Neurological outcomes and mortality after neonatal seizures with electroencephalographical verification. A systematic review.

AIM: To conduct a systematic review of post-neonatal neurological outcomes and mortality following neonatal seizures with electroencephalographical verification. METHODS: The databases Medline, Embase and Web of Science were searched for eligible studies. All abstracts were screened in a blinded fashion between research team members and reports found eligible were obtained and screened in full text by two members each. From studies included, outcome results for post-neonatal epilepsy, cerebral palsy, intellectual disability, developmental delay, mortality during and after the neonatal period and composite outcomes were extracted. A quality assessment of each study was performed. RESULTS: In total, 5518 records were screened and 260 read in full text. Subsequently, 31 studies were included, containing cohorts of either mixed or homogenous etiologies. Follow-up time and gestational ages varied between studies. No meta-analysis could be performed due to the low number of studies with comparable outcomes and effect measures. Reported cumulative incidences of outcomes varied greatly between studies. For post-neonatal epilepsy the reported incidence was 5-84%, for cerebral palsy 9-78%, for intellectual disability 24-67%, for developmental delay 10-67% and for mortality 1-62%. Subgroup analysis had more coherent results and in cohorts with status epilepticus a higher incidence of post-neonatal epilepsy from 46 to 84% was shown. CONCLUSION: The large variation of reported incidences for neurological outcomes and mortality found even when restricting to cohorts with electroencephalographically verified neonatal seizures indicates selection bias as a significant confounder in existing studies. Population-based approaches are thus warranted to correctly predict outcomes in this group.

Association of Obesity on Outcomes of Hospitalized Patients with Cerebral Palsy.

OBJECTIVE: Among hospitalized adults with cerebral palsy (CP), it is unknown whether obesity is associated with clinical and resource utilization outcomes. We sought to identify the association of obesity on clinical and resource utilization outcomes in this population. METHODS: This retrospective cohort study analyzed years 2016 and 2017 of the Nationwide Inpatient Sample database and examined hospitalized adults with CP. Regression analyses were used to evaluate mortality and resource utilization. RESULTS: In total, 154,219 adults with CP were hospitalized. Among them, 13,475 (8.7%) had a secondary diagnosis for obesity. Patients with obesity were older (mean age ± standard error of the mean: 49.9 ± 0.18 versus 44.7 ± 0.18 years, P < 0.01), a greater proportion were female (60.7% vs 43.2%, P < 0.01), and were more likely to be insured by Medicare (65.2% vs 56.2%, P < 0.01). Patients with obesity had higher comorbidity burdens (Charlson comorbidity score ≥ 3: 22.3% vs 9.8%, P < 0.01). Those with obesity had lower mortality rates (1.6% vs 2.4%; P < 0.01). After adjustment for confounders, mortality for patients with obesity remained lower (adjusted odds ratio 0.5, 95% confidence interval [CI] 0.4-0.7, P < 0.01). Hospital charges (adjusted mean difference $2499, 95% CI $6202-$1202, P = 0.18) and length of stay (adjusted mean difference 0.01 days; 95% CI -0.28 to 0.31, P = 0.93) were not significantly different between the groups. CONCLUSIONS: Obesity was associated with reduced mortality among adult patients in the hospital who had CP. This finding is consistent with the obesity paradox that has been observed repeatedly in patients with other chronic diseases. Further studies investigating hospitalized patients with CP are needed to corroborate these findings.

Survival of South African children with cerebral palsy.

BACKGROUND: The South African (SA) public healthcare sector has experienced a surge in birth injury claims in recent years, particularly in respect of cerebral palsy (CP). The lump sum settlements in these matters are a function of the expected survival curve of the individual concerned. It is known from international studies that the life expectancy of children with CP is shorter than that of the general population, and depends on the pattern and severity of their disabilities. However, empirical estimates of survival for children with CP in SA are not available. OBJECTIVES: To construct survival curves according to the pattern of gross motor skills for CP children in SA and compare these with international studies. METHODS: We collected data on mortality and functional status for 339 CP children on whose behalf claims for medical negligence had been instituted. Motor disabilities were classified according to the five-level Gross Motor Function Classification System (GMFCS). Children who were unable to walk unaided were further classified according to more basic motor skills, including the ability to lift their heads or chests in the prone position, rolling and sitting. Mortality rates were calculated and survival curves were estimated using the Kaplan-Meier method. RESULTS: No deaths were observed among 119 children in GMFCS levels I - IV. Among the 220 children in GMFCS V, there were 20 observed deaths. The proportions surviving to ages 10 and 15 years were 85% (standard error (SE) 5%) and 55% (SE 11%), respectively. The former is comparable to what has been reported for children in California and Sweden, but the survival to age 15 is lower. Among 82 children who could not lift their heads in the prone position, there were 11 observed deaths for a mortality rate of 48.5 (95% confidence interval (CI) 24.2 - 86.9) deaths per 1 000 person-years. Among 72 children who could lift their heads but not their chests, there were 6 observed deaths for a mortality rate of 33.5 (95% CI 12.3 - 73.0) deaths per 1 000 person-years. These mortality rates are 22% and 15% higher than the corresponding figures documented for children with comparable abilities and disabilities in California. CONCLUSIONS: Life expectancy of children with CP in SA is lower than that of children with comparably severe disabilities in high-income countries.

