Variability in Newborn Screening Across Canada: Spinal Muscular Atrophy and Beyond.

BACKGROUND: Newborn screening (NBS) identifies infants with severe, early-onset diseases, enabling early diagnosis and treatment. In Canada, decisions regarding disease inclusion in NBS programs occur at the provincial level, which leads to variability in patient care. We aimed to determine whether important differences exist in NBS programs across provinces and territories. Given that spinal muscular atrophy (SMA) is the most recent disease added to NBS programs, we hypothesized that its inclusion would show interprovincial variability and be more likely in provinces already screening for a greater number of diseases. METHODS: We conducted a cross-sectional survey of all NBS labs in Canada to understand: 1) what conditions were included in their program; 2) what genetic-based testing was performed and; 3) if SMA was included. RESULTS: All NBS programs (N = 8) responded to this survey by June 2022. There was a 2.5-fold difference in the number of conditions screened (N = 14 vs N = 36) and a 9-fold difference in the number of conditions screened by gene-based testing. Only nine conditions were common to all provincial NBS programs. NBS for SMA was performed in four provinces at the time of our survey, with BC recently becoming the fifth province to add SMA to their NBS on October 1, 2022. Currently, 72% of Canadian newborns are screened for SMA at birth. CONCLUSION: Although healthcare in Canada is universal, its decentralization gives rise to regional differences in NBS programs which creates inequity in the treatment, care, and potential outcomes of affected children across provincial jurisdictions.

Disease Burden of Spinal Muscular Atrophy: A Comparative Cohort Study Using Insurance Claims Data in the USA.

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion or loss-of-function mutations of the survival of motor neuron 1 (SMN1) gene, resulting in reduced levels of SMN protein throughout the body. Patients with SMA may have multiple tissue defects, which could present prior to neuromuscular symptoms. OBJECTIVE: To assess the signs, comorbidities and potential extraneural manifestations associated with SMA in treatment-naïve patients. METHODS: This observational, retrospective and matched-cohort study used secondary insurance claims data from the US IBM® MarketScan® Commercial, Medicaid and Medicare Supplemental databases between 01/01/2000 and 12/31/2013. Treatment-naïve individuals aged≤65 years with≥2 International Classification of Diseases, Ninth Revision (ICD-9) SMA codes were stratified into four groups (A-D), according to age at index (date of first SMA code recorded) and type of ICD-9 code used, and matched with non-SMA controls. The occurrence of ICD-9 codes, which were converted to various classifications (phecodes and system classes), were compared between groups in pre- and post-index periods. RESULTS: A total of 1,457 individuals with SMA were included and matched to 13,362 controls. Increasing numbers of SMA-associated phecodes and system classes were generally observed from pre- to post-index across all groups. The strongest associations were observed in the post-index period for the youngest age groups. Endocrine/metabolic disorders were associated with SMA in almost all groups and across time periods. CONCLUSIONS: This exploratory study confirmed the considerable disease burden in patients with SMA and identified 305 unique phecodes associated with SMA, providing a rationale for further research into the natural history and progression of SMA, including extraneural manifestations of the disease.

Global prevalence of cerebral palsy: A systematic analysis.

