Understanding social cognition in children with cerebral palsy: exploring the relationship with executive functions and the intervention outcomes in a randomized controlled trial.

Children with Cerebral Palsy (CP) experience Social Cognition (SC) difficulties, which could be related to executive functioning. While motor interventions are common, there is limited knowledge about the impact of cognitive interventions on SC in this population. This study examined the relationship between SC and Executive Function (EF) skills and the effectiveness of an EF intervention that included some SC tasks for improving SC in children with CP. SC and EF domains were assessed in 60 participants with CP (30 females; 8-12 years). The relationship between SC and EF baseline scores was analyzed by bivariate correlations and contingency tables. Participants were matched by age, sex, motor ability, and intelligence quotient and randomized into intervention or control groups. The intervention group underwent a 12-week home-based computerized EF intervention. Analysis of covariance was used to examine differences in SC components between groups at post-intervention and 9 months after. Significant positive correlations were found between the SC and EF scores. The frequencies of impaired and average scores in SC were distributed similarly to the impaired and average scores in EFs. The intervention group showed significant improvements in Affect Recognition performance post-intervention, which were maintained at the follow-up assessment, with a moderate effect size. Long-term improvements in Theory of Mind were observed 9 months after. CONCLUSIONS: This study highlights the association between SC and EFs. A home-based computerized cognitive intervention program improves SC in children with CP. Including SC tasks in EF interventions may lead to positive short- and long-term effects for children with CP. CLINICAL TRIAL REGISTRATION: NCT04025749 retrospectively registered on 19 July 2019. WHAT IS KNOWN: • Executive functions and social cognition are associated with social and community participation in people with cerebral palsy. • A home-based computerized cognitive intervention can improve the executive functioning of children with cerebral palsy. WHAT IS NEW: • Social cognition performance is related to core and higher-order executive functions. • A home-based computerized executive function intervention, including social cognition tasks, has positive short- and long-term effects on social cognition skills in children with cerebral palsy.

The search for blood biomarkers that indicate risk of adverse neurodevelopmental outcomes in fetal growth restriction.

Fetal growth restriction (FGR) impacts 5%-10% of pregnancies and is associated with increased risk of mortality and morbidity. Although adverse neurodevelopmental outcomes are observed in up to 50% of FGR infants, a diagnosis of FGR does not indicate the level of risk for an individual infant and these infants are not routinely followed up to assess neurodevelopmental outcomes. Identifying FGR infants at increased risk of adverse neurodevelopmental outcomes would greatly assist in providing appropriate support and interventions earlier, resulting in improved outcomes. However, current methods to detect brain injury around the time of birth lack the sensitivity required to detect the more subtle alterations associated with FGR. Blood biomarkers have this potential. This systematic review assessed the current literature on blood biomarkers for identifying FGR infants at increased risk of adverse neurodevelopmental outcomes at >12 months after birth. Four databases were searched from inception to 22 February 2024. Articles were assessed for meeting the inclusion criteria by two reviewers. The quality of the included article was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. A summary of findings is presented as insufficient articles were identified for meta-analysis. Excluding duplicates, 1,368 records were screened with only 9 articles considered for full text review. Only one article met all the inclusion criteria. Quality assessment indicated low risk of bias. Both blood biomarkers investigated in this study, neuron specific enolase and S100B, demonstrated inverse relationships with neurodevelopmental assessments at 2 years. Four studies did not meet all the inclusion criteria yet identified promising findings for metabolites and cytokines which are discussed here. These findings support the need for further research and highlight the potential for blood biomarkers to predict adverse outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369242, Identifier CRD42022369242.

Sensitivity and specificity of the Neonatal Visual Assessment to predict motor and cognitive outcomes in infants born very preterm.