Long-term effect of botulinum toxin A on the hip and spine in cerebral palsy: A national retrospective cohort study in Taiwan.

OBJECTIVES: To investigate the effect of botulinum toxin A (BTA) on the development of hip dislocation and scoliosis, surgical rates for hip and spine, and mortality in cerebral palsy (CP). STUDY DESIGN: A cohort study was conducted using CP data from a Taiwan National Insurance Health Research Database. Diagnoses were defined using the International Classification of Diseases codes, 9th revision. Adjusted hazard ratios for outcomes were calculated using Cox regression analysis and adjusted for the following variables: BTA injection, sex, age, severities of CP, comorbidities, location, urbanization level, and level of care. RESULTS: A total of 1,405 CP children (670 female vs. 735 male), 281 in the BTA group and 1,124 in the controls, were followed-up for a mean of 5 years 4 months. There were no significant differences in the outcomes in both groups, in the incidence rates of hip dislocation and scoliosis, nor in the surgical rates for hip and spine surgery. Mortality rate in the BTA group was 0.49 times lower than that in the controls (p = 0.001). Moderate to severe types of CP had higher incidence rates of hip dislocation, scoliosis, hip surgery, spine surgery, and mortality. CONCLUSION: Moderate to severe types of CP had poorer outcomes in all aspects, including a higher risk of hip dislocation, scoliosis, surgical rate for hip and spine, and mortality. Although BTA injection in children with CP proved to not significantly reduce hip dislocation and scoliosis, it is considered safe as an anti-spasticity treatment and may be beneficial for survival.

Development of a new comorbidity index for adults with cerebral palsy and comparative assessment with common comorbidity indices.

AIM: To develop a new comorbidity index for adults with cerebral palsy (CP), the Whitney Comorbidity Index (WCI), which includes relevant comorbidities for this population and better predicts mortality than the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). METHOD: Data from the Optum Clinformatics Data Mart was used for this retrospective cohort study. Diagnosis codes were used to identify adults aged 18 years or older with CP (n=1511 females, n=1511 males; mean [SD; range] age=48y [19y 2mo; 18-89y]) and all comorbidities in the year 2014. The WCI was developed based on the comorbidities of the CCI and ECI and other relevant comorbidities associated with 2-year mortality using Cox regression and competing risk analysis. The WCI was examined as unweighted (WCIunw ) and weighted (WCIw ). The model fit and discrimination (C-statistic) of each index was assessed using Cox regression. RESULTS: Twenty-seven comorbidities were included in the WCI; seven new comorbidities that were not part of the CCI or ECI were added. The WCIunw and WCIw showed a better model fit and discrimination for 1- and 2-year mortality compared to the CCI and ECI. The WCIunw and WCIw were strong predictors for 1- and 2-year mortality (C-statistic [95% confidence interval] ranging from 0.81 [0.76-0.85] to 0.88 [0.82-0.94]). INTERPRETATION: The new WCI, designed to include clinically relevant comorbidities, provides a better model fit and discrimination of mortality for adults with CP. WHAT THIS PAPER ADDS: Common comorbidity indices exclude relevant comorbidities for adults with cerebral palsy (CP). A new comorbidity index for adults with CP was created by harmonizing clinical theory and data-driven methods. The Whitney Comorbidity Index better predicted 1- and 2-year mortality than other commonly used comorbidity indices.

Excessive premature mortality among children with cerebral palsy in rural Uganda: A longitudinal, population-based study.

