[Schooling and care of mild intellectual disability children]. / Parcours scolaire et prise en charge médico-éducative des enfants avec déficience intellectuelle légère.

Studies on mild intellectual disability (MID) are scarce. The aim of this study was to describe the educational and medical care trajectories and their determinants in children with MID. The study population concerned children born in 1997 and resident in a French county (Isère) in 2008. MID was defined as an overall IQ score between 50 and 69. For the present study, this definition was adjusted by integrating the IQ confidence intervals so that the risk of IQ measurement relativity and possible score discrepancy could be taken into account. Of the 267 children included, 180 (67%) were identified through an institute that decides upon special education and allowances (MDPH) and 87 (33%) through the educational system. The parents of 181 children (68%) accepted to answer a telephone questionnaire, describing their child's educational and medical history. Children with MID frequently presented clinical signs and comorbidities. Educational trajectories were quite varied: a majority of the children (52.9%) were oriented toward sections with adapted general and professional education (SEGPA) after finishing primary school, a minority (41.3%) were oriented towards specialized schools, such as medical-educational institutions, and a small proportion of children (5.8%) stayed in ordinary school. Children followed the SEGPA orientation more frequently when a relative written language disorder was present, and autism-spectrum disorders or other clinical signs were absent. Concerning follow-up care and rehabilitation, children mostly took part in speech therapy (76.2%) and psychotherapy (55.8%). The French law dating from 2005, ensuring equal opportunity for people with disabilities, has borne fruit in the diversification of educational trajectories.

[Can caesarean delivery prevent cerebral palsy? Medico-legal implications of a French ecological study]. / La césarienne peut-elle prévenir la paralysie cérébrale ? Implications médico-légales d'une étude écologique française.

OBJECTIVE: For a long time, the benefit of a caesarean delivery in the prevention of cerebral palsy (CP) has been put forward, which was based on the assumption that CP is due to asphyxia in more than 50 % of the cases. However, from register-based data, this rate has been estimated less than 4 %. The aim of this study was to evaluate whether the rate of caesarean sections for fetal indication was correlated with the prevalence rate of CP in a French county. PATIENTS AND METHODS: This was an ecological study of register-based prevalence estimates of children with CP (postnatal cases excluded) born between 1997 and 2003 in a French county compared with the rates of caesarean section for fetal distress obtained from the maternal and infant protection service of the county. RESULTS: Whilst the rate of caesarean section for fetal indication increased by 44% during the period studied, the prevalence of CP remained nearly stable around 1.5 per 1000 live births. There was no correlation between caesarean section and CP prevalence (r'=-0.36, P=0.43). DISCUSSION AND CONCLUSION: The present study was in accordance with the results of a recent meta-analysis which concluded that emergency and prophylactic caesarean deliveries were not efficient in the prevention of CP. Indication of caesarean delivery for foetal heart rhythm anomaly, which is the most relevant cause for the growing rate of caesarean sections, should be justified by additional examinations in ambivalent cases, in order not to consider it as defensive medicine, which is ethically and therefore juridically blameworthy.

Prevalence and characteristics of children with mild intellectual disability in a French county.

BACKGROUND: Studies conducted on mild intellectual disability (MID) in children are infrequent and the prevalence rates vary widely. This study aimed to estimate the prevalence of MID in children in a French county (Isère), to describe the clinical signs and associated comorbidities, and to specify the aetiologies of this disability. METHODS: The target population was comprised of the 15 100 children born in 1997 residing in Isère County, France, in 2008. Our goal was to find the children in this group with MID diagnosed between 9 and 13 years of age. MID was defined as an overall IQ score of between 50 and 69 [International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10)]; this definition was adjusted for the study by integrating confidence intervals so that the risk of IQ measurement relativity and possible discrepancy of scores could be taken into account. Children were identified through an administrative data source designed to assist disabled persons that contains health information, and an educational data source. Parents who agreed to let their children participate responded to an in-depth questionnaire on their child's medical and academic history. A genetic investigation was proposed for those children whose MID had an unknown aetiology. RESULTS: The preliminary selection included 267 children, resulting in a prevalence rate of 18 per 1000 (CI [15.6; 19.9]), within the expected mean. Of these 267 cases, 181 families agreed to participate in the study (68%). MID more often affected boys [male gender ratio = 1.4 (CI [1.2; 1.6])], low socioeconomic groups, and families with a history of intellectual disability. The clinical signs and comorbidities associated with MID were very frequent, with 54% spoken language disorders and 10% pervasive developmental disorder. Only 9% of the children had undergone a genetic investigation before the study. The known aetiology rate for MID was 19% among all the children who had had genetic tests performed. CONCLUSION: MID is an important public health issue based on its prevalence. The associated clinical signs and comorbidities may be warning signs of MID in case of learning difficulties. This study may help decision-makers to develop and organise screening and care for MID.

