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Cerebral palsy (CP) is a nonprogressive neurological disorder and the most common physical disability of childhood. There is no cure for CP, but stem cells have the potential to improve brain injury and hence function. This phase 1 clinical trial investigated the safety of the intravenous infusion of full-matched sibling cord blood cells for children with CP aged 1 to 16 years. Preliminary efficacy outcomes were also investigated. Twelve participants received 12/12 HLA-matched sibling cord blood cell infusions. One treatable serious adverse reaction to cryoprotectant was observed, and no adverse reactions occurred beyond 24 h after infusion. Gross motor function measure (GMFM-66) scores did not improve compared with baseline beyond what could be expected from developmental levels, and participants had varied changes in the Quality of Upper Extremity Skills Test (QUEST) and Vineland Adaptive Behavior Scales (VABS-II) scores. In conclusion, matched sibling cord blood cell infusion for children with CP is relatively safe when conducted in an appropriate facility. Australian and New Zealand Clinical Trials Registry (ACTRN12616000403437) and Clinicaltrials.gov (NCT03087110).Copyright © 2022 International Society for Cell & Gene Therapy

Importance: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain. Objective(s): To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures. Design, Setting, and Participant(s): This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks' gestation or more and younger than 48 hours old. Data analysis was completed in April 2021. Intervention(s): Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. Main Outcomes and Measures: Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years. Result(s): Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in th

AIMS: Cytomegalovirus (CMV) is a preventable cause of neurodevelopmental disability. Australian guidelines recommend that pregnant women are informed about CMV to reduce their risk of infection; however, less than 10% of maternity health professionals routinely provide prevention advice. The aim was to develop and evaluate the effectiveness of an eLearning course for midwives to improve knowledge and confidence about CMV. MATERIALS AND METHODS: Participants undertaking the course between March and November 2020 were invited to complete an evaluation questionnaire: before the course (T1), immediately after (T2) and three months post completion (T3). A linear mixed model was used to evaluate change in participant scores; P < 0.05 was considered statistically significant. RESULTS: Midwives (316/363, 87%), midwifery students (29/363, 8%) and nurses (18/363, 5%) participated. At T1 80% indicated they had not received education about CMV. Total adjusted mean scores for questionnaires completed between T1 (n = 363) and T2 (n = 238) increased significantly (from 17.2 to 22.8, P < 0.001). Limited available T3 scores (n = 27) (-1.7, P < 0.001), while lower than T2, remained higher than at T1 (+3.6, P < 0.001). Participants' awareness of CMV information resources improved from 10 to 97% from T1 to T2. Confidence in providing CMV advice increased from 6 to 95% between T1 and T2 (P < 0.001) and was maintained at T3. Almost all (99%) participants indicated they would recommend the course to colleagues. CONCLUSION: Participants who completed the eLearning course had significantly improved knowledge and confidence in providing advice about CMV. Programs targeting other maternity health professionals should be considered, to further support the implementation of the congenital CMV prevention guidelines.

AIM: To define clinical common data elements (CDEs) and a mandatory minimum data set (MDS) for genomic studies of cerebral palsy (CP). METHOD: Candidate data elements were collated following a review of the literature and existing CDEs. An online, three-round Delphi survey was used to rate each data element as either 'core', 'recommended', 'exploratory', or 'not required'. Members of the International Cerebral Palsy Genomics Consortium (ICPGC) rated the core CDEs as either mandatory or not, to form the MDS. For both the CDEs and the MDS, a data element was considered to have reached consensus if more than 75% of respondents agreed. RESULTS: Forty-six individuals from around the world formed the Delphi panel: consumers (n=2), scientists/researchers (n=17), medical (n=19), and allied health professionals (n=8). The CDEs include 107 data elements across six categories: demographics, diagnostics, family history, antenatal and neonatal details, clinical traits, and CP-specific assessments. Of these, 10 are mandatory, 42 core, 41 recommended, and 14 are exploratory. INTERPRETATION: The ICPGC CDEs provide a foundation for the standardization of phenotype data captured in CP genomic studies and will benefit international collaborations and pooling of data, particularly in rare conditions. WHAT THIS PAPER ADDS: A set of 107 common data elements (CDEs) for genomics studies in cerebral palsy is provided. The CDEs include standard definitions and data values domains. The CDEs will facilitate international data sharing, collaboration, and improved clinical interpretation of findings.

