An international survey of cerebral palsy registers and surveillance systems.

AIM: To describe cerebral palsy (CP) surveillance programmes and identify similarities and differences in governance and funding, aims and scope, definition, inclusion/exclusion criteria, ascertainment and data collection, to enhance the potential for research collaboration. METHOD: Representatives from 38 CP surveillance programmes were invited to participate in an online survey and submit their data collection forms. Descriptive statistics were used to summarize information submitted. RESULTS: Twenty-seven surveillance programmes participated (25 functioning registers, two closed owing to lack of funding). Their aims spanned five domains: resource for CP research, surveillance, aetiology/prevention, service planning, and information provision (in descending order of frequency). Published definitions guided decision making for the definition of CP and case eligibility for most programmes. Consent, case identification, and data collection methods varied widely. Ten key data items were collected by all programmes and a further seven by at least 80% of programmes. All programmes reported an interest in research collaboration. INTERPRETATION: Despite variability in methodologies, similarities exist across programmes in terms of their aims, definitions, and data collected. These findings will facilitate harmonization of data and collaborative research efforts, which are so necessary on account of the heterogeneity and relatively low prevalence of CP.

Decreasing prevalence in cerebral palsy: a multi-site European population-based study, 1980 to 2003.

AIM: To monitor the trends in prevalence of cerebral palsy (CP) by birthweight in Europe, 1980 to 2003. METHOD: Data were collated from 20 population-based registers contributing to the Surveillance of Cerebral Palsy in Europe database. Trend analyses were conducted in four birthweight groups: <1000g (extremely low birthweight [ELBW]); 1000 to 1499g (very low birthweight [VLBW]); 1500 to 2499g (moderately low birthweight [MLBW]); and >2499g (normal birthweight [NBW]). RESULTS: The overall prevalence of CP decreased from 1.90 to 1.77 per 1000 live births, p<0.001, with a mean annual fall of 0.7% (95% confidence interval [CI] -0.3% to -1.0%). Prevalence in NBW children showed a non-significant trend from 1.17 to 0.89 per 1000 live births (p=0.22). Prevalence in MLBW children decreased from 8.5 to 6.2 per 1000 live births (p<0.001), but not linearly. Prevalence in VLBW children also declined from 70.9 to 35.9 per 1000 live births (p<0.001) with a mean annual fall of 3.4% (95% CI -2.4% to -4.3%). Prevalence in ELBW children remained stable, at a mean rate of 42.4 per 1000 live births. INTERPRETATION: The decline in prevalence of CP in children of VLBW continues, and confirms that previously reported. For the first time, there is also a significant decline among those of MLBW, resulting in a significant overall decrease in the prevalence of CP.

Low but increasing prevalence of autism spectrum disorders in a French area from register-based data.

Register-based prevalence rates of childhood autism (CA), Asperger's syndrome (AS) and other autism spectrum disorders (ASD) were calculated among children aged 7 years old of the 1997-2003 birth cohorts, living in four counties in France. The proportion of children presenting comorbidities was reported. 1123 children with ASD were recorded (M/F ratio: 4.1), representing an overall prevalence rate of 36.5/10,000 children (95 % CI 34.4-38.7): 8.8/10,000 for CA (95 % CI 7.8-9.9), 1.7/10,000 for AS (95 % CI 1.3-2.3) and 25.9/10,000 for other ASD (95 % CI 24.2-27.8). ASD prevalence significantly increased (p < 0.0001) during the period under study. The proportion of children with an intellectual disability was 47.3 %, all other comorbidities were present in less than 5 % of the cases.

Visual-perceptual impairment in children with cerebral palsy: a systematic review.

AIM: Visual perception is one of the cognitive functions often impaired in children with cerebral palsy (CP). The aim of this systematic literature review was to assess the frequency of visual-perceptual impairment (VPI) and its relationship with patient characteristics. METHOD: Eligible studies were relevant papers assessing visual perception with five common standardized assessment instruments in children with CP published from January 1990 to August 2011. RESULTS: Of the 84 studies selected, 15 were retained. In children with CP, the proportion of VPI ranged from 40% to 50% and the mean visual perception quotient from 70 to 90. None of the studies reported a significant influence of CP subtype, IQ level, side of motor impairment, neuro-ophthalmological outcomes, or seizures. The severity of neuroradiological lesions seemed associated with VPI. The influence of prematurity was controversial, but a lower gestational age was more often associated with lower visual motor skills than with decreased visual-perceptual abilities. INTERPRETATION: The impairment of visual perception in children with CP should be considered a core disorder within the CP syndrome. Further research, including a more systematic approach to neuropsychological testing, is needed to explore the specific impact of CP subgroups and of neuroradiological features on visual-perceptual development.