[Neonatal exposure to anesthesia and adverse cognitive outcome in childhood. Insight from epidemiology]. / L'anesthésie en période néonatale a-t-elle un effet défavorable sur le devenir cognitif ? Le point de vue de l'épidémiologiste.

Adverse effects of general anesthesia have been observed repeatedly, mainly in animal model studies and in rodents. Already in 2005, the Food and Drug Administration recommended proceeding to similar studies in human infants, highlighting that there were several methodological issues to solve before being able to appreciate the risk of anesthetic agents on the developing brain. Most studies conducted in humans were observational studies, showing a very mild adverse effect on cognitive functions, an effect that disappeared when properly adjusted analysis was performed (with various modalities for analysis and protocols for these adjusted results). Due to numerous biases in these observational studies - bias related to selection of the population and the control subjects and their comparability as well as outcome measure assessment, it has become extremely important to conduct prospective studies. Two international studies are currently under way, but their results will not be available for a few years. How animal model results can be relevant to human babies remains controversial. Until today, and according to the current state of the art, no changes in practices are indicated, and it is important for infants and their families to avoid sensationalist messages.

[Impact on parents of cerebral palsy in children: a literature review]. / Impact sur les parents de la paralysie cérébrale chez l'enfant : revue de la littérature.

Cerebral palsy is the commonest cause of motor impairment in childhood. Parents of children with this particular neurodevelopmental disorder face many problems encountered by disabled children's parents. The aim of the present paper is to report the current knowledge on this parental impact, highlighting consensus and disagreement. A literature search was conducted using the key words "Cerebral palsy" and "Parents/Father/Mother" and "Adapt/Adjust/Cost/Economic/Impact/Well-being" in the Medline and PsycInfo databases searching for articles published between 1989 and 2009. Seven parental impact dimensions were distinguished: time spent, occupational restrictions, social relationships, family relationships, psychological well-being, physical health, and financial burden. Of 40 selected references, the studies were mostly cross-sectional, although longitudinal surveys highlighted the causal relationship between factors. Despite various methodologies, this review confirms that parents of CP children have greater risk of experiencing a sense of burden than parents of typically normally developing children. Time spent caring for the child appears to be an important factor that depends on the child's autonomy. The 7 impact dimensions seem to be related to each other and to child's and caregiver's characteristics. The severity of motor impairment is not unanimously viewed as a worsening factor: however, the child's behavioral problems influence the impact experienced by the parents. The level of intellectual impairment also has a negative influence on family relationships and on the parent's psychological well-being. The child's developmental stage seems to be related to the level of parental impact, but there is no agreement on the dimensions involved. We also observed that the mother and father do not experience this situation in the same way, probably because of the role played by each one in the family. The current literature lacks data on caregiver characteristics, identifying families at risk of burden, and the environmental context that would allow for a less negative impact on parents. In addition, the tools measuring the impact lack standardization. No questionnaire covering all 7 dimensions exists, but useful validated questionnaires for different dimensions were identified. We consider that the caregiver's occupation and physical health needs further research. The current knowledge is insufficient for proposing an overall model taking all the dimensions into account. Research is needed before a complete model of the CP child's impact on parents can be tested in view of providing guidelines to professionals for identifying families with a risk of maladaptation and suggesting solutions to decrease the negative impact.

[Preterm births circumstances in babies born before 35 weeks in French Alpes: PREMALP study]. / Etude des circonstances de naissance prématurée avant 35SA dans le sillon alpin : étude PREMALP.