Aim To define clinical common data elements (CDEs) and a mandatory minimum data set (MDS) for genomic studies of cerebral palsy (CP). Method Candidate data elements were collated following a review of the literature and existing CDEs. An online, three-round Delphi survey was used to rate each data element as either ‘core’, ‘recommended’, ‘exploratory’, or ‘not required’. Members of the International Cerebral Palsy Genomics Consortium (ICPGC) rated the core CDEs as either mandatory or not, to form the MDS. For both the CDEs and the MDS, a data element was considered to have reached consensus if more than 75% of respondents agreed. Results Forty-six individuals from around the world formed the Delphi panel: consumers (n=2), scientists/researchers (n=17), medical (n=19), and allied health professionals (n=8). The CDEs include 107 data elements across six categories: demographics, diagnostics, family history, antenatal and neonatal details, clinical traits, and CP-specific assessments. Of these, 10 are mandatory, 42 core, 41 recommended, and 14 are exploratory. Interpretation The ICPGC CDEs provide a foundation for the standardization of phenotype data captured in CP genomic studies and will benefit international collaborations and pooling of data, particularly in rare conditions.

AIM: To investigate temporal trends in birth prevalence, disability severity, and motor type for singletons with prenatal or perinatally acquired cerebral palsy (CP). METHOD: Numerator data, number of children with CP born a singleton between 1995 and 2014, confirmed at 5 years of age, were drawn from three state registers with population-level ascertainment. Birth prevalence estimates and 95% confidence intervals (CI) were calculated per 1000 singleton live births for the three states combined, overall, by gestational age group, by dichotomized disability severity, and spastic laterality. Poisson regression models were used to analyse trends. Using data from all eight registers, trends in the proportional distribution of CP subtypes overall and stratified by gestational age were examined. RESULTS: Birth prevalence of CP declined from 1.8 (95% CI 1.6-2.0) in 1995 to 1996 to 1.2 (95% CI 1.1-1.4) in 2013 to 2014 (average 5% per 2-year epoch, p < 0.001). Declines in birth prevalence were observed across all gestational age groups with the largest decline in children born at <28 weeks (average 8% per epoch, p < 0.001). Prevalence of moderate-severe disability declined for children born at <28 and ≥37 weeks (average 11% and 7% per epoch respectively, p < 0.001). The proportions of bilateral spastic CP declined (p < 0.001) at <28 weeks (p = 0.014) and ≥37 weeks (p < 0.001). The proportion of children with dyskinesia increased (28-31 weeks: p = 0.021, 32-36 weeks: p = 0.001, and ≥37 weeks: p < 0.001). INTERPRETATION: Birth prevalence of CP and moderate-severe disability (<28 and ≥37 weeks) declined in Australian singletons between 1995 and 2014, reflecting changes in prenatal and perinatal care over time. WHAT THIS PAPER ADDS: Declines in birth prevalence of prenatal or perinatally acquired cerebral palsy were observed for singletons born in Australia between 1995 and 2014. These declines were evident across all gestational age groups. Declines in birth prevalence of moder

Introduction: The goal of this study was to understand individuals with cerebral palsy (CP) and their family’s attitudes and preferences to genomic research, including international data sharing and biobanking. Methods: Individuals with CP and their family members were invited to participate in the web-based survey via email (NSW/ACT CP Register) or via posts on social media by Cerebral Palsy Alliance, CP Research Network, and CP Now. Survey responses included yes/no/unsure, multiple choices, and Likert scales. Fisher’s exact and χ2 tests were used to assess if there were significant differences between subgroups. Results: Individuals with CP and their families (n = 145) were willing to participate in genomics research (68%), data sharing (82%), and biobanking efforts (75%). This willingness to participate was associated with completion of tertiary education, previous genetic testing experience, overall higher genomic awareness, and trust in international researchers. The survey respondents also expressed ongoing communication and diverse information needs regarding the use of their samples and data. Major concerns were associated with privacy and data security. Discussion: The success of genomic research and international data sharing efforts in CP are contingent upon broad support and recruitment. Ongoing consultation and engagement of individuals with CP and their families will facilitate trust and promote increased awareness of genomics in CP that may in turn maximize participant uptake and recruitment.

