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.

Consensus definition and diagnostic criteria for neonatal encephalopathy-study protocol for a real-time modified delphi study.

BACKGROUND: 'Neonatal encephalopathy' (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families. The DEFINE study aims to use a modified Delphi approach to form a consensus definition for NE, and diagnostic criteria. METHODS: Directed by an international steering group, we will conduct a systematic review of the literature to assess the terminology used in trials of NE, and with their guidance perform an online Real-time Delphi survey to develop a consensus diagnosis and criteria for NE. A consensus meeting will be held to agree on the final terminology and criteria, and the outcome disseminated widely. DISCUSSION: A clear and consistent consensus-based definition of NE and criteria for its diagnosis, achieved by use of a modified Delphi technique, will enable more comparability of research results and improved communication among professionals and with families. IMPACT: The terms Neonatal Encephalopathy and Hypoxic Ischaemic Encephalopathy tend to be used interchangeably in the literature to describe a term newborn with signs of encephalopathy at birth. This creates difficulty in communication with families and carers, and between medical professionals and researchers, as well as creating difficulty with performance of research. The DEFINE project will use a Real-time Delphi approach to create a consensus definition for the term 'Neonatal Encephalopathy'. A definition formed by this consensus approach will be accepted and utilised by the neonatal community to improve research, outcomes, and parental experience.

Neonatal magnesium sulphate for neuroprotection: A systematic review and meta-analysis.

AIM: To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE). METHOD: This was a systematic review of randomized controlled trials (RCTs) (with meta-analysis) and non-RCTs assessing magnesium sulphate for treating perinatal asphyxia and HIE at 35 weeks or more gestation (primary outcomes: neonatal death and death or long-term major neurodevelopmental disability). RESULTS: Twenty-five RCTs (2099 infants) and four non-RCTs (871 infants) were included, 23 in low- and middle-income countries (LMICs). In RCTs, reductions in neonatal death with magnesium sulphate versus placebo or no treatment (risk ratio [RR] = 0.68; 95% confidence interval [CI] = 0.53-0.86; 13 RCTs), and magnesium sulphate with melatonin versus melatonin alone (RR = 0.74; 95% CI = 0.58-0.95; one RCT) were observed. No difference in neonatal death was seen for magnesium sulphate with therapeutic hypothermia versus therapeutic hypothermia alone (RR = 0.66, 95% CI = 0.34-1.26; three RCTs), or magnesium sulphate versus phenobarbital (RR = 3.00; 95% CI = 0.86-10.46; one RCT). No reduction in death or long-term neurodevelopmental disability (RR = 0.52; 95% CI = 0.14-1.89; one RCT) but reductions in several short-term adverse outcomes were observed with magnesium sulphate. Evidence was low- to very-low certainty because of risk of bias and imprecision. INTERPRETATION: Given the uncertainty of the current evidence, further robust neonatal magnesium sulphate research is justified. This may include high-quality studies to determine stand-alone effects in LMICs and effects with and after therapeutic hypothermia in high-income countries.

Hospital-based surveillance of children with cerebral palsy in Suriname: The Suriname cerebral palsy register.

AIM: To describe the aetiological risk factors, clinical characteristics, access to rehabilitation, and educational status of children with cerebral palsy (CP) in Suriname. METHOD: Hospital-based surveillance of children with CP aged younger than 18 years was conducted at the Academic Hospital Paramaribo, Suriname (known as the Suriname CP Register [SUR-CPR]). Data were collected on sociodemographic characteristics, aetiological risk factors, clinical characteristics, rehabilitation, and educational status. Registry data on aetiological risk factors were compared with available national prevalence rates in Suriname. Descriptive statistics were reported. RESULTS: Between August 2018 and March 2020, 82 children with CP (mean [SD] age 5 years 10 months [3 years 10 months]) attending the Academic Hospital Paramaribo were registered in the SUR-CPR. The mean (SD) age at diagnosis was 5 years 5 months (4 years 1 month). Spastic CP was predominant in 90.8% of children and 58.8% were classified in Gross Motor Function Classification System levels III to V. Overall, 43.9% had preterm birth compared with 13.9% reported nationally (p < 0.001) and 61.6% had birth-related complications compared with 15% reported nationally (p < 0.001). Additionally, 39.1% had birth asphyxia and 23.2% had early feeding difficulties. Sixty-two percent were admitted to the neonatal intensive care unit, 54.0% of whom required ventilation. Most children (82.5%) had CP acquired pre- or perinatally and 17.5% had CP acquired postneonatally. Seventeen percent had never received any rehabilitation services, and 31.9% of the school-aged children were not enrolled in any education system. INTERPRETATION: The high burden of known aetiological risk factors, delayed diagnosis, and severe functional impairment among children with CP registered at the Academic Hospital Paramaribo is concerning. Public health interventions targeting early diagnosis and early intervention could improve the functional outcome of children with CP in Suriname.

