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Bisphosphonate use in children with cerebral palsy.
Hurley, T, Zareen, Z, Stewart, P, McDonnell, C, McDonald, D, Molloy, E
The Cochrane database of systematic reviews. 2021;(7):CD012756
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Abstract
BACKGROUND Cerebral palsy (CP) is a heterogeneous group of non-progressive disorders of posture or movement, caused by a lesion of the developing brain. Osteoporosis is common in children with cerebral palsy, particularly in children with reduced gross motor function, and leads to an increased risk of fractures. Gross motor function in children with CP can be categorised using a tool called the Gross Motor Function Classification System (GMFCS). Bisphosphonate increases bone mineral density (BMD) and reduces fracture rates. Bisphosphonate is used widely in the treatment of adult osteoporosis. However, the use of bisphosphonate in children with CP remains controversial, due to a paucity of evidence and a lack of recent trials examining the efficacy and safety of bisphosphonate use in this population. OBJECTIVES To examine the efficacy and safety of bisphosphonate therapy in the treatment of low BMD or secondary osteoporosis (or both) in children with cerebral palsy (GMFCS Levels III to V) who are under 18 years of age. SEARCH METHODS In September 2020, we searched CENTRAL, MEDLINE, Embase, six other databases, and two trial registers for relevant studies. We also searched the reference lists of relevant systematic reviews, trials, and case studies identified by the search, and contacted the authors of relevant studies in an attempt to identify unpublished literature. SELECTION CRITERIA All relevant randomised controlled trials (RCTs), and quasi-RCTs, comparing at least one bisphosphonate (given at any dose, orally or intravenously) with placebo or no drug, for the treatment of low BMD or osteoporosis in children up to 18 years old, with cerebral palsy (GMFCS Levels III to V). DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We were unable to conduct any meta-analyses due to insufficient data, and therefore provide a narrative assessment of the results. MAIN RESULTS We found two relevant RCTs (34 participants). Both studies included participants with non-ambulatory CP or CP and osteoporosis. Participants in both studies were similar in severity of CP, age distribution, and sex distribution. The two trials used different bisphosphonate medications and different intervention durations, but further comparison of the interventions was not possible due to a lack of published data from one trial. One trial received funding and support from research, academic, and hospital foundations, with pharmaceutical companies providing components of the calcium and vitamin supplement; the other trial did not report sources of funding. We judged one study at an overall high risk of bias; the other as overall unclear risk of bias. PRIMARY OUTCOME Compared to placebo or no treatment, both studies provided very low certainty evidence of improved BMD at least four months post-intervention in children treated with bisphosphonate. Only one study (12 participants) provided sufficient detail to assess a measure of the effect, and reported an improvement at six months post-intervention in lumbar spine z-score (mean difference (MD) 18%, 95% confidence interval (CI) 6.57 to 29.43; very low certainty evidence). SECONDARY OUTCOMES Very low certainty evidence from one study found that bisphosphonate reduced serum N-telopeptides (NTX) more than placebo; the other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced NTX, but did not compare groups. One study reported inconclusive results between groups for serum bone-specific alkaline phosphatase (BAP). The other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced BAP, but did not compare groups. Neither study reported data for the effect of bisphosphonate treatment on changes in volumetric BMD in the distal radius or tibia, changes in fracture frequency, bone pain, or quality of life. One study reported that two participants had febrile events noted during their first dosing schedule, but no further adverse events were reported in either relevant study. AUTHORS' CONCLUSIONS Based on the available evidence, there is very low certainty evidence that bisphosphonate treatment may improve bone health in children with cerebral palsy. We could only include one study with 14 participants in the assessment of the effect size; therefore, the precision of the effect estimate is low. We could only evaluate one planned primary outcome, as there was insufficient detail reported in the relevant studies. Further research from RCTs on the effect and safety of bisphosphonate to improve bone health in children with cerebral palsy is required. These studies should clarify the optimal standard treatment regarding weight-bearing exercises, vitamin D and calcium supplementation, and should include fracture frequency as a primary outcome.
