title: Chronic Neuromotor Disability After Complex Cardiac Surgery in Early Life Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. Intraoperative Hyperglycemia during Infant Cardiac Surgery Is Not Associated with Adverse Neurodevelopmental Outcomes at 1, 4, and 8 Years Prediction of IQ and Achievement at Age 8 Years From Neurodevelopmental Status at Age 1 Year in Children With D-Transposition of the Great Arteries Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. Clinical and Functional Developmental Outcomes in Neonates Undergoing Truncus Arteriosus Repair: A Cohort Study. Structural cerebral abnormalities and neurodevelopmental status in single ventricle congenital heart disease before Fontan procedure Prevalence of Childhood Permanent Hearing Loss after Early Complex Cardiac Surgery Prospective follow-up study of children with univentricular heart: neurodevelopmental outcome at age 12 months. Fetal cerebrovascular resistance and neonatal EEG predict 18-month neurodevelopmental outcome in infants with congenital heart disease. Early childhood language outcomes after arterial switch operation: a prospective cohort study How much loss to follow-up is acceptable in long-term randomised trials and prospective studies? Effect of prenatal diagnosis on outcomes in D-transposition of the great arteries. Neurodevelopmental Burden at Age 5 Years in Patients With Univentricular Heart Sepsis After Cardiac Surgery Early in Infancy and Adverse 4.5-Year Neurocognitive Outcomes Relation of seizures after cardiac surgery in early infancy to neurodevelopmental outcome. Boston Circulatory Arrest Study Group. Patterns of Developmental Dysfunction After Surgery During Infancy to Correct Transposition of the Great Arteries Two-Year Survival and Mental and Psychomotor Outcomes After the Norwood Procedure: An Analysis of the Modified Blalock-Taussig Shunt and Right Ventricle–to–Pulmonary Artery Shunt Surgical Eras Neurodevelopmental Outcomes in Children Surviving d‐Transposition of the Great Arteries Mortality and neurodevelopmental outcome at 1 year of age comparing hybrid and Norwood procedures. Adolescents With d-Transposition of the Great Arteries Corrected With the Arterial Switch Procedure: Neuropsychological Assessment and Structural Brain Imaging Changing expectations for neurological outcomes after the neonatal arterial switch operation. Prediction of preschool functional abilities after early complex cardiac surgery. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. Risk factors for preoperative periventricular leukomalacia in term neonates with hypoplastic left heart syndrome are patient related. Association of hemoglobin and transfusion with outcome after operations for hypoplastic left heart. Neurologic and psycho-intellectual outcome related to structural brain imaging in adolescents and young adults after neonatal arterial switch operation for transposition of the great arteries. Visual‐Spatial Skills in Children After Open‐Heart Surgery Brain maturation is delayed in infants with complex congenital heart defects. The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: the Boston Circulatory Arrest Trial. Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery. Early developmental influences on self-esteem trajectories from adolescence through adulthood: Impact of birth weight and motor skills. Cerebral tissue oxygenation index and lactate at 24 hours postoperative predict survival and neurodevelopmental outcome after neonatal cardiac surgery Neurotoxicity of sedative and analgesia drugs in young infants with congenital heart disease: 4-year follow-up. Behaviour at eight years in children with surgically corrected transposition: The Boston Circulatory Arrest Trial. Relationship between Social-Emotional and Neurodevelopment of 2-Year-Old Children with Congenital Heart Disease. Perioperative risk factors for impaired neurodevelopment after cardiac surgery in early infancy Neurodevelopmental outcome following exposure to sedative and analgesic drugs for complex cardiac surgery in infancy. Neurodevelopmental outcomes after regional cerebral perfusion with neuromonitoring for neonatal aortic arch reconstruction. Neurologic status of newborns with congenital heart defects before open heart surgery. Impact of prenatal diagnosis on neurocognitive outcomes in children with transposition of the great arteries. Overestimating Neurodevelopment Using the Bayley-III After Early Complex Cardiac Surgery Severe Congenital Heart Defects Are Associated with Global Reduction of Neonatal Brain Volumes. Neurodevelopment in children with hypoplastic left heart syndrome. Neurodevelopmental pathways to preterm children's specific and general mathematic abilities. Erythropoietin neuroprotection in neonatal cardiac surgery: a phase I/II safety and efficacy trial. Length of stay after infant heart surgery is related to cognitive outcome at age 8 years. Performance of 2-year-old children after early surgery for congenital heart disease on the Bayley Scales of Infant and Toddler Development, Third Edition. White matter injury in term neonates with congenital heart diseases: Topology & comparison with preterm newborns Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation Neuromotor performance in infants before and after early open-heart surgery and risk factors for delayed development at 6 months of age.
abstract: BACKGROUND AND OBJECTIVES : Little is known about chronic neuromotor disability ( CND ) including cerebral palsy and motor impairments after acquired brain injury in children surviving early complex cardiac surgery ( CCS ) . We sought to determine the frequency and presentation of CND in this population while exploring potentially modifiable acute care predictors . METHODS : This prospect i ve follow-up study included 549 children after CCS requiring cardiopulmonary bypass at ≤6 weeks of age . Groups included those with only 1 CCS , mostly biventricular CHD , and those with > 1 CCS , predominantly single ventricle defects . At 4.5 years of age , 420 ( 94.6 % ) children received multidisciplinary assessment .  Frequency of CND is given as percentage of assessed survivors . Predictors of CND were analyzed using multiple logistic regression analysis . RESULTS : CND occurred in 6 % ( 95 % confidence interval [ CI ] 3.7%–8.2 % ) of 4.5-year survivors ; for 1 CCS , 4.2 % ( CI 2.3%–6.1 % ) and > 1 , 9.8 % ( CI 7%–12.6 % ) . CND presentation showed : hemiparesis , 72 % ; spasticity , 80 % ; ambulation , 72 % ; intellectual disability , 44 % ; autism , 16 % ; epilepsy , 12 % ; permanent vision and hearing impairment , 12 % and 8 % , respectively . Overall , 32 % of presumed causative events happened before first CCS . Independent odds ratio for CND are age ( days ) at first CCS , 1.08 ( CI 1.04–1.12 ; P < .001 ) ; highest plasma lactate before first CCS ( mmol/L ) , 1.13 ( CI 1.03–1.23 ; P = 0.008 ) ; and > 1 CCS , 3.57 ( CI 1.48–8.9 ; P = .005 ) . CONCLUSIONS : CND is not uncommon among CCS survivors . The frequency of associated disabilities characterized in this study informs pediatricians caring for this vulnerable population . Shortening the waiting period and reducing preoperative plasma lactate levels at first CCS may assist in reducing the frequency of CND BACKGROUND It is not known whether developmental and neurological outcomes in the preschool period differ depending on whether the predominant vital organ support strategy used in infant heart surgery was total circulatory arrest ( CA ) or low-flow cardiopulmonary bypass . METHODS AND RESULTS Infants with D-transposition of the great arteries who underwent an arterial-switch operation were r and omly assigned to a support method consisting predominantly of CA or low-flow cardiopulmonary bypass .  Developmental and neurological status were evaluated blindly at 4 years of age in 158 of 163 eligible children ( 97 % ) . Neither IQ scores nor overall neurological status were significantly associated with either treatment group or duration of CA . The CA group scored lower on tests of motor function ( gross motor , P=0.01 ; fine motor , P=0.03 ) and had more severe speech abnormalities ( oromotor apraxia , P=0.007 ) . Seizures in the perioperative period , detected either clinical ly or by continuous electroencephalographic monitoring , were associated with lower mean IQ scores ( 12.6 and 7.7 points , respectively ) and increased risk of neurological abnormalities ( odds ratios , 8.4 and 5.6 , respectively ) . The performance of the full cohort was below expectations in several domains , including IQ , expressive language , visual-motor integration , motor function , and oromotor control . CONCLUSIONS Use of CA to support vital organs during open heart surgery in infancy is associated , at the age of 4 years , with worse motor coordination and planning but not with lower IQ or with worse overall neurological status Background : It is unknown whether intraoperative hyperglycemia in infants is associated with worse neurodevelopmental outcomes after  low-flow cardiopulmonary bypass ( LF ) , deep hypothermic circulatory arrest ( CA ) , or both . Methods : In a data base review of a prospect i ve trial of 171 infants undergoing arterial switch for D-transposition of the great arteries who were r and omly assigned to predominately LF or CA , glucose was measured after induction ( T1 ) , 5 min after cardiopulmonary bypass onset ( T2 ) , at the onset of CA or LF ( T3 ) , 5 min after CPB resumption ( T4 ) , at rewarming to 32 ° C ( T5 ) , 10 min after cardiopulmonary bypass weaning ( T6 ) , and 90 min after CA or LF ( T7 ) . Outcomes included seizures , electroencephalographic findings , and neurodevelopmental evaluation at 1 , 4 , and 8 yr . Results : Glucose concentrations were affected by support strategy and age at surgery . Lower glucose in the entire group at T6–T7 tended to predict electroencephalographic seizures ( P = 0.06 and P = 0.007 ) but was not related to clinical seizures . Within the predominantly CA group , higher glucose did not correlate with worse outcomes . Rather , it was associated with more rapid electroencephalographic normalization of “ close burst ” and “ relative continuous ” activity at all times except T2 ( P ≤ 0.03 ) , a finding more pronounced in infants aged 7 days old or younger . Intraoperative serum glucose concentrations were unrelated to neurodevelopmental outcomes at ages 1 , 4 , and 8 yr . Conclusions : Low glucose after cardiopulmonary bypass tended to relate to electroencephalographic seizures and slower electroencephalogram recovery , independent of CA duration . High glucose concentrations were not associated with worse neurodevelopmental outcomes . Avoiding hypoglycemia may be preferable to restricting glucose in infants undergoing heart surgery Objective . Studies of developmental outcomes in children with congenital heart disease ( CHD ) frequently use assessment s conducted in infancy as primary endpoints . Whether test scores of CHD patients in infancy are predictive of status at school age has not been evaluated , however . Methods . In the Boston Circulatory Arrest Study , 135 children with D-transposition of the great arteries repaired by arterial switch operation  were administered the  Bayley Scales of Infant Development  and the Fagan Test of Infant Intelligence  at 1 year of age and the Wechsler Intelligence Scale for Children , Third Edition and the Wechsler Individual Achievement Test at 8 years . Results . Although most 1-year test scores were significantly associated with 8-year test scores , the amounts of shared variance were modest ( < 10 % ) . All 1-year test scores had poor sensitivity ( 16%–32 % ) and poor positive predictive value ( 35%–42 % ) but good specificity ( 80%–93 % ) and negative predictive value ( 78%–79 % ) . More than half of the children with low scores at 8 years ( ≤85 ) had had scores > 84 at 1 year . Conclusion . This pattern suggests