C S P M Uiterwaal

Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study

BACKGROUNDnNon-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial.nnnMETHODSn34 children recruited from the Dutch national centre for osteogenesis imperfecta were randomly assigned olpadronate (10 mg/m2 daily; n=16) or placebo (n=18) for 2 years. All children also received calcium and vitamin D supplements. Primary endpoints were incident fractures of long bones and changes in bone mineral content (BMC), bone mineral density (BMD), and functional outcome. Anthropometry, vertebral height, and urinary markers of bone resorption were also studied. Analyses were by intention to treat.nnnFINDINGSnFracture follow-up was complete for all the children, including two who withdrew from the study (one from each group). Olpadronate treatment was associated with a 31% reduction in relative risk of fracture of long bones (hazard ratio 0.69 [95% CI 0.52-0.91], p=0.01). The olpadronate group showed significantly greater increases than the placebo group in spinal BMC (difference between groups 2.24 g/year [0.20-4.29], p=0.03) and spinal BMD (difference between groups 0.054 g/cm2 per year [0.012-0.096], p=0.01). There were no detectable effects on functional outcome, anthropometrics, or vertebral height and no differences between the groups in changes in urinary markers of bone resorption.nnnINTERPRETATIONnOral treatment with olpadronate at a daily dose of 10 mg/m2 results in a reduction of fracture risk of long bones in children with osteogenesis imperfecta. However, the issue of whether bisphosphonates will alter the natural course of osteogenesis imperfecta remains unresolved, and further studies are needed.

Neonatal cranial ultrasound versus MRI and neurodevelopmental outcome at school age in children born preterm

Aim: To examine the correlation between neonatal cranial ultrasound and school age magnetic resonance imaging (MRI) and neurodevelopmental outcome. Methods: In a prospective 2 year cohort study, 221 children (gestational age ⩽32 weeks and/or birth weight ⩽1500 g) participated at a median age of 8.1 years (inclusion percentage 78%). Conventional MRI, IQ (subtests of the WISC), and motor performance (Movement Assessment Battery for Children) at school age were primary outcome measurements. Results: Overall, there was poor correspondence between ultrasound group classifications and MRI group classifications, except for the severe group (over 70% agreement). There was only a 1% chance of the children with a normal cranial ultrasound having a major lesion on MRI. Mean IQ (standard deviation) was significantly lower in children with major ultrasound or MRI lesions, but was also lower in children with minor lesions on MRI compared to children with a normal MRI (91±16, 100±13, 104±13 for major lesions, minor lesions, and normal MRI, respectively). Median total impairment score (TIS) was significantly higher in children with major lesions on ultrasound or MRI as well as in children with minor lesions on MRI (TIS 4.0 and 6.25 for normal and minor lesions on MRI, respectively; p<0.0001). Conclusions: A normal neonatal cranial ultrasound excluded a severe lesion on MRI in 99% of cases. MRI correlated more strongly with mean IQ and median TIS than ultrasound. Subtle white matter lesions are better detected with MRI which could explain the stronger correlation of MRI with IQ and motor performance.

Adolescent Chronic Fatigue Syndrome: Prevalence, Incidence, and Morbidity

OBJECTIVE: To determine nationwide general practitioner (GP)-diagnosed prevalence and pediatrician–diagnosed incidence rates of adolescent chronic fatigue syndrome (CFS), and to assess CFS morbidity. DESIGN AND SETTING: We collected data from a cross-sectional national sample among GPs and prospective registration of new patients with CFS in all pediatric hospital departments in the Netherlands. PATIENTS AND METHODS: Study participants were adolescents aged 10 to 18 years. A representative sample of GPs completed questionnaires on the prevalence of CFS in their adolescent patients. Pediatric hospital departments prospectively reported new cases of CFS in adolescent patients. For every new reported case, a questionnaire was sent to the reporting pediatrician and the reported patient to assess CFS morbidity. Prevalence was estimated through the data from GP questionnaires and incidence was estimated on the basis of cases newly reported by pediatricians from January to December 2008. RESULTS: Prevalence was calculated as 111 per 100 000 adolescents and incidence as 12 per 100 000 adolescents per year. Of newly reported patients with CFS, 91% scored at or above cutoff points for severe fatigue and 93% at or above the cutoff points for physical impairment. Forty-five percent of patients with CFS reported >50% school absence during the previous 6 months. CONCLUSIONS: Clinically diagnosed incidence and prevalence rates show that adolescent CFS is uncommon compared with chronic fatigue. The primary adverse impact of CFS is extreme disability associated with considerable school absence.

