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.

Predictors of school attendance among children with cerebral palsy in Bangladesh.

AIM: To determine school attendance and its predictors among children with cerebral palsy (CP) in Bangladesh using population-based data. METHOD: This study utilized data from the Bangladesh Cerebral Palsy Register (BCPR), a population-based register of children with CP aged less than 18 years in Bangladesh. Sociodemographic, clinical, and educational data were documented, and descriptive statistics and multivariate regression analyses were used to identify potential predictors of school attendance. RESULTS: Between January 2015 and January 2019, 2725 children with CP were registered into BCPR of which 1582 were school-aged children (i.e. aged 6-18 years). The majority of those children had not attended school (73.9%); 50% (n = 239) children in Gross Motor Function Classification System (GMFCS) levels I to II did not attend schools. Adjusted odds ratios (OR) showed significantly higher odds of school attendance among children whose mothers had completed secondary education or higher (adjusted OR: 2.2; 95% confidence interval [CI]: 1.2-4.0) and received rehabilitation (adjusted OR: 2.1; 95% CI: 1.4-3.1). Conversely, lower odds of school attendance were observed among children aged 15 to 18 years (adjusted OR: 0.4; 95% CI: 0.2-0.8), those with bilateral CP (adjusted OR: 0.5; 95% CI: 0.3-0.8), GMFCS levels III to V (adjusted OR: 0.3; 95% CI: 0.2-0.5), Manual Ability Classification System levels III to V (adjusted OR: 0.5; 95% CI: 0.4-0.8), and speech impairment (adjusted OR: 0.3; 95% CI: 0.2-0.6). INTERPRETATION: A large number of children with CP in Bangladesh, including half of those with milder forms, do not attend schools. These findings underscore a deficiency in awareness and support, encompassing the provision of resources and trained teachers, highlighting the necessity for policy-level changes. Sociodemographic and clinical predictors should be taken into account when devising educational programmes to enhance school attendance for children with CP in Bangladesh.

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. WHAT THIS PAPER ADDS: Almost half of the children with cerebral palsy (CP) had preterm birth, low birthweight, and signs of birth asphyxia. Most of the children were diagnosed after 5 years of age. Overall, 52.5% of children had severe forms of CP of whom only 36.6% received any assistive devices.

Mother-Infant Dyadic Synchrony and Interaction Patterns After Infant Cardiac Surgery.

OBJECTIVE: Parents and their infants with complex congenital heart disease (CHD) face relational challenges, including marked distress, early separations, and infant hospitalizations and medical procedures, yet the prevalence of parent-infant interaction difficulties remains unclear. Using a standardized observational paradigm, this study investigated mother-infant dyadic synchrony, interactional patterns, and associated predictors in mother-infant pairs affected by CHD, compared with typically-developing pairs. METHODS: In this prospective, longitudinal cohort study, mothers and their infants requiring cardiac surgery before age 6-months (n=110 pairs) and an age- and sex-matched Australian community sample (n=85 pairs) participated in a filmed, free-play interaction at 6.9±1.0 months. Mother-infant dyadic synchrony, maternal and infant interactional patterns, and relational risk were assessed using the Child-Adult Relationship Experimental (CARE) Index. Maternal and infant predictors were assessed at 32 weeks gestation, 3- and 6-months postpartum. RESULTS: Most mother-infant interactions were classified as "high risk" or "inept" (cardiac: 94%, control: 81%; p=.007). Dyadic synchrony (p<.001), maternal sensitivity (p=.001), and infant cooperativeness (p=.001) were lower for cardiac than control pairs. Higher maternal traumatic stress at 6-months postpartum predicted lower dyadic synchrony for mother-infant pairs affected by CHD (B=-.04, p=.03). Dyadic synchrony was higher among older infants in the total (B=.40, p=.003) but not cardiac sample (B=.24, p=.06). CONCLUSIONS: Relational difficulties were almost universal among mother-infant pairs affected by CHD and were also high in the Australian community sample. Widespread education initiatives are recommended to increase awareness of heightened mother-infant relational risk in congenital heart care and well-child settings, alongside relationally-focused prevention and early intervention programs.

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.

Severe Congenital Heart Defects and Cerebral Palsy.