Array-CGH in children with mild intellectual disability: a population-based study.

UNLABELLED: Intellectual disability (ID) is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of ID originate from chromosomal imbalances. During the last years, array-CGH has successfully contributed to improve the diagnostic detection rate of genetic abnormalities in patients with ID. Most array-CGH studies focused on patients with moderate or severe intellectual disability. Studies on genetic etiology in children with mild intellectual disability (ID) are very rare. We performed array-CGH analysis in 66 children with mild intellectual disability assessed in a population-based study and for whom no genetic etiology was identified. We found one or more copy number variations (CNVs) in 20 out of 66 (~30 %) patients with a mild ID. In eight of them (~12 %), the CNVs were certainly responsible for the phenotype and in six they were potentially pathogenic for ID. Altogether, array-CGH helped to determine the etiology of ID in 14 patients (~21 %). CONCLUSION: Our results underscore the clinical relevance of array-CGH to investigate the etiology of isolated idiopathic mild ID in patients or associated with even subtle dysmorphic features or congenital malformations.

What constitutes cerebral palsy in the twenty-first century?

AIM: Determining inclusion/exclusion criteria for cerebral palsy (CP) surveillance is challenging. The aims of this paper were to (1) define inclusion/exclusion criteria that have been adopted uniformly by surveillance programmes and identify where consensus is still elusive, and (2) provide an updated list of the consensus concerning CP inclusion/exclusion when a syndrome/disorder is diagnosed. METHOD: Data were drawn from an international survey of CP registers, the New South Wales CP Register (1993-2003), the Western Australian CP Register (1975-2008), and the Surveillance of CP in Europe (SCPE; 1976-1998). An expert panel used a consensus building technique, which utilized the SCPE 'decision tree' and the original 'What constitutes cerebral palsy?' paper as frameworks. RESULTS: CP surveillance programmes agree on key clinical criteria pertaining to the type, severity, and origin of motor disorder in CP. Further work is warranted to reach agreement for (1) minimum age of survival and maximum age of postneonatal brain injury, and (2) metabolic disorders with highly variable clinical courses/responses to treatment. One hundred and ninety-seven syndromes/disorders were reviewed and advice on their inclusion/exclusion is provided. INTERPRETATION: What constitutes CP will continue to evolve as diagnostics improve. Surveillance programmes throughout the world are committed to addressing their differences regarding inclusion/exclusion criteria for the umbrella term CP.

Monitoring the prevalence of severe intellectual disability in children across Europe: feasibility of a common database.

AIM: Our aim was to study the feasibility of creating a framework for monitoring and undertaking collaborative research on intellectual disability at the European level, based on existing databases of children with such disability. METHOD: The characteristics of five existing European intellectual disability databases from four countries (Iceland, Latvia, Ireland, and two in France), were discussed on the basis of ideal criteria set by a working group on childhood intellectual disability as part of the Surveillance of Cerebral Palsy in Europe Network (SCPE-NET). Mean prevalence values for severe intellectual disability for the birth years 1990 till 2002 were compared across databases. RESULTS: Methods of case recruitment and diagnosis differed across databases, but classification of intellectual disability and completeness were similar. Severe intellectual disability (IQ<50) prevalence estimates were significantly (p<0.001) different across databases (south-east France: 3.3 out of 1000; south-west France: 3.0 out of 1000; Latvia: 3.9 out of 1000; Ireland: 5.0 out of 1000; and Iceland 5.1 out of 1000). INTERPRETATION: In spite of differences in diagnosis and case inclusion across databases, the construction of a common database for severe intellectual disability was deemed feasible through harmonization of certain criteria, such as age, and through restriction to those with severe intellectual disability.