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Leucine Supplementation Increases Muscle Strength and Volume, Reduces Inflammation, and Affects Wellbeing in Adults and Adolescents with Cerebral Palsy.
Theis, N, Brown, MA, Wood, P, Waldron, M
The Journal of nutrition. 2021;(1):59-64
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Abstract
BACKGROUND Spastic cerebral palsy (CP) is characterized by muscle weakness owing, in part, to a blunted muscle protein synthetic response. This might be normalized by long-term leucine supplementation. OBJECTIVES The study assessed the effects of 10 wk leucine supplementation in adolescents and adults with CP. METHODS The study was a single-center randomized controlled trial. Twenty-four participants were randomly assigned to a control group (n = 12) or a leucine group (n = 12). l-Leucine (192 mg/kg body mass) was dissolved in water and administered daily for 10 wk. The primary outcome measures of elbow flexor muscle strength and muscle volume (measured by 3D ultrasound technique) and inflammation [C-reactive protein (CRP) concentration] were assessed before and after the 10 wk, alongside the secondary outcomes of body composition (measured by CP-specific skinfold assessment), metabolic rate (measured by indirect calorimetry), and wellbeing (measured by a self-reported daily questionnaire). Data were compared via a series of 2-factor mixed ANOVAs. RESULTS Twenty-one participants completed the intervention (control group: n = 11, mean ± SD age: 18.3 ± 2.8 y, body mass: 48.8 ± 11.9 kg, 45% male; leucine group: n = 10, age: 18.6 ± 1.7 y, body mass: 58.3 ± 20.2 kg, 70% male). After 10 wk, there was a 25.4% increase in strength (P = 0.019) and a 3.6% increase in muscle volume (P = 0.001) in the leucine group, with no changes in the control group. This was accompanied by a 59.1% reduction in CRP (P = 0.045) and improved perceptions of wellbeing (P = 0.006) in the leucine group. No changes in metabolism or body composition were observed in either group (P > 0.05). CONCLUSIONS Improvements in muscle strength and volume with leucine supplementation might provide important functional changes for adults and adolescents with CP and could be partly explained by reduced inflammation. The improved wellbeing highlights its capacity to improve the quality of daily living. This trial was registered at clinicaltrials.gov as NCT03668548.
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[Nutritional status of a population with moderate-severe cerebral palsy: Beyond the weight].
Martínez de Zabarte Fernández, JM, Ros Arnal, I, Peña Segura, JL, García Romero, R, Rodríguez Martínez, G
Anales de pediatria. 2020;(4):192-199
Abstract
INTRODUCTION Cerebral palsy (CP) is the most frequent cause of motor disability in the paediatric age. The aim of this article is the study of the nutritional status of patients with CP followed-up in a reference hospital, as well as the relationship between neurological and nutritional state. MATERIAL AND METHODS A cross-sectional, observational, descriptive and analytical study was conducted on a sample consisting of 4-15years old patients with CP with Gross Motor Function Classification System (GMFCS) gradesIII-IV-V, from a specialised paediatric hospital reference area. An interview (collection of general data, medications and nutritional habits), anthropometric study and bioimpedance (BIA) measurements were carried out. RESULTS The study included 69 patients (recruitment 84.15%), with a mean age of 10.46±0.43years, and 50.7% females. The distribution according to GMFCS scale was: gradeIII (36.2%), gradeIV (29%), and gradeV (34.8%). According to weight for height: moderate malnutrition 21.8% (gradeV: 33.3%), severe malnutrition 5.8% (gradeV: 12.6%), overweight/obesity 23.2% (gradeIII: 24%, gradeIV: 35%). Adequate level of lean mass for height: gradeIII (36%), gradeIV (55%), and gradeV (16.7%). Fat excess: gradeIII (36%), gradeIV (40%), and gradeV (29.2%). Fat mass comparison: BIA 6.89±0.64kg versus anthropometry 5.56±4.43kg. CONCLUSIONS In CP grade GMFCSV, the weight deficit associated with a decrease in lean body mass is common. Patients with CP grades GMFCSIII-IV have a significant prevalence of overweight/obesity. Anthropometry is a useful tool for nutritional assessment in children with CP, although fat levels could be underestimated.
