Catherine Arnaud

Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study.

BACKGROUND The increasing survival rates of children who are born very preterm raise issues about the risks of neurological disabilities and cognitive dysfunction. We aimed to investigate neurodevelopmental outcome and use of special health care at 5 years of age in a population-based cohort of very preterm children. METHODS We included all 2901 livebirths between 22 and 32 completed weeks of gestation from nine regions in France in Jan 1-Dec 31, 1997, and a reference group of 667 children from the same regions born at 39-40 weeks of gestation. At 5 years of age, children had a medical examination and a cognitive assessment with the Kaufman assessment battery for children (K-ABC), with scores on the mental processing composite (MPC) scale recorded. Data for health-care use were collected from parents. Severe disability was defined as non-ambulatory cerebral palsy, MPC score less than 55, or severe visual or hearing deficiency; moderate deficiency as cerebral palsy walking with aid or MPC score of 55-69; and minor disability as cerebral palsy walking without aid, MPC score of 70-84, or visual deficit (<3/10 for one eye). FINDINGS In total, 1817 (77%) of the 2357 surviving children born very preterm had a medical assessment at 5 years and 396 (60%) of 664 in the reference group. Cerebral palsy was diagnosed in 159 (9%) of children born very preterm. Scores for MPC were available for 1534 children born very preterm: 503 (32%) had an MPC score less than 85 and 182 (12%) had an MPC score less than 70. Of the 320 children in the reference group, the corresponding values were 37 (12%) and 11 (3%), respectively. In the very preterm group, 83 (5%) had severe disability, 155 (9%) moderate disability, and 398 (25%) minor disability. Disability was highest in children born at 24-28 completed weeks of gestation (195 children [49%]), but the absolute number of children with disabilities was higher for children born at 29-32 weeks (441 children [36%]). Special health-care resources were used by 188 (42%) of children born at 24-28 weeks and 424 (31%) born at 29-32 weeks, compared with only 63 (16%) of those born at 39-40 weeks. INTERPRETATION In children who are born very preterm, cognitive and neuromotor impairments at 5 years of age increase with decreasing gestational age. Many of these children need a high level of specialised care. Prevention of the learning disabilities associated with cognitive deficiencies in this group is an important goal for modern perinatal care for children who are born very preterm and for their families.

Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial

BACKGROUND Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. METHODS In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. FINDINGS 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial seizure (one [<1%] vs 0). INTERPRETATION In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit. FUNDING Public French National Programme for Clinical Research.

Self-reported quality of life of 8–12-year-old children with cerebral palsy: a cross-sectional European study

BACKGROUND Little is known about the quality of life (QoL) of disabled children. We describe self-reported QoL of children with cerebral palsy, factors that influence it, and how it compares with QoL of the general population. METHODS 1174 children aged 8-12 years were randomly selected from eight population-based registers of children with cerebral palsy in six European countries and 743 (63%) agreed to participate; one further region recruited 75 children from multiple sources. Researchers visited these 818 children. 318 (39%) with severe intellectual impairment could not self-report; 500 (61%) reported their QoL using KIDSCREEN, an instrument with scores in ten domains, each with SD=10. Multivariable regression was used to relate QoL to impairments, pain, and sociodemographic characteristics. Comparisons were made with QoL data from the general population. FINDINGS Impairments were not significantly associated with six KIDSCREEN domains. Comparison of least and most able groups showed that severely limited self-mobility was significantly associated with reduced mean score for physical wellbeing (7.6, 95% CI 2.7-12.4); intellectual impairment with reduced mean for moods and emotions (3.7, 1.5-5.9) and autonomy (3.3, 0.9-5.7); and speech difficulties with reduced mean for relationships with parents (4.5, 1.9-7.1). Pain was common and associated with lower QoL on all domains. Impairments and pain explained up to 3% and 7%, respectively, of variation in QoL. Children with cerebral palsy had similar QoL to children in the general population in all domains except schooling, in which evidence was equivocal, and physical wellbeing, in which comparison was not possible. INTERPRETATION Parents can be reassured that most children aged 8-12 years with cerebral palsy will have similar QoL to other children. This finding should guide social and educational policy to ensure that disabled children participate fully in society. Because of its association with QoL, childrens pain should be carefully assessed.