Stillbirth classification in population-based data and role of fetal growth restriction: the example of RECODE.

BACKGROUND: Stillbirth classifications use various strategies to synthesise information associated with fetal demise with the aim of identifying key causes for the death. RECODE is a hierarchical classification of death-related conditions, which grants a major place to fetal growth restriction (FGR). Our objective was to explore how placement of FGR in the hierarchy affected results from the classification. METHODS: In the Rhône-Alpes region, all stillbirths were recorded in a local registry from 2000 to 2010 in three districts (N = 969). Small for gestational age (SGA) was defined as a birthweight below the 10th percentile. We applied RECODE and then modified the hierarchy, including FGR as the penultimate category (RECODE-R). RESULTS: 49.0% of stillbirths were SGA. From RECODE to RECODE-R, stillbirths attributable to FGR decreased from 38% to 14%, in favour of other related conditions. Nearly half of SGA stillbirths (49%) were reclassified. There was a non-significant tendency toward moderate SGA, singletons and full-term stillbirths to older mothers being reclassified. CONCLUSIONS: The position of FGR in hierarchical stillbirth classification has a major impact on the first condition associated with stillbirth. RECODE-R calls less attention to monitoring SGA fetuses but illustrates the diversity of death-related conditions for small fetuses.

Reporting of perinatal health indicators for international comparisons--enhancing the appearance of geographical plots.

BACKGROUND: Tabulating annual national health indicators sorted by outcome may be misleading for two reasons. The implied rank order is largely a result of heterogeneous population sizes. Distinctions between geographically adjacent regions are not visible. METHODS: Regional data are plotted in a geographical map shaded in terms of percentiles of the indicator value. Degree of departure is determined relative to control limits of a corresponding funnel plot. Five methods for displaying outcome and degree of departure from a reference level are proposed for four indicators selected from the 2004 European Perinatal Health Report. RESULTS: Spread of indicator values was generally largest for small population sizes, with results for large populations lying mostly close to respective European medians. The high neonatal mortality rate for Poland (4.9 per 1000); high low-birthweight rates for England and Wales (7.8%), Germany (7.3%) and Estonia (4.5%); and high caesarean section rates for Italy (37.8%), Poland (26.3%), Portugal (33.1%) and Germany (27.3%) were statistically significant exceptions to this pattern. Estonia also showed an extreme result for maternal mortality (29.6 per 100 000). CONCLUSION: Extreme deviations from EU reference levels are either correlated with small population sizes or may be interpreted in terms of differing medical practices, as in the case of caesarean section rate. EURO-PERISTAT has now decided to use 5-year averages for maternal mortality to reduce the variance in outcome. Use of two colours in three intensities and solid fill versus crosshatching is best suited to display rate and significance of difference.

Adherence to hypothermia guidelines: a French multicenter study of fullterm neonates.

AIM: The objective of this study was to describe the French practice of hypothermia treatment (HT) in full-term newborns with hypoxic-ischemic encephalopathy (HIE) and to analyze the deviations from the guidelines of the French Society of Neonatology. MATERIALS AND METHODS: From May 2010 to March 2012 we recorded all cases of HIE treated by HT in a French national database. The population was divided into three groups, "optimal HT" (OHT), "late HT" (LHT) and "non-indicated" HT (NIHT), according to the guidelines. RESULTS: Of the 311 newborns registered in the database and having HT, 65% were classified in the OHT group, 22% and 13% in the LHT and NIHT groups respectively. The severity of asphyxia and HIE were comparable between newborns with OHT and LHT, apart from EEG. HT was initiated at a mean time of 12 hours of life in the LHT group. An acute obstetrical event was more likely to be identified among newborns with LHT (46%), compared to OHT (34%) and NIHT (22%). There was a gradation in the rate of complications from the NIHT group (29%) to the LHT (38%) group and the OHT group (52%). Despite an insignificant difference in the rates of death or abnormal neurological examination at discharge, nearly 60% of newborns in the OHT group had an MRI showing abnormalities, compared to 44% and 49% in the LHT and NIHT groups respectively. CONCLUSION: The conduct of the HT for HIE newborns is not consistent with French guidelines for 35% of newborns, 22% being explained by an excessive delay in the start of HT, 13% by the lack of adherence to the clinical indications. This first report illustrates the difficulties in implementing guidelines for HT and should argue for an optimization of perinatal care for HIE.