Exploring early life social and executive function development in infants and risk for autism: a prospective cohort study protocol of NICU graduates and infants at risk for cerebral palsy.

BACKGROUND: Delays in early social and executive function are predictive of later developmental delays and eventual neurodevelopmental diagnoses. There is limited research examining such markers in the first year of life. High-risk infant groups commonly present with a range of neurodevelopmental challenges, including social and executive function delays, and show higher rates of autism diagnoses later in life. For example, it has been estimated that up to 30% of infants diagnosed with cerebral palsy (CP) will go on to be diagnosed with autism later in life. METHODS: This article presents a protocol of a prospective longitudinal study. The primary aim of this study is to identify early life markers of delay in social and executive function in high-risk infants at the earliest point in time, and to explore how these markers may relate to the increased risk for social and executive delay, and risk of autism, later in life. High-risk infants will include Neonatal Intensive Care Unit (NICU) graduates, who are most commonly admitted for premature birth and/or cardiovascular problems. In addition, we will include infants with, or at risk for, CP. This prospective study will recruit 100 high-risk infants at the age of 3-12 months old and will track social and executive function across the first 2 years of their life, when infants are 3-7, 8-12, 18 and 24 months old. A multi-modal approach will be adopted by tracking the early development of social and executive function using behavioural, neurobiological, and caregiver-reported everyday functioning markers. Data will be analysed to assess the relationship between the early markers, measured from as early as 3-7 months of age, and the social and executive function as well as the autism outcomes measured at 24 months. DISCUSSION: This study has the potential to promote the earliest detection and intervention opportunities for social and executive function difficulties as well as risk for autism in NICU graduates and/or infants with, or at risk for, CP. The findings of this study will also expand our understanding of the early emergence of autism across a wider range of at-risk groups.

Clinical characteristics and outcomes of perinatal stroke in Australia: Population-based longitudinal study.

AIM: Perinatal stroke is one of the main causes of hemiplegia and seizure disorder. This study aimed to analyse the clinical characteristics and outcomes of perinatal stroke in a cohort of Australian children for its early detection. METHODS: A population-based prospective longitudinal study on perinatal stroke up to 2 years of age, was conducted from 2017 to 2019. RESULTS: Eighty-seven children with perinatal stroke included 79% (69/87) acute and 21% (18/87) presumed perinatal stroke. Seventy-four per cent (51/69) acute symptomatic perinatal strokes presented in the first 3 days of life and 78% (14/18) presumed perinatal strokes presented by 6 months of age. 62% had an arterial stroke, 29% had a venous stroke and 5% had a combined arterial and venous stroke. Unexpectedly, 35% (24/69) acute symptomatic perinatal stroke had only respiratory symptoms and 50% (9/18) presumed perinatal stroke were asymptomatic. The incidence of cerebral palsy was 29% (20/69) with acute symptomatic perinatal stroke and 72% (13/18) with presumed perinatal stroke. CONCLUSIONS: The first week of a child's life is the most critical period in terms of lifelong disability from perinatal stroke. Recognising diverse clinical presentations will ensure early diagnosis and timely intervention treatments.

Clinical characteristics, associated comorbidities and hospital outcomes of neonates with sleep disordered breathing: a retrospective cohort study.