BACKGROUND: Studies from high-income countries reported reduced life expectancy in children with cerebral palsy (CP), while no population-based study has evaluated mortality of children with CP in sub-Saharan Africa. This study aimed to estimate the mortality rate (MR) of children with CP in a rural region of Uganda and identify risk factors and causes of death (CODs). METHODS AND FINDINGS: This population-based, longitudinal cohort study was based on data from Iganga-Mayuge Health and Demographic Surveillance System in eastern Uganda. We identified 97 children (aged 2-17 years) with CP in 2015, whom we followed to 2019. They were compared with an age-matched cohort from the general population (n = 41 319). MRs, MR ratios (MRRs), hazard ratios (HRs), and immediate CODs were determined. MR was 3952 per 100 000 person years (95% CI 2212-6519) in children with CP and 137 per 100 000 person years (95% CI 117-159) in the general population. Standardized MRR was 25·3 in the CP cohort, compared with the general population. In children with CP, risk of death was higher in those with severe gross motor impairments than in those with milder impairments (HR 6·8; p = 0·007) and in those with severe malnutrition than in those less malnourished (HR = 3·7; p = 0·052). MR was higher in females in the CP cohort, with a higher MRR in females (53·0; 95% CI 26·4-106·3) than in males (16·3; 95% CI 7·2-37·2). Age had no significant effect on MR in the CP cohort, but MRR was higher at 10-18 years (39·6; 95% CI 14·2-110·0) than at 2-6 years (21·0; 95% CI 10·2-43·2). Anaemia, malaria, and other infections were the most common CODs in the CP cohort. CONCLUSIONS: Risk of premature death was excessively high in children with CP in rural sub-Saharan Africa, especially in those with severe motor impairments or malnutrition. While global childhood mortality has significantly decreased during recent decades, this observed excessive mortality is a hidden humanitarian crisis that needs to be addressed.

Nomogram for pneumonia prediction among children and young people with cerebral palsy: A population-based cohort study.

BACKGROUND: Pneumonia is the leading cause of death among children and young people (CYP) with severe cerebral palsy (CP). Only a few studies used nomogram for assessing risk factors and the probability of pneumonia. Therefore, we aimed to identify risk factors and devise a nomogram for identifying the probability of severe pneumonia in CYP with severe CP. METHODS: This retrospective nationwide population-based cohort study examined CYP with newly diagnosed severe CP before 18 years old between January 1st, 1997 and December 31st, 2013 and followed them up through December 31st, 2013. The primary endpoint was defined as the occurrence of severe pneumonia with ≥ 5 days of hospitalization. Logistic regression analysis was used for determining demographic factors and comorbidities associated with severe pneumonia. These factors were assigned integer points to create a scoring system to identify children at high risk for severe pneumonia. RESULTS: Among 6,356 CYP with newly diagnosed severe CP, 2,135 (33.59%) had severe pneumonia. Multivariable logistic regression analysis revealed that seven independent predictive factors, namely age <3 years, male sex, and comorbidities of pressure ulcer, gastroesophageal reflux, asthma, seizures, and perinatal complications. A nomogram was devised by employing these seven significant predictive factors. The prediction model presented favorable discrimination performance. CONCLUSIONS: The nomogram revealed that age, male sex, history of pressure ulcer, gastroesophageal reflux, asthma, seizures, and perinatal complications were potential risk factors for severe pneumonia among CYP with severe CP.

Neonatal seizures in preterm infants: A systematic review of mortality risk and neurological outcomes from studies in the 2000's.

INTRODUCTION: Neonatal seizures (NS) are associated with increased mortality and risk of cerebral palsy, epilepsy and intellectual disability. We performed a systematic review with the primary objective to delineate the rate of these outcomes following NS in preterm infants from studies published in the 2000's and the secondary objective to identify risk factors. METHODS: Inclusion criteria: original articles published between 1/1/2000 and 12/31/2018, written in English, evaluating newborns ≤37 weeks of gestational age and suffering from NS, in which at least one of these was evaluated: epilepsy, cerebral palsy, intellectual disability/developmental delay, normal outcome, death. RESULTS: Twenty-two papers were selected and all were observational, with a retrospective design in 15. Three were population-based and twenty-one have a comparison. It has been found a 22-80 % of mortality, 11.3-38.9 % of epilepsy, 12-84.6 % of cerebral palsy, and 20-42.7 % of intellectual disability/developmental delay rate. An increased risk for all outcomes considered was reported. Risk factors for specific outcomes were provided by a minority of studies. However, inclusion criteria, definition of NS and measured outcomes, follow-up lengths differed considerably between studies. DISCUSSION: Results of the selected studies are only partially comparable or generalizable because of differences in study design. They have a risk for potential biases, although they provide (if analyzed) readily available prognostic factors, easy to apply in clinical practice. Prospective, population-based studies with EEG-defined NS are warranted in order to produce evidence-based guidance for management of preterm newborns with seizures.

Factors associated with death in people with intellectual disability.