OBJECTIVE: To report the prevalence of cerebral palsy (CP) in children with severe congenital heart defects (sCHD) and the outcome/severity of the CP. METHODS: Population-based, data linkage study between CP and congenital anomaly registers in Europe and Australia. The EUROCAT definition of severe CHD (sCHD) was used. Linked data from 4 regions in Europe and 2 in Australia were included. All children born in the regions from 1991 through 2009 diagnosed with CP and/or sCHD were included. Linkage was completed locally. Deidentified linked data were pooled for analyses. RESULTS: The study sample included 4989 children with CP and 3684 children with sCHD. The total number of livebirths in the population was 1 734 612. The prevalence of CP was 2.9 per 1000 births (95% CI, 2.8-3.0) and the prevalence of sCHD was 2.1 per 1000 births (95% CI, 2.1-2.2). Of children with sCHD, 1.5% (n = 57) had a diagnosis of CP, of which 35 (61%) children had prenatally or perinatally acquired CP (resulting from a brain injury at ≤28 days of life) and 22 (39%) children had a postneonatal cause (a brain injury between 28 days and 2 years). Children with CP and sCHD more often had unilateral spastic CP and more intellectual impairments than children with CP without congenital anomalies. CONCLUSIONS: In high-income countries, the proportion of children with CP is much higher in children with sCHD than in the background population. The severity of disease in children with CP and sCHD is milder compared with children with CP without congenital anomalies.

Temporal trends, clinical characteristics, and sociodemographic profile of post-neonatally acquired cerebral palsy in Australia, 1973-2012: A population-based observational study.

AIM: To describe post-neonatally acquired (PNN) cerebral palsy (CP) in terms of temporal trends in prevalence, clinical and sociodemographic profiles, known causes and associations between causes, and sociodemographic variables. METHOD: Numerator data, a count of children with PNN-CP confirmed at 5 years of age (n = 523), was drawn from two Australian state CP registers (birth years 1973-2012). Poisson regression was used to investigate temporal trends in the prevalence of PNN-CP by 5-year intervals, calculated per 10 000 live births. Using data from all state and territory Australian CP registers (n = 469), distributions of clinical characteristics, PNN-CP causes, and sociodemographic factors were tabulated (birth years 1995-2012). χ2 and logistic regression analyses were used to assess associations between sociodemographic profile, Australian reference data, and known causes. RESULTS: A significant temporal decline in PNN-CP in Victoria (p = 0.047) and Western Australia (p = 0.033) was observed. The most common proximal causes of PNN-CP were cerebrovascular accidents (34%, n = 158), infection (25%, n = 117), and non-accidental injuries (12%, n = 58). Children born to teenage mothers, Aboriginal and/or Torres Strait Islander mothers, or children born in remote areas were over-represented in this cohort compared with reference data (all p ≤ 0.001). Infectious causes were strongly associated with teenage motherhood (odds ratio 3.0 [95% confidence interval 1.1-8.2], p = 0.028) and remote living (odds ratio 4.5 [95% confidence interval 2.0-10.2], p < 0.001). INTERPRETATION: Although prevalence of PNN-CP has declined, the over-representation of priority populations, and the relative severity of a condition that is largely preventable, suggest the need for more specific primary preventive measures and support. WHAT THIS PAPER ADDS: Prevalence of post-neonatally acquired (PNN) cerebral palsy (CP) in Australia significantly declined between 1973 and 2012. Cerebrovascular accidents are the most common proximal cause of PNN-CP. Children born in remote areas are at greater risk of PNN-CP.

SUpporting People in extreme POverty with Rehabilitation and Therapy (SUPPORT CP): A trial among families of children with cerebral palsy in Bangladesh.

AIM: To test the efficacy of an integrated microfinance/livelihood and community-based rehabilitation (IMCBR) programme in improving health-related quality of life (HRQoL) and motor function of children with cerebral palsy (CP) and gain in social capital to their ultra-poor families in rural Bangladesh. METHOD: This was an open-label cluster randomized control trial. Children with CP aged 5 years or under were randomly allocated to three arms; Arm A: IMCBR; Arm B: community-based rehabilitation (CBR); and Arm C: care-as-usual. The CBR was modified with phone follow-up followed by home-based CBR at 2.5 months post-enrolment because of the COVID-19 pandemic. Intention-to-treat analysis was performed. RESULTS: Twenty-four clusters constituting 251 children-primary caregivers' dyads were assigned to three arms (Arm A = 80; Arm B = 82; Arm C = 89). Between baseline and endline, the percentage mean change in the physical functioning domain of HRQoL was highest in Arm A (30.0%) with a significant mean difference between Arm A and Arm B (p = 0.015). Improvement in the mean social capital score was significantly higher in Arm A compared to Arm C (p < 0.001). INTERPRETATION: The findings suggest that IMCBR could improve the HRQoL of children with CP and the social capital of their ultra-poor families. Long-term follow-up of the trial participants and future exploration of such interventions are essential. The integrated livelihood and CBR programme holds potential to improve health and well-being of children with CP and their ultra-poor families. WHAT THIS PAPER ADDS: Half of the families who received livelihoods were impacted by a cold-wave, suggesting the need for a more disaster-resilient livelihood asset. The integration of livelihood with community-based rehabilitation programme helps to improve health-related quality of life of children with cerebral palsy and the social capital of their ultra-poor families.