that although test scores at 1 year are modestly associated with test scores at 8 years , many children who are at risk for poor late outcomes will not be identified on the basis of 1-year test scores . Long-term follow-up of children with CHD is necessary to draw inferences about the developmental sequelae of preoperative , intraoperative , and postoperative factors BACKGROUND Deep hypothermia with either total circulatory arrest or low-flow cardiopulmonary bypass is used to support vital organs during heart surgery in infants . We compared the developmental and neurologic sequelae of these two strategies one year after surgery . METHODS Infants with D-transposition of the great arteries who underwent an arterial-switch operation were r and omly assigned to a method of support consisting predominantly of circulatory arrest or a method consisting predominantly of low-flow bypass . Developmental and neurologic evaluations and magnetic resonance imaging ( MRI ) were performed at one year of age . RESULTS Of the 171 patients enrolled in the study , 155 were evaluated . After adjustment for the presence or absence of a ventricular septal defect , the infants assigned to circulatory arrest , as compared with those assigned to low-flow bypass , had a lower mean score on the Psychomotor Development Index of the Bayley Scales of Infant Development ( a 6.5-point deficit , P = 0.01 ) and a higher proportion had scores < or = 80 ( i.e. , 2 SD or more below the population mean ) ( 27 percent vs. 12 percent , P = 0.02 ) . The score on the Psychomotor Development Index was inversely related to the duration of circulatory arrest ( P = 0.02 ) . The risk of neurologic abnormalities increased with the duration of circulatory arrest ( P = 0.04 ) . The method of support was not associated with the prevalence of abnormalities on MRI scans of the brain , scores on the Mental Development Index of the Bayley Scale , or scores on a test of visual-recognition memory . Perioperative electroencephalographic seizure activity was associated with lower scores on the Psychomotor Development Index ( P = 0.002 ) and an increased likelihood of abnormalities on MRI scans of the brain ( P < 0.001 ) . CONCLUSIONS Heart surgery performed with circulatory arrest as the predominant support strategy is associated with a higher risk of delayed motor development and neurologic abnormalities at the age of one year than is surgery with low-flow bypass as the predominant support strategy BACKGROUND Truncus arteriosus ( TA ) is an uncommon congenital cardiac lesion that portends an exceedingly poor prognosis if not repaired . The objective of this study was to assess the clinical and developmental outcomes in a prospect i ve cohort of patients who underwent TA repair .  METHODS All patients who underwent a TA repair between 1996 and 2012 were included . Follow-up clinical , neurologic , and developmental data were obtained from the Western Canadian Complex Pediatric Therapies Follow-up Program data base . Functional developmental outcomes were assessed at 21.1 ± 2.5 months of age with the Adaptive Behavior Assessment System-II , General Adaptive Composite ( GAC ) score . Survival and outcomes were compared between those with and without chromosomal abnormalities ( CA ) . Survival and freedom from reintervention were assessed by Kaplan-Meier analysis . RESULTS The study comprised 36 infants ( 19 male ) . CA was identified in 13 , with 22q11.2 deletion in 10 patients . Patients underwent TA repair at a median age of 10 days ; 5 patients underwent concomitant interrupted arch repair . There were 8 deaths , 2 of which occurred in the hospital . The 5-year survival was 79.4 % . Survival was similar between those with and without CA . At 5 years , freedom from reoperation was 77.2 % . The mean GAC was higher in the patients without CA ( 93.6 ± 12.8 vs 76.1 ± 13.1 , p = 0.0016 ) . CONCLUSIONS Patients with surgically repaired TA continue to have significant postoperative mortality . Reoperation and cardiac catheterization are eventualities for a quarter of patients in the first 5 years of life . Functional developmental outcome in patients without CA is good , although it is significantly impaired in those with CA Objectives Neonates with single ventricle congenital heart disease are at risk for structural cerebral abnormalities . Little is known about the further evolution of cerebral abnormalities until Fontan procedure . Methods Between August 2012 and July 2015 , we conducted a prospect i ve cross-sectional two centre study using cerebral magnetic resonance imaging ( MRI ) and neuro-developmental outcome assessed by the Bayley-III . Forty-seven children ( 31 male ) were evaluated at a mean age of 25.9 ± 3.4 months with hypoplastic left heart syndrome ( 25 ) or other single ventricle ( 22 ) . Results  Cerebral MRI  was abnormal in 17 patients ( 36.2 % ) including liquor space enlargements ( 10 ) , small grey ( 9 ) and minimal white ( 5 ) matter injuries . Eight of 17 individuals had combined lesions . Median ( range ) cognitive composite score ( CCS ) ( 100 , 65 - 120 ) and motor composite score ( MCS ) ( 97 , 55 - 124 ) were comparable to the reference data , while language composite score ( LCS ) ( 97 , 68 - 124 ) was significantly lower ( P = 0.040 ) . Liquor space enlargement was associated with poorer performance on all Bayley-III subscores ( CCS : P = 0.02 ; LCS : P = 0.002 ; MCS : P = 0.013 ) . The number of re-operations [ odds ratio ( OR ) 2.2 , 95 % confidence interval ( CI ) 1.1 - 4.3 ] ( P = 0.03 ) and re- interventions ( OR 2.1 , 95 % CI 1.1 - 3.8 ) ( P = 0.03 ) was associated with a higher rate of overall MRI abnormalities . Conclusions Cerebral MRI abnormalities occur in more than one third of children with single ventricle , while the neuro-developmental status is less severely affected before Fontan procedure . Liquor space enlargement is the predominant MRI finding associated with poorer neuro-developmental status , warranting further studies to determine aetiology and further evolution until school-age Objectives To estimate the prevalence of  childhood permanent hearing loss ( PHL ) after early cardiac surgery .  Study design This prospect i ve observational ( 1996‐2015 ) study after complex cardiac surgery with cardiopulmonary bypass at ≤6 weeks of life reports audiology follow‐up by registered pediatric‐experienced audiologists at 6‐8 months postsurgery , age 2 years , and as required throughout and thereafter to complete diagnoses . PHL at any frequency ( 500‐4000 Hz ) is defined as responses of > 25‐decibel hearing level in either ear . PHL was evaluated by type ( conductive or sensorineural ) , pattern ( flat or sloping ) , and severity ( mild to profound ) . Results Survival rate was 83.4 % ( 706 of 841 children ) with a 97.9 % follow‐up rate ( 691 children ) ; 41 children  had PHL , 5.9 % ( 95 % CI 4.3 % , 8.0 % ) . By cardiac defect , prevalence was biventricular , 4.0 % ( 95%CI 2.5 % , 6.1 % ) ; single ventricle , 10.8 % ( 95%CI 6.8 % , 16.1 % ) . Eighty‐seven ( 12.6 % ) of 691 had syndromes/genetic abnormalities with known association with PHL ; of these , 17 ( 41.5 % ) had PHL . Of 41 children , 4 had permanent conductive , moderate to severe loss ( 1 bilateral ) ; 37 had moderate to profound sensorineural loss ( 29 bilateral with 20 sloping and 9 flat ) , 6 with cochlear implant done or recommended . Conclusions Infants surviving complex cardiac surgery are at high risk for PHL . Over 40 % with PHL have known syndromes/genetic abnormalities , but others do not have easily identifiable risk indicators . Early cardiac surgery should be considered a risk indicator for PHL OBJECTIVES Despite recent advances in the treatment of children with univentricular heart , their neurodevelopmental outcome remains a major concern . METHODS This prospect i ve follow-up study evaluated the neurodevelopmental outcome of 23 patients with hypoplastic left heart syndrome , 14 with other forms of univentricular heart , and 46 healthy control subjects at a median age of 12.2 months . The  Griffiths Developmental Scale and Alberta Infant Motor Scale  served for developmental evaluation . RESULTS The mean Griffiths developmental quotient of children with hypoplastic left heart syndrome was significantly less ( 91.6 ) than that of control children ( 106.8 , P < .001 ) . Patients with univentricular heart scored significantly lower than control subjects only in the gross motor domain ( P = .001 ) but not in overall development ( 100.6 ) . Alberta Infant Motor Scale scores were significantly lower in children with hypoplastic left heart syndrome ( 37.5 , P < .001 ) and univentricular heart ( 43.5 , P = .011 ) than in control subjects ( 53.3 ) . In linear regression a diagnosis of hypoplastic left heart syndrome ( P = .016 ) , a clinical history of seizure ( P = .002 ) , and the highest plasma lactate level after the bidirectional Glenn operation ( P = .045 ) were significantly associated with the developmental quotient . CONCLUSIONS At age 1 year , the level of development of children with univentricular heart was significantly lower than for control subjects only in motor skills , whereas children with hypoplastic left heart syndrome had a more widespread developmental delay . The diagnosis , a clinical seizure history , and increased plasma lactate levels after the bidirectional Glenn operation emerged as risk factors OBJECTIVES The purpose of this study was to investigate early markers of risk for neurobehavioral compromise in survivors with congenital heart disease ( CHD ) . METHODS Pregnant women in whom a fetal CHD had been diagnosed before 24 weeks ' gestational age ( GA ) were enrolled in this prospect i ve pilot study for serial Doppler ultrasound assessment of the fetal middle cerebral artery ( MCA ) and umbilical arteries . The cerebral-to-placental resistance ratio ( CPR ) and MCA pulsatility index ( PI ) Z-scores for GA were calculated . After birth , subjects underwent high-density ( 128-lead ) electroencephalography ( EEG ) , and beta frequency ( 12 - 24 Hz ) b and EEG power  , a measure of local neural synchrony , was analyzed . Neurodevelopment was assessed at 18 months with the Bayley Scales of Infant Development (BSID)-III . RESULTS Thirteen subjects were enrolled : four with hypoplastic left heart syndrome ( HLHS ) , four with transposition of the great arteries ( TGA ) and five with tetralogy of Fallot ( TOF ) . Compared with subjects with normal CPR , those with CPR < 1 ( n = 7 ) had lower mean BSID cognitive scores ( 91.4 ± 4.8 vs. 99.2 ± 3.8 , P = 0.008 ) . Fetal MCA-PI Z-score also correlated with BSID cognitive score ( r = 0.589 , P = 0.03 ) as did neonatal EEG left frontal polar ( r = 0.58 , P = 0.037 ) and left frontal ( r = 0.77 , P = 0.002 ) beta power . Furthermore , fetal Doppler measures were associated with EEG power : fetuses with CPR < 1 had lower left frontal polar ( t = 2.36 , P = 0.038 ) and left frontal ( t = 2.85 , P = 0.016 ) beta power as newborns than did fetuses with normal CPR , and fetal MCA-PI Z-score correlated with neonatal EEG left frontal polar ( r = 0.596 , P = 0.04 ) and left frontal ( r = 0.598 , P = 0.04 ) beta power . CONCLUSION In fetuses with HLHS , TGA and TOF , abnormal cerebrovascular resistance predicts decreased neonatal EEG left frontal beta power and lower 18-month cognitive development scores Background Developmental and language outcomes at 2 years of age of children who had arterial switch operation ( ASO ) for transposition of the great arteries 2004–2010 are described . Methods In this prospect i ve cohort study , 91/98 ( 93 % ) children who underwent ASO  were assessed at 2 years of age with the Bayley Scales of Infant & Toddler Development—3rd Edition . Outcomes were compared by patient and perioperative variables using bivariate and multivariate regression analyses to identify predictors of language delay . Results