BACKGROUND: People with intellectual disability (ID) experience higher mortality than the general population. This study examines factors contributing to deaths in people with intellectual disability. METHOD: Linked administrative data spanning ten years for 49,947 people with intellectual disability receiving disability services were analysed to assess the impact of demographic variables, comorbidities and health service utilization on the risk of death using Cox proportional hazard models. RESULTS: People admitted for cancer were 8 times more likely to die within the study period compared to people not admitted for cancer. Down syndrome, cerebral palsy and heart disease also increased the risk of death. Emergency department presentations and/or mental health admissions increased the risk of death 4 times. CONCLUSIONS: Our findings provide a basis for policy changes and public health interventions. Cancer screening, mental health interventions, inclusion of people with intellectual disability in health policy and improved health care are needed to meet the needs of this population.

[Mechanisms of brain injury of the premature baby]. / Mecanismos de lesión cerebral en niños prematuros.

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.

Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

CP-North: living life in the Nordic countries? A retrospective register research protocol on individuals with cerebral palsy and their parents living in Sweden, Norway, Denmark, Finland and Iceland.

INTRODUCTION: Cerebral palsy (CP) is one of the most common neurodevelopmental disabilities. Yet, most individuals with CP are adults. How individuals with CP fare in terms of health, quality of life (QoL), education, employment and income is largely unknown. Further, little is known about the effects of having a child with CP on the parents. The Nordic countries are known for their strong welfare systems, yet it is unknown to what extent the added burden related to disability is actually compensated for. We will explore how living with CP affects health, QoL, healthcare utilisation, education, labour market outcomes, socioeconomic status and mortality throughout the lifespan of individuals with CP and their parents. We will also investigate if these effects differ between subgroups, within and across the Nordic countries. METHODS AND ANALYSES: CP-North is a multidisciplinary 4-year (1 August 2017 to 31 July 2021) register research project. The research consortium comprises researchers and users from Sweden, Norway, Denmark, Iceland and Finland. Data from CP registries and follow-up programmes, or cohorts of individuals with CP, will be merged with general national registries. All individual studies are structured under three themes: medical outcomes, social and public health outcomes, and health economics. Both case-control and cohort designs will be included depending on the particular research question. Data will be analysed in the individual countries and later merged across nations. ETHICS AND DISSEMINATION: The ethics approval processes in each individual country are followed. Findings will be published (open access) in international peer-reviewed journals in related fields. Updates on CP-North will be published online at http://rdi.arcada.fi/cpnorth/en/.

Mecanismos de lesión cerebral en niños prematuros / Mechanisms of brain injury of the premature baby

Los nacimientos prematuros son uno de los principales indicadores de salud de un país. Están asociados a una alta mortalidad e importante morbilidad en niños con parálisis cerebral y otros trastornos del neurodesarrollo, incluyendo problemas cognitivos y del aprendizaje. Los principales tipos de lesión encefálica en los recién nacidos prematuros son: a) las lesiones de la sustancia blanca, generalmente asociadas a alteraciones neuronales y axonales en la corteza cerebral y otras zonas de sustancia gris; b) hemorragias intracraneanas que incluyen las de la matriz germinal, intraventriculares e intraparenquimatosas y c) del cerebelo. Las lesiones de sustancia blanca incluyen la leucomalacia periventricular quística, no quística (con focos de necrosis microscópicos) y lesiones difusas de sustancia blanca, no necróticas. Estas lesiones tienen múltiples factores etiológicos. Las características anatómicas y fisiológicas de las estructuras vasculares periventriculares predisponen a la sustancia blanca a ser muy vulnerable a las situaciones de isquemia cerebral y, en interacción con factores infecciosos/inflamatorios, activan a las microglías generando estrés oxidativo (por liberación de radicales libres del oxígeno y del nitrógeno), liberación de citoquinas proinflamatorias, liberación de glutamato, fallo energético y alteración de la integridad vascular. Todo lo anteriormente mencionado genera una particular vulnerabilidad de los pre-oligodendrocitos que termina alterando la mielinización. La hipoxia-isquemia también puede producir necrosis neuronal selectiva en diferentes regiones encefálicas. La matriz germinal es un área altamente vascularizada en la región subependimaria periventricular con una estructura capilar muy frágil que la predispone a las hemorragias.

Preterm birth is one of the main country health indicators. It is associated with high mortality and significant morbidity in preterm newborns with cerebral palsy and potential long-term neurodevelopmental disabilities like cognitive and learning problems. The main lesions could be: a) white matter injuries, generally associated with cortical and other regions of grey matter neuronal-axonal disturbances; b) intracranial hemorrhage that includes germinal matrix, intraventricular and parenchymal, c) cerebellum injuries. The white matter lesions include cystic and non-cystic (with microscopic focal necrosis) periventricular leukomalacia and non-necrotic diffuse white matter injury. Multiple etiologic factors are associated with these injuries. Anatomical and physiological characteristics of periventricular vascular structures predispose white matter to cerebral ischemia and, interacting with infection/inflammation factors, activate microglia, generating oxidative stress (mediated by free oxygen and nitrogen radicals), pro-inflammatory cytokine and glutamate toxicity, energetic failure and vascular integrity disturbances. All these factors lead to a particular vulnerability of pre-oligodendrocytes that will affect myelination. Hypoxia-ischemia also may produce selective neuronal necrosis in different cerebral regions. Germinal matrix is a highly vascularized zone beneath ependymal or periventricular region that constitutes a capillary bed with a particular structural fragility that predispose it to hemorrhage.