Maternal and Infant Characteristics Associated With Perinatal Arterial Stroke in the Preterm Infant

Background and Purpose— Most perinatal arterial stroke (PAS) studies that investigated infant characteristics have excluded preterm infants from the study population. We sought to analyze the imaging findings and antenatal and perinatal risk factors in preterm infants with PAS. Methods— This was a hospital-based, case-control study of preterm infants. Case infants were confirmed by reviewing brain imaging scans and medical records (n=31). Three controls per case were individually matched with case infants from the study population. Results— Gestational age ranged between 27 and 36 weeks, and birth weight ranged between 580 and 3180 g. PAS was more common on the left side (61%), and 7% had bilateral PAS. The majority of strokes involved the middle cerebral artery distribution. Involvement of 1 or more lenticulostriate branches was most common among infants with a gestational age of 28 to 32 weeks, but main branch involvement was seen only in those with a gestational age of >32 weeks. Twin-to-twin-transfusion syndrome, fetal heart rate abnormality, and hypoglycemia were identified as independent risk factors for PAS. Conclusions— Preterm PAS is associated with prenatal, perinatal, and postpartum risk factors. We were unable to identify any maternal risk factors. Involvement of the different branches of the middle cerebral artery changed with an increase in gestational age.

Postnatal hydrocortisone treatment for chronic lung disease in the preterm newborn and long-term neurodevelopmental follow-up.

The benefits versus the risks of postnatal administration of steroids in preterm-born infants are still debatable. This review examines the literature on postnatal hydrocortisone treatment for chronic lung disease (CLD) in preterm-born infants with a particular focus on the effects of such treatment on long-term neurodevelopmental outcomes. Quantitative published evidence does not point to a clear advantage of treatment with hydrocortisone over dexamethasone with regard to the impact on long-term neurological outcomes. However, in the absence of a randomised comparison, a consensus may soon have to be reached on the basis of the best available evidence whether hydrocortisone should replace dexamethasone in the treatment of CLD.

Scoliosis in children with osteogenesis imperfecta: influence of severity of disease and age of reaching motor milestones

Abstract. We studied the relationship between the age of reaching motor milestones, especially anti-gravity activities, and the age of development of pathological spinal curvatures in children with osteogenesis imperfecta (OI). We hypothesized that earlier achievement of anti-gravity motor milestones predicts a later development of pathological spinal curvatures. Ninety-six children participated in this retrospective study. The severity of the disease was classified according to Sillence into types I–IV. Spinal radiography was performed annually and spinal deformities were measured according to the Cobb angle. Scoliosis was defined as a Cobb angle exceeding 9°. Pathological thoracic kyphosis was defined as a Cobb angle exceeding 40°. The parents were asked to report the age at which the child achieved motor milestones, and data were checked against health care records. Thirty-seven of 96 children (39%) developed a scoliosis of more than 9°. Nine of 96 children (9%) developed a pathological kyphosis. The age of developing scoliosis was significantly lower than the age of development of the pathological kyphosis (P=0.01). Bone mineral density was measured by dual energy X-ray absorptiometry (DEXA) in 53 children, 28 of whom developed scoliosis, and 25 of whom did not. The mean DEXA Z-score of the 28 children with scoliosis was significantly lower than that of the 25 children without (–5.2, SD 1.3 vs –3.2, SD 1.9; P-value <0.001). Children with OI type IV, but particularly OI type III, reached motor milestones much later than children with OI type I. The motor milestone supported sitting showed a significant inverse association with time of the first presence of scoliosis with a Cobb angle greater than 9° (linear regression coefficient: –1.3, 95% confidence interval: –2.6 to –0.03). The age of achieving the motor milestones lifting the head to 45° in prone position, rolling, and supported- and unsupported standing were not significantly associated with age of the first presence of scoliosis with a Cobb angle greater than 9°. However, the directions of associations suggest that here, too, there is a tendency for later development of scoliosis in those who reach milestones at earlier ages. Multivariable analyses showed that the motor milestone sitting with support was significantly associated with age of first achieving scoliosis, independent of gender and type of OI (linear regression coefficient: –0.9, 95% confidence interval: –1.3 to –0.5). We conclude that in children with OI, the age of anti-gravity motor milestones was associated with the age of development of pathological spinal curvatures. Earlier achievement of the motor milestone supported sitting predicted significantly a later development of pathological spinal curvatures, independent of gender and type of OI.