AIM: To determine trends and current estimates in regional and global prevalence of cerebral palsy (CP). METHOD: A systematic analysis of data from participating CP registers/surveillance systems and population-based prevalence studies (from birth year 1995) was performed. Quality and risk of bias were assessed for both data sources. Analyses were conducted for pre-/perinatal, postnatal, neonatal, and overall CP. For each region, trends were statistically classified as increasing, decreasing, heterogeneous, or no change, and most recent prevalence estimates with 95% confidence intervals (CI) were calculated. Meta-analyses were conducted to determine current birth prevalence estimates (from birth year 2010). RESULTS: Forty-one regions from 27 countries across five continents were represented. Pre-/perinatal birth prevalence declined significantly across Europe and Australia (11 out of 14 regions), with no change in postneonatal CP. From the limited but increasing data available from regions in low- and middle-income countries (LMICs), birth prevalence for pre-/perinatal CP was as high as 3.4 per 1000 (95% CI 3.0-3.9) live births. Following meta-analyses, birth prevalence for pre-/perinatal CP in regions from high-income countries (HICs) was 1.5 per 1000 (95% CI 1.4-1.6) live births, and 1.6 per 1000 (95% CI 1.5-1.7) live births when postneonatal CP was included. INTERPRETATION: The birth prevalence estimate of CP in HICs declined to 1.6 per 1000 live births. Data available from LMICs indicated markedly higher birth prevalence. WHAT THIS PAPER ADDS: • Birth prevalence of pre-/perinatal cerebral palsy (CP) in high-income countries (HICs) is decreasing. • Current overall CP birth prevalence for HICs is 1.6 per 1000 live births. • Trends in low- and middle-income countries (LMICs) cannot currently be measured. • Current birth prevalence in LMICs is markedly higher than in HICs. • Active surveillance of CP helps to assess the impact of medical advancements and social/economic development. • Population-based data on prevalence and trends of CP are critical to inform policy.

Improving Care and Empowering Adults Living with SMA: A Call to Action in the New Treatment Era.

While Spinal Muscular Atrophy (SMA) has historically been managed with supportive measures, the emergence of innovative medicines has given those living with SMA hope for improved quality of life and has revolutionized care. Despite these advances, the use of therapies and changes in disease management strategies have focused on pediatric populations, leaving adults living with SMA, and those transitioning into adulthood, relatively neglected. Through a multi-faceted approach that gathered unbiased perspectives from clinical experts, validated insights from individuals with lived experiences, and substantiated findings with evidence from the literature, we have exposed unmet needs that are hindering the field and, ultimately, impacting care and quality of life for adults living with SMA. Here, we set new aspirations and calls to action to inspire continued research in this field, stimulate dialogue across the SMA community and inform policies that deliver effective management and care throughout an adult's journey living with SMA.

Look Around Me: Environmental and Socio-Economic Factors Related to Community Participation for Children with Cerebral Palsy in Québec.

Aims: This study aimed at gaining a deeper understanding of the environmental and socio-economic factors affecting participation outcomes in community and leisure activities for children with disabilities, as well as the trajectories of participation for these children to promote their health and guarantee their rights are respected.Methods: A participatory action research (PAR) approach and linear regression analysis were employed to identify contextual factors associated with the community participation of children with cerebral palsy (CP) living in Quebec, Canada. Stakeholders engaged through the entire research process supported the development of questionnaires, data collection, analysis and interpretation of results.Results: Neighborhood outings were ranked among the most practiced activities by children with CP. Only in a few cases (9%) did children participate in more than two types of activities outside of school. Factors limiting children's participation were predominantly extrinsic in origin, including financial burden and lack of information about existing opportunities.Conclusions: There is a serious need for communities and local governments to inform parents about available resources, programs and policies that can support their child's participation. Rehabilitation professionals could partner with stakeholders to inform the development of public policies that target the identified barriers and promote children's integration and fulfillment.

Cerebral palsy in Canada, 2011-2031: results of a microsimulation modelling study of epidemiological and cost impacts. / La paralysie cérébrale au Canada, 2011-2031 : résultats d'une étude de modélisation par microsimulation des répercussions épidémiologiques et économiques.