BACKGROUND: Very preterm infants are at increased risk of neurodevelopmental impairments. The Neonatal Visual Assessment (NVA) assesses visual function and outcomes and has been used to assess early neurodevelopmental outcomes. This study aimed to compare NVA results of very preterm and term-born infants and to calculate the sensitivity and specificity of the NVA at term equivalent age (TEA) and three months corrected age (CA) to predict motor and cognitive outcomes at 12 months CA in very preterm infants. METHODS: This prospective observational cohort study recruited infants born before 31 weeks gestation and a healthy term-born control group. The NVA was assessed at TEA and three months CA, and neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development, Third Edition; Neurosensory Motor Developmental Assessment; Alberta Infant Motor Scale) were performed at 12 months CA. The sensitivity and specificity of the NVA to predict outcomes were calculated based on a previously published optimality score. RESULTS: 248 preterm (54 % male) and 46 term-born infants (48 % male) were analysed. The mean NVA scores of preterm and term-born infants were significantly different at TEA (preterm 3.1±2.1; term-born 1.2±1.7, p < 0.001). The NVA had moderate sensitivity (59-78 %) and low specificity (25-27 %) at TEA, and low sensitivity (21-28 %) and high specificity (86-87 %) at three months CA for the prediction of preterm infants' outcomes at 12 months CA. CONCLUSION: The NVA at TEA and three months CA was not a strong predictor of motor and cognitive impairments in this contemporary cohort of very preterm infants.

Health care resource use in preschool children with cerebral palsy.

AIM: To estimate the burden of disease and evaluate which factors affect health care resource use (HCRU) in young children with cerebral palsy (CP). METHOD: Data were collected as part of a prospective, longitudinal cohort study of children with CP born in Queensland, Australia between 2006 and 2009. HCRU questionnaires were administered at six time points. Data on resource use, socio-demographics, and disease severity were collected. Costs were sourced from Medicare, the Australian National Hospital Cost Data Collection, and market prices. A generalized linear model was used to identify factors influencing CP-related costs. RESULTS: A total of 794 questionnaires were completed by 222 participants (mean = 3.6 per participant). Physiotherapy (94%, n = 208) was the most widely accessed allied health care therapy; almost half of the participants (45%; 354 of 794) reported one or more hospital admissions. From the health care funder perspective, a child with CP costs on average A$24 950 per annum (A$12 475 per 6 months). Higher costs were associated with increased motor impairment (Gross Motor Function Classification System, p < 0.001) and increased comorbidities (p = 0.012). INTERPRETATION: HCRU in preschool children with CP can be analysed according to disease severity. Both increased motor impairments and increased comorbidities were associated with higher health care costs.

Hip displacement in children with post-neonatal cerebral palsy and acquired brain injury: a systematic review.

AIM: To systematically review the prevalence, risk factors and timing of onset of hip displacement in children with a post-neonatal (PNN) brain injury with regards to hip surveillance recommendations. METHOD: A search of PubMed, MEDLINE, Embase, CINAHL and Web of Science was conducted on 22nd February 2022. Studies were included if they reported presence of, and risk factors for, hip displacement in children with PNN brain injury. Data was extracted on patient characteristics, and analyzed in terms of risk factors of interest and timing of development of hip displacement. RESULTS: Six studies met the inclusion criteria (n = 408 participants). All were cohort studies: five retrospective and one prospective. Rates of hip displacement ranged from 1% to 100%, and were higher in children with diffuse brain injury at an early age, who were non-ambulant and had spastic quadriplegia. Hip displacement and hip dislocation were first identified at one and three months respectively following PNN brain injury. INTERPRETATION: Evidence on hip displacement in children with PNN brain injury is sparse and low quality. Children who remain non-ambulant after diffuse PNN brain injury before five years of age appear most at risk of developing progressive hip displacement and earlier hip surveillance is recommended.

As for children with cerebral palsy (CP), children with a post-neonatal (PNN) brain injury who are non-ambulant are most at risk of progressive hip displacement.Children with a diffuse brain injury before five years of age appear to be at greater risk.Hip displacement can occur very early and progress rapidly following PNN brain injury.

Relationship between early infant motor repertoire and neurodevelopment on the hammersmith infant neurological examination in a developmentally vulnerable First Nations cohort.