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Nutritional red flags in children with cerebral palsy.
Huysentruyt, K, Geeraert, F, Allemon, H, Prinzie, P, Roelants, M, Ortibus, E, Vandenplas, Y, De Schepper, J
Clinical nutrition (Edinburgh, Scotland). 2020;(2):548-553
Abstract
BACKGROUND & AIMS Children with cerebral palsy (CP) are at risk for under-nutrition. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines identified anthropometric nutritional red flags for neurologically impaired children: weight for age z-score (WFA) < -2, triceps skinfold (TSF) or arm muscle area (AMA) < 10th centile and faltering weight. This study aimed to (1) evaluate the nutritional status of Flemish children and adolescents with CP using different anthropometric indicators; (2) assess the prevalence of nutritional red flags and (3) identify risk factors for low anthropometric parameters. METHODS This study was a prospective, longitudinal observational study recruiting children and adolescents with CP (2-20 years) in 9 specialized Flemish centres. Measurements were performed at baseline (t1, n = 325), after 6 (t2, total n = 268) and 12 months (t3, total n = 191). WFA z-scores were based on Flemish growth charts; TSF, subscapular skinfolds (SSF) and AMA compared with US reference data. Weight faltering was defined as ≥0.5 decrease in weight SDS at t2 or t3. RESULTS At t1 50 patients (15.4%) were classified as gross motor function classification system (GMFCS) 1, 95 (29.2%) as GMFCS 2, 49 (15.1%) as GMFCS 3, 54 (16.6%) as GMFCS 4, and 77 (23.7%) as GMFCS 5. The overall median (Q1; Q3) age was 11.7 (8.2; 15.9) years; 61.5% were boys and 22 (6.8%) had a gastrostomy (17 (22.1%) of GMFCS 5 group). The median (Q1; Q3) WFA z-score was -1.13 (-2.6; -0.1); 71.4% of the GMFCS 5 children had a WFA z-score < -2. The median (Q1; Q3) MUAC z-score was 0.17 (-0.7; 1.0); 16.9% of the GFMCS 5 children had MUAC z-score < -2. Median (Q1; Q3) TSF and SSF z-scores were respectively -0.01 (-0.8; 0.9) and 0.27 (-0.3; 0.9). All anthropometric indices tended to decrease with increasing GMFCS (p < 0.001). At t1 42.1% had at least one nutritional red flag, at t2 40.3% and at t3 41.4%. Of those with at least one nutritional red flag at t1 or t2, respectively 14.7% and 18.8% suffered weight loss 6 months later. A GMFCS >2 and dysphagia were associated with a higher risk for lower scores of nearly all nutritional indices. CONCLUSIONS Underweight was detected in almost three quarters of CP patients with GMFCS 5 classification, whereas deficits in subcutaneous fat and arm muscle reserve were observed in one fifth. Nutritional red flags, present in about 40% of the Flemish CP children, were apparently not successfully addressed in clinical practice, since up to one-fifth of CP patients with warning signs lost even further weight in the following 6 months. Beside a GMFCS >2, dysphagia was one of the most common conditions influencing the presence of low nutritional indices.
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Does Whole-Body Vibration Treatment Make Children's Bones Stronger?
Swolin-Eide, D, Magnusson, P
Current osteoporosis reports. 2020;(5):471-479
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PURPOSE OF REVIEW To summarize the last 10 years of literature regarding the effects of whole-body vibration (WBV) on bone in children, and if WBV results in increased bone acquisition. RECENT FINDINGS WBV intervention appears to be a safe intervention with beneficial effects on bone mass in some diseases and syndromes, but there is still low evidence for WBV in clinical practice. The positive effects on muscle strength, balance, and walking speed are more conclusive. One of the takeaways of this review is that well-trained individuals may not further improve bone mass with WBV; thus, interventions are more beneficial in pediatric individuals with Down syndrome or severe motor disabilities with low bone mass and reduced activity levels. WBV appears to be a safe non-pharmacological anabolic approach to increase bone mass in some pediatric populations; however, longer (> 6 months) and larger prospective studies are needed to elucidate the efficacy of WBV on bone health in young individuals.
