Assessing body composition and energy expenditure in children with severe neurological impairment and intellectual disability

__Abstract__ Children with severe neurological impairment and intellectual disability are at increased risk of developing malnutrition. While in recent years increased use of gastrostomy feeding has turned this trend, children receiving tube feeding run the opposite risk of overnutrition. Maintaining a healthy diet for these children requires regular measurements of body composition and estimates of energy needs. However, a review of available literature did not provide enough evidence of valid instruments for measuring body composition. In addition, no equations exist to reliably estimate energy expenditure in these children. This thesis aimed to develop equations to measure body composition and estimate energy expenditure in these children. To accomplish this, in 61 children (32 male, age 10.1 ± 4.3) the outcomes of skinfold measurements and bioimpedance analysis (BIA) were compared to a reference method: the doubly labeled water method. While a newly-developed equation for skinfolds did not improve agreement, the new BIA equation did (R2 = 0.92, SEE=1.7 kg, RMSE=1.8 kg). In order to develop an equation to estimate energy expenditure, in 61 children data was recorded on degree of movement, mobility, muscle tone and presence of epilepsy. After analysis the variables degree of movement and mobility were selected by the statistical model. The resulting equation was based on 52 children, in whom all measurements were successfull (R2=0.69, SEE=207 kcal, RMSE=213 kcal). Although the standard error of this new equation is still considerable, it is a first step in the development of a group-specific equation. This thesis concludes with a preliminary guideline that aims to diagnose undernutrition and overnutrition in children with severe neurological impairment and intellectual disability

Risperidone plasma concentrations are associated with side effects and effectiveness in children and adolescents with autism spectrum disorder

Aim: Risperidone is the most commonly prescribed antipsychotic drug to children and adolescents worldwide, but it is associated with serious side effects, including weight gain. This study assessed the relationship of risperidone and 9-hydroxyrisperidone trough concentrations, maximum concentrations and 24-hour area under the curves (AUCs) with body mass index (BMI) z-scores in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side effects and effectiveness. Methods: Forty-two children and adolescents (32 males) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side effects and effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including medication adherence and CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were measured. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 205 risperidone and 205 9-hydroxyrisperidone concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-hour AUCs were analysed to predict outcomes using generalized and linear mixed-effects models. Results: A risperidone two-compartment model combined with a 9-hydroxyrisperidone one-compartment model best described the measured concentrations. Of all the pharmacokinetic parameters, higher risperidone sum trough concentrations best predicted higher BMI z-scores during follow-up (P <.001). Higher sum trough concentrations also predicted more sedation (P <.05), higher prolactin levels (P <.001) and more effectiveness measured with Aberrant Behavior Checklist irritability score (P <.01). Conclusion: Our results indicate a therapeutic window exists, which suggests that therapeutic drug monitoring of risperidone might increase safety and effectiveness in children and adolescents with ASD and behavioural problems

Validation of skinfold measurements and bioelectrical impedance analysis in children with severe cerebral palsy: A review

Background & aims: Accurately measuring nutritional status in children with severe cerebral palsy (CP) is a challenge. This review seeks to assess the validity of skinfold measurements and bioelectrical impedance analysis (BIA) for measuring body composition in children with severe CP. Methods: We executed a literature search on the validation of both methods in children with severe CP. To be eligible for inclusion, a study had to report on a statistical comparison between these two methods and any method of reference. The QUADAS tool was used for quality assessment. Results: The search strategy resulted in 1549 studies of which 5 studies eventually met the inclusion criteria. When comparing body composition outcomes of skinfold measurements to a reference method, correlation coefficients were found ranging from 0.406 to 0.988. Correlation coefficients between body composition data of BIA and a reference method ranged from 0.515 to 0.95. Conclusions: Although a number of authors found favorable agreement between skinfold measurements and BIA in comparison with reference methods, the small numbers studied, the lack of methodological quality measured by QUADAS, and the use of inappropriate analytical methods hamper solid conclusions. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved

Validation of deuterium and oxygen18 in urine and salica samples from children using on-line continuous-flow isotope ratio mass spectrometry

The doubly labelled water method is valuable for measuring energy expenditure in humans. It usually involves blood or urine sampling, which might be difficult in neonates and children with cerebral palsy or other disabilities. We therefore aimed to validate a method making use of saliva samples analyzed by automated thermal conversion elemental analyzer in combination with isotope ratio mass spectrometry (TC-EA/IRMS). The subjects received labelled water orally and urine and saliva samples were collected and analyzed. Deuterium as well as oxygen18 was measured in one single run using a peak jump method. Excellent linearity was found for measurement of enrichments of deuterium (R2 = 0.9999) and oxygen18 (R2 = 0.9999). The intra-assay precision and the inter-assay precision of the measurement of two standards were good for both deuterium and oxygen18. The variation between urine and saliva samples was small (4.83% for deuterium and 2.33% for oxygen18 n = 40). Saliva sampling is to be preferred, therefore, as it can be easily collected and is non-invasive. Moreover, its time of production is almost exactly known. The TC-EA/IRMS method is a good alternative to the more laborious off-line IRMS measurement