Infants without ventricular septal defect ( VSD ) ( n = 60 ) were more likely to be outborn ( 73 vs 58 % , p = 0.038 ) , require septostomy ( 80 vs 58 % , p = 0.026 ) , have a shorter cross clamp time ( min ) ( 62.7 vs 73.0 , p = 0.019 ) , and a lower day 1 post-operative plasma lactate ( mmol/L ) ( 3.9 vs 4.8 , p = 0.010 ) . There were no differences in cognitive , motor and language outcomes based on presence of a VSD . Language delay ( < 85 ) of 29 % was 1.8 times higher than the normative sample ; risk factors for this in multivariate analyses included < 12 years of maternal education ( AOR 19.3 , 95 % CI 2.5–148.0 ) and cross-clamp time ≥70 min ( AOR 14.5 , 95 % CI 3.1–68.5 ) . Maternal education < 12 years was associated with lower Language Composite Scores ( −20.2 , 95 % CI −32.3 to −9.1 ) . Conclusions Outcomes at 2 years of age in children who undergo ASO are comparable to the normative sample with the exception of language . There is a risk of language delay for which maternal education and cross-clamp duration are predictors . These findings suggest that focused post-operative early language interventions could be considered to test early  nutritional interventions  and prospect i ve observational cohorts . RCTs are generally accepted as method ologically the best approach for informing health policy . They can equalise unknown as well as known confounding factors and so can demonstrate causation ; they permit estimation of effect size and so can be used to assess likely BACKGROUND By decreasing preoperative morbidity , prenatal diagnosis could improve neurodevelopmental outcomes in infants with critical congenital heart disease . We explored the impact of prenatal diagnosis on perinatal and perioperative variables and on outcomes at 1 year of age . METHODS We analyzed a data base of children enrolled in prospect i ve studies on surgical support techniques from 1988 to 2000 . Selection criteria included a diagnosis of D-transposition of the great arteries with intact ventricular septum or ventricular septal defect , no extracardiac congenital anomalies , birth weight > 2.3 kg , and repair by arterial switch procedure .  RESULTS Of 346 patients at enrollment , 25 had a prenatal diagnosis , and 321 did not . Children with prenatal diagnosis , compared with those without , had a lower likelihood of birth by spontaneous labor , lower birth weights , lower Apgar 5 scores , a higher rate of preoperative endotracheal intubation , and surgery at a younger age . They tended to have a lower incidence of fetal distress during labor . At 1 year of age , 272 patients were tested with the Psychomotor Development Index and Mental Development Index of the Bayley Scales . Mean z scores were similar in those with and without prenatal diagnosis for both Psychomotor Development Index ( -0.92 + /- 0.93 vs -0.88 + /- 1.05 ) and Mental Development Index ( -0.29 + /- 1.13 vs -0.41 + /- 0.93 ) . CONCLUSIONS Infants with D-transposition of the great arteries with and without prenatal diagnosis differed with respect to perinatal and perioperative variables , but their development at 1 year of age was similar . Future studies should include a greater number of children with prenatal diagnosis and a variety of congenital heart lesions BACKGROUND : Despite increasing survival , patients with hypoplastic left heart syndrome ( HLHS ) and other forms of functionally univentricular heart defects ( UVHs ) remain at increased risk of long-term neurodevelopmental deficits . METHODS : A nationwide sample of 23 patients with HLHS , 13 with UVH , and 40 controls were followed prospect ively until the age of 5 years , when neurologic , neuropsychological , and motor examinations and brain MRI were performed . RESULTS : The median full-scale IQ was significantly lower in patients with HLHS ( 97 , P < .001 ) and patients with UVH ( 112 , P = .024 ) compared with controls ( 121 ) . Major neurodevelopmental impairment was found in 26 % of the patients with HLHS and 23 % of those with UVH , and minor neurologic dysfunction was found in 43 % and 46 % , respectively . MRI revealed abnormalities , mostly ischemic changes of different degrees , in 82 % of the patients with HLHS and in 56 % of those with UVH . Prominent changes were significantly associated with neurodevelopmental findings and parental reports of adaptive behavior . In linear regression , significant risk factors for a worse outcome were a history of clinical seizures in connection with the primary operation , a lower diameter of the neonatal ascending aorta , and several pre- , peri- , and postoperative factors related to the primary and bidirectional Glenn operations . CONCLUSIONS : Although median cognitive performance was within the normal range , neurodevelopmental and brain MRI abnormalities were found in the majority of the patients with UVH , and especially in those with HLHS , at preschool age . Both a narrowed ascending aorta and operation-related factors contributed to these findings Background We aim ed to determine whether sepsis is associated with neurocognitive outcomes 4.5 years after congenital heart disease surgery in early infancy . Methods and Results A secondary analysis from a prospect i ve inception cohort included all children having congenital heart disease surgery done at ≤6 weeks of age with cardiopulmonary bypass at the Western Canadian referral center from 1996 to 2009 . Follow-up at the referral center determined the primary outcomes at 4.5 years with full-scale , performance , and verbal intelligence quotients on the Wechsler Preschool and Primary Scale of Intelligence . Perioperative variables were collected prospect ively , and confirmation of blood culture – positive sepsis was done retrospectively . Multiple linear regression models for neurocognitive outcomes and multiple Cox proportional hazards regression for mortality were determined . Sepsis occurred in 97 of 502 patients ( 19 % ) overall and in 76 of 396 survivors ( 19 % ) with 4.5-year follow-up . By 4.5 years , there were 91 ( 18 % ) deaths , and 396 of 411 survivors ( 96 % ) had follow-up completed . Extracorporeal membrane oxygenation was associated with worse scores on all neurocognitive outcomes on multivariable regression ; the association between extracorporeal membrane oxygenation and full-scale intelligence quotient had a regression coefficient of −13.6 ( 95 % CI −21.3 to −5.9 ; P = 0.001 ) . Sepsis perioperatively was associated with performance and verbal intelligence quotients , with a trend for full-scale intelligence quotient ( P = 0.058 ) on multivariable regression . The regression coefficient for sepsis was strongest for performance intelligence quotient ( −5.31 ; 95 % CI −9.84 to −0.78 ; P = 0.022 ) . Sepsis was not but extracorporeal membrane oxygenation was associated with mortality by 4.5 years . Conclusions Perioperative sepsis and extracorporeal membrane oxygenation were associated with adverse neurocognitive outcomes on multivariable regression . Quality improvement to prevent sepsis has the potential to improve long-term neurocognitive outcomes in infants after surgery for congenital heart disease BACKGROUND The outcome of infants who have transient seizures after open heart surgery has not been studied . Using the data base of the Boston Circulatory Arrest Study involving 171 children with D-transposition of the great arteries , we explored the relationship between early postoperative clinical and EEG seizures and neurodevelopmental outcomes at ages 1 and 2 1/2 years . METHODS AND RESULTS At 1 year , children returned for developmental and neurological evaluations  and MRI . Parent-completed developmental question naires were collected at 2 1/2 years of age . At 1 year , children with early postoperative seizures had lower Psychomotor Development Index ( motor function ) scores ( clinical seizures : 12.9 mean difference [ MD ] ; 95 % confidence interval [ CI ] , 2.2 to 23.6 ; P=.02 ; EEG seizures : 13.3 MD ; 95 % CI , 6.8 to 19.7 ; P<.001 ) . Mental Developmental Index scores of children with clinical or EEG seizures were also lower , but the differences were not statistically significant . Infants with seizures were more likely to have an abnormal neurological examination ( clinical seizures : 78 % versus 31 % ; P=.008 ; EEG seizures : 58 % versus 34 % ; P=.04 ) . Children with EEG seizures were more likely to have MRI abnormalities ( 43 % versus 13 % , P=.002 ) . At age 2 1/2 , children with EEG seizures had lower scores in several areas of function . CONCLUSIONS In infants undergoing the arterial switch operation for correction of D-transposition of the great arteries , transient postoperative clinical and EEG seizures were associated with worse neurodevelopmental outcomes at ages 1 and 2 1/2 years as well as neurological and MRI abnormalities at 1 year of age . The occurrence of such seizures may provide an early sign of brain injury with neurological and developmental sequelae A r and omized clinical trial was conducted to compare the early development of children with d-transposition of the great arteries ( N=171 ) repaired by an arterial switch operation that used either  predominantly total circulatory arrest or predominantly continuous low-flow cardiopulmonary bypass . The children assigned to the circulatory arrest group scored lower than those assigned to low-flow bypass on the Bayley Scales of Infant Development at 1 year of age . Responses to parental question naires completed when the children were 2.5 years old indicated that the children in the circulatory arrest group , especially those with a ventricular septal defect , also manifested poorer expressive language and were considered to display more internalizing and externalizing problem behaviors . The use of circulatory arrest to protect vital organs during open heart surgery might place children at increased risk of early developmental difficulties , especially in the domains of motor and language function Background — The Norwood procedure for stage 1 palliation of hypoplastic left heart syndrome is performed with either the modified Blalock-Taussig ( MBTS ) or the right ventricle – to – pulmonary artery ( RVPA ) shunt . In our institution , surgical practice changed from use of the MBTS to use of the RVPA shunt in 2002 . We analyzed survival and mental and psychomotor outcomes of the 2 consecutive surgical eras . Methods and Results — Between September 1996 and July 2005 , 94 neonates with hypoplastic left heart syndrome underwent the Norwood procedure .  Patients were recruited as neonates and followed up prospect ively . Health , mental , and psychomotor outcomes ( Bayley Scales of Infant Development-II ) were assessed at 2 years . The study subjects were from the Norwood-MBTS era ( n=62 ; 1996 to 2002 ) or the Norwood-RVPA era ( n=32 ; 2002 to 2005 ) . In the MBTS era , early and 2-year mortality rates were 23 % ( 14/62 ) and 52 % ( 32/62 ) ; the mean ( SD ) mental and psychomotor developmental indices were 79 ( 18 ) and 67 ( 19 ) . In the RVPA era , early and 2-year mortality rates were 6 % ( 2/32 ) and 19 % ( 6/32 ) ; the mean ( SD ) mental and psychomotor developmental indices were 85 ( 18 ) and 78 ( 18 ) . The 2-year mortality rate ( P=0.002 ) and the psychomotor developmental index ( P=0.029 ) were improved in the more recent surgical era . On multivariable Cox regression analysis , postoperative highest serum lactate independently predicted 2-year mortality in the MBTS and RVPA eras . Conclusions — Analysis of 2 consecutive surgical eras of hypoplastic left heart syndrome patients undergoing the Norwood procedure showed a significant improvement in 2-year survival and psychomotor development in the more recent era . Adverse neurodevelopmental outcome in this patient population remains a concern & NA ; We investigated the prevalence of neurological abnormalities and learning problems in a population cohort of children with dextro‐transposition of the great arteries ( d‐TGA ) born between January 1 , 1981 and July 1 , 1990 . Fifty‐seven of the 60 survivors and 35 siblings in the control group underwent  neurodevelopmental assessment s. As compared with population norms , children with d‐TGA were more likely to have abnormal neurological examination findings , learning disabilities , and behavioral disorders . There was no significant difference in IQ or frequency of abnormal neurological examination results between children undergoing atrial as compared with arterial switch procedures .  