AIM: To implement a culturally-adapted screening program aimed to determine the ability of infant motor repertoire to predict early neurodevelopment on the Hammersmith Infant Neurological Examination (HINE) and improve Australian First Nations families' engagement with neonatal screening. METHODS: A prospective cohort of 156 infants (55 % male, mean (standard deviation [SD]) gestational age 33.8 (4.6) weeks) with early life risk factors for adverse neurodevelopmental outcomes (ad-NDO) participated in a culturally-adapted screening program. Infant motor repertoire was assessed using Motor Optimality Score-revised (MOS-R), captured over two videos, 11-13+6 weeks (V1; <14 weeks) and 14-18 weeks (V2; ≥14 weeks) corrected age (CA). At 4-9 months CA neurodevelopment was assessed on the HINE and classified according to age-specific cut-off and optimality scores as; developmentally 'on track' or high chance of either adverse neurodevelopmental outcome (ad-NDO) or cerebral palsy (CP). RESULTS: Families were highly engaged, 139/148 (94 %) eligible infants completing MOS-R, 136/150 (91 %), HINE and 123 (83 %) both. Lower MOS-R at V2 was associated with reduced HINE scores (ß = 1.73, 95 % confidence interval [CI] = 1.03-2.42) and high chance of CP (OR = 2.63, 95%CI = 1.21-5.69) or ad-NDO (OR = 1.38, 95%CI = 1.10-1.74). The MOS-R sub-category 'observed movement patterns' best predicted HINE, infants who score '4' had mean HINE 19.4 points higher than score '1' (95%CI = 12.0-26.9). Receiver-operator curve analyses determined a MOS-R cut-off of <23 was best for identifying mild to severely reduced HINE scores, with diagnostic accuracy 0.69 (sensitivity 0.86, 95%CI 0.76-0.94 and specificity 0.40, 95 % CI 0.25-0.57). A trajectory of improvement on MOS-R (≥2 point increase in MOS-R from 1st to 2nd video) significantly increased odds of scoring optimally on HINE (OR = 5.91, 95%CI 1.16-29.89) and may be a key biomarker of 'on track' development. INTERPRETATION: Implementation of a culturally-adapted program using evidence-based assessments demonstrates high retention. Infant motor repertoire is associated with HINE scores and the early neurodevelopmental status of developmentally vulnerable First Nations infants.

Efficacy of Early Intervention for Infants With Cerebral Palsy in an LMIC: An RCT.

OBJECTIVE: To test efficacy of a parent-delivered multidomain early intervention (Learning through Everyday Activities with Parents [LEAP-CP]) for infants with cerebral palsy (CP) compared with equal-dose of health advice (HA), on (1) infant development; and (2) caregiver mental health. It was hypothesized that infants receiving LEAP-CP would have better motor function, and caregivers better mental health. METHODS: This was a multisite single-blind randomized control trial of infants aged 12 to 40 weeks corrected age (CA) at risk for CP (General Movements or Hammersmith Infant Neurologic Examination). Both LEAP-CP and HA groups received 15 fortnightly home-visits by a peer trainer. LEAP-CP is a multidomain active goal-directed intervention. HA is based on Key Family Practices, World Health Organization. Primary outcomes: (1) infants at 18 months CA: Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT mobility); and (2) caregiver: Depression Anxiety and Stress Scale. RESULTS: Of eligible infants, 153 of 165 (92.7%) were recruited (86 males, mean age 7.1±2.7 months CA, Gross Motor Function Classification System at 18 m CA: I = 12, II = 25, III = 9, IV = 18, V = 32). Final data were available for 118 (77.1%). Primary (PEDI-CAT mobility mean difference = 0.8 (95% CI -1.9 to 3.6) P = .54) and secondary outcomes were similar between-groups. Modified-Intention-To-Treat analysis on n = 96 infants with confirmed CP showed Gross Motor Function Classification System I and IIs allocated to LEAP-CP had significantly better scores on PEDI-CAT mobility domain (mean difference 4.0 (95% CI = 1.4 to 6.5), P = .003) compared with HA. CONCLUSIONS: Although there was no overall effect of LEAP-CP compared with dose-matched HA, LEAP-CP lead to superior improvements in motor skills in ambulant children with CP, consistent with what is known about targeted goal-directed training.

Sleep problems in a population-based cohort of primary school age children with Cerebral Palsy.