Which growth parameters can affect mortality in cerebral palsy?

BACKGROUND: The objective of this study was to identify growth parameters that can affect mortality of cerebral palsy (CP). METHOD: This was a birth cohort study based on the National Health Screening Program for Infants and Children database along with the National Health Insurance Service, which were linked using a personal identifier number. The birth cohort consisted of 2 191 956 subjects, representing 93.5% of live births from 2007-2011, with maximal 10-year follow-up (range, 5-10 years) until October 2016. Subjects with CP were identified. Growth parameters in terms of birth weight, underweight (weight-for-age below the 3rd percentile), rate of body weight gain were collected, along with all-cause mortality after the age of 1 year. RESULT: Prevalence of CP was 2.0 per 1000 live births (95% CI, 1.94-2.06). All-cause mortality after the age of 1 year was 0.09 deaths/1000 person-years (95% CI, 0.08-0.09) in the general population (GP) and 2.85 deaths/1000 person-years (95% CI, 2.32-3.50) in subjects with CP during the follow-up. Therefore, the incidence rate ratio for all-cause mortality was 32.15 (95% CI, 25.72-39.76) in subjects with CP compared to GP. Presence of underweight was significantly associated with higher mortality in both subjects with CP and GP, where the adjusted hazard ratio of death was 2.60 (95% CI, 1.93-3.50) at the age of 18-24 months, 3.12 at 30-36 months, 4.37 at 42-48 months, 5.12 at 54-60 months, and 4.17 at 66-71 months. Birth weight did not affect mortality in both subjects with CP and GP after the age of 1 year (p > 0.05). CONCLUSION: While subjects with CP shows higher mortality, underweight is an important growth parameter that affects all-cause mortality of both subjects with CP and GP. This study urges increased awareness that subjects with CP who are underweight require special care.

Survival and mortality in cerebral palsy: observations to the sixth decade from a data linkage study of a total population register and National Death Index.

BACKGROUND: Likely duration of survival of children described as having cerebral palsy is of considerable interest to individuals with cerebral palsy, their families, carers, health professionals, health economists and insurers. The aim of this paper is to describe patterns of survival and mortality to the sixth decade in a geographically defined population of people with cerebral palsy stratified according to the clinical description of their impairments in early childhood. METHODS: Identifiers of persons born in Western Australia 1956-2011, registered with cerebral palsy on the Western Australian Register of Developmental Anomalies and surviving at least 12 months, were linked to the Australian National Death Index in December 2014. Patterns of mortality were investigated using survival analysis methods. RESULTS: Of 3185 eligible persons, 436 (13.7%) had died. Of that sample the 22% with the mildest impairment had survival patterns similar to the general population. Mortality increased with increasing severity of impairment. Of 349 (75%) with available cause of death data, 58.6% were attributed to respiratory causes, including 171 (49%) to pneumonia at a mean age of 14.6 (sd 13.4) years of which 77 (45%) were attributed to aspiration. For the most severely impaired, early childhood mortality increased in succeeding decades of birth cohorts from 1950s to 1990 with 20% dying by 4 years of age in the 1981-1990 birth cohort; it then decreased for subsequent birth cohorts, 20% mortality not being attained until 15 years of age. However by 20 years of age mortality of the most severely impaired born in the 1991-2000 birth cohort exceeded that of all other birth cohorts. Remaining life expectancies by age to 50 years have been estimated for two strata with more severe impairments. CONCLUSION: For 22% of individuals with cerebral palsy with mild impairment survival to 58 years is similar to that of the general population. Since 1990 mortality for those with severe cerebral palsy in Western Australia has tended to shift from childhood to early adulthood.

Mortality in children with cerebral palsy in rural Bangladesh: a population-based surveillance study.