OBJECTIVE: Awareness of the need for early identification and treatment of sleep disordered breathing (SDB) in neonates is increasing but is challenging. Unrecognised SDB can have negative neurodevelopmental consequences. Our study aims to describe the clinical profile, risk factors, diagnostic modalities and interventions that can be used to manage neonates with SDB to facilitate early recognition and improved management. METHODS: A single-centre retrospective study of neonates referred for assessment of suspected SDB to a tertiary newborn intensive care unit in New South Wales Australia over a 2-year period. Electronic records were reviewed. Outcome measures included demographic data, clinical characteristics, comorbidities, reason for referral, polysomnography (PSG) data, interventions targeted to treat SDB and hospital outcome. Descriptive analysis was performed and reported. RESULTS: Eighty neonates were included. Increased work of breathing, or apnoea with oxygen desaturation being the most common reasons (46% and 31%, respectively) for referral. Most neonates had significant comorbidities requiring involvement of multiple specialists (mean 3.3) in management. The majority had moderate to severe SDB based on PSG parameters of very high mean apnoea-hypopnoea index (62.5/hour) with a mean obstructive apnoea index (38.7/hour). Ten per cent of patients required airway surgery. The majority of neonates (70%) were discharged home on non-invasive ventilation. CONCLUSION: SDB is a serious problem in high-risk neonates and it is associated with significant multisystem comorbidities necessitating a multidisciplinary team approach to optimise management. This study shows that PSG is useful in neonates to diagnose and guide management of SDB.

Causes and Terminology in Neonatal Encephalopathy: What is in a Name? Neonatal Encephalopathy, Hypoxic-ischemic Encephalopathy or Perinatal Asphyxia.

Neurologic depression in term/near-term neonates (neonatal encephalopathy, NE) is uncommon with modern obstetric care. Asphyxial birth, with or without co-factors, accounts for a minority of NE, while maldevelopment (congenital malformations, growth aberrations, genetic, metabolic and placental abnormalities) plays an enlarging role in identifying etiologic subgroups of NE. The terms NE and hypoxic-ischemic encephalopathy (HIE) have not been employed uniformly, hampering research and clinical care. The authors propose the term NE as an early working-diagnosis, to be supplemented by a diagnosis of NE due to HIE or to other factors, as a final diagnosis once workup is complete.

Postoperative pain and pain management following selective dorsal rhizotomy.

BACKGROUND: Selective dorsal rhizotomy (SDR) is a neurosurgical procedure that reduces lower limb spasticity, performed in some children with spastic diplegic cerebral palsy. Effective pain management after SDR is essential for early rehabilitation. This study aimed to describe the anaesthetic and early pain management, pain and adverse events in children following SDR. METHODS: This was a retrospective cohort study. Participants were all children who underwent SDR at a single Australian tertiary hospital between 2010 and 2020. Electronic medical records of all children identified were reviewed. Data collected included demographic and clinical data (pain scores, key clinical outcomes, adverse events and side effects) and medications used during anaesthesia and postoperative recovery. RESULTS: 22 children (n=8, 36% female) had SDR. The mean (SD) age at surgery was 6 years and 6 months (1 year and 4 months). Common intraoperative medications used were remifentanil (100%), ketamine (95%), paracetamol (91%) and sevoflurane (86%). Postoperatively, all children were prescribed opioid nurse-controlled analgesia (morphine, 36%; fentanyl, 36%; and oxycodone, 18%) and concomitant ketamine infusion. Opioid doses were maximal on the day after surgery. The mean (SD) daily average pain score (Wong-Baker FACES scale) on the day after surgery was 1.4 (0.9), decreasing to 1.0 (0.5) on postoperative day 6 (POD6). Children first attended the physiotherapy gym on median day 7 (POD8, range 7-8). Most children experienced mild side effects or adverse events that were managed conservatively. Common side effects included constipation (n=19), nausea and vomiting (n=18), and pruritus (n=14). No patient required return to theatre, ICU admission or prolonged inpatient stay. CONCLUSIONS: Most children achieve good pain management following SDR with opioid and ketamine infusions. Adverse events, while common, are typically mild and managed with medication or therapy. This information can be used as a baseline to improve postoperative care and to support families' understanding of SDR before surgery.

Long-Term Outcomes Following Hypoxic Ischemic Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy and results in significant morbidity and mortality. Long-term outcomes of the condition encompass impairments across all developmental domains. While therapeutic hypothermia (TH) has improved outcomes for term and late preterm infants with moderate to severe HIE, trials are ongoing to investigate the use of TH for infants with mild or preterm HIE. There is no evidence that adjuvant therapies in combination with TH improve long-term outcomes. Numerous trials of various adjuvant therapies are underway in the quest to further improve outcomes for infants with HIE.