AIMS: To examine sleep problems in a population-based sample of school-aged children (8-12yo) with Cerebral Palsy (CP) METHOD: Eighty-six children (mean 9 years, 5 months, SD = 1 year, 6 months; male = 60) with CP (Gross Motor Function Classification System; GMFCS I=46; II=21; III=9; IV=6; V=6) participated. Classifications/assessments included: Sleep Disturbance Scale for Children (SDSC), Gross Motor Function Measure (GMFM-66), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), Strengths and Difficulties Questionnaire (SDQ) and the Cerebral Palsy- Quality of Life (CP-QOL) Pain Impact subscale. Analysis included linear and logistic regression. RESULTS: 38 (44 %) children were within the clinical range for sleep problems. Sleep problems were significantly associated with epilepsy, (95 % CI) = 14.48 (7.95 to 21.01), gross motor function, -0.13 (-0.26 to -0.01), manual ability, 7.26 (0.82 to 13.69), communication, 10.01 (2.21 to 17.80), child behaviour, 1.134 (0.74 to 1.53), and pain related QOL, 0.33 (0.12 to 0.53). For the multivariable model, sleep problems remained significantly associated with epilepsy, b (95 % CI) = 11.72 (4.88 to 18.57), child behaviour, 1.03 (0.65 to 1.41) and pain-related QOL, 0.21 (0.29 to 0.38). CONCLUSIONS: Sleep problems are common and associated with epilepsy, child behaviour and pain related QOL.

The Knowledge Translation of Early Cerebral Palsy (KiTE CP) Study: Implementing Screening Among a High-Risk Prospective Cohort of Australian Infants.

OBJECTIVE: To describe the implementation of the international guidelines for the early diagnosis of cerebral palsy (CP) and engagement in the screening process in an Australian cohort of infants with neonatal risk factors for CP. STUDY DESIGN: Prospective cohort study of infants with neonatal risk factors recruited at <6 months corrected age from 11 sites in the states of Victoria, New South Wales, and Queensland, Australia. First, we implemented a multimodal knowledge translation strategy including barrier identification, technology integration, and special interest groups. Screening was implemented as follows: infants with clinical indications for neuroimaging underwent magnetic resonance imaging and/or cranial ultrasound. The Prechtl General Movements Assessment (GMA) was recorded clinically or using an app (Baby Moves). Infants with absent or abnormal fidgety movements on GMA videos were offered further assessment using the Hammersmith Infant Neurological Examination (HINE). Infants with atypical findings on 2/3 assessments met criteria for high risk of CP. RESULTS: Of the 597 infants (56% male) recruited, 95% (n = 565) received neuroimaging, 90% (n = 537) had scorable GMA videos (2% unscorable/8% no video), and 25% (n = 149) HINE. Overall, 19% of the cohort (n = 114/597) met criteria for high risk of CP, 57% (340/597) had at least 2 normal assessments (of neuroimaging, GMA or HINE), and 24% (n = 143/597) had insufficient assessments. CONCLUSIONS: Early CP screening was implemented across participating sites using a multimodal knowledge translation strategy. Although the COVID-19 pandemic affected recruitment rates, there was high engagement in the screening process. Reasons for engagement in early screening from parents and clinicians warrant further contextualization and investigation.

Longitudinal assessment of brain lesions in children with cerebral palsy and association with motor functioning.

BACKGROUND: The semi-quantitative scale of structural brain Magnetic Resonance Imaging (sqMRI) is a valid and reliable measure of brain lesion extent in children with cerebral palsy (CP) >3-years. This system scores lesion burden for each major brain region. The sum of the scores gives a global score ranging from 0 to 48. PURPOSE: To investigate how sqMRI scores changed from infancy to school-age, and whether these were associated with lesion load, age at first assessment, and gross motor function and its changes. MATERIALS AND METHODS: Twenty-eight children with CP underwent MRI and motor (Gross Motor Function Measure-66; GMFM-66) assessments when <40-months and again when 8-12-years. We investigated whether (i) toddler/preschool-age sqMRI scores (Time 1) reflected school-age sqMRI scores (Time 2); (ii) temporal changes in sqMRI scores (Time 1-Time 2 difference) were related to the child's age at Time 1 and lesion extent; (iii) early or later sqMRI scores were associated with motor functioning; (iv) sqMRI scores' longitudinal changes were associated with motor changes. RESULTS: Except for the corticosubcortical (grey-matter only) layers, sqMRI scores were significantly higher ('higher lesion load') at Time 1 than at Time 2. Age at Time 1 was not associated with temporal changes in global sqMRI scores. Higher lesion load at Time 2, but not at Time 1, was associated with smaller temporal changes in the global sqMRI score. The sqMRI scores were associated with concurrent, but not future or past motor GMFM-66 scores. Longitudinal changes in sqMRI scores were not associated with longitudinal changes in motor GMFM-66 scores. CONCLUSION: sqMRI scores of brain lesion extent at school-age are lower and a better indication of later-life motor functioning than very early life sqMRI scores. It may be best to interpret MRI white matter lesions with caution in very early life due to possible changes in lesion appearance and the unpredictable role of functional plasticity.