AIM: To determine the mortality rate, immediate cause of death (CoD), and predictors of death in children with cerebral palsy (CP) in rural Bangladesh. METHOD: We carried out a prospective population-based surveillance study of children with CP aged 0 to 18 years registered with the Bangladesh Cerebral Palsy Register (BCPR) between January 2015 and December 2016, with subsequent follow-up until December 2017. Verbal autopsy was applied to assign immediate CoD. Crude mortality rates, hazard ratios of death, and survival probabilities were estimated. RESULTS: Twenty-nine of the 678 children in the BCPR died during the study period, resulting in a crude mortality rate of 19.5 per 1000 person-years of observation (total follow-up duration 1486.8 person-years; mean 2y [standard deviation 6mo]). The leading immediate CoD was meningitis (n=9) and pneumonia (n=8). Survival probability and hazard ratio of death was significantly associated with age, Gross Motor Functional Classification System level, and associated impairments. Severe underweight and/or severe stunting was significantly overrepresented among deceased children than others in the cohort (p<0.05) when compared with the World Health Organization reference population. INTERPRETATION: The majority of deaths were due to potentially preventable causes. The life expectancy of these children could have been extended by ensuring primary healthcare and nutritional supplementation. WHAT THIS PAPER ADDS: Mortality rate in children with cerebral palsy (CP) in rural Bangladesh is 19.5 per 1000 person-years. The majority of children with CP died from potentially preventable and treatable conditions. Motor severity, associated impairments, and malnutrition make children with CP vulnerable to premature death in rural Bangladesh.

Mortality due to cardiovascular disease, respiratory disease, and cancer in adults with cerebral palsy.

AIM: To compare mortality rates for cardiovascular disease, cancer, and respiratory disease between adults with cerebral palsy (CP) and the general population. METHOD: A cohort study was conducted using data from adults with CP in England, identified through a primary care data set (the Clinical Practice Research Datalink), with linked data on death registrations from the Office for National Statistics. Cause of death was categorized according to International Classification of Diseases codes. Standardized mortality ratios (SMRs) were calculated to compare mortality rates between adults with CP and the general population, adjusted for age, sex, and calendar year. RESULTS: Nine hundred and fifty-eight adults with CP were identified (52.5% males, 47.5% females; median age at start of follow-up 31y [interquartile range 22-43y]) and followed for a total of 7693 person-years. One hundred and forty-two patients (15%) died during follow-up. Adults with CP had an increased risk of death due to cardiovascular disease (SMR: 3.19, 95% confidence interval [CI] 2.20-4.62) and respiratory disease (SMR: 13.59, 95% CI 9.89-18.67), but not from malignant neoplasms (SMR: 1.42, 95% CI 0.83-2.45). INTERPRETATION: We found that adults with CP in England have increased risk of death due to diseases of the circulatory and respiratory systems, supporting findings from two studies that compared cause-specific mortality rates between adults with CP in the USA and the general population. Further research is required into primary and secondary prevention of cardiovascular and respiratory disease in people with CP worldwide. WHAT THIS PAPER ADDS: Adults with cerebral palsy (CP) in England have 14-fold increased risk of mortality due to diseases of the respiratory system. They have a 3-fold increased risk of mortality due to diseases of the circulatory system. Adults with CP had an increased risk of death due to cerebrovascular disease and ischaemic heart disease. The elevated risk of ischaemic heart disease, however, did not reach statistical significance at the 5% per cent level.

MORTALIDAD POR ENFERMEDAD CARDIOVASCULAR, ENFERMEDAD RESPIRATORIA Y CÁNCER EN ADULTOS CON PARÁLISIS CEREBRAL: OBJETIVO: Comparar tasas de mortalidad por enfermedad cardiovascular, cáncer y enfermedad respiratoria entre adultos con parálisis cerebral (PC) y la población general. MÉTODO: Se llevó a cabo un estudio de cohorte utilizando datos de adultos con PC en Inglaterra, identificados a través de un set de datos de atención primaria (the Clinical Practice Research Datalink) con datos vinculados sobre los registros de defunciones de la Oficina Nacional de Estadísticas. Las causas de muertes fueron categorizadas de acuerdo con los códigos de la Clasificación Internacional de Enfermedades. Las tasas de mortalidad estandarizadas (TME) fueron calculadas a fin de comparar las tasas de mortalidad entre adultos con PC y la población general, ajustadas por edad, sexo y año calendario. RESULTADOS: Se identificaron 958 adultos con PC (52,5% varones, 47,5% mujeres; edad mediana al comienzo del seguimiento 31 años [rango intercuartilo 22-43 años] y fueron seguidos por un total de 7.693 años-persona. Ciento cuarenta y dos pacientes (15%) fallecieron durante el seguimiento. Los adultos con PC tuvieron un mayor riesgo de muerte por enfermedad cardiovascular (TME:3,19, 95% intervalo de confidencia [IC] 2,20-4,62) y enfermedad respiratoria (TME:13,59,95% IC 9,89-18,67), pero no tuvieron mayor riesgo de neoplasias malignas (TME:1,42, 95% IC 0,83-2,45). INTERPRETACIÓN: Encontramos que los adultos con PC en Inglaterra tienen un riesgo incrementado de muerte por enfermedades de los sistemas circulatorio y respiratorio, sosteniendo los hallazgos con dos estudios que compararon tasas de mortalidad causa-específicas entre adultos con PC en los EEUU y la población general. Se necesita avanzar con la investigación hacia prevención primaria y secundaria de enfermedades cardiovascular y respiratoria en personas con PC en todo el mundo.