Cerebral Palsy Among Very Preterm Children in Relation to Gestational Age and Neonatal Ultrasound Abnormalities: The EPIPAGE Cohort Study

OBJECTIVE. To estimate the prevalence of cerebral palsy at 2 years of age among children born very preterm, according to gestational age, infant gender, plurality, and neonatal cranial ultrasound abnormalities. METHODS. All infants born between 22 and 32 weeks of gestation in 9 regions of France in 1997 were included in this prospective, population-based, cohort study. The main outcome measure was cerebral palsy prevalence at 2 years. Of the 2364 survivors eligible for follow-up evaluation, 1954 (83%) were assessed at 2 years of age. RESULTS. Among the 1954 children assessed at 2 years, 8.2% had cerebral palsy. Bilateral spastic cerebral palsy, hemiplegia, and monoplegia accounted for 72%, 9%, and 10% of cases, respectively. Fifty percent of the children with cerebral palsy walked independently at the age of 2, 31% were unable to walk but could sit independently, and 19% could not sit (unable to maintain head and trunk control). The prevalence of cerebral palsy was 20% at 24 to 26 weeks of gestation, compared with 4% at 32 weeks. On the basis of ultrasound findings in the neonatal period, we found that 17% of children with isolated grade III intraventricular hemorrhage and 25% of children with white matter damage (ie, ventricular dilation, persistent echodensities, or cystic periventricular leukomalacia) had cerebral palsy, compared with 4% of children with normal ultrasound scans. CONCLUSIONS. Despite recent improvements in survival rates, cerebral palsy remains highly prevalent among very preterm children. Severe cranial ultrasound abnormalities predict motor disability strongly, but one third of infants with cerebral palsy had no ultrasound abnormalities.

Determinants of child-parent agreement in quality-of-life reports: a European study of children with cerebral palsy.

OBJECTIVES. The differences between child self-reports and parent proxy reports of quality of life in a large population of children with cerebral palsy were studied. We examined whether child characteristics, severity of impairment, socioeconomic factors, and parental stress were associated with parent proxy reports being respectively higher or lower than child self-reports of quality of life. METHODS. This study was conducted in 2004–2005 and assessed child quality of life (using the Kidscreen questionnaire, 10 domains, each scored 0–100) through self-reports and parent proxy reports of 500 children aged 8 to 12 years who had cerebral palsy and were living in 7 countries in Europe. RESULTS. The mean child-reported scores of quality of life were significantly higher than the parent proxy reports in 8 domains, significantly lower for the finances domain, and similar for the emotions domain. The average frequency of disagreement (child-parent difference greater than half an SD of child scores) over all domains was 64%, with parents rating their childs quality of life lower than the children themselves in 29% to 57% of child-parent pairs. We found that high levels of stress in parenting negatively influenced parents’ perception of their childs quality of life, whereas the main factor explaining parents’ ratings of childrens quality of life higher than the children themselves is self-reported severe child pain. CONCLUSIONS. This study shows that the factors associated with disagreement are different according to the direction of disagreement. In particular, parental well-being and child pain should be taken into account in the interpretation of parent proxy reports, especially when no child self-report of quality of life is available. In the latter cases, it may be advisable to obtain additional proxy reports (from caregivers, teachers, or clinicians) to obtain complementary information on the childs quality of life.

Participation in life situations of 8-12 year old children with cerebral palsy: cross sectional European study

Objectives To evaluate how involvement in life situations (participation) in children with cerebral palsy varies with type and severity of impairment and to investigate geographical variation in participation. Design Cross sectional study. Trained interviewers visited parents of children with cerebral palsy; multilevel multivariable regression related participation to impairments, pain, and sociodemographic characteristics. Setting Eight European regions with population registers of children with cerebral palsy; one further region recruited children from multiple sources. Participants 1174 children aged 8-12 with cerebral palsy randomly selected from the population registers, 743 (63%) joined in the study; the further region recruited 75 children. Main outcome measure Children’s participation assessed by the Life-H questionnaire covering 10 main areas of daily life. Scoring ignored adaptations or assistance required for participation. Results Children with pain and those with more severely impaired walking, fine motor skills, communication, and intellectual abilities had lower participation across most domains. Type of cerebral palsy and problems with feeding and vision were associated with lower participation for specific domains, but the sociodemographic factors examined were not. Impairment and pain accounted for up to a sixth of the variation in participation. Participation on all domains varied substantially between regions: children in east Denmark had consistently higher participation than children in other regions. For most participation domains, about a third of the unexplained variation could be ascribed to variation between regions and about two thirds to variation between individuals. Conclusions Participation in children with cerebral palsy should be assessed in clinical practice to guide intervention and assess its effect. Pain should be carefully assessed. Some European countries facilitate participation better than others, implying some countries could make better provision. Legislation and regulation should be directed to ensuring this happens.