Compared with their siblings , the children with d‐TGA had more neurological findings and learning disabilities . The siblings of children with d‐TGA had more learning problems than expected . The findings suggest that ongoing surveillance is indicated for children surviving d‐TGA . Furthermore , a familial tendency for learning differences should to be taken into consideration when neurodevelopmental outcomes of various perioperative parameters are examined OBJECTIVES Neonates with hypoplastic left heart syndrome ( HLHS ) are at risk of high mortality and neurodevelopmental morbidity . As an alternative to Norwood-type stage I palliation , the hybrid procedure has been developed . It consists of bilateral pulmonary artery b and ing , catheter-based stenting of the arterial duct and balloon atrioseptostomy and delays open-heart surgery . Thus , it may be associated with a better outcome . The aim of this study was to determine the mortality and neurodevelopmental outcome in patients with HLHS and other univentricular heart ( UVH ) defects treated with hybrid or Norwood procedures . METHODS Thirty-one children ( 18 males ) with HLHS and other UVH defects undergoing Norwood or hybrid procedure between 2004 and 2008 were consecutively enrolled . Mortality and neurodevelopmental outcome at 1 year of age were determined . RESULTS One-year mortality was 36 % ( 31 % in the hybrid vs. 39 % in the Norwood group , P=0.71 ) . Predictors of mortality were lower birth weight ( P=0.02 ) , older age at first procedure ( P=0.02 ) and smaller size of ascending aorta ( P=0.05 ) . Overall , median psychomotor development index ( PDI ) and mental development index ( MDI ) of the Bayley Scales of Infant Development II were lower than the norm of 100 [ PDI 57 ( 49 - 99 ) , P<0.001 ; MDI 91 ( 65 - 109 ) , P=0.002 ] . No effect of surgical treatment on neurodevelopmental outcome was found . Predictors of impaired motor outcome were length of hospital stay ( LOHS ) ( P=0.01 ) , lower body weight at second procedure ( P=0.004 ) and female sex ( P=0.01 ) . Predictors of impaired cognitive outcome were longer mechanical ventilation time ( P=0.03 ) , intensive care unit stay ( P=0.04 ) and LOHS ( P<0.001 ) , respectively . CONCLUSIONS Mortality at 1 year of age is comparable between patients undergoing hybrid and Norwood procedures . Early neurodevelopmental outcome is significantly impaired in patients with both HLHS and other UVH defects . Multicentre r and omized studies are needed to determine the long-term neurodevelopmental outcome of children treated with the hybrid procedure Background — We report neuropsychological and structural brain imaging assessment s in children 16 years of age with d-transposition of the great arteries who underwent the arterial switch operation as infants . Children were r and omly assigned to a vital organ support method , deep hypothermia with either total circulatory arrest or continuous low-flow cardiopulmonary bypass . Methods and Results — Of 159 eligible adolescents , 139 ( 87 % ) participated .  Academic achievement , memory , executive functions , visual-spatial skills , attention , and social cognition were assessed . Few significant treatment group differences were found . The occurrence of seizures in the postoperative period was the medical variable most consistently related to worse outcomes . The scores of both treatment groups tended to be lower than those of the test normative population s , with substantial proportions scoring ≥1 SDs below the expected mean . Although the test scores of most adolescents in this trial cohort are in the average range , a substantial proportion have received remedial academic or behavioral services ( 65 % ) . Magnetic resonance imaging abnormalities were more frequent in the d-transposition of the great arteries group ( 33 % ) than in a referent group ( 4 % ) . Conclusions — Adolescents with d-transposition of the great arteries who have undergone the arterial switch operation are at increased neurodevelopmental risk . These data suggest that children with congenital heart disease may benefit from ongoing surveillance to identify emerging difficulties . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00000470 BACKGROUND Expectations for outcomes after the neonatal arterial switch operation ( ASO ) continue to change . This cohort study describes neurodevelopmental outcomes at age 12 months after neonatal ASO , and analyzes both modifiable and nonmodifiable factors for association with adverse outcomes . METHODS Patients who underwent an ASO ( n=30 ) were enrolled in a prospect i ve outcome study , with comprehensive clinical data collection during the first 12 months of life . Brain magnetic resonance imaging was done preoperatively and 7 days postoperatively , and the Bayley Scales of Infant Development III was performed at age 12 months . RESULTS Ten of 30 patients ( 33 % ) had preoperative magnetic resonance imaging injury ; 13 of 30 patients ( 43 % ) had new postoperative magnetic resonance imaging injury . Twenty patients ( 67 % ) had Bayley Scales of Infant Development III : Cognitive Composite st and ard score mean was 104.8±15.0 , Language Composite st and ard score median was 90.0 ( 25th to 75th percentile , 83 to 94 ) , and Motor Composite st and ard score mean was 92.3±14.2 . Best subsets multivariable analysis found associations between lower preoperative and intraoperative cerebral oxygen saturation , preoperative magnetic resonance imaging brain injury , total bypass time , and total midazolam dose and lower Bayley Scales of Infant Development III scores at age 12 months . CONCLUSIONS At 12 months after ASO , neurodevelopmental outcome means were within normal population ranges . The new associations reported in this study between potentially modifiable perioperative factors and outcomes require investigations in larger patient cohorts . Beyond survival , which was 100 % in this cohort , factors influencing quality of life including neurodevelopmental outcomes should be routinely investigated in studies of ASO patients BACKGROUND It is important to identify early predictors of functional limitations in children after congenital heart surgery to optimise their independence as they prepare for school . The purpose of this study is to determine potentially modifiable predictor variables of functional abilities in pre-school children who underwent complex cardiac surgery at 6 weeks of age or earlier . METHODS This prospect i ve inception cohort study comprised a sample of 165 survivors ( 63 % boys ) who had complex cardiac surgery ( 75 % biventricular repairs ) at Stollery Children 's Hospital , Edmonton , Alberta . We excluded children with chromosomal abnormalities . When children were 4 - 5 years of age , the parents completed the Adaptive Behavioral Assessment System II . Regression analysis was used to assess the association between multiple risk factors and each of the four continuous composite scores . RESULTS The mean scores for the practical domain and general adaptive composite score of the Adaptive Behavioural Assessment System were lower than the conceptual and social domains , with 13.3 % of the children having a delay in the practical domain . There was a significant association between the general adaptive ( p=0.003 ; 0.012 ) , conceptual ( p=0.0004 ; 0.042 ) , social ( p=0.0007 ; 0.028 ) , and the practical ( p=0.046 ; 0.003 ) domain composite scores with the mother 's education and preoperative plasma lactate , respectively . CONCLUSION Maternal education may be a marker for the social context of children , and warrants societal attention to improve functional outcomes . Preoperative lactate as a potentially modifiable variable may warrant increased attention to early diagnosis and aggressive resuscitation of young infants with congenital heart disease OBJECTIVES Our goal was to determine which of the two major methods of vital organ support used in infant cardiac surgery , total circulatory arrest and low-flow cardiopulmonary bypass , results in better neurodevelopmental outcomes at school age . METHODS In a single-center trial , infants with dextrotransposition of the great arteries underwent the arterial switch operation after r and om assignment to either total circulatory arrest or low-flow cardiopulmonary bypass .  Developmental , neurologic , and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children ( 97 % ) . RESULTS Treatment groups did not differ in terms of most outcomes , including neurologic status , Full-Scale or Performance IQ score , academic achievement , memory , problem solving , and visual-motor integration . Children assigned to total circulatory arrest performed worse on tests of motor function including manual dexterity with the nondominant h and ( P = .003 ) , apraxia of speech ( P = .01 ) , visual-motor tracking ( P = .01 ) , and phonologic awareness ( P = .003 ) . Assignment to low-flow cardiopulmonary bypass was associated with a more impulsive response style on a continuous performance test of vigilance ( P < .01 ) and worse behavior as rated by teachers ( P = .05 ) . Although mean scores on most outcomes were within normal limits , neurodevelopmental status in the cohort as a whole was below expectation in many respects , including academic achievement , fine motor function , visual-spatial skills , working memory , hypothesis generating and testing , sustained attention , and higher-order language skills . CONCLUSIONS Use of total circulatory arrest to support vital organs during heart surgery in infancy is generally associated with greater functional deficits than is use of low-flow cardiopulmonary bypass , although both strategies are associated with increased risk of neurodevelopmental vulnerabilities BACKGROUND Preoperative brain injury is common in neonates with complex congenital heart disease . Increasing evidence suggests a complex interaction of prenatal and postnatal risk factors for development of brain white matter injury , called periventricular leukomalacia ( PVL ) , in neonates with complex congenital heart disease . To date , there remains a limited underst and ing of the risk factors contributing to preoperative PVL in hypoplastic left heart syndrome ( HLHS ) . METHODS Neonates with HLHS or HLHS variants from 3 prospect i ve magnetic resonance imaging studies ( 2003 - 2010 ) were selected for this cohort . Preoperative brain magnetic resonance imaging was performed the morning of the surgery . Stepwise multilogistic regression of patient characteristics , mode of delivery ( cesarean section vs vaginal ) , time of diagnosis ( prenatal vs postnatal ) , HLHS subtypes , brain total maturation score , time to surgery , individual averaged daily preoperative blood gases , and complete blood cell count values was used to determine significant associations . RESULTS A total of 57 neonates with HLHS were born at 38.7 ± 2.3 weeks ; 86 % ( 49/57 ) had a prenatal diagnosis , with 31 % ( 18/57 ) delivered by cesarean section . HLHS with aortic atresia ( AA ) was common in this cohort , 71 % ( 41/57 ) . Preoperative PVL was identified in 19 % ( 11/57 ) . Male patients with AA ( P = .004 ) were at higher risk for PVL . Lower total brain maturation score was also identified as a strong predictor for preoperative PVL ( P = .005 ) . CONCLUSIONS In neonates with