The evolution of nutrition management in children with severe neurological impairment with a focus on cerebral palsy.

Nutritional management of children with severe neurological impairment (SNI) is highly complex, and the profile of this population is changing. The aim of this narrative review was to give the reader a broad description of evolution of the nutritional management of children with SNI in a high resource setting. In the last decade, there has been an emphasis on using multiple anthropometric measures to monitor nutritional status in children with SNI, and several attempts at standardising the approach have been made. Tools such as the Feeding and Nutrition Screening Tool, the Subjective Global Nutrition Assessment, the Eating and Drinking Ability Classification System and the Focus on Early Eating and Drinking Swallowing (FEEDS) toolkit have become available. There has been an increased understanding of how the gut microbiome influences gastrointestinal symptoms common in children with SNI, and the use of fibre in the management of these has received attention. A new diagnosis, 'gastrointestinal dystonia', has been defined. The increased use and acceptance of blended food tube feeds has been a major development in the nutritional management of children with SNI, with reported benefits in managing gastrointestinal symptoms. New interventions to support eating and drinking skill development in children with SNI show promise. In conclusion, as the life expectancy of people with SNI increases due to advances in medical and nutrition care, our approach necessitates a view to long-term health and quality of life. This involves balancing adequate nutrition to support growth, development and well-being while avoiding overnutrition and its associated detrimental long-term effects.

Construct Validity of the Both Hands Assessment Using Wrist-Worn Accelerometers.

AIM: The aim of this study was to evaluate the construct validity of the Both Hands Assessment (BoHA) using activity of the upper limbs as detected by accelerometry in children with bilateral cerebral palsy (CP). METHODS: Observational study of children with CP (n = 44, n = 27 boys, aged 9.1 ± 1.6 years; Manual Ability Classification Scale I: n = 15, II: n = 22, III: n = 7) completing a BoHA assessment while wearing a triaxial accelerometer on each wrist. BoHA Each-Hand sub-scores, BoHA percentage difference between hands, BoHA Units, mean activity for each hand, mean activity asymmetry index and total mean activity were calculated. Linear regressions were used to analyze associations between measures. RESULTS: There were significant, positive associations between BoHA Units and total mean activity (B = 0.86, 95%CI: 0.32, 1.40), BoHA Percentage difference between hands and mean activity asymmetry index (B = 0.95, 95%CI: 0.75,1.15), and BoHA Each-Hand sub-score and mean activity for the non-dominant hand (B = 1.71, 95%CI: 1.16, 2.28), but not the dominant hand (B = 0.50, 95%CI: -0.45, 1.45). CONCLUSIONS: This study provides further evidence for the construct validity of the BoHA as a measure of upper limb performance. Wearable wrist sensors such as accelerometers capture and quantify gross upper limb movement in children with CP but cannot measure fine finger movements captured by the BoHA. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616001488493 and ACTRN12618000164291).

Participate CP 2: optimising participation in physically active leisure for children with cerebral palsy - protocol for a phase III randomised controlled trial.