Novel weight estimation equation for children with cerebral palsy in low-resource settings: Validation in a population-based cohort.

AIM: To validate a novel equation to estimate weight from mid-upper arm circumference (MUAC) among children with cerebral palsy (CP) in rural Bangladesh. METHOD: Children with CP aged 2 to 18 years registered in the Bangladesh CP Register were randomly selected. Data on sociodemographics, Gross Motor Function Classification System level, and anthropometric measurements were extracted. Bland-Altman plots with a 95% agreement limit and Lin's concordance correlation coefficient with 95% confidence intervals (CI) were reported to measure agreement between observed and estimated weight. Percentage error was used to determinate the method's accuracy. RESULTS: There were 497 participants with a mean age at assessment of 9 years (SD 4 years 11 months) (47.7% female). Lin's concordance correlation coefficient between the observed and estimated weights was 0.90 (95% CI 0.89-0.92). Bland-Altman plots showed a reasonable accuracy of the equation in the study cohort. The mean percentage error of the equation was 5.04%. The average difference between observed and estimated weights was -1.02 kg (SD 5.1). The differences between observed and estimated weights were significantly greater among children with weight-for-age, height-for-age, or BMI-for-age z-scores less than or equal to -4. INTERPRETATION: It is possible to predict the weight of children with CP from MUAC with sufficient accuracy. The equation can be used for populations in low-resources and low- and middle-income countries. WHAT THIS PAPER ADDS: The equations predict the weight of children with cerebral palsy from their mid-upper arm circumference reasonably accurately. The difference between observed and estimated weights ranged between 0 kg and ± 5 kg in 81.5% of children. Sex and Gross Motor Function Classification System level did not affect the accuracy of the equations. The equations were less accurate for estimating the weight of severely undernourished children.

The Sexual and Reproductive Health of Adolescents with Cerebral Palsy in Rural Bangladesh: A Qualitative Analysis.

Adolescents with disability in the Global South have unique sexual and reproductive health (SHR) experiences and needs; however, they are rarely included in SRH discourse. This qualitative study, conducted in rural Bangladesh, used semi-structured interviews to understand how adolescents with cerebral palsy (CP) experience their SRH. Participants were recruited from the Bangladesh Cerebral Palsy Register and included 24 adolescents with CP (n = 12 female; n = 12 male) and 76 parents (n = 56 mothers, n = 17 fathers, n = 3 other relatives). Data were analyzed using reflexive thematic analysis. Findings highlighted heterogeneity among adolescents with CP including differences for adolescent men versus women. For some adolescent men with CP, sexual maturity was viewed as bringing new opportunities, whereas for other men, adolescence affirmed exclusions and some transgressed sociocultural norms as they struggled to navigate their pubescent body alongside new privacy requirements. For adolescent women with CP, sexual maturity was associated with new domestic responsibilities, silence and secrecy regarding menstruation, and increased vulnerability to sexual violence and abuse. Adolescent men and women with CP spoke about marriage as something "everybody wants," however, was deemed "impossible" for those with more impairment-related support needs. Both adolescent men and women with CP lacked access to SRH information and support. Mothers positioned providing care to their adolescent child with CP after puberty as "shameful." Our findings suggest that disability, health, and education services in rural Bangladesh need to adopt a life-course approach that incorporates the SRH of adolescents with CP. We recommend the provision of SRH education that addresses the physical, cognitive, and social needs of adolescents with CP.

Quantitative end-tidal carbon dioxide at initiation of resuscitation may help guide the ventilation of infants born at less than 30 weeks gestation.

AIM: Estimation of end-tidal carbon dioxide (EtCO2 ) with capnography can guide mask ventilation in infants born at less than 30 weeks of gestation. Chemical-sensitive colorimetric devices to detect CO2 are widely used at resuscitation. We aimed to quantify EtCO2 in the first breaths following initiation of mask ventilation at birth and correlated need for endotracheal intubation. METHODS: Infants <30 weeks gestation receiving mask ventilation were randomised into two groups of mask-hold technique (one-person vs. two-person). Data on EtCO2 in the first 30 breaths, time to achieve 5 mmHg, 10 mmHg and 15 mmHg CO2 using a respiratory function monitor was determined. RESULTS: Twenty-five infants with a mean gestation of 27.3 (±3 weeks) and mean birth weight 920.4 (±188.3 g) were analysed. The median EtCO2 was 5.6 mmHg in the first 10 breaths, whereas it was 12.6 mmHg for 11-20 breaths and 18 mmHg for 21-30 breaths. There was no significant difference in maximum median EtCO2 for the first 20 breaths, although EtCO2 was significantly lower in infants who were intubated (32.0 vs. 15.0, p = 0.018). CONCLUSION: EtCO2 monitoring in infants <30 weeks gestation at birth is feasible and reflective of alveolar ventilation. EtCO2 may help guide ventilation of preterm infants at birth.

