvar regurgitation (in HLHS) Aortic arch obstruction (in HLHS)
Complexity of cardiac anatomy
24
FIGURE 2 Summary of factors examined in the 15 studies. AV, atrioventricular; ICU, intensive care unit;
SES, socioeconomic status; RACHS category, Risk Adjustment in Congenital Heart Surgery category. a, The cardiac surgical procedures defined in these studies were palliative procedures, Norwood stage 1, bidirectional Glenn, shunt construction, thoracic vessel procedures, truncus arteriosus repair, total anomalous pulmonary venous return repair and open valvotomy. Reproduced with permission from Tregay et al., 2015.20© Cambridge University Press 2014.
Discussion
We identified 15 studies that evaluated the potential risk factors associated with mortality or unplanned hospital readmission in children successfully discharged from hospital after cardiac surgery for serious CHDs. Factors identified most frequently by these studies as predicting significantly increased risk of adverse events were non-white ethnicity,26,29,32,34lower socioeconomic status,26,32,36comorbid conditions including non-cardiac malformations and syndromes,32,34,36age at surgery,23,31,34,35operative complexity or procedure type,23,25,26,29,31,34,37and postoperative feeding difficulties.33,34,36Patient sex, parent factors, intraoperative factors and postoperative complications were also investigated but not found to be independent predictors of postdischarge outcomes.
Context and limitations
Our review confirms the significant lack of research into adverse outcomes after hospital discharge following surgery and highlights the fact that the evidence base to inform postdischarge clinical care and identify infants at high risk for focused support is extremely limited. As many reports derive from North American studies, and the research population is often limited to infants who have severe and complex cardiac diagnoses requiring staged surgery, care must be taken in generalising the findings from these existing studies to the wider UK population of infants with CHDs.
Despite our broad search strategy, which was intended to capture research into other life-threatening anomalies that require surgery during infancy, such as gastroschisis and diaphragmatic hernia,39the only studies of postdischarge outcomes that met the inclusion criteria concerned CHDs. Of all congenital anomaly subgroups, the highest rate of infant deaths is associated with CHDs, and this may account for the greater interest in monitoring outcomes after hospital discharge. It is also notable that postdischarge outcomes of infants with CHDs came to prominence with the introduction of staged palliative surgery for HLHS, which led to improved early in-hospital outcomes40,41and highlighted later interstage mortality as an important concern.15,26
A limitation of our review was the rigour of our eligibility criteria, which excluded any studies that did not clearly differentiate between deaths that occurred before and after hospital discharge, and thus may have excluded from the review some studies that evaluated additional risk factors to those reported here.
The relative lack of studies reporting postdischarge surgical outcomes may also simply reflect the limited monitoring of late adverse events and, specifically, of events occurring in the community or primary care setting.31
Ethnicity and deprivation
In three US studies26,32,34included in our review, patients of Hispanic ethnicity were found to be at a greater risk of adverse outcomes relative to white patients post hospital discharge. This confirms previous research which has shown that US Hispanic communities are more likely to experience multiple barriers to health care including language and immigration status, and financial barriers, such as lack of health insurance or low family incomes.42,43However, the impact of ethnicity and socioeconomic deprivation demonstrated in US-based studies may be influenced by an individual family’s ability to pay for care42–49 and the relevance of these findings for the UK health-care system is uncertain. Nevertheless, there is evidence that lower-income families in the UK also experience a considerable financial burden when caring for their child with CHD and that this may affect care-seeking behaviours.49The results of our review
In three US studies26,32,34included in our review, patients of Hispanic ethnicity were found to be at a greater risk of adverse outcomes relative to white patients post hospital discharge. This confirms previous research which has shown that US Hispanic communities are more likely to experience multiple barriers to health care including language and immigration status, and financial barriers, such as lack of health insurance or low family incomes.42,43However, the impact of ethnicity and socioeconomic deprivation demonstrated in US-based studies may be influenced by an individual family’s ability to pay for care42–49 and the relevance of these findings for the UK health-care system is uncertain. Nevertheless, there is evidence that lower-income families in the UK also experience a considerable financial burden when caring for their child with CHD and that this may affect care-seeking behaviours.49The results of our review