INTRODUCTION: Children with cerebral palsy (CP) participate less in physical activities and have increased sedentary behaviour compared with typically developing peers. Participate CP is a participation-focused therapy intervention for children with CP with demonstrated efficacy in a phase II randomised controlled trial (RCT) to increase perceived performance of physical activity participation goals. This study will test the effectiveness of Participate CP in a multisite phase III RCT. METHODS AND ANALYSIS: One hundred children with CP, aged 8-14 years, classified Gross Motor Function Classification System levels I-IV will be randomised to either (1) receive Participate CP once/week for 1 hour for 12 weeks, or (2) waitlist control, usual care group. The waitlist group will then receive Participate CP following the 26-week retention time point. Outcomes will be assessed at baseline, 12 weeks and then 26 weeks post baseline. The primary outcomes are (1) self-reported participation goal performance on the Canadian Occupational Performance Measure at 12 weeks and (2) daily time in moderate-to-vigorous physical activity. Secondary outcomes include home and community participation frequency, involvement and environmental supportiveness, contextual barriers to participation, quality of life, intrinsic motivation for physical activities, child perception of an autonomy-supportive climate for physical activities and physical literacy at 12 and 26 weeks post study entry. ETHICS AND DISSEMINATION: The Children's Health Queensland Hospital and Health Service, The University of Queensland and the New Zealand Health and Disability Ethics Committees have approved this study. Findings will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12618000206224.

Effect of Adaptive Seating Systems on Postural Control and Activity Performance: A Systematic Review.

PURPOSE: To systematically review the effectiveness of adaptive seating systems on sitting posture, postural control, and seated activity performance in children with cerebral palsy (CP). SUMMARY OF KEY POINTS: From 5 databases, 3 of 21 (14%) articles were of good quality based on the Downs and Black checklist. Commercial modular contoured seating and paper-based low-cost, and contoured foam seating were effective at improving sitting posture, postural control, and seated activity performance. Parents and service providers reported that seating systems reduced stress, burden and psychosocial well-being, and quality of life in children with CP. CONCLUSION: Limited evidence demonstrated that adaptive seating systems were effective at improving sitting ability and postural control. Randomized controlled trials with objective outcome measures of seating performance in children with CP are needed to evaluate effectiveness. RECOMMENDATIONS FOR CLINICAL PRACTICE: Adaptive seating devices are preferred by parents and therapists for children with CP; however, objective measures of seating outcomes are needed.

Fidelity of Delivery in a Multisite Randomized Clinical Trial of Intervention Efficacy for Infants With Unilateral Cerebral Palsy.

PURPOSE: To investigate the reliability of a measure of fidelity of therapist delivery, quantify fidelity of delivery, and determine factors impacting fidelity in the Rehabilitation EArly for Congenital Hemiplegia (REACH) clinical trial. METHODS: Ninety-five infants (aged 3-9 months) with unilateral cerebral palsy participated in the REACH clinical trial. The Therapist Fidelity Checklist (TFC) evaluated key intervention components. Video-recorded intervention sessions were scored using the TFC. RESULTS: Inter- and intrarater reliability was percentage agreement 77% to 100%. Fidelity of delivery was high for 88.9% of sessions and moderate for 11.1% of sessions. Sessions with moderate scores included infants receiving infant-friendly bimanual therapy and occurred at the intervention midpoint or later. No significant relationships were found for TFC scores and infant age, manual ability, or parent engagement. CONCLUSIONS: Fidelity of delivery was high for the REACH trial in most intervention sessions. Standardized therapist training with intervention manuals and monthly peer-to-peer support likely contributed to these results.

A randomized controlled trial of a home-based computerized executive function intervention for children with cerebral palsy.

Children with cerebral palsy (CP) often show executive function (EF) impairments that are key to quality of life. The aim of this study was to assess whether a home-based computerized intervention program improves executive functions (EFs) compared to usual care. Sixty participants (30 females) with CP (8-12 years old) were paired by age, sex, motor ability, and intelligence quotient score and then randomized to intervention and waitlist control groups. The intervention group received a 12-week home-based computerized EF intervention (5 days/week, 30 min/day, total dose 30 h). Core and higher-order EFs were assessed before, immediately after, and 9 months after completing the intervention. The intervention group performed better than the waitlist control group in the three core EFs (immediately and 9 months after the intervention): inhibitory control (F = 7.58, p = 0.13 and F = 7.85, p = 0.12), working memory (F = 8.34, p = 0.14 and F = 7.55, p = 0.13), and cognitive flexibility (F = 4.87, p = 0.09 and F = 4.19, p = 0.08). No differences were found between the groups in higher-order EFs or EF manifestations in daily life. CONCLUSIONS: A home-based computerized EF intervention improved core EFs in children with CP, but further research is needed to identify strategies that allow the transfer of these improvements to everyday life. TRIAL REGISTRATION: NCT04025749 retrospectively registered on 19 July 2019. WHAT IS KNOWN: • One in two children with cerebral palsy has an intellectual impairment. Visual perception and executive functions are the most reported specific cognitive deficits. • The majority of interventions for cerebral palsy focus on motor impairments, but only a few randomized controlled trials have explored the effect of interventions on executive functions. WHAT IS NEW: • A home-based computerized cognitive intervention can improve the core executive functions of children with cerebral palsy. • Short- and long-term effects on core executive functions have been found.