HLHS , nonmodifiable patient-related factors , including male sex with AA ( lack of ante grade blood flow ) and lower total brain maturation score , placed neonates at the greatest risk for preoperative white matter injury BACKGROUND Red blood cell transfusions may or may not improve oxygen delivery to the tissues . Some studies suggest transfusion might contribute to adverse outcomes . This study investigated the association between hemoglobin concentration and transfusion with outcome in cyanotic neonates undergoing Norwood operations . METHODS Infants 6 weeks old or younger with hypoplastic left heart syndrome undergoing staged Norwood operations between September 1996 and July 2005 were included . Demographics and preoperative , operative , and postoperative variables were collected prospect ively . Hemoglobin concentration , transfusion , fluid balance , and chest tube losses were collected retrospectively . The association of variables with outcomes , including early and 2-year mortality , mental and psychomotor developmental indices at 18 to 24 months of age , and ventilator days were determined by univariate and multiple regression analyses . RESULTS Ninety-four patients had Norwood operations . Excluded were 10 requiring postoperative extracorporeal life support and 2 with chromosomal abnormalities . By multiple regression analysis , only a higher nadir hemoglobin on days 2 to 5 postoperatively was associated with higher early mortality ( odds ratio , 2.09 ; 95 % confidence interval [ CI ] , 1.14 to 3.87 ; p = 0.018 ) , and the highest preoperative dopamine dose and highest epinephrine dose on day 2 to 5 postoperatively were associated with 2-year mortality ; however , neither hemoglobin concentration nor number of transfusions were associated with mental or psychomotor developmental indices . The number of transfusions on day 2 to 5 postoperatively was associated with ventilator days in multiple variable analysis ( effect size , 1.85 ; 95 % CI , 0.33 to 3.36 ; p = 0.018 ) . CONCLUSIONS This single-center cohort study found transfusion was not associated with improved outcomes in neonates undergoing Norwood operations OBJECTIVE We studied brain structure abnormalities in adolescents and young adults who had undergone the neonatal arterial switch operation for transposition of the great arteries and related them to the neurologic and psycho-intellectual outcomes . METHODS In a prospect i ve longitudinal study , 60 unselected adolescents and young adults who had undergone surgery with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were re-evaluated at a mean age of 16.9±1.7 years to determine their clinical neurologic status , intellectual development , and psychological condition . The results were related to population norms and anatomic structural abnormalities assessed by brain magnetic resonance imaging , with consideration of the risk factors in the preoperative and perioperative periods . RESULTS Neurologic impairment was more frequent ( 10 % ) than in the normal population . Although the average full-scale , verbal , and performance intelligence quotients were not reduced , scores>2 st and ard deviations less than the expected mean were increased . Above average scores were found for analytical thinking , but the orthography testing results were reduced . The self-rated psychological condition was better than expected . Magnetic resonance imaging demonstrated moderate or severe structural brain abnormalities in 32 % of the patients . Periventricular leukomalacia was detected in > 50 % ; its severity correlated with the grade of neurologic impairment , which correlated significantly with reduced intelligence , analytical thinking , and orthography . Preoperative acidosis and hypoxia were the only independent patient-related risk factors for neurologic dysfunction , reduced intelligence , periventricular leukomalacia , and reduced brain volume . CONCLUSIONS Despite encouraging overall neurodevelopmental outcomes , a significant minority had performances below the expected level , emphasizing the need for ongoing surveillance . Considering the high frequency of structural brain abnormalities , prospect i ve long-term studies are needed to define their prognostic value with respect to the neuropsychological outcomes in childhood and adolescence ABSTRACT . This study was part of a r and omized clinical trial comparing the central nervous system effects of the two vital organ‐support methods used in  infant cardiac surgery : total circulatory arrest and low‐flow cardiopulmonary bypass . The extent to which visual‐spatial deficits are ( 1 ) associated with surgical and perioperative variables , ( 2 ) attributable to visual‐perceptual , motor control , or metacognitive deficits , and ( 3 ) associated with adaptive difficulties at home or school was evaluated . The subjects were 155 8‐year‐old children with D‐transposition of the great arteries who underwent the arterial switch operation before 3 months of age . As part of a comprehensive evaluation , the Rey‐Osterrieth Complex Figure ( ROCF ) was administered . ROCF copy productions were classified as having a Basal Organization Level of 1 ( low ) or 2 or greater . A five‐category clinical rating was also assigned . More than half of the children in the cohort ( 52 % ) had copy productions scored at Level 1 , more than twice the expected frequency . The risk of having a low score was not associated with vital organ support method or other surgical variables . On the basis of comparisons of the relative fits of nested logistic regression models , poor visual‐perceptual abilities were more predictive of having a Level 1 score than either motor control or metacognitive deficits . Children with poor copy production scores had lower mathematics scores , but not lower reading scores or poorer parent and teacher ratings of adaptive competence . The percentage of children receiving remedial school services was associated with ROCF clinical rating , ranging from 58 % in the worst category to 8 % in the best category . Visual‐spatial deficits are common among children after infant heart surgery and seem to reflect visual‐perceptual rather than motor control or metacognitive deficits . In addition , these deficits do not seem to be clearly associated with the intraoperative methods or postoperative events evaluated . J Dev Behav Pediatr 24:169‐179 , 2003 . Index terms : congenital heart disease , visual‐spatial skills , transposition of the great arteries , Rey‐Osterrieth Complex Figure OBJECTIVE Small head circumferences and white matter injury in the form of periventricular leukomalacia have been observed in population s of infants with severe forms of congenital heart defects . This study tests the hypothesis that congenital heart defects delay in utero structural brain development . METHODS Full-term infants with hypoplastic left heart syndrome or transposition of the great arteries were prospect ively evaluated with preoperative brain magnetic resonance imaging .  Patients with independent risk factors for abnormal brain development ( shock , end-organ injury , or intrauterine growth retardation ) were excluded . Outcome measures included head circumferences and the total maturation score  on magnetic resonance imaging .  Total maturation score is a previously vali date d semiquantitative anatomic scoring system used to assess whole brain maturity . The total maturation score evaluates 4 parameters of maturity : ( 1 ) myelination , ( 2 ) cortical infolding , ( 3 ) involution of glial cell migration b and s , and ( 4 ) presence of germinal matrix tissue . RESULTS The study cohort included 29 neonates with hypoplastic left heart syndrome and 13 neonates with transposition of the great arteries at a mean gestational age of 38.9 + /- 1.1 weeks .  Mean head circumference was 1 st and ard deviation below normal . The mean total maturation score for the cohort was 10.15 + /- 0.94 , significantly lower than reported normative data in infants without congenital heart defects , corresponding to a delay of 1 month in structural brain development . CONCLUSION Before surgery , term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected . This delay in brain development may foster susceptibility to periventricular leukomalacia in the preoperative , intraoperative , and postoperative periods OBJECTIVES Despite the technical advantages of total circulatory arrest for vital organ support during infant heart surgery , many centers have moved away from its use because of the demonstrated effects of circulatory arrest of long duration on neurodevelopmental outcomes . Our goal was to determine the functional form of the association between duration of circulatory arrest and risk of neurodevelopmental dysfunction . METHODS From 1988 to 1992 , in a single-center trial , infants with d-transposition of the great arteries underwent the arterial switch operation after r and om assignment to circulatory arrest or low-flow bypass .  The alpha-stat method was used , and hematocrit on bypass was maintained at 20 % . Developmental , neurologic , and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children ( 97 % ) . Outcomes selected for analysis were Full-Scale , Verbal , and Performance IQ , Reading and Mathematics Composite , time to complete the Grooved Pegboard ( dominant h and ) , and the Mayo Test for Apraxia . RESULTS Nonparametric regression and piecewise linear models indicated that neurodevelopmental outcomes were generally not adversely affected unless the duration of circulatory arrest exceeded a threshold of 41 minutes ( 95 % 1-sided lower confidence limit of 32 minutes ) . CONCLUSIONS We found that the effect of duration of total circulatory arrest on later neurodevelopmental outcomes is nonlinear , with little influence at shorter duration s and with steadily worsening outcomes after longer duration s of circulatory arrest . Because the effects of duration of circulatory arrest may vary according to diagnosis , age at surgery , and other bypass and perioperative variables , this study can not ascertain a universally " safe " duration of total circulatory arrest BACKGROUND There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects . Even among children with the same cardiac defect , significant interindividual variation exists in developmental outcome . Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury . METHODS A single-institution prospect i ve study of patients < or=6 months of age undergoing cardiopulmonary bypass for repair of congenital heart defects was undertaken to evaluate the association between apolipoprotein E genotype and postoperative neurodevelopmental dysfunction . Developmental outcomes were evaluated at 1 year of age by using the Bayley Scales of Infant Development . RESULTS One-year evaluation was performed in 244 patients . After adjustment for preoperative and postoperative covariates-including gestational age , age at operation , sex , race , socioeconomic status , cardiac defect , and use of deep hypothermic circulatory arrest-the apolipoprotein E epsilon2 allele was associated with a worse neurologic outcome as assessed by the Psychomotor Developmental Index of the Bayley Scales of Infant Development ( P = .036 ) . Patients with the apolipoprotein E epsilon2 allele had approximately a 7-point decrease in the Psychomotor Developmental Index . CONCLUSIONS Apolipoprotein E epsilon2 allele carriers had significantly lower Psychomotor Development Index scores at 1 year of age after infant cardiac surgery . The effect was independent of ethnicity , socioeconomic status , cardiac defect , and use of deep hypothermic circulatory arrest . An effect of the apolipoprotein E epsilon4 allele was not detected . Genetic polymorphisms that decrease neuroresiliency and impair neuronal repair after central nervous system injury are important risk factors for neurodevelopmental dysfunction after infant cardiac surgery While the trajectory of self-esteem from adolescence to adulthood varies from person to person , little research has examined how differences in early developmental processes might affect these pathways . This study examined how early motor skill development interacted with preterm birth status to predict self-esteem from adolescence through the early 30s . We addressed this using the oldest known , prospect ively followed cohort of extremely low birth weight ( < 1000 g ) survivors ( N = 179 ) and normal birth weight controls ( N = 145 ) in the world , born between 1977 and 1982 .  