OBJECTIVES: In a regional study of preterm infants born before 35weeks of gestation, the aim was to propose a new classification of preterm births into three groups, and to describe the pregnancy complications and fetal disorders in each group. PATIENTS AND METHODS: In two areas covered by a perinatal network, all preterm births, live births and stillbirths, which occurred between 22 and 34 completed weeks were recorded over a 21-month period. Each case was classified either in the medically-indicated preterm birth (I) group, or in the accepted spontaneous preterm birth (ASp) group or in the non-accepted spontaneous preterm birth (NASp) group. RESULTS: One thousand and sixty cases of preterm births were included; among them, 981 were live births or ended with per partum infant death. Forty-nine percent of these births were medically indicated, 32 % were ASp and 19 % were NASp. The distribution of pregnancy complications and fetal disorders differed between preterm birth groups: ischemic placental diseases were present in 38,2 % of medically-indicated births; preterm premature rupture of membranes occurred twice more often in I and ASp preterm births than in NASp preterm births. CONCLUSION: This classification is based on the medical decision; it allows to compare medical practices in given obstetrical situations. It appears to be reproducible and easy to use.

Dyskinetic cerebral palsy in Europe: trends in prevalence and severity.

OBJECTIVE: To describe the trends for and severity of dyskinetic cerebral palsy in a European collaborative study between cerebral palsy registers, the Surveillance of Cerebral Palsy in Europe (SCPE). METHODS: The prevalence of dyskinetic cerebral palsy was calculated in children born in 1976-1996. Walking ability, accompanying impairments and perinatal adverse events were analysed. RESULTS: 578 children had dyskinetic cerebral palsy, of whom 70% were born at term. The prevalence per 1000 live births increased from 0.08 in the 1970s to 0.14 in the 1990s. For the 386 children (70%) with a birth weight of > or =2500 g, the increase was significant (0.05 to 0.12). There was a concurrent decrease in neonatal mortality among children with a birth weight of > or =2500 g. Overall, 16% of the children walked without aids, 24% with aids and 59% needed a wheelchair. Severe learning disability was present in 52%, epilepsy in 51% and severe visual and hearing impairment in 19% and 6%, respectively. Accompanying impairments increased with motor severity. In children born in 1991-1996, perinatal adverse events, that is an Apgar score of <5 at 5 min and convulsions before 72 h, had occurred more frequently compared with children with bilateral spastic cerebral palsy (BSCP, n = 4746). Children with dyskinetic cerebral palsy had more severe cognitive and motor impairments than children with BSCP. CONCLUSIONS: The prevalence of dyskinetic cerebral palsy appears to have increased in children with a normal birth weight. They have frequently experienced perinatal adverse events. Most children have a severe motor impairment and several accompanying impairments.

Rare diseases in disabled children: an epidemiological survey.

AIM: To estimate the contribution of rare diseases (RD) to severe impairment in 7-year-old children. METHODS: Data from a morbidity register of childhood impairments in a single French region were used. Impairments were classified as a mental, sensorial, neuromuscular (skeletal or movement-related) impairment (MSN_I) according to the International Classification of Functioning. Details of children born from 1980 to 1994 and resident in the county under study when they were 7 years old were recorded. A rare disease was defined as a prevalence rate of <1 per 2000 general population. RESULTS: 26% of children with severe MSN_I had a rare disease; in 36% the MSN_I was of unknown origin. The proportion of impairments that were due to a rare disease varied according to the type of impairment: 3.3% for severe psychiatric disorders; 16.0% for intellectual impairment; 37.2% for hearing impairment; 41.2% for neuromuscular, skeletal and movement impairment; and 81.1% for visual impairment. The overall prevalence rate of rare diseases was 2.1 per 1000 (459/218 283), and it increased significantly over time (p = 0.003). The latter increase was not associated with a decrease in the proportion of impairments of unknown origin, indicating an improvement in the survival of the children with a rare disease. CONCLUSIONS: In this study, a rare disease was at the origin of 26% of cases of severe MSN_I. This proportion remained stable over time, whereas the prevalence rate, as well as the prevalence rate of MSN_I disability, increased over time.