Introduction The current diagnostic pathways for cognitive impairment rarely identify babies at risk before 2 years of age. Very early detection and timely targeted intervention has potential to improve outcomes for these children and support them to reach their full life potential. Early Moves aims to identify early biomarkers, including general movements (GMs), for babies at risk of cognitive impairment, allowing early intervention within critical developmental windows to enable these children to have the best possible start to life. Method and analysis Early Moves is a double-masked prospective cohort study that will recruit 3000 term and preterm babies from a secondary care setting. Early Moves will determine the diagnostic value of abnormal GMs (at writhing and fidgety age) for mild, moderate and severe cognitive delay at 2 years measured by the Bayley-4. Parents will use the Baby Moves smartphone application to video their babies' GMs. Trained GMs assessors will be masked to any risk factors and assessors of the primary outcome will be masked to the GMs result. Automated scoring of GMs will be developed through applying machine-based learning to the data and the predictive value for an abnormal GM will be investigated. Screening algorithms for identification of children at risk of cognitive impairment, using the GM assessment (GMA), and routinely collected social and environmental profile data will be developed to allow more accurate prediction of cognitive outcome at 2 years. A cost evaluation for GMA implementation in preparation for national implementation will be undertaken including exploring the relationship between cognitive status and healthcare utilisation, medical costs, health-related quality of life and caregiver burden. Ethics and dissemination Ethics approval has been granted by the Medical Research Ethics Committee of Joondalup Health Services and the Health Service Human Research Ethics Committee (1902) of Curtin University (HRE2019-0739). Tria

Birth prevalence of cerebral palsy (CP) is declining in high-income countries, to as low as 1.4 per 1000 live births in the most recent international reports. This represents a 35% reduction in birth prevalence over a 15-year period. This reduction is underpinned by a heightened focus of attention towards all aspects of CP, including: increased awareness, better data collection, development of national networks and registries, an explosion of research in basic science, perinatal care, neonatal neurology, public health, early detection, and targeted early intervention. Quick uptake of evidence into practice has ensued and overall improvements in clinical care occurred concurrently. It is anticipated that with continued partnerships with families, ongoing research driving further clinical improvement and vice versa, birth prevalence and severity of CP will further decline and the focus will shift to prevention in low- and middle-income countries. What this paper adds: Research in the field of perinatal care and cerebral palsy (CP) prevention has increased significantly. In high-income countries, increased awareness of CP and scientific advances have improved clinical care. Population-based registers have limitations but remain the best mechanism to quantify birth prevalence of CP and accurately track trends. There have been recent reductions in the birth prevalence of CP.Copyright © 2020 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press

AIM: To describe the birth prevalence, temporal trends, and clinical outcomes of twins, triplets, or quadruplets with cerebral palsy (CP). METHOD: This was a cross-sectional study using data for twins, triplets, and quadruplets with prenatally or perinatally acquired CP and pooled from the Surveillance of Cerebral Palsy in Europe network (born 1992-2009) and Australian Cerebral Palsy Register (born 1993-2009). Children were at least 4 years old at time of registration. Children born in regions with population ascertainment and available denominator data were included in prevalence calculations (n=1033 twins, 81 triplets, and 11 quadruplets). Clinical data from children registered in all participating registers were described, including 2163 twins (56% male), 187 triplets (59% male), and 20 quadruplets (45% male). RESULTS: The birth prevalence of CP was higher with increasing plurality (twins 6.5 per 1000 live births [95% confidence interval {CI} 6.1-6.9], triplets 17.1 [95% CI 13.6-21.2], quadruplets 50.7 [95% CI 25.6-88.9]); however, prevalence by gestational age was similar across all pluralities. Between 1992-1994 and 2007-2009, prevalence of CP among twins declined (p=0.001) but prevalence of CP among triplets did not change significantly over time (p=0.55). The distributions of Gross Motor Function Classification System, epilepsy, and impairments of intellect, vision, and hearing were similar regardless of plurality. INTERPRETATION: The data combined from two CP register networks indicated that triplets and quadruplets had increased risk of CP compared to twins. The higher prevalence of CP in triplets and quadruplets is due to their higher risk of preterm birth. Prevalence of CP among twins significantly declined in Europe and Australia. Clinical outcomes were similar for all multiple births.