Motor skills were measured using a  performance-based assessment at age 8 and a retrospective self-report  , and self-esteem was reported during three follow-up periods ( age 12 - 16 , age 22 - 26 , and age 29 - 36 ) . We found that birth weight status moderated the association between early motor skills and self-esteem . Stable over three decades , the self-esteem of normal birth weight participants was sensitive to early motor skills such that those with poorer motor functioning manifested lower self-esteem , while those with better motor skills manifested higher self-esteem . Conversely , differences in motor skill development did not affect the self-esteem from adolescence to adulthood in individuals born at extremely low birth weight . Early motor skill development may exert differential effects on self-esteem , depending on whether one is born at term or prematurely IMPORTANCE There are no well-established noninvasive biomarkers for identifying patients at risk for poor outcome after surgery for congenital heart disease . Few studies have assessed prognostic accuracy of cerebral tissue oxygenation index ( cTOI ) measured by near infrared spectroscopy ( NIRS ) . OBJECTIVE To assess the utility of noninvasive NIRS monitoring as a predictor of outcomes after neonatal cardiac surgery through measurement of cTOI . To examine the utility of noninvasive NIRS monitoring in combination with lactate concentration and inotropic score in prediction of outcomes after neonatal cardiac surgery . DESIGN Prospect i ve longitudinal cohort study . SETTING Operating room and cardiac intensive care unit , Children 's National Heart Institute . PARTICIPANTS Seventy-five patients with complex congenital heart disease undergoing surgical repair within first month of life .  EXPOSURE Cerebral TOI , blood lactate , and inotropic scores were measured preoperative , intraoperative and up to 24 hours postoperative . MAIN OUTCOME MEASURES Postoperative mortality and neurodevelopmental outcome assessed by the Bayley Scales of Infant Development ( BSID II ) . Mental and motor scores were obtained at 6 , 15 , and 21 months . Good outcome was defined as survival and BSID mental and motor scores ≥70 points . Poor outcome was defined as death or BSID scores < 70 at most recent follow-up . RESULTS Cohort of 75 patients prospect ively followed including 40 patients with single ventricle and 35 with two ventricles . Four patients died before discharge and ten died within 21 months . Seven patients were lost to follow-up . Among survivors with follow-up ( n = 54 ) , BSID was abnormal in 25 ( 46 % ) . Patients with poor outcome ( n = 39 ) had lower mean cTOI 60 minutes off-CPB ( 48 % vs. 58 % , P = .003 ) and 24 hours postoperative ( 49 % vs. 59 % , P < .001 ) , higher lactate ( 8.2 vs. 5.0 mmol/L , P = .005 ) and higher inotropic scores ( 10 vs. 6 , P = .02 ) at 24 hours postoperative . ROC analysis indicated that cTOI had moderate predictive accuracy of outcome ( AUC = 0.751 , P < .001 ) . Multivariable regression analysis confirmed that predictive accuracy was improved using both cTOI and lactate at 24 hours postoperative ( AUC = 0.813 , 95 % CI : 0.705 - 0.921 , P < .001 ) with optimal cutoff values < 58 % and > 7.4 mmol/L , respectively ( sensitivity = 95 % ) . CONCLUSION Cerebral TOI combined with lactate at 24 hours postoperative are accurate non-invasive predictive biomarkers of patient survival and neurodevelopmental outcome in neonates with CHD undergoing cardiac surgery OBJECTIVES / AIM To determine whether sedation/analgesia drugs used before , during , and after infant cardiac surgery are associated with neurocognitive and functional outcomes . BACKGROUND Some animal models suggest neurotoxic effects of anesthetic drugs on the developing brain ; however , potential human effects are unknown . Whether these results can be extrapolated to humans is unknown . METHODS / MATERIAL S Prospect i ve follow-up project of all infants ≤6 weeks old having surgery for congenital heart disease between 04/03 and 12/06 . Demographic , perioperative , and sedation/analgesia variables were collected . Outcomes at kindergarten age were Wechsler Preschool and Primary Scale of Intelligence-III , Beery-Buktenica Developmental Test of Visual Motor Integration ( VMI-V ) , and General Adaptive Composite ( GAC ) of the Adaptive Behavior Assessment System-II .  Multivariable linear regression was used to identify predictor variables . RESULTS From 135 infants who underwent heart surgery , 19 died , 17 were excluded , 8 were lost to follow-up , leaving 91 children for analysis . Multiple linear regression found days on chloral hydrate [ 3.5 ( 3.7 ) days ] was associated with lower performance intelligence quotient ( PIQ ) ( Effect size -1.03 ; 95 % CI -1.96 , -0.10 ; P = 0.03 ) , and cumulative dose [ 54.2 ( 60.3 ) mg·kg(-1 ) ] of benzodiazepines was associated with lower VMI scores ( Effect size -0.07 ; 95 % CI -0.12 , -0.01 ; P = 0.026 ) . No other associations were found between sedation/analgesia variables and full-scale IQ , PIQ , Verbal IQ , VMI , or GAC . CONCLUSION Assessment of this cohort at kindergarten age found a small statistically significant association between days on chloral hydrate and PIQ , and benzodiazepine cumulative dose and lower VMI . No other association between sedation/analgesia drugs and outcomes was found Uncertainty exists regarding the degree to which infants with congenitally malformed hearts are at risk of  behavioural disorders in childhood . Data was collected as part of a r and omized clinical trial involving 155 children with surgically corrected transposition ( concordant atrioventricular and ventriculo-arterial connections or alignments ) . As infants , they underwent the arterial switch operation , involving deep hypothermia with predominantly total circulatory arrest or predominantly low-flow continuous cardiopulmonary bypass as the method of providing support to the vital organs . Parents completed the  Child Behavior Checklist  when the patients were aged 4 and 8 years , and the  Connors ' Parent Rating Scale at the age of 8 years . When the children were aged 8 , teachers completed the  Teacher 's Report Form  and the  Connors ' Teacher Rating Scale .  In the cohort as a whole , the frequencies of behavioural problems identified by both parents and teachers were elevated , particularly on the scales for competence of the Child Behavior Checklist , and the Adaptive scales of the Teacher 's Report Form . Approximately 1 in 5 patients had scores for Total Problem Behavior in the range of clinical concern on both the Child Behavior Checklist and the Teacher 's Report Form . Few differences were found , however , according to the method of operative treatment . Postoperative seizures were associated with social and attention problems . Children experiencing academic problems at the age of 8 showed a larger increase in behavioural problems between the ages of 4 and 8 than did children making adequate academic progress . Children with congenitally malformed hearts who underwent reparative surgery in infancy using a strategy of severe haemodilution and alpha stat are at increased risk of behavioural problems in middle childhood OBJECTIVE The purpose of this study was to describe social-emotional outcomes and the relationship with neurodevelopmental outcomes in a cohort of 2-year-old children who underwent surgery for congenital heart disease ( CHD ) in infancy , and explore the relationship between the outcomes and parental and surgical factors . DESIGN A two-center prospect i ve cross-sectional cohort study . PATIENTS A cohort of 105 2-year-olds who underwent surgery in infancy for severe CHD MEASURES : Social-emotional and neurodevelopment was evaluated with the  Infant and Toddler Social and Emotional Assessment tool ( ITSEA ) , and the Bayley Scales of Infant Toddler Development , Third Edition . RESULTS Neurodevelopment was delayed in the CHD cohort with significantly worse results compared to published Australian-based norms in all domains ( P < .001 ) and in the Cognitive ( P < .001 ) and Language ( P < .001 ) domains with respect to the reported American norms . Social-emotional outcome was similar to Australian norms in all domains but better than the American based norms in the Internalizing domain ( P < .05 ) . Higher maternal education was associated to better neurodevelopmental outcome in all domains and better scores in the internalizing and externalizing domains of the ITSEA . There was a moderate correlation ( r = 0.43 , P < .001 ) between Language and social-emotional competence . Motor development was influenced by the need for a significant cardiac reoperation . CONCLUSIONS The influences of social factors may be underestimated in the outcome of children with CHD .  Language development in those with CHD may be improved with intervention targeting social-emotional competence ; further research is needed in this area Objective Historical cohort studies have reported adverse neurodevelopment following cardiac surgery during early infancy . Advances in surgical techniques and perioperative care have coincided with updating of neurodevelopmental assessment tools . We aim ed to determine perioperative risk factors for impaired neurodevelopment at 2 years following surgery for congenital heart disease ( CHD ) in early infancy . Design and patients We undertook a prospect i ve longitudinal study of 153 full-term infants undergoing surgery for CHD before 2 months of age . Infants were excluded if they had a genetic syndrome associated with neurodevelopmental impairment . Outcome measures Predefined perioperative parameters were recorded and infants were classified according to cardiac anatomy . At 2 years , survivors were assessed using the Bayley Scales of Infant Development-III . Results At 2 years , 130 children ( 98 % of survivors ) were assessed . Mean cognitive , language and motor scores were 93.4±13.6 , 93.6±16.1 and 96.8±12.5 respectively ( 100±15 norm ) . Twenty ( 13 % ) died and 12 ( 9 % ) survivors had severe impairment ( score < 70 ) , mostly language ( 8 % ) . The lowest scores were in infants born with single ventricle physiology with obstruction to the pulmonary circulation who required a neonatal systemic-to-pulmonary artery shunt . Additional risk factors for impairment included reduced gestational age , postoperative elevation of lactate or S100B and repeat cardiac surgery . Conclusions In the modern era of infant cardiac surgery and perioperative care , children continue to demonstrate neurodevelopmental delays . The use of up date d assessment tools has revealed early language dysfunction and relative sparing of motor function . Ongoing follow-up is critical in this high-risk population OBJECTIVES / AIM To determine whether sedation/analgesia drugs used before , during , and after infant cardiac surgery are associated with neurodevelopmental outcome . BACKGROUND Animal models suggest detrimental effects of anesthetic drugs on the developing brain . Whether these results can be extrapolated to human neonates is unclear . METHODS / MATERIAL S This is a prospect i ve follow-up project conducted in Western Canada . In all infants ≤6 weeks of age having surgery for congenital heart disease between April 2003 and December 2006 , demographic and perioperative variables were collected prospect ively .  