[Epidemiology and clinical characteristics of childhood parapneumonic empyemas]. / Epidémiologie et caractéristiques cliniques des complications suppuratives des pneumonies de l'enfant.

UNLABELLED: Several studies have reported an increasing incidence of childhood parapneumonic empyemas in various countries. AIM OF THE STUDY: The aim of our study was to estimate the annual incidence of complicated community-acquired pneumonias in children during a 9-year period in a French area and to describe the epidemiological and clinical characteristics of these complications. POPULATION AND METHODS: We have listed the children from 28 days to 15 years old, hospitalized in the 2 children hospitals of the Isere district for a community-acquired pneumonia complicated with a pleural empyema or a pulmonary abscess from 1995 to 2003. RESULTS: During the study period, 90 children were hospitalized for a complicated pneumonia including 83 pleural empyemas and 7 isolated lung abscess. The average number of cases was 4 per year from 1995 to 1998 then increased since 1999 to reach 34 cases in 2003, according to a linear model (P<0,001). The incidence of the complicated pneumonia, plotted to the paediatric population of the area has gone up from 0.5 per 100000 to 13 per 100000 children between 1995 and 2003. CONCLUSION: The incidence of the complicated pneumonias in children increased since 1999 in a French area. Additional investigations are necessary to identify the causes of this increase.

Predictive factors for an increased risk of sperm aneuploidies in oligo-astheno-teratozoospermic males.

Patients with severe spermatogenesis impairment can now successfully father a child thanks to the use of intracytoplasmic sperm injection (ICSI). In oligozoospermic patients, many studies have reported significantly higher sperm aneuploidy rates and therefore an increased risk of transmitting a chromosomal abnormality via the injection of abnormal spermatozoa. However, the frequency of aneuploidy is highly variable between patients. The aim of the present work was to identify clinical and biological factors, which, together with non-obstructive oligozoospermia, could be predictive of elevated sperm aneuploidies. The sperm aneuploidy rates for chromosomes X, Y, 13, 18 and 21 were assessed in 31 infertile men with well-characterized spermatogenesis impairment, and in a population of control men with proven fertility. The frequency of sperm aneuploidy was compared between several patient subgroups according to their clinical and biological factors. Nearly half of the oligozoospermic males (15/31) had a significantly increased disomy rate for at least one of the five chromosomes compared with that observed in the control population (mean disomy rates + 1.96 standard deviation). Factors significantly associated with higher numbers of aneuploid sperm were cigarette smoking, an elevated follicle-stimulating hormone level, a sperm concentration less than 1 m/mL, and a severe teratozoospermia. Hence, several factors predictive of an increased risk of sperm aneuploidy rates were identified in ICSI male candidates with a non-obstructive oligozoospermia.

[Role of "subtle" ultrasonographic signs during antenatal screening for trisomy 21 during the second trimester of pregnancy: meta-analysis and CPDPN protocol of the Grenoble University Hospital]. / Quelle est la place des signes d'appels échographiques dits "mineurs" dans le dépistage prénatal de la trisomie 21 au 2e trimestre de la grossesse? Méta-analyse de la littérature et protocole du Centre pluridisciplinaire de Dignostic Prénatal (CPDPN) du CHU de Grenoble.

OBJECTIVE: A meta-analysis about subtle ultrasonographic signs in second trimester of pregnancy. MATERIALS AND METHODS: 196 articles dealing with the subject--from 1985 to July 2002--were studied. Data on the 11 reported signs were collected from 92 theoretically and/or statistically valid studies. Then, the studies were selected according to several criteria: isolated characteristic, defined thresholds, calculable sensitivity and specificity. After checking for homogeneity, a likelihood ratio was calculated for some of the signs. RESULTS: This meta-analysis of the second trimester ultrasonographic signs of Down's syndrome enabled us to estimate the likelihood ratio (LHR) of six signs. At 22 weeks'gestation (WG) these signs are: pyelectasis equal to or greater than 5 mm; nuchal fold thickness equal to or greater than 6 mm; persistence of choroid plexus cysts; shortness of the femur and humerus below the tenth percentile; hyperechogenic bowe; and nasal bone length less than 2.5 mm. CONCLUSION: These validated ultrasonographic signs are independent of nuchal translucency thickness at 12 WG and of maternal serum biochemistry. This allows to calculate a combinate risk for nuchal translucency, maternal serum biochemistry and second trimester ultrasonographic signs when they are validated.