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Children and Teens in Charge of their Health (CATCH): A protocol for a feasibility randomised controlled trial of solution-focused coaching to foster healthy lifestyles in childhood disability.
McPherson, AC, Biddiss, E, Chen, L, Church, PT, de Groot, JF, Keenan, S, King, G, Lui, T, Maltais, DB, Mérette, C, et al
BMJ open. 2019;(3):e025119
Abstract
INTRODUCTION Children with physical disabilities are rarely included in interventions to promote healthy lifestyles, despite being at higher risk for suboptimal dietary and physical activity behaviours. The Children and Teens in Charge of their Health study explores the feasibility and acceptability of conducting a randomised controlled trial (RCT) of a strengths-based, solution-focused coaching intervention for improving and sustaining physical activity and healthy dietary habits in children and young people with physical disabilities. METHODS AND ANALYSIS Thirty children aged 10-18 years with a diagnosis of spina bifida or cerebral palsy who are able to set healthy lifestyle goals will be recruited from two children's rehabilitation hospitals in Ontario, Canada. Participants will be enrolled in the study for twelve months. All participants will receive standard care and printed information about healthy lifestyles. Of the 30 participants, 15 will be randomised to receive a coaching intervention for the first 6 months. Health indicators and psychosocial outcomes will be assessed by blinded assessors four times: at the start of the trial, immediately postintervention (6 months after randomisation), and at 3 and 6 months postintervention (9 and 12 months after randomisation, respectively). Predefined success criteria will be used to assess the feasibility of trial processes such as recruitment, attrition, stratification and intervention fidelity. Acceptability and perceived impact of the intervention will be explored qualitatively. ETHICS AND DISSEMINATION The study has been approved by Holland Bloorview Kids Rehabilitation Hospital's Research Ethics Board (Ref: 17-752). A knowledge translation planning template will be used to ensure our findings have maximum reach. TRIAL REGISTRATION NUMBER NCT03523806.
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Respiratory morbidity in children with cerebral palsy: an overview.
Boel, L, Pernet, K, Toussaint, M, Ides, K, Leemans, G, Haan, J, Van Hoorenbeeck, K, Verhulst, S
Developmental medicine and child neurology. 2019;(6):646-653
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Respiratory problems have a significant impact on morbidity and mortality in patients with cerebral palsy (CP). In particular, recurrent aspiration, impaired airway clearance, spinal and thoracic deformity, impaired lung function, poor nutritional status, and recurrent respiratory infections negatively affect respiratory status. Bronchopulmonary dysplasia may contribute to pulmonary problems, but asthma is not more common in CP than in the general population. We discuss treatment options for each of these factors. Multiple coexisting and interacting factors that influence the respiratory status of patients with CP should be recognized and effectively addressed to reduce respiratory morbidity and mortality. WHAT THIS PAPER ADDS Respiratory problems are a significant cause of morbidity in patients with cerebral palsy (CP). Respiratory status in patients with CP is influenced by recurrent aspiration and impaired airway clearance. Spinal and thoracic deformity, impaired lung function, poor nutrition, and respiratory infections also negatively affect respiratory status. These factors should all be addressed to reduce respiratory problems in patients with CP.
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Magnesium Sulfate and Novel Therapies to Promote Neuroprotection.
Jameson, RA, Bernstein, HB
Clinics in perinatology. 2019;(2):187-201
Abstract
Cerebral palsy occurs more often in preterm than in term deliveries and is one of the major neurologic injuries seen in preterm infants. Magnesium sulfate has been found to reduce the risk of cerebral palsy in patients at risk of delivery before 32 weeks' gestational age. Multiple large clinical trials have shown this effect. The authors recommend magnesium sulfate bolus followed by continuous dosing of magnesium sulfate in those at risk of delivery before 32 weeks' gestation until delivery occurs or is no longer imminent. This article also discusses novel and emerging therapies for the prevention of cerebral palsy.
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Malnutrition is common in children with cerebral palsy in Saudi Arabia - a cross-sectional clinical observational study.