MORTALIDADE DEVIDO A DOENÇA CARDIOVASCULAR, RESPIRATÓRIA, E CÂNCER EM ADULTOS COM PARALISIA CEREBRAL: OBJETIVO: Comparar as taxas de mortalidade por doença cardiovascular, câncer, e doença respiratória em adultos com paralisia cerebral (PC) e a população em geral. MÉTODO: Um estudo de coorte foi realizado usando dados de adultos com PC na Inglaterra, identificados por meio de um conjunto de dados de atenção primária (o Datalink Pesquisa em Prática Clínica,), com dados sobre registros de óbitos do Escritório Nacional de Estatística. A causa da morte foi categorizada de acordo com os códigos da Classificação Internacional de Doenças. Taxas de mortalidade padronizadas (TMPs) foram calculadas para comparar as taxas de mortalidade entre adultos com PC e a população em geral, ajustadas por idade, sexo e ano calendário. RESULTADOS: Novecentos e cinquenta e oito adultos com PC foram identificados (52,5% do sexo masculino, 47,5% do sexo feminino; idade mediana no início do acompanhamento 31a [intervalo interquartil 22-43a]) e acompanhados por um total de 7,693 anos-pessoa. Cento e quarenta e dois pacientes (15%) morreram durante o acompanhamento. Adultos com PC tiveram risco aumentado de morte por doença (TMP: 3,19, intervalo de confiança [IC] a 95% 2,20-4,62) e doença respiratória (TMP: 13,59, IC 95% 9,89-18,67), mas não por neoplasias malignas (TMP: 1,42, IC 95% 0,83-2,45). INTERPRETAÇÃO: Observamos que adultos com PC na Inglaterra têm risco aumentado de more por doenças dos sistemas circulatório e respiratório, o que apóia achados de dois estudos qu compararam taxas de mortalidade causa-específica em adultos com PC nos EUA e na população em geral. Mais pesquisas são necessárias sobre a prevenção primária e secundária de doenças cardiovasculares e respiratórias em pessoas com PC em todo o mundo.

Intrapartum magnesium sulfate is associated with neuroprotection in growth-restricted fetuses.

BACKGROUND: Intrapartum magnesium sulfate administration is recommended for fetal neuroprotection in women with imminent very preterm birth. However, previous studies have not included or separately analyzed the outcomes of pregnancies with fetal growth restriction that were treated with intrapartum magnesium sulfate. OBJECTIVE: We sought to evaluate the neonatal and neurodevelopmental outcomes of growth-restricted fetuses born <29 weeks' gestation and exposed to maternal intrapartum magnesium sulfate. STUDY DESIGN: We conducted a retrospective cohort study of infants born <29 weeks' gestation from 2010 through 2011, admitted to participating Canadian Neonatal Network units, and followed by the Canadian Neonatal Follow-up Network centers. Growth restriction was defined either as estimated fetal or actual neonatal birthweight <10th percentile according to fetal or neonatal growth standards for gestational age and sex, respectively. Infants exposed to intrapartum magnesium sulfate were compared with unexposed infants. The primary outcome was composite of death or significant neurodevelopmental impairment at 18-36 months' corrected age. Secondary outcomes were death or any neurodevelopmental impairment at 18-36 months' corrected age. Neonatal morbidities were also compared. RESULTS: Of the 336 growth-restricted fetuses, 112 (33%) received magnesium sulfate and of the 177 growth-restricted infants, 61 (34%) received magnesium sulfate. Administration of magnesium sulfate was at the discretion of the treating physician. Intrapartum magnesium sulfate was associated with reduced odds of composite of death or significant neurodevelopmental impairment for infants classified according to both fetal standards (adjusted odds ratio, 0.42; 95% confidence interval, 0.22-0.80) and neonatal standards (adjusted odds ratio, 0.44; 95% confidence interval, 0.20-0.98). CONCLUSION: Intrapartum administration of magnesium sulfate to women with growth-restricted fetuses born <29 weeks' gestation was associated with reduced odds of composite of death or significant neurodevelopmental impairment.

Systemic adverse events after botulinum neurotoxin A injections in children with cerebral palsy.

