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.

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.

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.

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.

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.

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.

Trends in prevalence of cerebral palsy in children born with a birthweight of 2,500 g or over in Europe from 1980 to 1998.

Time trends for cerebral palsy (CP) prevalence in children born > or =2,500 g vary across studies and scarce data exist on trends by subtype of CP. The objective of this study was to describe changes in prevalence of CP in infants born > or =2,500 g between 1980 and 1998 in Europe. Data were collated from the SCPE (Surveillance of Cerebral Palsy in Europe collaboration) common database. Poisson regression was used to test for change in prevalence over time. Birth year and register effects were explored and trends in prevalence were estimated by CP subtype and severity. Four thousand and two children with CP and birthweight > or =2,500 g were recorded in 15 population based-registers. The overall prevalence of CP was 1.16 per 1,000 live births (99% CI, 0.88-1.48) in 1980 and 0.99 (CI, 0.80-1.20) in 1998. The trend was not significant (P = .14), except in two registers. However, there were significant changes in the prevalence of spastic CP subtypes, with a decrease in the bilateral spastic form (P < .001), and an increase in the unilateral spastic form (P = .004). There was a concurrent reduction in neonatal mortality of children with birthweight > or =2,500 g: from 1.7 (CI, 1.4-2.1) to 0.9 (CI, 0.7-1.1) per 1,000 live births. In conclusion, for children born with birthweight > or =2,500 g, the prevalence of CP in Europe was stable in spite of changes by subtype and a significant decrease in neonatal mortality.

Congenital anomalies in children with cerebral palsy: a population-based record linkage study.

AIM: Our aim was to determine the proportion of children with cerebral palsy (CP) who have a congenital anomaly (CA) in three regions (Isère Region, French Alps; Funen County, Denmark; Northern Region, England) where population-based CP and CA registries exist, and to classify the children according to CA subtype. METHOD: Data for children born between 1991 and 1999 were linked using electronic matching of cases. All potential matches were checked manually by each centre and verified as true matches. RESULTS: A total of 1104 children with CP were born during the study period (663 males, 441 females). Of these, 166 (15%; 95% Confidence Interval [CI] 13.0-17.3) children with CP had a CA: 8.8% had a cerebral anomaly, 4.8% had a non-cerebral anomaly, and 1.4% had a non-cerebral-related syndrome or a chromosomal/genetic anomaly. INTERPRETATION: The prevalence of cerebral anomaly was highest in children with ataxic CP (41.7%) and lowest in those with dyskinetic CP (2.1%). Cerebral anomalies were found in 8.4% and 7% of children with bilateral and unilateral spastic CP respectively. The most frequent cerebral anomalies were primary microcephaly (26.5%) and congenital hydrocephalus (17.3%). The most common non-cerebral anomalies recorded were cardiac (12.6% of children with CP and CA), urinary (5.4%), and musculoskeletal (5.4%). The prevalence of cerebral anomalies was higher among children born at term (13%) than among those born preterm (3.8%). Associated sensorineural or intellectual impairments occurred more often in children with CP and cerebral anomalies. We concluded that cerebral and non-cerebral CA prevalence was higher among the CP population than in the general population of live births.

Prevalence and risk factors of suppurative complications in children with pneumonia.

AIM: To identify the baseline characteristics associated with suppurative complications in children with community-acquired primary pneumonia. METHODS: A retrospective study included all children from 28 days to 15 years old, who presented with community-acquired pneumonia at two French hospitals from 1995 to 2003. Complicated pneumonia was defined by the presence of empyema and/or lung abscess. RESULTS: Of 767 children with community-acquired pneumonia, 90 had suppurative complications: 83 cases of pleural empyema and seven cases of lung abscess. The mean prevalence of complicated pneumonia was 3% during the 1995-1998 period, and then steadily increased following a linear trend to reach 23% in 2003. Children with complicated pneumonia were older and had a longer symptomatic period preceding hospitalization. They were more likely to receive antibiotics, especially aminopenicillins (p < 0.01), and nonsteroidal anti-inflammatory drugs, especially ibuprofen (p < 0.001). In multivariable analysis, ibuprofen was the only preadmission therapy that was independently associated with complicated pneumonia [adjusted OR = 2.57 (1.51-4.35)]. CONCLUSION: This study confirms an association between the use of prehospital ibuprofen and suppurative pneumonic complications.

Trends in cerebral palsy among infants of very low birthweight (<1500 g) or born prematurely (<32 weeks) in 16 European centres: a database study.

BACKGROUND: The risk of cerebral palsy, the commonest physical disability of children in western Europe, is higher in infants of very low birthweight (VLBW)--those born weighing less than 1500 g--and those from multiple pregnancies than in infants of normal birthweight. An increasing proportion of infants from both of these groups survive into childhood. This paper describes changes in the frequency and distribution of cerebral palsy by sex and neurological subtype in infants with a birthweight below 1000 g and 1000-1499 g in the period 1980-96. METHODS: A group of 16 European centres, Surveillance of Cerebral Palsy in Europe, agreed a standard definition of cerebral palsy and inclusion and exclusion criteria. Data for children with cerebral palsy born in the years 1980-96 were pooled. The data were analysed to describe the distribution and prevalence of cerebral palsy in VLBW infants. Prevalence trends were expressed as both per 1000 livebirths and per 1000 neonatal survivors. FINDINGS: There were 1575 VLBW infants born with cerebral palsy; 414 (26%) were of birthweight less than 1000 g and 317 (20%) were from multiple pregnancies. 1426 (94%) had spastic cerebral palsy, which was unilateral (hemiplegic) in 336 (24%). The birth prevalence fell from 60.6 (99%CI 37.8-91.4) per 1000 liveborn VLBW infants in 1980 to 39.5 (28.6-53.0) per 1000 VLBW infants in 1996. This decline was related to a reduction in the frequency of bilateral spastic cerebral palsy among infants of birthweight 1000-1499 g. The frequency of cerebral palsy was higher in male than female babies in the group of birthweight 1000-1499 g (61.0 [53.8-68..2] vs 49.5 [42.8-56.2] per 1000 livebirths; p=0.0025) but not in the group of birthweight below 1000 g. INTERPRETATION: These data from a large population base provide evidence that the prevalence of cerebral palsy in children of birthweight less than 1500 g has fallen, which has important implications for parents, health services, and society.

Cerebral palsy and congenital malformations.

AIM: To determine the proportion of children with cerebral palsy (CP) who have cerebral and non-cerebral congenital malformations. METHODS: Data from 11 CP registries contributing to the European Cerebral Palsy Database (SCPE), for children born in the period 1976-1996. The malformations were classified as recognized syndromes, chromosomal anomalies, cerebral malformations or non-cerebral malformations. Prevalence of malformations was compared to published data on livebirths from a European database of congenital malformations (EUROCAT). RESULTS: Overall 547 out of 4584 children (11.9%) with CP were reported to have a congenital malformation. The majority (8.6% of all children) were diagnosed with a cerebral malformation. The most frequent types of cerebral malformations were microcephaly and hydrocephaly. Non-cerebral malformations were present in 97 CP children and in further 14 CP children with cerebral malformations. The most frequent groups of non-cerebral malformations were cardiac, facial clefts and limb and skeleton malformations. Children born at term had a significantly higher prevalence of cerebral malformations compared to children born before 32 weeks (12.1% versus 2.1%, p<0.001). CONCLUSION: Cerebral malformations were much more frequent among children with CP than among all livebirths in the population. Malformations in organ systems close to the brain (eye, facial clefts) were more frequent in the CP population while malformations in organ systems further from the brain (renal, genital) were more frequent in the general population.