Saudi Cerebral Palsy Register (SCPR): Protocol on the Methods and Technical Details.

This protocol presents a comprehensive proposal for the establishment of the Saudi Cerebral Palsy Register (SCPR), a crucial project for investigating and addressing the prevalence, etiology, and management of cerebral palsy (CP) in Saudi Arabia. The SCPR will not only provide a robust database for ongoing research and analysis but will also serve as a platform for investigating the causes of CP, implementing preventative strategies, and improving the quality of care and outcomes for people with CP and their families in Saudi Arabia. Detailed case definitions, inclusion/exclusion criteria, and data collection protocols are discussed to ensure the integrity and comparability of the data. The plan also outlines strategic funding, institutional and government endorsement, sustainability considerations, potential challenges and proposed solutions, and expected outcomes and impact. These include creating research and educational opportunities, fostering regional and international collaborations, and significantly contributing to CP prevention strategies. Overcoming anticipated obstacles, such as stigma, institutional policies, and collaborations, and securing both necessary funding and endorsements are highlighted as critical for the success of the SCPR. The project is not only aligned with promote prevention of health risks, a target of Vision 2030 in Saudi Arabia, but is also expected to have a substantial impact on the health and quality of life of people with CP and their families in Saudi Arabia, serving as inspiration for similar efforts worldwide.

Nutritional status of children with cerebral palsy in Ghana.

Background: Limited knowledge on nutritional epidemiology in Ghanaian children with Cerebral Palsy (CP) necessitates a comprehensive investigation for an improved understanding of malnutrition in this population. Objectives: We aimed to describe the epidemiology of malnutrition among children with CP in Ghana. Methods: The study used data collected as part of the Ghana CP Register (GCPR). The GCPR is an institution-based surveillance of children with CP aged < 18 years in Ghana. Between October 2018 and April 2020, N = 455 children with CP were registered. Data were collected on (i) weight, length or height, mid-upper-arm-circumference of children with CP; (ii) socio-demographic characteristics; (iii) motor type and topography, gross motor function classification system level (GMFCS); (iv) associated impairments; (v) educational and rehabilitation status for each child. Descriptive and bivariate analyses were performed. Results: Mean and standard deviation age of the registered children at assessment was 5.9 ± 4.1 years, and 42.1% were female. Two-thirds of the children had ≥ one form of undernutrition (underweight or severely underweight: 38.9%, stunted or severely stunted: 51.2%, thin or severely thin: 23.8%). In the adjusted analysis, low maternal education, GMFCS-IV, speech impairment and epilepsy significantly increased the odds of undernutrition among participating children (aOR: 2.6 [95% CI:1.3-5.4]; 2.2 [95% CI:1.0-4.8]; 2.0 [95% CI:1.1-3.6]; 2.9 [95% CI:1.1-7.5] respectively). Conclusions: The high malnutrition rate indicates an urgent need for nutrition interventions and translational research to improve nutritional status and prevent adverse outcomes among children with CP in Ghana. Contribution: Our study contributes important data and a framework to develop guidelines and evidence-based interventions for children with CP in Ghana.

Prevalence & Risk Factors for Perinatal Stroke: A Population-Based Study.

Objectives: The study objective was to calculate the birth prevalence of perinatal stroke and examine risk factors in term infants. Some risk factors are present in healthy infants, making it difficult to determine at-risk infants. Study Design: Prospective population-based perinatal stroke data were compared to the Australian general population data using chi-squared and Fisher's exact tests and multivariable logistic regression analysis. Results: Sixty perinatal stroke cases were reported between 2017 and 2019. Estimated stroke prevalence was 9.6/100,000 live births/year including 5.8 for neonatal arterial ischemic stroke and 2.9 for neonatal hemorrhagic stroke. Eighty seven percent had multiple risk factors. Significant risk factors were cesarean section (p = 0.04), 5-min Apgar score <7 (p < 0.01), neonatal resuscitation (p < 0.01) and nulliparity (p < 0.01). Conclusions: Statistically significant independent risk factors do not fully explain the cause of perinatal stroke, because they are not a direct causal pathway to stroke. These data now require validation in a case-control study.