INTRODUCTION: The objective of our study was to present model-based estimates and projections on current and future health and economic impacts of cerebral palsy in Canada over a 20-year time horizon (2011-2031). METHODS: We used Statistics Canada's Population Health Model (POHEM)-Neurological to simulate individuals' disease states, risk factors and health determinants and to describe and project health outcomes, including disease incidence, prevalence, life expectancy, health-adjusted life expectancy, health-related quality of life and health care costs over the life cycle of Canadians. Cerebral palsy cases were identified from British Columbia's health administrative data sources. A population-based cohort was then used to generate the incidence and mortality rates, enabling the projection of future incidence and mortality rates. A utility-based measure (Health Utilities Index Mark 3) was also included in the model to reflect various states of functional health to allow projections of health-related quality of life. Finally, we estimated caregiving parameters and health care costs from Canadian national surveys and health administrative data and included them as model parameters to assess the health and economic impact of cerebral palsy. RESULTS: Although the overall crude incidence rate of cerebral palsy is projected to remain stable, newly diagnosed cases of cerebral palsy will rise from approximately 1800 in 2011 to nearly 2200 in 2031. In addition, the number of people with the condition is expected to increase from more than 75 000 in 2011 to more than 94 000 in 2031. Direct health care costs in constant 2010 Canadian dollars were about $11 700 for children with cerebral palsy aged 1-4 years versus about $600 for those without the condition. In addition, people with cerebral palsy tend to have longer periods in poorer health-related quality of life. CONCLUSION: Individuals with cerebral palsy will continue to face challenges related to an ongoing need for specialized medical care and a rising need for supportive services. Our study offers important insights into future costs and impacts associated with cerebral palsy and provides valuable information that could be used to develop targeted health programs and strategies for Canadians living with this condition.

International expert recommendations of clinical features to prompt referral for diagnostic assessment of cerebral palsy.

AIM: To establish international expert recommendations on clinical features to prompt referral for diagnostic assessment of cerebral palsy (CP). METHOD: An online Delphi survey was conducted with international experts in early identification and intervention for children with CP, to validate the results obtained in two previous consensus groups with Canadian content experts and knowledge users. We sent two rounds of questionnaires by e-mail. Participants rated their agreement using a 4-point Likert scale, along with optional open-ended questions for additional feedback. Additionally, a panel of experts and knowledge-users reviewed the results of each round and determined the content of subsequent surveys. RESULTS: Overall, there was high-level of agreement on: (1) six clinical features that should prompt referral for diagnosis; (2) two 'warning sign' features that warrant monitoring rather than immediate referral for diagnosis; and (3) five referral recommendations to other healthcare professionals to occur simultaneously with referral for diagnosis. INTERPRETATION: There was high agreement among international experts, suggesting that the features and referral recommendations proposed for primary care physicians for early detection of CP were broadly generalizable. These results will inform the content of educational tools to improve the early detection of CP in the primary care context. WHAT THIS PAPER ADDS: International experts provide strong agreement on clinical features to detect cerebral palsy. Consensus on clinical 'warning signs' to monitor over time. Referral recommendations from primary care to specialized health services are identified.

RECOMENDACIONES DE EXPERTOS INTERNACIONALES SOBRE CARACTERÍSTICAS CLÍNICAS PARA UNA DERIVACIÓN RÁPIDA PARA LA EVALUACIÓN DIAGNÓSTICA DE LA PARÁLISIS CEREBRAL: OBJETIVO: Establecer recomendaciones de expertos internacionales sobre características clínicas para iniciar derivación para la evaluación diagnóstica de la parálisis cerebral (PC). MÉTODO: Se realizó una encuesta online tipo Delphi con expertos en identificación e intervención temprana de niños con PC a fin de validar los resultados obtenidos en dos grupos de consenso realizados previamente en Canadá con expertos en contenidos y usuarios. Se enviaron dos rondas de cuestionarios por correo electrónico. Los participantes calificaron su acuerdo con un puntaje de 4 puntos en una escala Likert y con preguntas opcionales de respuesta abierta para comentarios adicionales. Además, un panel de expertos y usuarios revisaron los resultados de cada ronda y determinaron el contenido de las encuestas subsiguientes. RESULTADOS: En general, hubo un alto nivel de acuerdo sobre: ​​(1) seis características clínicas que requieren derivación rápida para el diagnóstico, (2) dos características de "señales de advertencia" que requieren monitoreo en lugar de referencia inmediata para el diagnóstico, y (3) cinco recomendaciones de referencia a otros profesionales de la salud que deben realizarse simultáneamente con la derivación para el diagnóstico. INTERPRETACIÓN: Hubo gran acuerdo entre los expertos internacionales, sugiriendo que las características y recomendaciones de referencia propuestas para los médicos de atención primaria para la detección de PC fue ampliamente generalizable. Estos resultados informarán el contenido de herramientas educativas para mejorar la detección precoz de PC en el contexto de atención primaria.