Case gender and severity in cerebral palsy varies with intrauterine growth.

BACKGROUND: There is an unexplained excess of cerebral palsy among male babies. There is also variation in the proportion of more severe cases by birth weight. It has recently been shown that the rate of cerebral palsy increases as intrauterine size deviates up or down from an optimum about one standard deviation heavier than population mean weight-for-gestation. AIMS: To determine whether the gender ratio or the severity of cases also varies with intrauterine size. METHODS: A total of 3454 cases of cerebral palsy among single births between 1976 and 1990 with sufficient data to assign case severity (based on intellectual impairment and walking ability) and to compare weight-for-gestation at birth to sex specific fetal growth standards, were aggregated from nine separate registers in five European countries. RESULTS: The greater the degree to which growth deviates either up or down from optimal weight-for-gestation at birth, the higher is the rate of cerebral palsy, the larger is the proportion of male cases, and the more severe is the functional disability. Compared to those with optimum growth the risk of more severe cerebral palsy in male babies is 16 times higher for those with a birth weight below the 3rd centile and four times higher when birth weight is above the 97th centile. In contrast, for mild cerebral palsy in female babies the excess risks at these growth extremes are about half these magnitudes. CONCLUSIONS: Among singleton children with cerebral palsy, abnormal intrauterine size, either small or large, is associated with more severe disability and male sex.

Trends in elective terminations of pregnancy between 1989 and 2000 in a French county (the Isère).

OBJECTIVES: This study was performed in order to provide a description of indications for induced elective terminations of pregnancy (ETOP), their characteristics (e.g. gestational age), and their evolution over time. DESIGN OF THE STUDY: This is an epidemiological study. The geographic area covered is the French county of 'Isère', which represents a mean of 14 000 births per year over the study period. MATERIALS AND METHODS: Data on ETOPs were collected actively from medical records by a register of childhood deficiencies and adverse perinatal events in this county. Between 1989 and 2000, 996 ETOPs were notified. RESULTS: Four main grounds for ETOPs were identified: (1) morphological anomalies with normal karyotype (39%), (2) chromosomal anomalies (35%), (3) other fetal grounds (16%), and (4) maternal indications (10%). Prevalence rates for the first two grounds increased significantly over the study period respectively from 2.0 to 2.9 and from 1.4 to 2.7 per 1000. Among the ETOPs carried out because of fetal indications, the percentage of late ETOPs (from 24 weeks of gestation) was 34.6%, and remained stable over the studied period. In some cases, a medical consensus was not reached with respect to indications for termination (sex chromosome anomalies, limb defects). We estimated the percentage of these cases as being 2.7% of the figure for fetal indications, without any variation in prevalence over the whole period (p = 0.59). The increasing number of ETOPs that occurred in the chromosomal aberrations group during the study period is thought to be due to an increase in diagnostic sensitivity. The increase that occurred in the morphological anomalies group is thought to be due both to an increase in sensitivity and to a widening of the field with respect to indications, some of which have an uncertain prognosis (e.g. agenesis of the corpus callosum). CONCLUSION: This study provides useful data for monitoring medical practice consistency within the field of prenatal diagnosis, and for the drive to keep medical practice within ethically acceptable limits.

[Evaluation of maternal morbidity after drug-induced termination of pregnancy (TOP) after 12 gestation weeks]. / Evaluation de la morbidité maternelle après interruption médicamenteuse de grossesse à partir de 12 semaines d'aménorrhée.