Risk factors for perinatal stroke in term infants: A case-control study in Australia.

AIM: The aetiology of perinatal stroke is poorly understood. This study aimed to prospectively confirm the risk factors and identify any previously unknown variables. METHODS: A prospective case-control study was conducted in Australia. Univariate odds ratios (ORs), associated 95% confidence intervals (CIs) and multivariable logistic regression models fitted with backwards stepwise variable selection were used. RESULTS: Sixty perinatal stroke cases reported between 2017 and 2019 included 95% (57/60) with multiple risk factors. Univariate analysis identified emergency caesarean section rather than NVD (P < 0.01), low Apgar score (<7) at 1, 5 and 10 min of age (P < 0.01), resuscitation at birth (P < 0.01), abnormal cord blood gas (P < 0.01), neonatal infection/sepsis (P < 0.01), congenital heart disease (P < 0.01) and hypoglycaemia (P < 0.01) as significant risk factors. Multivariate analysis found smoking during pregnancy (OR: 1.48; 95% CI: 1.09-1.99), 1-min Apgar score < 7 (OR: 1.54; 95% CI: 1.15-2.08), 10-min Apgar score < 7 (OR: 1.26; 95% CI: 1.02-1.54) and hypoglycaemia (OR: 1.49; 95% CI: 1.07-2.06). CONCLUSIONS: Perinatal stroke is associated with multiple risk factors. Exposure to smoking, 10-min Apgar score < 7, neonatal infection and hypoglycaemia were independent risk factors. Emergency caesarean section, resuscitation at birth and abnormal cord blood gas were additional risk factors.

Prospective cohort study of neurodevelopmental outcomes following extreme neonatal hyperbilirubinaemia in Australia.

AIM: This study aimed to establish the incidence and nature of neurodevelopmental outcomes following extreme neonatal hyperbilirubinaemia in an Australian cohort. METHODS: A prospective cohort study of neurodevelopmental outcomes up to 3 years of age of infants born between 2010 and 2013 at ≥34 weeks gestation, with total serum bilirubin ≥450 µmol/L and/or clinical signs of acute bilirubin encephalopathy. Outcome measures comprised neurological examination, Bayley Scales of Infant and Toddler Development, 3rd edition and Ages and Stages Questionnaire, 3rd edition. RESULTS: The Australian estimated incidence of kernicterus is 0.35 per 100 000 live births. Within the follow-up cohort of 26, three children have clinical neurodevelopmental impairment: one has gross motor function classification system level 4 cerebral palsy, audiological deficiency and visual impairment; the second has gross motor function classification system level 1 cerebral palsy and the third has global developmental delay with autism spectrum disorder. Mean Bayley Scales of Infant and Toddler Development, 3rd edition scores were: cognition 10.3 (SD 1.5), receptive communication 9.4 (SD 1.8), expressive communication 9.2 (SD 2.4), fine motor 10.4 (SD 2.6) and gross motor 9.2 (SD 2.3). CONCLUSION: The Australian national rate of kernicterus compares favourably with global estimates. Future preventative strategies in this context include universal neonatal hyperbilirubinaemia assessment and mandated adverse outcome reporting and investigation.

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

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

Safety of sibling cord blood cell infusion for children with cerebral palsy.

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).

Regional oxygenation, perfusion and body and/or head position: Are preterm infants adversely impacted? A systematic review.

This review addresses regional oxygenation and perfusion changes for preterm infants and changes with body position, with or without head rotation. Future directions for improving neurodevelopmental and clinical outcomes are suggested. The MEDLINE, Embase and Scopus databases were searched up to July 2021. Fifteen out of 470 studies met the inclusion criteria. All were prospective, observational studies with a moderate risk of bias. Significant variation was found for the baseline characteristics of the cohort, postnatal ages, and respiratory support status at the time of monitoring. When placed in a non-supine position, preterm infants showed a transient reduction in cardiac output and stroke volume without changes to heart rate or blood pressure. No studies reported on long-term neurodevelopmental outcomes. Overall, side lying or prone position does not appear to adversely affect regional, and specifically cerebral, oxygenation or cerebral perfusion. The effect of head rotation on regional oxygenation and perfusion remains unclear.

Delivering paediatric precision medicine: Genomic and environmental considerations along the causal pathway of childhood neurodevelopmental disorders.

Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A 'pathway' driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the 'gene-environment neuroscience interaction'. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench-to-bedside scientific discovery agenda with ongoing clinician and patient engagement. WHAT THIS PAPER ADDS: Precision medicine has predominantly focused on genetic risk factors. The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied. A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented. The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.