Overweight Proxies Are Associated with Atopic Asthma: A Matched Case–Control Study

Background: Many studies have documented a link between overweight and asthma in children with contradictory results regarding the best way to measure overweight. Moreover, often, the dynamic development of atopy, overweight, and asthma is controlled for age dependency insufficiently. Objective: This study assesses and compares the associations of overweight measured as waist circumference, waist to height ratio (WHtR), neck circumference, and body mass index with the occurrence of asthma – best possibly controlling for age-dependencies of these parameters. Methods: From a sample of 2,511 children aged 6–17 years, we matched 157 children with asthma with 2 controls (n = 471) according to age and atopy status and performed conditional logistic regression analyses. We further investigated the role of known influencing factors of asthma occurrence. Results: In children with atopy, all overweight proxies were consistently positively associated with asthma. Statistical significance was reached for WHtR-SD score (OR 1.26, 95% CI 1.03–1.54, p = 0.025) and persisted when further covariates, such as birth weight or social status, were added to the model. Groups of atopic versus nonatopic participants do not differ in levels of interleukin-6 or high-sensitivity C-reactive protein. Conclusion: In our cohort, overweight seems to carry a risk for asthma only if accompanied with atopy. We call for more strict age matching in pediatric cohort studies and longitudinal studies for a better understanding for causal links of overweight, atopy, and asthma

Age- and Sex-Related Percentiles of Skinfold Thickness, Waist and Hip Circumference, Waist-to-Hip Ratio and Waist-to-Height Ratio: Results from a Population-Based Pediatric Cohort in Germany (LIFE Child)

Background: Skinfold thickness (ST), waist circumference (WC) and hip circumference (HC) measurements are simple methods for assessing fat tissue at defined body parts. We examined these parameters in a cohort of healthy children and adolescents in Leipzig. Our study provides current percentile curves for biceps, triceps, subscapular and iliac crest ST, plus WC, HC, waist-to-hip ratio and waist-to-height ratio. Methods: 6,344 visits were recorded involving 2,363 individuals from 3 to 16 years in age. Continuous age- and gender-related percentiles (3rd, 10th, median, 90th, 97th percentiles) were estimated using Cole’s LMS method. Results: For biceps and triceps ST, boys show a peak at the beginning of adolescence with a subsequent decrease, while percentile values among girls rise across the age range. Subscapular and iliac crest percentiles also show increasing curves with disproportionately high values for P90 and P97. Boys show higher values of WC, girls have higher levels of HC. WC and HC median percentiles constantly increase in both sexes with a plateau at the age of 16 for girls. Conclusion: Trends for all parameters of body fat are in line with other national and international studies. Unlike the KiGGS study, our study provides circumference data across the whole of our age range, i.e. from 3 to 16 years

A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Background: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Methods: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. Results: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. Conclusions: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.</p