Sedation/analgesia variables were collected retrospectively . For each drug class ( inhalationals , opioids , benzodiazepines , ketamine , and chloral hydrate ) , we calculated the cumulative dose received during hospitalization , average dose received per day , and cumulative number of days the patient received the drug . The outcomes at 18 - 24 months were as follows : General Adaptive Composite and motor scaled scores of the Adaptive Behavior Assessment System , significant mental , motor , and vocabulary delay . Multivariable logistic and linear regression was used to analyze the data . RESULTS One hundred and thirty-five neonates underwent open heart surgery ; 19 died , 16 had chromosomal abnormality , and five were lost to follow up , leaving 95 survivors for analysis . Multiple linear regression analysis found no evidence of an association between sedation/analgesia variables and ABAS-GAC score or motor scale score . Multiple logistic regression analysis found no evidence of an association between sedation/analgesia variables and significant mental , motor , or vocabulary delay . CONCLUSION We found no evidence of an association between dose and duration of sedation/analgesia drugs during the operative and perioperative period and adverse neurodevelopmental outcomes BACKGROUND In this study we report magnetic resonance imaging ( MRI ) brain injury and 12-month neurodevelopmental outcomes when regional cerebral perfusion ( RCP ) is used for neonatal aortic arch reconstruction . METHODS Fifty-seven neonates receiving RCP during aortic arch reconstruction were enrolled in a prospect i ve outcome study . RCP flows were determined by near-infrared spectroscopy and transcranial Doppler monitoring . Brain MRI was performed preoperatively and 7 days postoperatively . Bayley Scales of Infant Development III was performed at 12 months . RESULTS Mean RCP time was 71 ± 28 minutes ( range , 5 to 121 minutes ) and mean flow was 56.6 ± 10.6 mL/kg/min . New postoperative MRI brain injury was seen in 40 % of patients . For 35 RCP patients at age 12 months , mean Bayley Scales III Composite st and ard scores were : Cognitive , 100.1 ± 14.6 ( range , 75 to 125 ) ; Language , 87.2 ± 15.0 ( range , 62 to 132 ) ; and Motor , 87.9 ± 16.8 ( range , 58 to 121 ) . Increasing duration of RCP was not associated with adverse neurodevelopmental outcomes . CONCLUSIONS Neonatal aortic arch repair with RCP using a neuromonitoring strategy results in 12-month cognitive outcomes that are at reference population norms . Language and motor outcomes are lower than the reference population norms by 0.8 to 0.9 st and ard deviations . The neurodevelopmental outcomes in this RCP cohort demonstrate that this technique is effective and safe in supporting the brain during neonatal aortic arch reconstruction UNLABELLED Controversy exists regarding the integrity of the nervous system in the newborn with a congenital heart defect who must undergo corrective or palliative open heart surgery .  Neurodevelopmental sequelae have been primarily attributed to surgical procedures without st and ardized evaluation of the preoperative neurologic status . OBJECTIVE To determine whether newborns with congenital heart defects demonstrate abnormalities in neurobehavioral status before surgery . STUDY DESIGN In this prospect i ve study , a st and ardized neonatal neurobehavioral assessment and a neurologic examination  were conducted independently in a consecutive series of 56 neonates referred to our hospital for investigation of open heart surgery . RESULTS Neurobehavioral and neurologic abnormalities were documented in greater than half of the cohort and included hypotonia , hypertonia , jitteriness , motor asymmetries , and absent suck . Poor state regulation ( 62 % ) and feeding difficulties ( 34 % ) also were commonly observed . Furthermore , 3 subjects had seizures , 35.7 % were microcephalic , and 12.5 % were macrocephalic . The overall likelihood of neurobehavioral abnormalities was not enhanced by indicators of cardiorespiratory compromise . Interestingly , newborns with acyanotic congenital heart defects were more likely to demonstrate neurologic compromise than were those with cyanotic defects . CONCLUSIONS Findings suggest that the prevalence of neurobehavioral abnormalities before surgery in newborns with congenital heart defects has been underappreciated and would indicate that factors other than intraoperative procedures should be considered in the genesis of brain injury in this population .congenital heart defects , neurologic examination , newborn OBJECTIVES To assess the effect of prenatal diagnosis of congenital heart disease on neurocognitive outcomes in children with d-transposition of the great arteries ( TGA ) after surgical correction . STUDY DESIGN A prospect i ve study of children born with a TGA between 2003 and 2005 and aged 4 to 6 years was conducted . General intelligence , language , executive functions , and social cognition scores and preoperative , intraoperative , and postoperative factors were evaluated according to time of TGA diagnosis . Neurocognitive data were also compared with a control group . RESULTS Forty-five eligible patients ( 67 % male ) were examined ; 29 had a prenatal diagnosis of TGA and 16 did not . All children were comparable in age , sex , and demographic variables . Diagnostic groups did not differ in preoperative , intraoperative , and postoperative variables . Preoperative acidosis was more frequent in the postnatal group ( 18 % versus 3 % ) . All patients had normal IQ scores , language , and verbal working memory . However , neurocognitive deficits were more prevalent and more severe in children with a postnatal-TGA . Prenatal diagnosis was associated with better outcomes in executive functions . CONCLUSIONS Prenatal diagnosis of TGA is associated with better neurocognitive outcomes . Time of diagnosis may influence the development of early complex cognitive skills such as executive functions BACKGROUND : The newest measure of neurodevelopmental outcomes , the Bayley Scales of Infant and Toddler Development , 3rd Edition ( Bayley-III ) , gives higher-than-expected scores for preterm infants ; results after cardiac surgery are unknown . OBJECTIVES : The goal of this study was to report Bayley-III scores after cardiac surgery and compare the results with those of the Bayley Scales of Infant Development , 2nd Edition ( BSID-II ) on a subset of the same children . METHODS : In this prospect i ve , inception cohort , neurodevelopmental outcome study after complex cardiac surgery in infants from 2004 to 2007 , the Bayley-III was given to 110 survivors ( 68 % boys ) at a mean age of 21 months ( SD : 4 months ) . Analysis of variance was used to compare intergroup differences . Results for both test editions on the same 25 children were compared by using paired- sample s statistics . RESULTS : Mean ( SD ) Bayley-III mean composite scores ( CSs ) for 110 children were as follows : cognitive , 95.9 ( 14.1 ) ; language , 90.8 ( 18.1 ) ; and motor , 93.7 ( 14.2 ) , differentiating selected cardiac surgery groups . The average difference in mean CSs was 7.4 points higher than BSID-II scores for a previous cohort from this site and 7.2 points higher than a systematic review report . Direct comparison of BSID-II and Bayley-III revealed an average difference in mean CSs of 6.1 points , similar to normative results . Mean cognitive CSs increased by 10.0 ( P < .001 ) , language by 1.4 ( P = .526 ) , and motor by 6.9 points ( P = .009 ) . CONCLUSIONS : Research ers should be careful attributing higher Bayley-III scores to changes in acute care . At-risk children who previously qualified for early developmental intervention may no longer do so . School-age longitudinal studies are needed to determine the accuracy of early developmental estimates using the Bayley-III OBJECTIVES To determine neonatal global and regional brain volumes in infants with congenital heart disease ( CHD ) in comparison with healthy controls and to determine brain growth . STUDY DESIGN Prospect i ve cohort study in infants undergoing open-heart surgery for complex CHD . Global and regional volumetric measurements on preoperative cerebral magnetic resonance imaging were manually segmented in children without overt brain lesions . RESULTS Preoperative brain volumetry of 19 patients demonstrates reduction in total and regional brain volumes , without any specific regional predilection compared with 19 healthy control infants ( total brain volume reduction : 21 % , regional brain volume reduction 8%-28 % , all P < .001 ) . CONCLUSIONS Infants with CHD undergoing bypass surgery  have smaller brain volumes prior to surgery without a specific regional predilection . This suggests a fetal origin of reduced brain growth OBJECTIVE To assess neurodevelopment in children with hypoplastic left heart syndrome ( HLHS ) or other types of functionally single ventricle ( univentricular heart , UVH ) and to estimate the effect of possible clinical predictors on outcome . STUDY DESIGN A total of 22 patients with HLHS and 14 with UVH , surviving after palliative surgery performed in the same center , and 42 healthy control subjects were examined at a median age of 30.2 months neurologically and according to the Bayley Scales of Infant Development  in a population based prospect i ve neurodevelopmental follow-up study . RESULTS The mean Mental Developmental Index was significantly lower ( 89.9 ) in patients with HLHS than in control subjects ( 105.5 , P<.001 ) , whereas there was no difference between patients with UVH ( 98.5 ) and control subjects . The mean Psychomotor Developmental Index in patients with HLHS ( 80.7 , P<.001 ) as well as in those with UVH ( 94.5 , P=.016 ) was significantly inferior to that in control subjects ( 105.3 ) . CONCLUSIONS In patients with HLHS , mean Mental Developmental Index lags behind control subjects . Psychomotor Developmental Index is impaired in patients with both HLHS and UVH . Routine neurodevelopmental follow-up is recommended for this seriously ill patient group BACKGROUND Preterm children have problems with mathematics but knowledge about the predictors of specific mathematic abilities in preterm population s is scarce . AIMS This study investigated neurodevelopmental pathways to children 's general and specific mathematic abilities across the full gestational age range . STUDY DESIGN Prospect i ve geographically defined longitudinal investigation in Germany . SUBJECTS 947 children across the full gestational age range ( 23 - 41 weeks ) . Outcome measures . At 8 years , children 's cognitive and mathematic abilities were measured and residuals of a regression predicting mathematic scores by IQ were used to identify specific mathematic abilities . RESULTS Neurodevelopmental cascade models revealed that adverse effects of preterm birth on mathematic abilities were mediated by neonatal risk . Specific mathematic abilities were uniquely predicted by the duration of hospitalization and ventilation . CONCLUSIONS Prolonged neonatal medical treatment and , in particular , mechanical ventilation may lead to specific impairments in mathematic tasks . These findings have implication s for the mode of respiratory support in neonates , routine follow-up and intervention planning as well as research about brain reorganization after preterm birth OBJECTIVES Neonates undergoing complex congenital heart surgery have a significant incidence of neurologic problems . Erythropoietin has antiapoptotic , antiexcitatory , and anti-inflammatory properties to prevent neuronal cell death in animal models , and improves neurodevelopmental outcomes in full-term neonates with hypoxic ischemic encephalopathy . We design ed a prospect i ve phase I/II trial of erythropoietin neuroprotection in neonatal cardiac