SuPreme Study: a protocol to study the neuroprotective potential of sulfate among very/extremely preterm infants.

INTRODUCTION: Antenatal maternal magnesium sulfate (MgSO4) administration is a proven efficacious neuroprotective treatment reducing the risk of cerebral palsy (CP) among infants born preterm. Identification of the neuroprotective component with target plasma concentrations could lead to neonatal treatment with greater efficacy and accessibility. METHODS AND ANALYSIS: This is a prospective observational cohort study, in three tertiary Australian centres. Participants are preterm infants, irrespective of antenatal MgSO4 exposure, born in 2013-2020 at 24+0 to 31+6 weeks gestation, and followed up to 2 years corrected age (CA) (to September 2023). 1595 participants are required (allowing for 17% deaths/loss to follow-up) to detect a clinically significant reduction (30% relative risk reduction) in CP when sulfate concentration at 7 days of age is 1 SD above the mean.A blood sample is collected on day 7 of age for plasma sulfate and magnesium measurement. In a subset of participants multiple blood and urine samples are collected for pharmacokinetic studies, between days 1-28, and in a further subset mother/infant blood is screened for genetic variants of sulfate transporter genes.The primary outcome is CP. Surviving infants are assessed for high risk of CP at 12-14 weeks CA according to Prechtl's Method to assess General Movements. Follow-up at 2 years CA includes assessments for CP, cognitive, language and motor development, and social/behavioural difficulties.Multivariate analyses will examine the association between day 7 plasma sulfate/magnesium concentrations with adverse neurodevelopmental outcomes. A population pharmacokinetic model for sulfate in the preterm infant will be created using non-linear mixed-effects modelling. ETHICS AND DISSEMINATION: The study has been approved by Mater Misericordiae Ltd Human Research Ethics Committee (HREC/14/MHS/188). Results will be disseminated in peer-reviewed journal publications, and provided to the funding bodies. Using consumer input, a summary will be prepared for participants and consumer groups.

Early detection of developmental delay in infants born very preterm or with very low birthweight.

AIM: This study aimed to identify early clinical biomarkers from birth to 16 weeks corrected age to predict typical outcome and developmental delay in infants born very preterm or with very low birthweight. METHOD: A prospective cohort of infants on the Sunshine Coast, Australia, was assessed using the Premie-Neuro Examination, the General Movement Assessment (GMA), the Alberta Infant Motor Scale, and the Infant Sensory Profile 2. At 24 months corrected age, delay was identified using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and Neurosensory Motor Developmental Assessment (NSMDA). RESULTS: One hundred and four infants were recruited; 79 completed outcome assessments (43 females, 36 males; mean gestational age 30 weeks [SD 1 week 6 days], mean birthweight 1346 g [SD 323]). The incidence of developmental delay (motor or cognitive) was 6.3%. Suboptimal quality of fidgety general movements (temporal organization) at 16 weeks corrected age demonstrated the best predictive accuracy (Bayley-III motor: sensitivity 100% [95% confidence interval {CI} 3-100], specificity 75% [95% CI 63-84], area under the curve [AUC] 0.87); Bayley-III cognitive: sensitivity 100% [95% CI 3-100], specificity 75% [95% CI 64-84], AUC 0.88); NSMDA motor: sensitivity 100% [95% CI 40-100], specificity 81% [95% CI 70-90], AUC 0.91 [95% CI 0.86-0.95]). GMA trajectories that combined abnormal writhing general movements at 4 to 5 weeks corrected age with suboptimal quality of fidgety movement at 16 weeks corrected age were strongly predictive of developmental delay, superior to all other clinical tools, and perinatal and demographic variables investigated (p = 0.01, Akaike information criterion method 18.79 [score corrected for small sample size], accounting for 93% of the cumulative weight). INTERPRETATION: Only the GMA had sufficient predictive validity to act as a biomarker for both conditions: typical outcome and developmental delay (motor or cognitive). GMA trajectories that assessed both writhing general movements at 4 to 5 weeks corrected age and quality of fidgety movement at 16 weeks corrected age predicted adverse neurodevelopmental outcome, accurately differentiating between infants with typical outcomes and those at increased risk for motor or cognitive delay.