Energy intake does not correlate with nutritional state in children with severe generalized cerebral palsy and intellectual disability

Background & aims: The majority of children with cerebral palsy and intellectual disability has a poor nutritional state compared with their healthy peers. Several studies have found reduced daily energy intake in this population. The hypothesis is tested that low daily energy intake correlates with poor nutritional state. Methods: In a population-based sample of 176 children with severe generalized cerebral palsy and intellectual disability (mean age 10 years, SD 2 months; 16% GMFCS score 4; 84% GMFCS score 5) anthropometric parameters (weight, upper arm and tibia length, biceps, triceps, subscapular and suprailiacal skinfold thickness, mid upper arm circumference) were measured and dietary intake was registered. Results: No correlation was found between energy intake%(EAR) and anthropometric Z-scores. Higher age, female gender, mobility, and to a lesser extent the absence of tube feeding predicted lower anthropometric Z-scores. Conclusions: In children with severe generalized cerebral palsy and intellectual disability nutritional state is not primarily determined by energy intake. Differences in energy expenditure presumably play an important role, although more research is needed to clarify the complex association between energy intake and nutritional state. Individualized nutritional care is suggested, preferably based on energy expenditure, in order to avoid malnutrition, but also overweight. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved

Childbirth related PTSD and its association with infant outcome: A systematic review

Introduction: Maternal postnatal mental health problems may negatively impact child development. Postpartum research has mainly focused on the impact of maternal depression and anxiety due to their high prevalence (13–25 % and 10–18 %, respectively). However, maternal childbirth-related PTSD (CB-PTSD) could be another important risk factor in child development (estimated prevalence: 4.7 %). Objective: We investigated whether maternal CB-PTSD (symptoms) are associated with a negative mother-child relationship and/or child developmental outcome for children aged 0–5 years. Furthermore, we examined whether maternal trauma-focused therapy can positively impact mother and child outcomes. Methods: We performed a systematic review by searching three databases (Embase, Medline, PsycInfo). Search terms involved: ‘birth or delivery modes’, ‘PTSD psychological trauma’, and ‘child development or child behavior’. Two independent reviewers evaluated all eligible papers. Results: Thirty-five papers (30 samples) were included and qualitatively reported. Results suggest a negative association of maternal CB-PTSD (symptoms) with mother-infant attachment and child behavior. However, confounding factors may explain this association. The evidence on associations with breastfeeding, sleeping, socio-emotional development, and weight gain is insufficient. Research investigating the effect of maternal trauma-focused therapy on a child's outcome is scarce, contradictory, and of low quality. Conclusion: This systematic review suggests that maternal CB-PTSD may be associated with an increased number of problems in mother-infant attachment and child behavior, but other domains remain scarcely investigated and methodologic issues are present (cross-sectional study design, influence of confounding variables, sample representativeness, diversity in assessment tools). Our results support a multidisciplinary approach to providing early prevention and screening of the maternal mental health state

Risk factors and pattern of weight gain in youths using antipsychotic drugs

Antipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term treatment with antipsychotic drugs in this young population. We analysed a combined prospective and a retrospective observational cohort of Dutch children and adolescents, starting with risperidone, aripiprazole or pipamperone treatment. Linear mixed models were used to test whether sex, age, baseline body-mass-index (BMI) z score, type of antipsychotic, dose equivalent/kg, duration of use, previous antipsychotic use, ethnicity, physical exercise, IQ, concomitant medication, and psychiatric classification predicted the BMI z score for a follow-up of 52 weeks. A total of 144 patients were included with a median [interquartile range ([IQR)] age of 9 (4) years and median follow-up of 30 (73) weeks. During the complete follow-up, the median (IQR) weight gain was 0.37 (0.95) BMI z score points. Antipsychotic-induced weight gain was found to be most pronounced during the first 15 weeks of use (BMI z score increase per week β = 0.02, 95% CI 0.01–0.03, p = 0.002). A higher baseline BMI z score and the absence of stimulant use were associated with a higher BMI z score during the entire follow-up and after 15 weeks, respectively. Previous treatment with an antipsychotic drug was associated with less weight gain during the first 15 weeks of treatment. Our findings underscore the importance of close patient monitoring during the first weeks of antipsychotic treatment with a focus on patients with a high baseline BMI z score