Interrater reliability study of cerebral palsy diagnosis, neurological subtype, and gross motor function.

AIM: To evaluate the interrater reliability of the inclusion in registries and classification of children with cerebral palsy (CP). METHOD: Two studies were conducted. In study 1, 12 paediatricians from 11 countries viewed video sequences of 12 children with or without CP (nine males, three females; median age 6y; range 2-16). In study 2, 19 professionals from eight countries participated in an online exercise. They had to classify the same children but based on written vignettes. All participants had to evaluate whether the child had CP, the neurological subtype (Surveillance of Cerebral Palsy in Europe classification system), and gross motor function level (Gross Motor Function Classification System [GMFCS]). Kappa (κ) coefficients were calculated for categorical variables and intraclass correlation coefficients (ICCs) for ordinal data. RESULTS: Reliability was excellent in assessing whether or not a child had CP in study 1 (κ=1.00) and substantial in study 2 (κ=0.73); 95% confidence interval [CI] 0.58-0.87). For the neurological subtype, overall κ between paediatricians was 0.85 (95% CI 0.68-0.98), with full agreement observed for eight children. In study 2, overall κ was 0.78 (95% CI 0.61-0.91) with full agreement seen for five children. For the GMFCS, the ICC was 0.88 (95% CI 0.78-0.95) in study 1 and 0.80 (95% CI 0.64-0.91) in study 2. INTERPRETATION: Reliability was excellent for all characteristics classified by paediatricians viewing the videos and substantial for professionals reading vignettes.

Measuring the concept of impact of childhood disability on parents: validation of a multidimensional measurement in a cerebral palsy population.

Living with a child with a disability can affect family life in various domains. Impacts on time, expenses, work, relationships within the family, social relationships and physical and psychological health can be observed. The Family Impact of Childhood Disability (FICD) is a specific instrument designed to assess this situation. Used in a cross-sectional survey, this questionnaire was extended to consider two missing aspects: impact on work and health (FICD+4). This paper addresses the psychometric qualities of the FICD in Europe among parents living with an adolescent with cerebral palsy. Expecting the FICD+4 could assess detailed impact dimensions, an exploratory analysis was conducted. We interviewed 242 families of 13- to 17-year-old adolescents with cerebral palsy living in Europe. Good psychometric properties were found in negative and positive FICD scales and in six underlying factors extracted from exploratory factor analysis on FICD+4. These results support the psychometric validity of the FICD in the assessment of the impact of disability in European families who live with an adolescent with cerebral palsy. They also highlight the multifaceted aspects of the impact of childhood disability on the family and suggest that the FICD+4 is a good tool for assessing specific negative impacts on time, finances, work, social relationships and positive impacts on parental feeling and family attitude. This scale needs further validation and could be helpful for research and clinical interventions.

Pre-, peri- and neonatal risk factors for autism.

OBJECTIVE: To identify pre-, peri- and neonatal risk factors for pervasive developmental disorders (PDD). METHODS: We searched the Medline database through March 2011 for relevant case-control and population-based studies on pre-, peri- and neonatal hazards related to PDD, including autism. We identified 85 studies for this review. Data were extracted systematically and organized according to risk factors related to family history, pregnancy, gestational age, delivery, birth milestones and the neonate's condition at birth. RESULTS: During the prenatal period, risk factors for PDD were advanced maternal or paternal ages, being firstborn vs. third or later, maternal prenatal medication use and mother's status as foreign born. During the perinatal and neonatal periods, the risk factors for PDD were preterm birth, breech presentation, planned cesarean section, low Apgar scores, hyperbilirubinemia, birth defect and a birthweight small for gestational age. The influence of maternal pre-eclampsia, diabetes, vomiting, infections and stress during pregnancy requires further study in order to determine risk for PDD. DISCUSSION: Despite evidence for the association of some pre-, peri- and neonatal risk factors associated with PDD, it remains unclear whether these risks are causal or play a secondary role in shaping clinical expression in individuals with genetic vulnerability. A plausible hypothsesis is that improvements in obstetric and neonatal management have led to an increased rate of survivors with pre-existing brain damage. Given the variety of risk factors, we propose that future studies should investigate combinations of multiple factors, rather than focusing on a single factor.