Effectiveness of early diagnosis of cerebral palsy guideline implementation: a systematic review.

INTRODUCTION: Tailored implementation interventions are required to overcome the diagnostic research-practice gap for cerebral palsy (CP). Evaluating the impact of interventions on patient outcomes is a priority. This review aimed to summarize the established evidence for the effectiveness of guideline implementations in lowering the age of CP diagnosis. EVIDENCE ACQUISITION: A systematic review was conducted according to PRISMA. CINAHL, Embase, PubMed and MEDLINE were searched (2017-October 2022). Inclusion criteria were studies that evaluated effect of CP guideline interventions on health professional behaviour or patient outcomes. GRADE was used to determine quality. Studies were coded for use of theory (Theory Coding Scheme). Meta-analysis was performed and a standardized metric used to summarize statistics of intervention effect estimates. EVIDENCE SYNTHESIS: Of (N.=249) records screened, (N.=7) studies met inclusion, comprising interventions following infants less than 2 years of age with CP risk factors (N.=6280). Guideline feasibility in clinical practice was established through health professional adherence and patient satisfaction. Efficacy of patient outcome of CP diagnosis by 12 months of age was established in all studies. Weighted averages were: (1) high-risk of CP (N.=2) 4.2 months and (2) CP diagnosis (N.=5) at 11.6 months. Meta-analysis of (N.=2) studies found a large, pooled effect size Z = 3.00 (P=0.003) favoring implementation interventions lowering age of diagnosis by 7.50 months, however study heterogeneity was high. A paucity of theoretical frameworks were identified in this review. CONCLUSIONS: Multifaceted interventions to implement the early diagnosis of CP guideline are effective in improving patient outcomes by lowering the age of CP diagnosis in high-risk infant follow-up clinics. Further targeted health professional interventions including low-risk infant populations are warranted.

Efficacy of very early interventions on neurodevelopmental outcomes for infants and toddlers at increased likelihood of or diagnosed with autism: A systematic review and meta-analysis.

The aim of this systematic review was to determine the efficacy of very early interventions for infants and toddlers at increased likelihood of or diagnosed with autism for autism symptomatology, developmental outcomes and/or neurocognitive markers. Eight databases were searched (14 April 2022) with inclusion criteria: (i) RCTs with care as usual (CAU) comparison group, (ii) participants at increased likelihood of or diagnosed with autism and aged <24 months corrected age (CA), (iii) parent-mediated and/or clinician directed interventions, and (iv) outcome measures were autism symptomatology, cognition, language, adaptive skills, or neurocognitive assessments (EEG and eye tracking). Quality was assessed using Risk of Bias 2 and GRADE. Nineteen publications from 12 studies reported on 715 infants and toddlers. There was low to moderate certainty evidence that clinician-assessed outcomes did not show significant treatment effects for: autism symptomatology (ADOS CSS: MD -0.08, 95% CI -0.61, 0.44, p = 0.75), cognitive outcome (Mullen Scales of Early Learning-Early Learning Composite (MSEL-ELC): SMD 0.05, 95% CI -0.19, 0.29, p = 0.67), receptive language (MSEL-Receptive Language: SMD 0.04, 95% CI -0.21, 0.3, p = 0.74) or expressive language (MSEL-Expressive Language: SMD 0.06, 95% CI -0.1, 0.23, p = 0.45). Neurocognitive outcomes (EEG and eye tracking) were heterogeneous, with inconsistent findings. There is low to moderate certainty evidence that very early interventions have limited impact on neurodevelopmental outcomes by age 3 years.