Risk of Developmental Coordination Disorder in 8- and 9-Year-Olds Following Newborn Cardiac and Non-Cardiac Surgery.

PURPOSE: To investigate the risk of developmental coordination disorder (DCD) and motor impairment for children aged 8 to 9 years following newborn surgery. METHODS: Prospective longitudinal cohort study. Motor proficiency and risk of DCD were assessed using the Movement Assessment Battery for Children (second edition) for children born 37 weeks of gestation and older who had undergone newborn cardiac surgery (CS) or non-cardiac surgery (NCS). RESULTS: Children who had undergone CS were 3.0 times more likely than controls and 1.7 times more likely than children who had undergone NCS to score below the 15th centile on MABC-2 and have increased risk of DCD. Children who had undergone CS were 1.9 times more likely than controls and 1.4 times more likely than children who had undergone NCS to score below the fifth centile on MABC-2. CONCLUSION: The surgical population should be considered at an increased risk of DCD.

Are boys and girls just different? Gender differences in the Movement Assessment Battery for Children, 2nd edition (M ABC-2) suggests that they are.

INTRODUCTION: The second edition of the Movement Assessment Battery for Children (M ABC-2) is a standardised, norm referenced assessment that is frequently used by therapists to identify children with motor difficulties. The norms for the M ABC-2 were derived from a sample of children in the United Kingdom (UK) and are combined across the age groups for boys and girls. The aims of this research were to investigate gender differences in the performance of 8- and 9-year-old Australian children and if the norms in our cohort differed from UK-based M ABC-2 norms. METHODS: Children aged 8 or 9 years of age who underwent major neonatal cardiac or non-cardiac surgery and healthy controls were assessed using the M ABC-2 as part of the Development After Infant Surgery (DAISy) study. RESULTS: There were statistically significant differences in the scores for boys and girls aged 8- and 9-years old on the M ABC-2. Girls performed better than boys in manual dexterity and on total standard scores. Our control group compared to the assessment norms scored significantly poorer in manual dexterity, aiming and catching and total standard scores. CONCLUSION: Caution should be used when interpreting the results of the M ABC-2 for Australian 8- and 9-year olds. Contemporary Australian, gender-specific M ABC-2 norms should be considered. Further research is required to investigate gender differences and differences in performance of Australian children compared to the assessment norms in other age groups on the M ABC-2.

Use of the General Movements Assessment for the Early Detection of Cerebral Palsy in Infants with Congenital Anomalies Requiring Surgery.

The general movements (GMs) assessment is recognised as one of the most important tools in the early detection of cerebral palsy (CP). However, there remains a paucity of data on its application to infants with congenital anomalies requiring surgery. This was a prospective study of 202 infants (mean gestation 38 weeks, SD 2.2) who had undergone major surgery for congenital anomalies in the neonatal period. Infants were assessed at three months of age (mean 12 weeks, SD 1.6) and GMs videos were independently rated by three clinicians, two blinded to clinical details. Developmental follow-up was at three years of age. Of the twenty-five infants (9%) rated as having an absence of fidgety movements, 22 were seen at 3 years, and 17 had an abnormal outcome: 11 with CP, and 6 with a developmental disability. Infants with absent fidgety movements were 21.5 (95% CI 7.3-63.8) times more likely to have an abnormal outcome including CP. None of the infants with normal fidgety movements had a diagnosis of CP and 86% were assessed to be developing normally. The GMs assessment has predictive value for cerebral palsy and neurodevelopment for infants with congenital anomalies, and should be incorporated into routine follow-up to facilitate early referral.

'Big issues' in neurodevelopment for children and adults with congenital heart disease.

It is established that neurodevelopmental disability (NDD) is common in neonates undergoing complex surgery for congenital heart disease (CHD); however, the trajectory of disability over the lifetime of individuals with CHD is unknown. Several 'big issues' remain undetermined and further research is needed in order to optimise patient care and service delivery, to assess the efficacy of intervention strategies and to promote best outcomes in individuals of all ages with CHD. This review article discusses 'gaps' in our knowledge of NDD in CHD and proposes future directions.