Epilepsy and cerebral palsy: characteristics and trends in children born in 1976-1998.

BACKGROUND: Although epilepsy is common in children with cerebral palsy (CP), no data exists on prevalence rates of CP and epilepsy. AIMS: To describe epilepsy in children with CP, and to examine the association between epilepsy and neonatal characteristics, associated impairments and CP subtypes. METHODS: Data on 9654 children with CP born between 1976 and 1998 and registered in 17 European registers belonging to the SCPE network (Surveillance of Cerebral Palsy in Europe) were analyzed. RESULTS: A total of 3424 (35%) children had a history of epilepsy. Among them, seventy-two percent were on medication at time of registration. Epilepsy was more frequent in children with a dyskinetic or bilateral spastic type and with other associated impairments. The prevalence of CP with epilepsy was 0.69 (99% CI, 0.66-0.72) per 1000 live births and followed a quadratic trend with an increase from 1976 to 1983 and a decrease afterwards. Neonatal characteristics independently associated with epilepsy were the presence of a brain malformation or a syndrome, a term or moderately preterm birth compared with a very premature birth, and signs of perinatal distress including neonatal seizures, neonatal ventilation and admission to a neonatal care unit. CONCLUSIONS: The prevalence of CP with epilepsy followed a quadratic trend in 1976-1998 and mirrored that of the prevalence of CP during this period. The observed relationship between epilepsy and associated impairments was expected; however it requires longitudinal studies to be better understood.

Cerebral palsy among children born moderately preterm or at moderately low birthweight between 1980 and 1998: a European register-based study.

AIM: The aim of this study was to describe trends in prevalence, subtypes, and severity among children with cerebral palsy (CP) born moderately preterm (MPT; (gestational age 32-36 wks) or at moderately low birthweight (MLBW; 1500-2499 g) in Europe. METHOD: We conducted trend analyses of data from 903 children with CP born between 1980 and 1998 who were MPT (gestational age 32-36 wks), taken from 11 registers in the Surveillance of Cerebral Palsy in Europe database and from 1835 children with CP who were born at moderately low birthweight (1500-2499 g), taken from 14 registers in the Surveillance of Cerebral Palsy in Europe database. RESULTS: The overall annual prevalence of CP in children born MPT varied between 12.2 (95% confidence interval [CI] 8.5-17.1) per 1000 live births in 1983 and 4.5 (95% CI 3.2-6.3) per 1000 in 1997. There was a significant decrease in the prevalence over time adjusted for register, with an annual change in prevalence of -3% (95% CI -5 to -2%). This was due to a decrease in the prevalence of bilateral spastic CP (annual change -5%; 95% CI -7 to -3%). INTERPRETATION: There was a trend towards a decrease in the prevalence of CP among children born MPT, but no difference in prevalence among children born at MLBW. Both results may represent an improvement in perinatal and neonatal care.

Risk factors for cerebral palsy in children born at term.

OBJECTIVE: To provide an overview of current research on risk factors for cerebral palsy (CP) in children born at term and hypothesize how new findings can affect the content of the CP registers worldwide. DESIGN: A systematic search in PubMed for original articles, published from 2000 to 2010, regarding risk factors for CP in children born at term was conducted. METHODS: Full text review was made of 266 articles. MAIN OUTCOME MEASURES: Factors from the prenatal, perinatal and neonatal period considered as possible contributors to the causal pathway to CP in children born at term were regarded as risk factors. RESULTS: Sixty-two articles met the criteria for an original report on risk factors for CP in children born at term. Perinatal adverse events, including stroke, were the focus of most publications, followed by genetic studies. Malformations, infections, perinatal adverse events and multiple gestation were risk factors associated with CP. The evidence regarding, for example, thrombophilic factors and non-CNS abnormalities was inconsistent. CONCLUSIONS: Information on maternal and neonatal infections, umbilical cord blood gases at birth, mode of delivery and placental status should be collected in a standardized way in CP registers. Information on social factors, such as education level, family income and area of residence, is also of importance. More research is needed to understand the risk factors of CP and specifically how they relate to causal pathways of cerebral palsy.