OBJECTIVE: The number of TOP for medical indications has increased regularly over the last ten years. At the same time, the methods used for TOP have evolved. The purpose of this study was to assess the frequency of complications after drug-induced termination of pregnancy in order to determine whether using this method for interrupting pregnancy during the second or third trimester adds further danger for the mother in terms of early severe risk (uterine rupture, hysterectomy) or less severe long-term risk (infection). MATERIAL AND METHODS: This metaanalysis included all articles devoted to pregnancy interruption from 12 gestation weeks retrieved from the Medline database and published between 1989 and 1999 in the United States, Canada, Australia, New Zealand, or the European Union. After excluding articles that included in utero death (n=8), isolated case reports and series involving a high-risk of maternal somatic complications (n=16), and surgical methods for pregnancy termination (n=4), we retained 23 articles for analysis. These articles had included 58,891 drug-induced terminations of pregnancy. For each article, we recorded the following complications: bleeding requiring transfusion, uterine rupture, ovular or placentar retention, and infection. A classical homogenicity test was performed for each type of complication. When this test was not significant, a mean rate, weighing by size of the study, was calculated. RESULTS: One study reported maternal deaths (3/143000). The weighted mean rate for late retention (>24 hr) was 1.5 [CI95: 1.1%-1.9%]. For infections, the rates were very variable between studies (from 0.7% to 3.6% with one study reporting 8%). For bleeding with transfusion, the weighted mean rate was 0.7% [CI95: 0.5%-0.9%]. This rate was significantly higher than the rate observed in 1999 in France after delivery excepting medically terminated pregnancy (p<10(-3)) but probably is a reflection of the variable transfusion practices during the eighties in these different countries. Th rate of uterine rupture after medically terminated pregnancy was 0.1% [CI95: 0.07%-0.17%] and would be higher after delivery (excepting terminations) but not significantly (p=0.07). CONCLUSION: This metaanalysis demonstrates that the risk of severe complications (uterine rupture and bleeding requiring transfusion) are rare but are more prevalent than after delivery except pregnancy termination. The metaanalysis approach is justified due to the low incidence of these severe complications. A prospective multicentric study of the complications using a geographical base would be useful to obtain unbiased data on risk level. A risk analysis by gestational age, maternal age, parity, and product used would thus be possible, as would long-term monitoring of maternal outcome.

Disabilities and trends over time in a French county, 1980-91.

AIM: To describe trends over time and types of disability for children born in a French county from 1980 to 1991. METHODS: Data were collected from medical records of a morbidity register; disabled children with at least one severe deficiency have been included. Prevalence rates are given per 1000 resident children, over four three-year periods. RESULTS: Overall, 7.73 per 1000 children (that is, 1360 children), had a severe childhood disability, and the prevalence rate had increased significantly since 1980. This increase was mainly owing to an increase in cerebral palsy and psychiatric disorder prevalence rates. CONCLUSION: Future research aimed to explain these trends over time can be based on such data. The present knowledge is useful for planning purposes.

[Birth mortality and pregnancy terminations: how can collected Diagnosis Related Group System data be used?]. / Mortinatalité et interruptions de grossesse: comment peut-on utiliser les données du PMSI?

In France since 1995, information on diagnoses and care are routinely collected for each patient hospitalised in a public or private hospital, using the Diagnosis Related Group system. Information on birth events constitutes a good example of possible use of this information for other aims than economic activity evaluation. In this paper, in order to highlight possible epidemiological use, some recommendations are proposed for collecting data on stillbirths and pregnancy terminations. The lack of usual knowledge on these two adverse events is the reason for this choice. While the improvements in prenatal diagnosis lead to an increase in pregnancy terminations, a minimum common core of collected data should allow routine epidemiological monitoring of these adverse perinatal events.

Nuclear tyrosine phosphorylation: the beginning of a map.

Tyrosine phosphorylation is usually associated with cytoplasmic events. Yet, over the years, many reports have accumulated on tyrosine phosphorylation of individual molecules in the nucleus, and several tyrosine kinases and phosphatases have been found to be at least partially nuclear. The question arises as to whether nuclear tyrosine phosphorylation represents a collection of loose ends of events originating in the cytoplasm or if there may be intranuclear signaling circuits relying on tyrosine phosphorylation to regulate specific processes. The recent discovery of a mechanism causing nuclear tyrosine phosphorylation has prompted us to review the cumulative evidence for nuclear tyrosine phosphorylation pathways and their possible role. While we found that no complex nuclear function has yet been shown to rely upon intranuclear tyrosine phosphorylation in an unambiguous fashion, we found a very high number of compelling observations on individual molecules that suggest underlying networks linking individual events. A systematic proteomics approach to nuclear tyrosine phosphorylation should help chart possible interaction pathways.