Impact of High-Risk Characteristics in Hypoplastic Left Heart Syndrome.

BACKGROUND: Management of hypoplastic left heart syndrome (HLHS) presents many challenges. We describe our institutional outcomes for management of patients with HLHS over the past 12 years and highlight our strategy for those with highly restrictive/intact interatrial septum (R/I-IAS). METHODS: Eighty-eight neonates with HLHS underwent surgical treatment, divided equally into Era-I (n = 44, April 2006 to February 2013) and Era-II (n = 44, March 2013 to June 2018). Up to 2013, all patients with R/I-IAS were delivered at an adjacent adult hospital and then moved to our hospital for intensive care and management. From 2014, these patients were delivered at a co-located theatre in our hospital with immediate atrial septectomy. The hybrid approach was occasionally used with preference for the Norwood procedure for suitable candidates. RESULTS: One-year survival after Norwood procedure was 62.5% and 80% for Era-I and Era-II (P = not significant (ns)), respectively, and 41% of patients were categorized as high risk using conventional criteria. Survival at 1 year differed significantly between high-risk and standard-risk patients (P = 0.01). For high-risk patients, survival increased from 42% to 65% between eras (P = ns). In the R/I-IAS subgroup (n = 15), 11 underwent Norwood procedure after emergency atrial septectomy. Of these, seven born at the adjacent adult hospital had 40% survival to stage II versus 60% for the four born at the colocated theatre. Delivery in a colocated theatre reduced the birth-to-cardiopulmonary bypass median time from 445 (150-660) to 62 (52-71) minutes. CONCLUSION: Reported surgical outcomes are comparable to multicenter reports and international databases. Proactive management for risk factors such as R/I-IAS may contribute to improved overall outcomes.

Developmental outcome at 3 years of age of infants following surgery for infantile hypertrophic pyloric stenosis.

PURPOSE: The study compared neurodevelopmental outcome at 3 years of age of infants with infantile hypertrophic pyloric stenosis (IHPS) who underwent pyloromyotomy with healthy control infants in New South Wales, Australia. METHODS: Infants with IHPS as well as controls were recruited between August 2006 and July 2008. Developmental assessments were performed using the Bayley scales of infant and toddler development (version III) (BSITD-III) at 1 and 3 years of age. RESULTS: Of the 43 infants originally assessed at 1 year, 39 returned for assessment at 3 years (90%). The majority were term infants (77%). Assessments were also performed on 156 control infants. Infants with IHPS scored significantly lower on four of the five Bayley subsets (cognitive, receptive and expressive language and fine motor) compared to control infants. Analysis of co-variance showed statistically significant results in favour of the control group for these four subsets. CONCLUSION: Compared with the outcomes at 1 year, infants with IHPS at 3 years of age continue to score below controls in four of the BSITD-III subscales. This suggests they should have developmental follow-up with targeted clinical intervention. There is a need for further studies into functional impact and longer term outcomes.

Genetic burden and associations with adverse neurodevelopment in neonates with congenital heart disease.

BACKGROUND: Up to 20% of children with congenital heart disease (CHD) undergoing cardiac surgery develop neurodevelopmental disabilities (NDD), with some studies reporting persistent impairment. Recent large-scale studies have demonstrated shared genetic mechanisms contributing to CHD and NDD. In this study, a targeted approach was applied to assess direct clinical applicability of this information. METHODS: A gene panel comprising 148 known CHD and/or NDD genes was used to sequence 15 patients with CHD + NDD, 15 patients with CHD, and 15 healthy controls. The number and types of variants between the 3 groups were compared using Poisson log-linear regression, and the SNP-set (Sequence) Kernel Association Test-Optimized was used to conduct single-gene and gene-pathway burden analyses. RESULTS: A significant increase in rare (minor allele frequency < 0.01) and novel variants was identified between the CHD + NDD cohort and controls, P < .001 and P = .001, respectively. There was also a significant increase in rare variants in the CHD cohort compared with controls (P = .04). Rare variant burden analyses implicated pathways associated with "neurotransmitters," "axon guidance," and those incorporating "RASopathy" genes in the development of NDD in CHD patients. CONCLUSIONS: These findings suggest that an increase in novel and rare variants in known CHD and/or NDD genes is associated with the development of NDD in patients with CHD. Furthermore, burden analyses point toward rare variant burden specifically in pathways related to brain development and function as contributors to NDD. Although promising variants and pathways were identified, further research, utilizing whole-genome approaches, is required prior to demonstrating clinical utility in this patient group.