AIM: To describe the major congenital anomalies present in children with postneonatally acquired cerebral palsy (CP), and to compare clinical outcomes and cause of postneonatally acquired CP between children with and without anomalies. METHOD: Data were linked between total population CP and congenital anomaly registers in five European and three Australian regions for children born 1991 to 2009 (n=468 children with postneonatally acquired CP; 255 males, 213 females). Data were pooled and children classified into mutually exclusive categories based on type of congenital anomaly. The proportion of children with congenital anomalies was calculated. Clinical outcomes and cause of postneonatally acquired CP were compared between children with and without anomalies. RESULTS: Major congenital anomalies were reported in 25.6% (95% confidence interval [CI] 21.7-29.9) of children with postneonatally acquired CP. Cardiac anomalies, often severe, were common and present in 14.5% of children with postneonatally acquired CP. Clinical outcomes were not more severe in children with congenital anomalies than those without anomalies. Cause of postneonatally acquired CP differed with the presence of congenital anomalies, with cerebrovascular accidents predominating in the anomaly group. Congenital anomalies were likely associated with cause of postneonatally acquired CP in 77% of children with anomalies. INTERPRETATION: In this large, international study of children with postneonatally acquired CP, congenital anomalies (particularly cardiac anomalies) were common. Future research should determine specific causal pathways to postneonatally acquired CP that include congenital anomalies to identify opportunities for prevention. WHAT THIS PAPER ADDS: One-quarter of children with postneonatally acquired cerebral palsy (CP) have a major congenital anomaly. Cardiac anomalies, often severe, are the most common anomalies. Causes of postneonatally acquired CP differ between children with and w

IMPORTANCE: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain. OBJECTIVE: To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks' gestation or more and younger than 48 hours old. Data analysis was completed in April 2021. INTERVENTIONS: Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. MAIN OUTCOMES AND MEASURES: Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years. RESULTS: Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG die

IMPORTANCE: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. OBJECTIVE: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. EVIDENCE REVIEW: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. FINDINGS: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (

In the field of disability research and advocacy, the notion of 'cures' is contentious. Cerebral palsy (CP) is no exception. In this narrative review, we combine perspectives gained during community consultation undertaken for the Australian and New Zealand Cerebral Palsy Strategy, 2020 with those published in the scientific and grey literature to understand whether 'cures for CP' is a reasonable and appropriate goal. We frame these perspectives through the lens of several ethical principles central to the discussion. These include maintaining hope while also being realistic, sensitivity to sharply different viewpoints amongst people with disability and their families, and responding to community priorities, societal attitudes, and identity. Through this exploration of the literature and perspectives, we arrived at a definition of 'cures for CP' that is pluralized and focuses on functional improvement and/or symptom reduction whilst still acknowledging the potential for neural repair/regeneration strategies.

Importance: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. Objective: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. Evidence Review: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. Findings: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (

Introduction Cerebral palsy (CP) is the most common physical disability of childhood but has no cure. Stem cells have the potential to improve brain injury and are proposed as a therapy for CP. However, many questions remain unanswered about the most appropriate cell type, timing of infusions, dose required and associated risks. Therefore, human safety and efficacy trials are necessary to progress knowledge in the field. Methods and analysis This is a single group study with sample size n=12 to investigate safety of single-dose intravenous 12/12 human leucocyte antigen-matched sibling cord blood cell infusion to children with CP aged 1-16 years without immune suppression. The study is similar to a 3+3 design, where the first two groups of participants have severe CP, and the final six participants include children with all motor severities. Children will be monitored for adverse events and the duration that donor cells are detected. Assessments at baseline, 3 and 12 months will investigate safety and preliminary evidence of change in gross motor, fine motor, cognitive and quality of life outcomes. Ethics and dissemination Full approval was obtained from The Royal Children's Hospital Human Research Ethics Committee, and a clinical trial notification was accepted by Australia's Therapeutic Goods Administration. Participant guardian informed consent will be obtained before any study procedures. The main results of this study will be submitted for publication in a peer-reviewed journal. Trial registration number ACTRN12616000403437, NCT03087110.Copyright © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Purpose of Review: Cerebral palsy is the most common physical disability of childhood, but the rate is falling, and severity is lessening. We conducted a systematic overview of best available evidence (2012-2019), appraising evidence using GRADE and the Evidence Alert Traffic Light System and then aggregated the new findings with our previous 2013 findings. This article summarizes the best available evidence interventions for preventing and managing cerebral palsy in 2019. Recent Findings: Effective prevention strategies include antenatal corticosteroids, magnesium sulfate, caffeine, and neonatal hypothermia. Effective allied health interventions include acceptance and commitment therapy, action observations, bimanual training, casting, constraint-induced movement therapy, environmental enrichment, fitness training, goal-directed training, hippotherapy, home programs, literacy interventions, mobility training, oral sensorimotor, oral sensorimotor plus electrical stimulation, pressure care, stepping stones triple P, strength training, task-specific training, treadmill training, partial body weight support treadmill training, and weight-bearing. Effective medical and surgical interventions include anti-convulsants, bisphosphonates, botulinum toxin, botulinum toxin plus occupational therapy, botulinum toxin plus casting, diazepam, dentistry, hip surveillance, intrathecal baclofen, scoliosis correction, selective dorsal rhizotomy, and umbilical cord blood cell therapy. Summary: We have provided guidance about what works and what does not to inform decision-making, and highlighted areas for more research.Copyright © 2020, The Author(s).