Developmental Language Disorders in Children with Orofacial Clefts

Abstrakt Hintergrund Bei Kindern mit angeborenen orofazialen Spalten ist ein Kausalzusammenhang zwischen peripher-organischem Defekt und resultierenden Sprechstörungen offensichtlich. Umstritten ist, ob darüber hinaus sprachsystematische Entwicklungsabweichungen vorliegen. Als Ursachenfaktoren werden begleitende Schallleitungsschwerhörigkeiten, persistierende phonetische Störungen und psychosoziale Aspekte in Betracht gezogen. Material und Methode Der Querschnittsstudie lag ein quasi-experimentelles Design zugrunde. Eine Gruppe vierjähriger Kinder (N=10) mit isolierter Gaumenspalte und Lippen-Kiefer-Gaumenspalte wurde hinsichtlich ihrer sprachlichen Kompetenzen mit einer Kontrollgruppe (N=10) verglichen. Die Sprachstandserhebung umfasste die Überprüfung phonetischer Fähigkeiten, expressiver/rezeptiver phonologischer, semantisch-lexikalischer und morphologisch-syntaktischer Leistungen sowie Aspekten der phonologischen Bewusstheit und des Arbeitsgedächtnisses anhand standardisierter und informeller Testverfahren. Neben der quantitativen Auswertung mittels U-Test von Mann-Whitney wurden qualitative Analysen vorgenommen. Ergebnisse Verglichen mit der Kontrollgruppe zeigten die Spaltkinder eine tendenziell signifikant größere Anzahl pathologischer phonologischer Prozesse in Form von Rückverlagerungen (p = .06). Hinsichtlich der sprachlichen Dimensionen wurden weder quantitativ noch qualitativ Gruppenunterschiede ermittelt. Hingegen wies die Spaltgruppe tendenziell signifikant schwächere metaphonologische Kompetenzen (Reime erkennen, p = .09) sowie ein signifikant schlechteres Leistungsvermögen bezüglich des Arbeitsgedächtnisses (p = .02) auf. Diskussion Ein physiologischer Erwerb linguistischer Kompetenzen ist auch bei spaltbedingten artikulatorischen Einschränkungen sowie wiederholten Schallleitungsschwerhörigkeiten möglich. Nicht auszuschließen sind jedoch subtile Auffälligkeiten auf metaphonologischer Ebene und bezüglich des Arbeitsgedächtnisses. Ob diese Defizite auf Phasen peripherer Hörbeeinträchtigungen zurückgeführt werden können und inwieweit ein Zusammenhang zwischen Hörvermögen, Artikulation und Arbeitsgedächtnis besteht, bedarf weiterer longitudinaler Forschungsbemühungen.Abstract Background Children with orofacial clefts are at risk for resonance and articulation problems directly related to the structural defects. Research exploring the language abilities in these children continues to be a controversial issue. Conductive hearing loss, articulatory deficits and psychosocial aspects are considered to be major etiological factors influencing the language development of individuals with cleft lip and palate. Objective To compare a group of children with nonsyndromic orofacial clefts with a group of noncleft, matched control children on measures of speech and language abilities, phonological awareness and verbal short-term memory at age 4. Methods and Procedures Using a quasi-experimental design, the speech and language performance of 10 children aged 4 years with cleft lip and palate (CLP) and cleft palate only (CP) and of 10 children of the same age without clefts were assessed. Assessment included speech production, expressive/ receptive phonological and morpho-syntactic abilities, receptive/ expressive lexical-semantic skills, aspects of phonological awareness and working memory. Non-parametric quantitative analysis based on Mann-Whitney U test was applied to identify statistical differences between groups. Additionally qualitative methods were used. Results Qualitative and quantitative data analysis revealed no differences between the cleft group and their noncleft peers in all levels of language abilities. Moderate significant group differences were found on expressive pathological phonological process usage (p = .06). The main phonological process backing was noted more frequently in the speech of children with clefts. Children in the cleftgroup performed moderate significantly below the children in the control group on phonological awareness tasks (rhyme judgement, p = .09) and significantly below the control group on verbal short-term memory (digit span, p = .02). Discussion Despite of expressive phonological delay and conductive hearing loss children with CLP/CP demonstrate normal language competence at age 4. However, the results of this study suggest that children with CLP/CP have subtle impairments at the level of perceptual-phonological analysis and working memory. Whether these deficits arise from fluctuant hearing loss and/or delays in speech development remains an open question. Further research is needed to understand the nature of the relationship among the three variables articulation, conductive hearing loss and working memory

Cross-sectional and longitudinal associations of screen time and physical activity with school performance at different types of secondary school

Abstract Background Previous studies have already reported associations of media consumption and/or physical activity with school achievement. However, longitudinal studies investigating independent effects of physical activity and media consumption on school performance are sparse. The present study fills this research gap and, furthermore, assesses relationships of the type of secondary school with media consumption and physical activity. Methods The consumption of screen-based media (TV/video, game console, PC/internet, and mobile phone) and leisure physical activity (organized and non-organized) of 10 – to 17-year old adolescents participating in the LIFE Child study in Germany were related to their school grades in two major school subjects (Mathematics and German) and in Physical Education. In addition to a cross-sectional analysis at baseline (N = 850), a longitudinal analysis (N = 512) investigated the independent effects of these activities on the school grades achieved 12 months later. All associations were adjusted for age, gender, socio-economic status, year of data assessment, body-mass-index, and school grades at baseline. A further analysis investigated differences in the consumption of screen-based media and physical activity as a function of the type of secondary school (highest vs. lower secondary school). Results Adolescents of lower secondary schools reported a significantly higher consumption of TV/video and game consoles than adolescents attending the highest secondary school. Independently of the type of school, a better school performance in Mathematics was predicted by a lower consumption of computers/internet, and a better performance in Physical Education was predicted by a lower consumption of TV/video and a higher frequency of non-organized physical activity. However, the association between non-organized physical activity and subsequent grades in Physical Education was significant in girls only. Conclusion The present results suggest that media consumption has a negative effect on school achievement, whereas physical activity has a positive effect, which, however, is restricted to the subject Physical Education. Future studies might explore the relationship between media consumption and school career, for example, the choice or change of the secondary school type, in more detail. Trial registration LIFE Child study: ClinicalTrials.gov, clinical trial number NCT0255023

Reference curves for refraction in a German cohort of healthy children and adolescents.

PURPOSE:Percentile curves of refractive development for German children were generated. We hypothesize that refraction in children in central Europe might differ from data in central Asia. METHODS:Non-cycloplegic refraction was measured using the ZEISS i.Profiler plus (Carl Zeiss Vision GmbH, Germany) in 1999 children, of which were 1046 male and 953 female, aged 3 to 18 years. Reference curves were calculated with the R-package GAMLSS as continuous function of age. RESULTS:There were only little differences for all centiles between the genders at 3 years and a general trend towards more myopia with increasing age. For the 97th centile and the 3rd centile, girls showed higher myopia/ less hyperopia than boys. Between the age of 3 and 18, the median refraction became -0.68 D and -0.74 D more myopic for boys and girls, respectively. At the same time, the 97th centile for boys changed +0.29 D towards hyperopia and in girls -0.52 D towards myopia. A general myopic trend was seen in the 3rd centile, which was -2.46 D for boys and -2.98 D for girls. For both genders, the median became less than zero at the age of 10 years but did not become myopic (less than -0.5 D) up to the age of 18. CONCLUSION:Our analysis presents the first reference curve for refraction in central Europe. In comparison to data from China and Korea, there is only little difference at the age of 5 years in all centiles which then increases continuously. For all ethnicities, a trend towards myopia with increasing age could be observed, but myopia progression is much higher in China and Korea than in Germany. The most marked differences can be seen in the lower centiles. Further investigations should clarify whether commencement of preschool activities with prolonged near-work initiates the divergence in refractive development