Prediction of three year outcomes using the Bayley-III for surgical, cardiac and healthy Australian infants at one year of age.

BACKGROUND: Previous predictive research has predominantly focussed on infants who are preterm, low birth weight, who have a specific condition or who have undergone a specific procedure. AIM: This study investigated the ability of outcomes at one year of age to predict outcomes at three years using the Bayley-III for infants who have undergone early major cardiac surgery (CS) or non-cardiac (NC) surgery and their healthy peers. STUDY DESIGN: Participants who were part of the Development After Infant Surgery (DAISy) study who had complete Bayley-III assessments at one and three years of age were included in the analyses. This included 103 infants who had undergone CS, 158 who had NC surgery and 160 controls. RESULTS: Bayley-III outcomes at one, although statistically significantly associated with three year outcomes in all domains were weak predictors of those outcomes for CS, NC surgical and healthy infants. Specificity for three year outcomes was good for cognitive, receptive language and fine motor domains for infants who had undergone CS and NC surgery. Sensitivity for <-1 SD at three years was poor for cognitive, expressive and receptive language, and fine motor outcomes for CS and NC surgical participants. CONCLUSION: It remains difficult to predict how performance at one year on the Bayley-IIII predicts performance at three on the Bayley-III for infants who have undergone early major CS or NC surgery and for healthy Australian infants.

Contemporary incidence of stroke (focal infarct and/or haemorrhage) determined by neuroimaging and neurodevelopmental disability at 12 months of age in neonates undergoing cardiac surgery utilizing cardiopulmonary bypass.

OBJECTIVES: When evaluated prospectively, acute brain injury is reported in up to 75% of neonates undergoing cardiopulmonary bypass (CPB), predominantly white matter injury rather than stroke. This study investigates the incidence of stroke (focal infarct and/or haemorrhage) detected by neuroimaging in contemporary clinical practice, whereby magnetic resonance imaging/computed tomography routinely occurs in response to clinical events, comparing those undergoing the Norwood procedure with those undergoing other neonatal procedures involving CPB, and defines the relationship between stroke and neurodevelopmental disability (NDD) at 12 months of age. METHODS: One hundred and twenty neonates underwent CPB between July 2011 and December 2014: 25 Norwood procedures and 95 non-Norwood procedures. Data were retrospectively collected including clinical data and 12-month neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS: Stroke was detected in 12% of neonates in current clinical practice: 24% of the Norwood group vs 8% of the non-Norwood group (P = 0.03). Significant predictors of stroke in the univariate analysis included the Norwood procedure, lowest operative temperature and use of extracorporeal membrane oxygenation (P < 0.05). The lowest operative temperature and use of extracorporeal membrane oxygenation remained significant in the multivariate analysis (P < 0.05). Fifty-seven percent were assessed using the BSID-III assessment, and 68% demonstrated NDD in at least 1 subscale. In neonates who suffered stroke, the incidence of NDD was significantly greater in 4/5 subscales compared with those with no injury (P < 0.05). The Norwood group had a significantly greater incidence of NDD in 2/5 subscales when compared with the non-Norwood group (P < 0.05). CONCLUSIONS: Stroke, established by neuroimaging in contemporary clinical practice, was detected in 12% of neonates having CPB, and those undergoing the Norwood procedure have a 3-fold risk of injury. Stroke was associated with NDD at 12 months of age.

Developmental outcomes at three years of age of infants with esophageal atresia.