PURPOSE OF REVIEW: Cerebral palsy is the most common physical disability of childhood, but the rate is falling, and severity is lessening. We conducted a systematic overview of best available evidence (2012-2019), appraising evidence using GRADE and the Evidence Alert Traffic Light System and then aggregated the new findings with our previous 2013 findings. This article summarizes the best available evidence interventions for preventing and managing cerebral palsy in 2019. RECENT FINDINGS: Effective prevention strategies include antenatal corticosteroids, magnesium sulfate, caffeine, and neonatal hypothermia. Effective allied health interventions include acceptance and commitment therapy, action observations, bimanual training, casting, constraint-induced movement therapy, environmental enrichment, fitness training, goal-directed training, hippotherapy, home programs, literacy interventions, mobility training, oral sensorimotor, oral sensorimotor plus electrical stimulation, pressure care, stepping stones triple P, strength training, task-specific training, treadmill training, partial body weight support treadmill training, and weight-bearing. Effective medical and surgical interventions include anti-convulsants, bisphosphonates, botulinum toxin, botulinum toxin plus occupational therapy, botulinum toxin plus casting, diazepam, dentistry, hip surveillance, intrathecal baclofen, scoliosis correction, selective dorsal rhizotomy, and umbilical cord blood cell therapy. We have provided guidance about what works and what does not to inform decision-making, and highlighted areas for more research.

INTRODUCTION: Cerebral palsy (CP) is the most common physical disability of childhood but has no cure. Stem cells have the potential to improve brain injury and are proposed as a therapy for CP. However, many questions remain unanswered about the most appropriate cell type, timing of infusions, dose required and associated risks. Therefore, human safety and efficacy trials are necessary to progress knowledge in the field. METHODS AND ANALYSIS: This is a single group study with sample size n=12 to investigate safety of single-dose intravenous 12/12 human leucocyte antigen-matched sibling cord blood cell infusion to children with CP aged 1-16 years without immune suppression. The study is similar to a 3+3 design, where the first two groups of participants have severe CP, and the final six participants include children with all motor severities. Children will be monitored for adverse events and the duration that donor cells are detected. Assessments at baseline, 3 and 12 months will investigate safety and preliminary evidence of change in gross motor, fine motor, cognitive and quality of life outcomes. ETHICS AND DISSEMINATION: Full approval was obtained from The Royal Children's Hospital Human Research Ethics Committee, and a clinical trial notification was accepted by Australia's Therapeutic Goods Administration. Participant guardian informed consent will be obtained before any study procedures. The main results of this study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12616000403437, NCT03087110.

Birth prevalence of cerebral palsy (CP) is declining in high-income countries, to as low as 1.4 per 1000 live births in the most recent international reports. This represents a 35% reduction in birth prevalence over a 15-year period. This reduction is underpinned by a heightened focus of attention towards all aspects of CP, including: increased awareness, better data collection, development of national networks and registries, an explosion of research in basic science, perinatal care, neonatal neurology, public health, early detection, and targeted early intervention. Quick uptake of evidence into practice has ensued and overall improvements in clinical care occurred concurrently. It is anticipated that with continued partnerships with families, ongoing research driving further clinical improvement and vice versa, birth prevalence and severity of CP will further decline and the focus will shift to prevention in low- and middle-income countries. WHAT THIS PAPER ADDS: Research in the field of perinatal care and cerebral palsy (CP) prevention has increased significantly. In high-income countries, increased awareness of CP and scientific advances have improved clinical care. Population-based registers have limitations but remain the best mechanism to quantify birth prevalence of CP and accurately track trends. There have been recent reductions in the birth prevalence of CP.