White matter damage and intraventricular hemorrhage in very preterm infants: the EPIPAGE study☆

OBJECTIVE To evaluate the prevalence of cranial ultrasound abnormalities in very preterm infants as a function of gestational age, plurality, intrauterine growth restriction, and death before discharge. STUDY DESIGN A prospective, population-based cohort of 2667 infants born between 22 and 32 weeks of gestation in 1997 in nine regions of France, transferred to a neonatal intensive care unit, for whom at least one cranial ultrasound scan was available. RESULTS The frequencies of white matter damage (WMD), major WMD, cystic periventricular leukomalacia (PVL), periventricular parenchymal hemorrhagic involvement, and intraventricular hemorrhage with ventricular dilatation were 21%, 8%, 5%, 3%, and 3%, respectively. The risk of WMD increased with decreasing gestational age. Mean age at diagnosis of cystic PVL was older for the most premature infants. Intraventricular hemorrhage with ventricular dilatation was associated with a higher risk of cystic PVL. Intrauterine growth restriction was not associated with a lower prevalence of cystic PVL. CONCLUSION The frequency of WMD is high in very preterm babies and is strongly related to gestational age. The incidence of cystic PVL did not differ between babies with intrauterine growth restriction and babies who were appropriate for gestational age.

Parent-Reported Quality of Life of Children With Cerebral Palsy in Europe

OBJECTIVE. The goal was to determine whether the type and severity of the childs impairments and the familys psychosocial, social, and economic characteristics influence parent-reported child quality of life across the spectrum of severity of cerebral palsy. METHODS. Our population-based, cross-sectional survey conducted in 2004 to 2005 involved 818 children with cerebral palsy, 8 to 12 years of age, from 7 countries (9 regions) in Europe. Child quality of life was assessed through parent reports by using the Kidscreen questionnaire, and data were analyzed separately for each of its 10 domains. RESULTS. The parental response rates were >93% for all domains except one. Gross motor function and IQ level were found to be associated independently with quality of life in most domains. However, greater severity of impairment was not always associated with poorer quality of life; in the moods and emotions, self-perception, social acceptance, and school environment domains, less severely impaired children were more likely to have poor quality of life. Pain was associated with poor quality of life in the physical and psychological well-being and self-perception domains. Parents with higher levels of stress were more likely to report poor quality of life in all domains, which suggests that factors other than the severity of the childs impairment may influence the way in which parents report quality of life. CONCLUSIONS. The parent-reported quality of life for children with cerebral palsy is associated strongly with impairment. However, depending on the areas of life, the most severely impaired children (in terms of motor functioning or intellectual ability) do not always have the poorest quality of life.

Behavioral Outcome at 3 Years of Age in Very Preterm Infants: The EPIPAGE Study

OBJECTIVES. Our goal was to compare the prevalence of behavioral problems between very preterm children and term children at 3 years of age and examine the factors associated with behavioral problems in very preterm children. METHODS. We conducted a prospective population-based cohort study: the EPIPAGE (Étude Epidémiologique sur les Petits Ages Gestationnels) study. All infants born between 22 and 32 weeks of gestation in 9 regions of France in 1997 were included and compared with a control group of infants born at term. Sociodemographic status, obstetric, and neonatal data were collected at birth and in the neonatal units. At 3 years of age, the behavioral problems of 1228 very preterm singleton children without major neurodisabilities, and 447 term children were studied using the Strengths and Difficulties Questionnaire completed by the parents. RESULTS. Very preterm children were more likely than controls to have behavioral difficulties. Among very preterm children, several medical conditions were associated with a high total difficulty score: major neonatal cerebral lesions diagnosed by cranial ultrasonographic studies, hospitalization within the last year, poor health, and psychomotor delay. A high birth order and sociodemographic factors such as young maternal age and low educational level of the mother were also identified as risk factors for behavioral difficulties. The differences between very preterm children and controls remained significant after adjustment for sociodemographic characteristics, neonatal complications, and neurodevelopmental status, for a high total difficulties score, hyperactivity, conduct problems, and for peer problems. For emotional problems, the difference was at the limit of significance. CONCLUSIONS. Very preterm children have a higher risk of behavioral problems at 3 years of age compared with term-born children. Health and neurodevelopmental status of the child were significantly associated with behavioral difficulties.

Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study.

Aim  The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population‐based cohort of very preterm infants.