BACKGROUND/AIMS: Previous work assessing early developmental outcomes of infants at one year of age following surgery for esophageal atresia (OA) and/or tracheoesophageal fistula (TOF) found a significantly lower score in expressive language compared with control infants. The purpose of this study was to determine whether these differences were still evident at three years of age. METHODS: Between August 2006 and July 2008, infants who required surgical correction of OA/TOF were prospectively enrolled as part of a large study which examined developmental outcomes following surgery. Patients were reassessed using the Bayley Scales of Infant and Toddler Development Version III. Cognition, expressive and receptive language, fine motor and gross motor skills scores were compared with both the standardized norms and also with contemporaneous control infants. RESULTS: 24 of the 31 infants (77%) assessed at one year were reassessed at three years of age. There was no significant difference between the Bayley scores of the infants with OA/TOF and the standardized norms of the tests in four of the subsets: cognition, expressive language, fine and gross motor skills. Infants with OA scored higher than normative values for the receptive language subscale (P=0.001). When compared with the controls, there were no significant differences in any of the subscales. CONCLUSION: Compared with the outcomes at one year, infants with OA/TOF have improved and were scoring within the normal range for the assessment at three years. This may in part be because of the early intervention services which many of these children were provided.

Developmental outcomes at 3 years of age following major non-cardiac and cardiac surgery in term infants: A population-based study.

OBJECTIVE: The objective of this study was to determine whether there remain developmental differences between term infants at 3 years of age following major non-cardiac surgery (NCS) and cardiac surgery (CS) compared with healthy control infants in New South Wales (NSW), Australia. STUDY DESIGN: Between 2006 and 2008, term infants who required NCS or CS within the first ninety days of life were enrolled in a prospective population-based study. Their developmental outcome was then compared with a cohort of healthy term infants. Infants initially assessed at 1 year of age were then re-assessed at 3 years of age using the Bayley scales of infant and toddler development (version- III) RESULTS: Of the 539 term infants assessed at 1 year of age, 417 returned for the 3-year assessment, with 378 complete assessments. The mean scores for the infants who underwent CS (P < 0.001) were significantly lower in all subscales of the assessment compared with the controls, while the mean scores for the infants who underwent NCS were significantly lower in three of the subscales (P < 0.05). The infants who underwent CS scored significantly lower in four of the subscales (P < 0.05), compared with the infants who underwent NCS. CONCLUSION: The second phase of this unique population-based study provides further data on the outcomes of infants who underwent major NCS and CS. Major surgery in infants continues to be associated with developmental delay at 3 years of age compared with control infants; however the majority of the delay is mild. The risk remains higher in CS group with the pattern and severity of delay similar to that observed in the first study.

The impact of surgery on the developmental status of late preterm infants - a cohort study.

AIMS: Despite increasing evidence in the literature regarding the impact of late prematurity on subsequent developmental impairment, the developmental outcome of late preterm infants who undergo major surgery remains unclear. The aim of this study therefore was to determine the developmental outcome for a cohort of late preterm surgical population. METHODS: Late preterm infants with a gestational age from 34-36 weeks inclusive who were enrolled in the state-wide prospective Development After Infant Surgery (DAISy) study and who had undergone non-cardiac major surgery within the first ninety days of life were eligible for inclusion. Infants were assessed at one and three years of ages. RESULTS: Forty-six infants were enrolled in the study, of which 38 infants had a complete developmental assessment at one year of age. Of these infants, late preterm infants scored significantly lower than the standardized norms of the assessment on the expressive language and gross motor subscales. At three years of age 26 infants were reassessed: late preterm infants who underwent major surgery only scored significantly lower than the standardized norms on the cognitive subscale (p less than 0.001). CONCLUSIONS: These data provide the evidence that late preterm infants who undergo major non-cardiac surgery are at risk of developmental impairment and consideration should be given to enrolling this cohort in multi-disciplinary developmental follow-up clinics.

A comparison of the performance of healthy Australian 3-year-olds with the standardised norms of the Bayley Scales of Infant and Toddler Development (version-III).