Internet-Based Therapy for Adolescents With Chronic Fatigue Syndrome: Long-term Follow-up

OBJECTIVE: Cognitive behavioral therapy (CBT) is known to be an effective treatment of adolescents with chronic fatigue syndrome (CFS), but its availability is limited. Fatigue in Teenagers on the Internet (FITNET), an Internet-based CBT program for adolescents with CFS, has been developed as an alternative to face-to-face CBT. Recently, its short-term effectiveness has been proven in a randomized clinical trial. Here we aimed to assess the long-term outcome of CFS in adolescents after FITNET treatment and after usual care. In addition, factors related to recovery at long-term follow-up (LTFU) for adolescents treated with the FITNET program were investigated. METHODS: The study was an LTFU of participants of the FITNET trial. Data were completed for 112 (88.2%) of 127 approached FITNET study participants. Primary outcomes were fatigue severity (Checklist Individual Strength–20), physical functioning (87-item Child Health Questionnaire), and school/work attendance. RESULTS: After a mean follow-up of 2.7 years, 66 (58.9%) adolescents had recovered from CFS. Most adolescents who recovered directly after treatment with FITNET were still recovered at LTFU. At LTFU there was no difference between the recovery rates for the different treatment strategies (original randomization: FITNET [64%] versus any form of usual care [52.8%]). Per additional month of “pretreatment disease duration,” the odds for recovery were 4% lower (odds ratio: 0.96; 95% confidence interval: 0.93–0.99; P = .016), and per added point on “focus on bodily symptoms” (Body Consciousness Scale) of the mother (0–20 points) the odds for recovery were 11% lower (odds ratio: 0.89; 95% confidence interval: 0.80–0.99; P = .029). CONCLUSIONS: The short-term effectiveness of Internet-based CBT on adolescent CFS is maintained at LTFU. At LTFU, usual care led to similar recovery rates, although these rates were achieved at a slower pace.

Osteogenesis imperfecta: profiles of motor development as assessed by a postal questionnaire.

Abstract This study was performed to achieve more detailed information regarding the age and sequence in the development of motor milestones in the different types of osteogenesis imperfecta (OI). The parents of 98 patients with a diagnosis of OI were sent a questionnaire regarding the age at which patients achieved motor milestones. All patients were attending the outpatient clinic for children with OI at the Wilhelmina Childrens Hospital. The motor milestones were classified into static motor milestones and dynamic motor milestones and all data were checked with health care records. The age of development of motor milestones was compared to reference values of the healthy population. The severity of the disease was classified according to Sillence based on clinical, genetic and radiological data. The age of intramedullary rodding of the first nail in the lower and upper extremity and the localisation was noted. A total of 76 parents responded to the 98 questionnaires (78%). In OI type I, a delay exists in achieving motor milestones, comparable to the 95th percentile of the normal population. In type III, the development of all motor milestones was significantly delayed compared to types I and IV with a discrepancy between static and dynamic milestones. In OI type IV, a retardation in motor development developed after the milestone `sitting without support was achieved. Motor development in types I and IV was not influenced by intramedullary rodding of the lower extremities, since rodding was rarely performed before the milestone `unsupported standing was achieved. In type III, the influence of intramedullary rodding on the age of achieving motor milestones remains questionable.nConclusion The severity of osteogenesis imperfecta has a large influence on the age and sequence in the development of motor milestones. No influence of intramedullary rodding of the lower extremities on motor development was found in osteogenesis imperfecta types I and IV, whereas the influence in type III remains questionable.

456 Change in Cerebral Palsy Incidence and Severity Among Children Born Preterm in 1990-2005: A Hospital-Based Cohort Study

456 Change in Cerebral Palsy Incidence and Severity Among Children Born Preterm in 1990-2005: A Hospital-Based Cohort Study