Cystatin C relates to metabolism in healthy, pubertal adolescents

Introduction!#!The cystatin C (CysC) serum level is a marker of glomerular filtration rate and depends on age, gender, and pubertal stage. We hypothesize that CysC might overall reflect energy homeostasis and be regulated by components of the endocrine system and metabolites in pubertal adolescents.!##!Methods!#!Serum CysC levels and further possible effector parameters in 5355 fasting, morning venous blood samples from 2035 healthy participants of the LIFE Child cohort study (age 8 to 18 years) were analyzed. Recruitment started in 2011, with probands followed up once a year. Linear univariate and stepwise multivariate regression analyses were performed.!##!Results!#!Annual growth rate, serum levels of thyroid hormones, parathyroid hormone, insulin-like growth factor 1, hemoglobin A1c (HbA1c), uric acid, and alkaline phosphatase show relevant and significant associations with CysC serum concentrations (p &amp;lt;0.001). Furthermore, male probands' CysC correlated with the body mass index and testosterone among other sexual hormones. Multivariate analyses revealed that uric acid and HbA1c are associated variables of CysC independent from gender (p &amp;lt;0.001). In males, alkaline phosphatase (p &amp;lt;0.001) is additionally significantly associated with CysC. Thyroid hormones show significant correlations only in multivariate analyses in females (p &amp;lt;0.001).!##!Conclusions!#!The described associations strongly suggest an impact of children's metabolism on CysC serum levels. These alterations need to be considered in kidney diagnostics using CysC in adolescents. Additionally, further studies are needed on CysC in children

Overweight Proxies Are Associated with Atopic Asthma: A Matched Case–Control Study

Background: Many studies have documented a link between overweight and asthma in children with contradictory results regarding the best way to measure overweight. Moreover, often, the dynamic development of atopy, overweight, and asthma is controlled for age dependency insufficiently. Objective: This study assesses and compares the associations of overweight measured as waist circumference, waist to height ratio (WHtR), neck circumference, and body mass index with the occurrence of asthma – best possibly controlling for age-dependencies of these parameters. Methods: From a sample of 2,511 children aged 6–17 years, we matched 157 children with asthma with 2 controls (n = 471) according to age and atopy status and performed conditional logistic regression analyses. We further investigated the role of known influencing factors of asthma occurrence. Results: In children with atopy, all overweight proxies were consistently positively associated with asthma. Statistical significance was reached for WHtR-SD score (OR 1.26, 95% CI 1.03–1.54, p = 0.025) and persisted when further covariates, such as birth weight or social status, were added to the model. Groups of atopic versus nonatopic participants do not differ in levels of interleukin-6 or high-sensitivity C-reactive protein. Conclusion: In our cohort, overweight seems to carry a risk for asthma only if accompanied with atopy. We call for more strict age matching in pediatric cohort studies and longitudinal studies for a better understanding for causal links of overweight, atopy, and asthma

Timing of ketogenic dietary therapy (KDT) introduction and its impact on cognitive profiles in children with Glut1-DS — a preliminary study

The aim of this research was to characterize cognitive abilities in patients with Glut1-Deficiency syndrome (Glut1DS) following ketogenic diet therapy (KDT). Methods: The cognitive profiles of eight children were assessed using the Wechsler Intelligence Scale (WISC-IV). The effect of ketogenic diet therapy (KDT) on individual subareas of intelligence was analyzed considering the potential influence of speech motor impairments. Results: Patients with Glut1DS showed a wide range of cognitive performance levels. Some participants showed statistically and clinically significant discrepancies between individual subdomains of intelligence. Both variables, KDT initiation as well as duration, had a positive effect on the overall IQ score. Significant correlations were partially found between the time of KDT initiation and the level of IQ scores, depending on the presence of expressive language test demands of the respective subtests of the WISC-IV. Accordingly, the participants benefited les in the linguistic cognitive domain. The discrepancies in cognitive performance profiles of patients with Glut1DS can be attributed to the possibility of a negative distortion of the results due to the influence of speech motor impairments. Conclusions: The individual access skills of test persons should be more strongly considered in test procedures for the assessment of intelligence to reduce the negative influence of motor deficits on test performance. Specific characterization and systematization of the speech disorder are indispensable for determining the severity of speech motor impairment in Glut1DS. Therefore, a stronger focus on dysarthria during diagnosis and therapy is necessary