BACKGROUND: Standardised developmental tests are now widely used in neurodevelopmental assessments of infants and children. In 2006, the revised and updated version of the Bayley Scales of Infant and Toddler Development (version III) replaced the previous version and is now widely used in neonatal developmental follow-up clinics. Several papers from Australia have highlighted underestimation of developmental impairment up to age 2 using this revised version. We aimed to ascertain how a cohort of healthy 3-year-old children performed compared to the standardised norms of the Bayley Scales of Infant and Toddler Development (version-III). METHOD: Term healthy newborn control infants from the prospective Development after Infant Surgery (DAISy) study were included. At 3 years of age, the mean scores on each of the five subscales for 156 children were compared with the standardised norms. RESULTS: At 3 years of age, the mean scores were higher than the standardised norms on four of the subscales, cognition (<0.05), receptive and expressive language and fine motor (p<0.001). There was no significant difference in the gross motor scale (p=0.435). CONCLUSIONS: Healthy term Australian children have a statistically significantly higher mean score on the Bayley Scales of Infant and Toddler Development (version-III) compared with the standardised means in four of the subtests, with the greatest difference in receptive language. This has implications for the assessment of children as the test may miss those with a minor delay and not reflect the severity of delay of infants that it does identify. We recommend that consideration ought to be given to re-standardising this assessment on Australian children.

Respiratory disease and early serum S100A12 changes in very premature infants.

AIM: The role of granulocyte-specific S100A12, a marker for inflammatory disorders, in newborn lung disease is unknown. We compared postnatal blood S100A12 concentrations against respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). METHODS: Blood samples from 92 newborns were collected on admission, 12 h, day 1, day 3-4 and day 7, and analysed for S100A12. IL-8 and IL-6 were assayed in 52 infants. RESULTS: Infants with RDS were significantly more premature (median 27 vs. 34 weeks), more likely to receive antenatal corticosteroids (84% vs. 26%) and have lower neutrophil counts (median 2.4 vs. 3.8 × 10(9) /L) at admission. S100A12 levels peaked during the first day and were significantly lower in preterm infants with RDS compared to those without (median 250 vs. 616 ng/mL at 12 h, 281 vs. 828 ng/mL day 1, respectively). S100A12 levels were low among the 35 very preterm infants (24-29 week gestation) regardless of the presence of BPD (285 vs. 288 ng/mL on day 1). In comparison, IL-8 and IL-6 levels were not different between groups. CONCLUSION: Plasma S100A12 is low in infants with RDS, possibly because of gestationally related differences in neutrophil response or to the effects of antenatal corticosteroids. It is therefore not a useful marker of BPD development.

Distraction osteogenesis and glossopexy for Robin sequence with airway obstruction.

BACKGROUND: We present six cases of infants with Robin sequence and severe obstructive sleep apnoea who failed treatment with nasal mask continuous positive airway pressure (CPAP). Surgical intervention with mandibular distraction osteoneogenesis with glossopexy meant tracheostomy was avoided. Polysomnography (PSG) was used to document the severity of the obstructive sleep apnoea. The aim of this report was to assess the value of mandibular distraction osteogenesis with glossopexy in children with Robin sequence using PSG preoperatively and post-operatively. METHODS: Retrospective review of medical records to assess details of preoperative clinical progress, CPAP therapy, endoscopy, PSG and respiratory parameters. RESULTS: Between 2003 and 2008, 20 infants with Robin sequence were admitted to the neonatal intensive care unit of our tertiary paediatric hospital. Six infants (30%) failed a treatment trial of CPAP during that period, but were subsequently successfully managed with mandibular distraction osteoneogenesis and glossopexy. At endoscopy, all had associated airway problems which included congenitally hypoplastic epiglottis (n= 2), laryngomalacia (n= 2), unilateral choanal atresia (n= 1) and long-segment tracheal stenosis (n= 1). CONCLUSION: Mandibular distraction osteogenesis with glossopexy provides relief of severe upper airway obstruction for infants with Robin sequence. Epiglottic maldevelopment was present in two infants (33%). Endoscopy and PSG assisted clinical management, but highlighted ongoing respiratory issues.