Almuneef, AR, Almajwal, A, Alam, I, Abulmeaty, M, Bader, BA, Badr, MF, Almuammar, M, Razak, S
BMC neurology. 2019;(1):317
Abstract
BACKGROUND Cerebral palsy (CP) is considered as the main cause of severe physical impairment and malnutrition in children. This cross-sectional study intended to survey the nutritional status of children cerebral palsy in Riyadh, Saudi Arabia. METHODS We examined 74 children (age: 1-10 yrs) with CP, who attended Sultan Bin Abdulaziz Humanitarian City (SBAHC), Riyadh Saudi Arabia. Data on age, general demographics, nutritional status, and dietary intake were collected. A child was considered underweight, wasted, stunted or thin if the standard deviation scores for his/her weight for age, weight for height, height for age and body mass index for age were ≤ -2.0 standard deviation (SD) using WHO growth standards. Multivariable logistic regression identified the factors associated with nutritional indicators. RESULTS More than half (56.4%) of the children with cerebral palsy were malnourished as they had z-score below <-2 SD in at least one of the four indicators. Thinness (50%) was the most common form of malnutrition, followed by underweight, stunting, and wasting. Arm anthropometrics gave similar results on the percent number of malnourished children. Factors that were independently associated with malnutrition with an adjusted OR (aOR) were as follow: age ≤ 5 yrs. (aOR: 4.29); presence of cognitive impairment (aOR: 4.13); presence of anemia (aOR: 3.41) and inadequate energy intake (aOR: 4.86) (p, for all trends <0.05). CONCLUSION Children with cerebral palsy of the current study have impaired growth and nutritional status as assessed by all four common nutritional status indicators. Further large-scale community-based studies for in-depth evaluation of nutritional status and growth patterns in children with CP are needed.
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Focus on Risk Factors for Cardiometabolic Disease in Cerebral Palsy: Toward a Core Set of Outcome Measurement Instruments.
Benner, JL, McPhee, PG, Gorter, JW, Hurvitz, EA, Peterson, MD, Obeid, J, Wright, M, Balemans, ACJ, Verschuren, O, van den Berg-Emons, RHJ, et al
Archives of physical medicine and rehabilitation. 2019;(12):2389-2398
Abstract
OBJECTIVE To identify existing outcome measurement instruments (OMIs) assessing risk factors for cardiometabolic disease in adolescents and adults with cerebral palsy (CP) reported on in the literature or used in the field. DATA SOURCES The COnsensus-based Standards for the selection of health Measurement Instruments database of systematic reviews and 4 electronic databases (Embase, MEDLINE/Ovid, MEDLINE/Pubmed, PsychINFO) were searched up to June 19, 2017, that yielded 2594 articles. Experts in the field were consulted to identify any additional OMIs. STUDY SELECTION Two reviewers independently applied inclusion criteria to select eligible studies using or evaluating measurement properties of OMIs assessing 1 of 8 outcomes: cardiorespiratory endurance, body size, body composition, physical behavior, sleep, nutrition, blood pressure, and blood lipids and glucose. Studies with an experimental or observational design including ≥10 adolescents or adults with CP were included. DATA EXTRACTION One reviewer extracted data that were summarized for study and sample characteristics, outcomes, OMIs used, and if applicable data on measurement properties. Two reviewers rated the methodological quality and the quality of the OMIs. Feasibility for clinical practice and research was rated by experts in the field. DATA SYNTHESIS Ninety OMIs were identified from 56 included articles and by the experts. Seventy OMIs pertained to cardiorespiratory endurance, body size, body composition, and physical behavior, whereas only 5 were identified for sleep and nutrition. Overall synthesis revealed that there is moderate to poor evidence for good quality of OMIs in this population. Based on feasibility for clinical practice, experts agreed on a single OMI per outcome (and 2 for cardiorespiratory endurance) to be included in a core set. CONCLUSION Despite the range of available OMIs to assess risk factors for cardiometabolic disease in adolescents and adults with CP, evidence of good quality is often lacking. Nonetheless, a preliminary core set of 9 OMIs was systematically developed.