RECOMENDAÇÕES DE ESPECIALISTAS INTERNACIONAIS SOBRE ASPECTOS CLÍNICOS DISPARADORES DE ENCAMINHAMENTO PARA AVALIAÇÃO DIAGNÓSTICA EM PARALISIA CEREBRAL: OBJETIVO: Estabelecer recomendações de especialistas internacionais sobre os aspectos clínicos disparadores de encaminhamento para avaliação diagnóstica em paralisia cerebral (PC). MÉTODO: Um levantamento online internacional do tipo Delphi foi realizado com especialistas em identificação e intervenção precoce para crianças com PC, para validar os resultados obtidos em dois consensos prévios com especialistas no conteúdo e usuários canadenses. Enviamos duas rodadas de questionários por email. Os participantes pontuaram sua concordância usando uma escala Likert de 4 pontos, junto com questões abertas opcionais para informações adicionais. Além disso, um painel de especialistas e usuários revisaram os resultados de cada rodada, e determinaram o conteúdo das pesquisas subsequentes. RESULTADOS: Em geral, houve alto nível de concordância em: 1) seis aspectos clínicos que devem disparar encaminhamento para diagnóstico. 2) dois 'sinais de alerta' que merecem monitoramento mas não encaminhamento imediato para diagnóstico, e 3) cinco recomendações de encaminhamento para outros profissionais da saúde simultaneamente ao encaminhamento para diagnóstico. INTERPRETAÇÃO: Houve alta concordância entre especialistas internacionais, sugerindo que os aspectos e recomendações para encaminhamento propostos para médicos na atenção básica para a identificação precoce da PC foram amplamente generalizáveis. Estes resultados informarão o conteúdo de ferramentas educacionais para melhorar a detecção precoce de PC no contexto da atenção básica.

Is Cerebral Palsy Changing in High Resource Settings? Data From the Quebec Cerebral Palsy Registry.

Advances in maternal and perinatal care in developed countries have led to improved health outcomes for children. These changes may have impacted the profile of children with a cerebral palsy (CP) and groups at risk for CP over time. Using data from the Canadian CP Registry, the objectives of this retrospective cohort study were to describe the profile of children with CP in Quebec born between 1999 and 2010 and identify possible temporal variation in CP risk factors and phenotypic profile. Our sample consisted of 662 children with CP in Quebec. No change in profile or associated risk factors was observed across the birth cohorts 1999 to 2010. Prematurity remains the largest risk factor for CP in Quebec, and children with CP have multiple comorbidities that contribute to overall CP burden. CP registries offer a unique platform to study spectrum disorders and their longitudinal changes over time.

Variation in cerebral palsy profile by socio-economic status.

AIM: Socio-economic differences in maternal and child health are well recognized, but the role of individual-level and area-level determinants in cerebral palsy (CP) phenotypes is debated. We set out to examine (1) the association between area-level and individual-level measures of socio-economic deprivation and CP phenotype among children, including subtype, severity, and comorbidities; and (2) the direct effect of area-level deprivation not mediated through individual-level deprivation. METHOD: Regional data from a provincial CP register were analyzed. The outcome of interest was CP phenotype. The area-level exposure was measured using the Pampalon Deprivation Index. Individual-level socio-economic status (SES) was determined using maternal education. We conducted multiple regression models, stratified by preterm birth, controlling for key covariates, and a mediation analysis of area-level deprivation on the association between individual SES and CP phenotype. RESULTS: A socio-economic gradient in mobility was seen in our cohort, above and beyond differences in maternal and perinatal factors. The added direct effect of area-level deprivation was seen only in children whose mothers were educated to a higher level, suggesting no additional contribution of area-level deprivation in children of mothers with a lower level of education. INTERPRETATION: Contextual socio-economic factors can impact the severity of CP. These findings indicate important areas for potential community-level or area-level public health intervention (i.e. neighborhood reinvestment, preventive measures), and suggest that neighborhood-level research in maternal and perinatal health should continue to be pursued.