AIM: To identify factors that increase the likelihood of systemic adverse events after botulinum neurotoxin A (BoNT-A) injections in children with cerebral palsy (CP). METHOD: A prospective observational study of patients attending a BoNT-A clinic at a tertiary paediatric hospital (2010-2014). Occurrences of systemic adverse events, defined as lower respiratory tract illnesses, generalized weakness, dysphagia, and death were determined at follow-up. The relationship between systemic adverse events and eight preinjection variables (age, Gross Motor Function Classification System [GMFCS] level, history of dysphagia, gastrostomy, aspiration pneumonia, recent history of illness, BoNT-A dose, and type of sedation) were examined using univariable and multivariable logistic regression with generalized estimating equations methods. RESULTS: In total 591 children underwent 2219 injection episodes with follow-up in 2158 (97%) cases. Systemic adverse events were reported in 77 (3.6%) injection episodes. Univariable analysis suggested that GMFCS levels IV and V, a history of dysphagia, gastrostomy, aspiration pneumonia, and increasing BoNT-A dose increase the likelihood of systemic adverse events. In multivariable analysis, a history of dysphagia (odds ratio [OR] 3.42) and/or aspiration pneumonia (OR 2.31) remained associated with increased likelihood of systemic adverse events. INTERPRETATION: A history of dysphagia and/or aspiration pneumonia are the factors that most increase the likelihood of systemic adverse events after BoNT-A. WHAT THIS PAPER ADDS: Systemic adverse events occur in 3.6% of botulinum neurotoxin A (BoNT-A) injection episodes. Dysphagia and/or aspiration pneumonia are associated with increased likelihood of systemic adverse events. Multivariable models showed no evidence of association between Gross Motor Function Classification System and systemic adverse events. Multivariable models showed no evidence of association between BoNT-A dose and systemic adverse events.

Logistic regression with a continuous exposure measured in pools and subject to errors.

In a multivariable logistic regression setting where measuring a continuous exposure requires an expensive assay, a design in which the biomarker is measured in pooled samples from multiple subjects can be very cost effective. A logistic regression model for poolwise data is available, but validity requires that the assay yields the precise mean exposure for members of each pool. To account for errors, we assume the assay returns the true mean exposure plus a measurement error (ME) and/or a processing error (PE). We pursue likelihood-based inference for a binary health-related outcome modeled by logistic regression coupled with a normal linear model relating individual-level exposure to covariates and assuming that the ME and PE components are independent and normally distributed regardless of pool size. We compare this approach with a discriminant function-based alternative, and we demonstrate the potential value of incorporating replicates into the study design. Applied to a reproductive health dataset with pools of size 2 along with individual samples and replicates, the model fit with both ME and PE had a lower AIC than a model accounting for ME only. Relative to ignoring errors, this model suggested a somewhat higher (though still nonsignificant) adjusted log-odds ratio associating the cytokine MCP-1 with risk of spontaneous abortion. Simulations modeled after these data confirm validity of the methods, demonstrate how ME and particularly PE can reduce the efficiency advantage of a pooling design, and highlight the value of replicates in improving stability when both errors are present.

Intellectual disability in cerebral palsy: a population-based retrospective study.

AIM: A population-based observational study design was used to describe the epidemiology of intellectual disability in cerebral palsy (CP) in terms of clinical and neuroimaging associations, and to report the impact of intellectual disability on utilization of health services and length of survival. METHOD: Population CP registry data were used to retrospectively assess the frequency of intellectual disability and strength of associations between intellectual disability and mobility, epilepsy, vision, hearing, communication, and neuroimaging patterns (n=1141). Data linkage was undertaken to assess usage of hospital inpatient and emergency department services. Survival analysis was performed in a 30-year birth cohort (n=3248). RESULTS: Intellectual disability, present in 45% of the cohort, was associated with non-ambulation (47% vs 8%), later walking (mean 2y 7mo vs 1y 9mo), hypotonic (8% vs 1%) or dyskinetic (9% vs 5%) CP, a quadriplegic pattern of motor impairment (42% vs 5%), epilepsy (52% vs 12%), more emergency and multi-day hospital admissions, and reduced 35-year survival (96% vs 71%). Grey matter injuries (13% vs 6%), malformations (18% vs 6%), and miscellaneous neuroimaging patterns (12% vs 4%) were more common in people with intellectual disability. INTERPRETATION: Intellectual disability adds substantially to the overall medical complexity in CP and may increase health and mortality disparities. WHAT THIS STUDY ADDS: Cerebral maldevelopments and grey matter injuries are associated with higher intellectual disability rates. Health care is more 'crisis-driven' and 'reactive' in children with co-occurring intellectual disability. Length of survival is reduced in individuals with CP and co-occurring intellectual disability.