surgery to assess safety and indicate efficacy . METHODS Neonates undergoing surgery for D-transposition of the great vessels , hypoplastic left heart syndrome , or aortic arch reconstruction were r and omized to 3 perioperative doses of erythropoietin or placebo . Neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development III was performed at age 12 months . RESULTS Fifty-nine patients received the study drug . Safety profile , including magnetic resonance imaging brain injury , clinical events , and death , was not different between groups . Three patients in each group died . Forty-two patients ( 22 in the erythropoietin group and 20 in the placebo group ; 79 % of survivors ) returned for 12-month follow-up . In the group receiving erythropoietin , mean Cognitive Scale scores were 101.1 ± 13.6 , Language Scale scores were 88.5 ± 12.8 , and Motor Scale scores were 89.9 ± 12.3 . In the group receiving placebo  , Cognitive Scale scores were 106.3 ± 10.8 ( P = .19 ) , Language Scores were 92.4 ± 12.4 ( P = .33 ) , and Motor Scale scores were 92.6 ± 14.1 ( P = .51 ) . CONCLUSIONS Safety profile for erythropoietin administration was not different than placebo . Neurodevelopmental outcomes were not different between groups ; however , this pilot study was not powered to definitively address this outcome . Lessons learned suggest optimized study design features for a larger prospect i ve trial to definitively address the utility of erythropoietin for neuroprotection in this population OBJECTIVE To test the hypothesis that postoperative length of stay ( LOS ) after infant heart surgery  might be an easily measured surrogate marker for various events that culminate in later adverse cognitive outcome . METHODS Among 160 eligible patients with D-transposition of the great arteries undergoing reparative surgery in infancy , 155 ( 97 % ) were reevaluated at age 8 years with IQ and achievement testing . We explored whether LOS quartiles were associated with these outcomes when adjusting for perioperative and sociodemographic variables . RESULTS Longer cardiac intensive care unit ( CICU ) LOS quartiles were associated at age 8 years with lower full-scale IQ ( P=.02 ) , lower verbal IQ ( P=.02 ) , and with tendencies toward lower performance IQ ( P=.08 ) and math achievement ( P=.08 ) in adjusted models . Compared with patients in the first quartile of CICU LOS , those in the fourth quartile had mean scores for full-scale IQ that were lower by 7.2 points ( P=.01 ) ; verbal IQ , 7.3 points ( P=.02 ) ; performance IQ , 5.8 points ( P=.05 ) ; and math achievement , 6.0 points ( P=.07 ) . Analyses on hospital LOS quartile were similar . CONCLUSIONS Longer postoperative LOS is associated with worse later cognitive function , even when adjusted for perioperative events , perfusion times , and sociodemographic variables . Further research is necessary to determine the mechanisms underlying this relation BACKGROUND Previous research on developmental outcomes of infants with congenital heart disease ( CHD ) has shown delays in both cognitive and motor skills . AIMS To describe outcomes on the Bayley Scales of Infant and Toddler Development , 3rd edition ( Bayley-III ) for infants with CHD and to compare those findings to published results for similar sample s of infants assessed on the 2nd edition of the Bayley Scales ( BSID-II ) . STUDY DESIGN Prospect i ve cohort . PARTICIPANTS AND OUTCOME MEASURES Of 50 infants with CHD who participated in this longitudinal study ( 2006 - 2008 ) at the Royal Children 's Hospital in Melbourne , Australia , 47 were assessed on the Bayley-III ( median age=24.5 months ) ,  administered by a psychologist or neonatologist . Although neither assessor was blind to the CHD diagnosis , they were unaware of results of previous developmental assessment s conducted in this longitudinal study . RESULTS For the Bayley-III cognitive composite score , 17.0 % of infants showed mild delays ( 1 - 2 SD below the mean ) , 2.1 % had moderate delays ( 2 - 3 SD below the mean ) , and none had severe delays ( greater than 3 SD below the mean ) . Motor composite scores showed mild delays in 10.9 % of infants and moderate delays in 2.2 % ; none had severe motor delays . These findings differ from study results using the BSID-II in similar infants . CONCLUSIONS The Bayley-III may underestimate developmental delay in 2-year-old children with CHD when compared to results of similar children tested at 12 - 36 months of age on the BSID-II Background : Neonates with congenital heart disease ( CHD ) are at high risk of punctate white matter injury ( WMI ) and impaired brain development . We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age ( GA ) is associated with larger WMI volume . Objective : ( 1 ) To quantitatively assess the volume and location of WMI in CHD neonates across three centres . ( 2 ) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping . Methods : In 216 term born CHD neonates from three prospect i ve cohorts ( mean birth GA : 39 weeks ) , WMI was identified in 86 neonates ( UBC : 29 ; UCSF : 43 ; UCZ : 14 ) on pre‐ and /or post‐operative T1 weighted MRI . WMI was manually segmented and volumes were calculated . A st and ard brain template was generated . Probabilistic WMI maps ( total , pre‐ and post‐operative ) were developed in this common space . Using these maps , WMI in the term CHD neonates was compared with that in preterm neonates : 58 at early‐in‐life ( mean postmenstrual age at scan 32.2 weeks ) ; 41 at term‐equivalent age ( mean postmenstrual age at scan 40.1 weeks ) . Results : The total WMI volumes of CHD neonates across centres did not differ ( p = 0.068 ) : UBC ( median = 84.6 mm3 , IQR = 26–174.7 mm3 ) ; UCSF ( median = 104 mm3 , IQR = 44–243 mm3 ) ; UCZ ( median = 121 mm3 , IQR = 68–200.8 mm3 ) . The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions . Predominance of anterior lesions was apparent on the post‐operative WMI map relative to the pre‐operative map . Lower GA at birth predicted an increasing volume of WMI across the full cohort ( 41.1 mm3 increase of WMI per week decrease in gestational age ; 95 % CI 11.5–70.8 ; p = 0.007 ) , when accounting for centre and heart lesion . While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms . Conclusions : WMI in term neonates with CHD occurs in a characteristic topology . The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre‐oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates . HighlightsWe quantitatively assess the volume and location of WMI in term CHD neonates .  WMI in term CHD neonates occurs in a characteristic topology . WMI distribution reflects regional variability in pre‐oligodendrocyte maturation . Term CHD neonates exhibit less central WMI relative to that of preterm newborns . Younger birth GA predicts greater WMI volume independent of other risk BACKGROUND Neurodevelopmental outcome after  neonatal arterial switch operation for complete transposition of the great arteries is an important topic needing prospect i ve assessment . METHODS A group of 33 unselected children ( 3.0 to 4.6 years ) operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass and a control group of 32 age-matched healthy children ( 3.0 to 4.8 years )  underwent evaluation of socioeconomic and clinical neurological status and a st and ardized test comprising all areas of child development . Results of patients were related to those of the control group , to population norms , and to preoperative , perioperative , and postoperative cerebral risk factors . RESULTS Clinical neurological status was normal in 26 patients ( 78.8 % ) and reduced in 7 ( 21.2 % ) . Complete developmental score and the subscores for motor function , visual perception , learning and memory , cognitive function , language , and socioemotional functions were not different compared to population norms . Compared to the patients , the children of the control group scored higher on tests of complete development , cognition , and language , but also on socioeconomic status . Complete developmental score and the scores for motor , cognitive , and language functions were weakly inversely related to the duration of circulatory arrest , but not to the duration of bypass . Cerebral risk factors such as serum levels of the neuron-specific enolase , perinatal acidosis , perinatal asphyxia , peri- and postoperative cardiocirculatory insufficiency , or clinical seizures were not correlated to the test results . CONCLUSIONS Neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with neurological impairment , but not with reduced development as assessed by formal testing of motor , cognitive , language , and behavioral functions . Perioperative serum level of the neuron-specific enolase is not a valid marker for later developmental impairment BACKGROUND Early identification of infants with CHD at heightened risk of developmental delays can inform surveillance priorities . This study investigated pre-operative and post-operative neuromotor performance in infants undergoing open-heart surgery , and their developmental status at 6 months of age , to identify risk factors and inform care pathways . METHODS Infants undergoing open-heart surgery before 4 months of age were recruited into a prospect i ve cohort study . Neuromotor performance was assessed pre-operatively and post-operatively using the  Test of Infant Motor Performance and Prechtl 's Assessment of General Movements .  Development was assessed at 6 months of age using the Ages and Stages Question naire third edition . Pre-operative and post-operative General Movements performance was compared using McNemar 's test and test of infant motor performance z-scores using Wilcoxon 's signed rank test . Risk factors for delayed development at 6 months were explored using logistic regression . RESULTS Sixty infants were included in this study . In the 23 ( 38 % ) infants . A total of 60 infants were recruited . In the 23 ( 38 % ) infants assessed pre-operatively , there was no significant difference between pre- and post-operative performance on the GMs ( p=0.63 ) or TIMP ( p=0.28 ) . At discharge , 15 ( 26 % ) infants presented with abnormal GMs , and the median TIMP z-score was -0.93 ( IQR : -1.4 to -0.69 ) . At 6 months , 28 ( 52.8 % ) infants presented with gross motor delay on the ASQ-3 , significantly negatively associated with gestational age ( p=0.03 ) , length of hospital stay ( p=0.04 ) and discharge TIMP score ( p=0.01 ) . CONCLUSIONS Post-operative assessment using the GMs and TIMP may be useful to identify infants requiring individualised care and targeted developmental follow-up . Long-term developmental surveillance beyond 6 months of age is recommended
target: Perioperative risk factors were inconsistently associated with developmental outcomes .
  INTERPRETATION The literature on children undergoing surgery in early infancy suggests that infants with a single ventricle are at highest risk of adverse developmental outcomes .
  WHAT THIS PAPER ADDS Children with complex congenital heart disease ( CHD ) are at increased risk of impaired developmental outcome .
  Children with single-ventricle CHD have worse outcomes than children with two-ventricle CHD .
  Children with two-ventricle CHD gradually grow out of their initial developmental impairment .
  Perioperative factors are inconsistently associated with outcome
background: AIM ( 1 ) To systematic ally review the literature on developmental outcomes from infancy to adolescence of children with complex congenital heart disease ( CHD ) who underwent early surgery ; ( 2 ) to run a meta-regression analysis on the Bayley Scales of Infant Development , Second Edition Mental Developmental Index and Psychomotor Developmental Index ( PDI ) of infants up to 24 months and IQs of preschool-aged children to adolescents ; ( 3 ) to assess associations between perioperative risk factors and outcomes .