Contribution of socio-economic status on the prevalence of cerebral palsy: a systematic search and review.

AIM: The association between socio-economic status (SES) and cerebral palsy (CP) remains controversial. Preterm birth, low birthweight, and postnatal injuries are accepted mediating risk factors for CP, but the question remains whether SES confers additional risk. The aim of this study was to analyse existing knowledge on the relationship between SES and the risk of CP. METHOD: We conducted a systematic search and review of potentially relevant research relating to SES and CP published from 1980 to 2012. Heterogeneity between studies did not allow for data aggregation or meta-analysis; therefore, a narrative review was used to summarize the findings. RESULTS: Twelve studies were included in the systematic review. Of these, eight found low SES to be a risk factor for increased CP prevalence. Three studies detected statistically significant associations even after controlling for birthweight and gestational age as variables. Two of these studies also accounted for additional confounding variables (multiple births and timing of CP acquisition) and continued to detect contributory effects of SES. Linear negative correlations between CP prevalence and SES were shown by three studies. INTERPRETATION: Evidence suggests that the effect of SES on CP prevalence goes beyond that of the mediating factors preterm birth, low birthweight, and postnatal trauma. These associations were seen in area-based and, to a lesser extent, individual measures of SES. A better understanding of mediating factors is imperative in developing targeted public health intervention programmes to reduce the prevalence of CP.

Screening for developmental delay in the setting of a community pediatric clinic: a prospective assessment of parent-report questionnaires.

OBJECTIVES: Our goal for this study was to prospectively test whether parent-completed questionnaires can be effectively used in the setting of a busy ambulatory pediatric clinic to accurately screen for developmental impairments. Specific objectives included (1) assessing the feasibility of using parent-report instruments in the setting of a community pediatric clinic, (2) evaluating the accuracy of 2 available screening tests (the Ages and Stages Questionnaire and Child Development Inventory), and (3) ascertaining if the pediatrician's clinical judgment could be used as a potential modifier. METHODS: Subjects were recruited from the patient population of a community clinic providing primary ambulatory pediatric care. Subjects without previous developmental delay or concerns noted were contacted at the time of their routine 18-month-old visit. Those subjects who agreed to participate were randomly assigned to 1 of 2 groups and completed either the Ages and Stages Questionnaire or Child Development Inventory. The child's pediatrician also completed a brief questionnaire regarding his or her opinion of the child's development. Those children for whom concerns were identified by either questionnaire underwent additional detailed testing by the Battelle Development Inventory, the "gold standard" for the purposes of this study. An equal number of children scoring within the norms of the screening measures also underwent testing with the Battelle Development Inventory. RESULTS: Of the 356 parents contacted, 317 parents (90%) agreed to participate. Most parents correctly completed the Ages and Stages Questionnaire (81%) and the Child Development Inventory (75%). Predictive values were calculated for the Ages and Stages Questionnaire and the Child Development Inventory (sensitivity: 0.67 and 0.50; specificity: 0.39 and 0.86; positive predictive value: 34% and 50%; negative predictive value: 71% and 86%, respectively). Incorporating the physician's opinion regarding the developmental status of the child did not improve the accuracy of the screening questionnaires. CONCLUSIONS: Three important conclusions were reached: (1) parent-completed questionnaires can be feasibly used in the setting of a pediatric clinic; (2) the pediatrician's opinion had little effect in ameliorating the accuracy of either questionnaire; and (3) single-point accuracy of these screening instruments in a community setting did not meet the requisite standard for development screening tests as set by current recommendations. This study raises important questions about how developmental screening can be performed, and we recommend additional research to elucidate a successful screening procedure.