Children's satisfaction with a comprehensive study program-Results from the LIFE Child cohort study.

BACKGROUND: Research participants' satisfaction is a topic of great interest, especially in the context of longitudinal studies. Evaluation also represents an important component of quality management in the health care system. Adult studies found that personal characteristics, e.g., age, sex, ethnicity, and SES, can influence satisfaction with health care or study participation. Studies on paediatric participants are sparse. OBJECTIVES: To examine how children rated the study day of a cohort study and how these ratings were associated with sociodemographic and socioeconomic characteristics and retention in the context of a large cohort study. METHODS: Analyses were performed on 4- to 17-year-old participants of the German longitudinal cohort study LIFE Child (n = 2033). To assess the associations between overall satisfaction (high versus low/middle) and age, sex, body-mass index, socioecomonic status, and participation in a follow-up visit, we applied logistic mixed-effects models. RESULTS: Participants' overall satisfaction with the LIFE Child study day was high ("very good": 67.8%). Overall satisfaction was higher in 7-9 years olds (odds ratio [OR] 2.00, 95% confidence interval [CI 1.51, 2.66) and 10-12 years olds (OR 1.51, 95% CI 1.16, 1.98) than in 4-6 years olds and 13-17 years olds. Children with obesity were less likely to participate in a follow-up visit (OR 0.56, 95% CI 0.39, 0.78). Children reporting high overall satisfaction at the first study visit completed a follow-up visit more frequently (OR 1.32, 95% CI 1.05,1.67). CONCLUSIONS: A high level of satisfaction increased participants' attendance at a follow-up visit. Our results might be helpful for adapting the study program to the participants' needs in order to maximise retention and minimise attrition rates.

Preclinical Cartilage Changes of the Knee Joint in Adolescent Competitive Volleyball Players: A Prospective T2 Mapping Study.

PURPOSE: To investigate the potential effects of volleyball as a competitive sport in adolescence on the cartilage of knee joints using T2 mapping in MRI and identification of preclinical cartilage changes. Volleyball as an impact sport often leads to damage of the knee joint cartilage in adulthood. As T2 mapping is widely available and highly capable of detecting cartilage changes prior to conventional MRI sequences, such a detection may allow adolescent volleyball players to change their training regime before structural damage can occur to the cartilage and pose the risk of osteoarthritis. MATERIALS AND METHODS: Comparative study of the patellar, femoral, and tibial cartilage of 60 knee joints using T2 mapping on 3 T MRI. In each case, both knees of 15 adolescent competitive volleyball athletes were compared with 15 controls. RESULTS: In the group of competitive athletes, more focal cartilage changes were detected in the medial facet of the patellofemoral cartilage and in the medial femoral condyle of the knee joint cartilage (p = .01 and p <.05, respectively). Furthermore, the latter showed a diffused increase in maximal T2 mapping values (p <.04 right and p = .05 left). The distribution of changes seems to further depend on the player's position. CONCLUSION: In adolescent volleyball players in competitive sports, T2 mapping demonstrates early cartilage changes in both the patellofemoral and medial femoral cartilages. The distribution of lesions depends on the player's position. Since the cascade from T2 relaxation time increase to conspicuous cartilage damage is well established, early counter-regulation (e. g., adapted training profile, targeted physiotherapy, and appropriate muscle building training) has the potential to prevent later damage. KEY POINTS: · Volleyball as a competitive sport in adolescence leads to preclinical knee cartilage changes.. · Cartilage changes are both focal and diffuse.. · Jumping-intensive player positions seem to show more patellofemoral and running-intensive more condylar cartilage changes.. · Early detection of these changes could prevent progression to cartilage damage through adapted training.. CITATION FORMAT: · Roth C, Hirsch F, Sorge I et al. Preclinical Cartilage Changes of the Knee Joint in Adolescent Competitive Volleyball Players: A Prospective T2 Mapping Study. Fortschr Röntgenstr 2023; 195: 913 - 923.

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.

Age-Dependent Reference Values for hs-Troponin T and NT-proBNP and Determining Factors in a Cohort of Healthy Children (The LIFE Child Study).

This study aimed to provide reliable pediatric reference values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive Troponin T (hsTnT) obtained from a population of well children and investigate for associations with sex, pubertal status, body mass index (BMI), and serum lipid levels. We analyzed hsTnT and NT-proBNP values obtained from 4826 samples provided by 2522 children aged 0.25-18 years participating in a prospective longitudinal population-based cohort study, "LIFE child" in Leipzig, Germany (Poulain et al., Eur J Epidemiol 32:145-158, 2017). NT-proBNP values decreased throughout childhood from values over 400 ng/L at 3 months to 138 ng/L in females and 65 ng/L in males by 18 years of age. Values dropped rapidly with advancing pubertal stage. We found a strong association between lower NT-proBNP values and higher BMI or elevated serum lipids, the latter effect being more pronounced in males. For hsTnT levels, approximately half of the measurements were below the detection limit. However, 76% of those aged 3 months and 21% of those aged 6 months had values exceeding the adult cut-off limit. Females had slightly higher levels in the first 2 years of life but this was reversed during puberty. In males, there was an upward trend from pubertal stage 2 onward. We identified a positive association between hsTnT and BMI but a negative association with low-density lipoprotein (LDL) cholesterol and triglyceride levels in boys but not in girls. Based on a large number of healthy children, we have established reliable reference values for NT-proBNP and hsTnT for use in everyday clinical practice. We have also identified important associations between certain metabolic and cardiac markers.Clinical Trial Registration ClinicalTrial.gov (NCT02550236).

Persistent organic pollutants in pregnant women potentially affect child development and thyroid hormone status.

BACKGROUND: Potentially harmful effects of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) on prenatal development and the endocrine system have been controversially discussed. METHODS: Working with a German cohort of 324 pregnant women, we assessed POP levels and used robust linear regression models to determine potential associations between maternal POP concentrations and pre- and postnatal development in the children, as well as the thyroid hormone status of the mother and child. RESULTS: Maternal p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and most measured PCBs positively correlated with postnatal weight gain. We detected no correlation between newborn birth weight and head circumference, respectively, and maternal PCB and p,p'-DDE serum levels, while body length at birth was negatively associated with the maternal serum concentration of PCB 183. Maternal p,p'-DDE and nearly all PCB serum levels showed a negative correlation with maternal free triiodothyronine (FT3). p,p'-DDE and PCB 74 and 118 were negatively associated with maternal thyroid-stimulating hormone levels. In addition, we identified significant associations between maternal POP levels and thyroid hormone parameters of the child. CONCLUSIONS: These results indicate that POP exposure likely affects different aspects of pre- and postnatal development and impacts the thyroid hormone status of both mother and child. IMPACT: Pregnant women in a German cohort display a substantial accumulation of POPs. Body mass index and age influence maternal serum POP levels. Maternal POP levels show correlations with the child's length at birth and weight gain, and FT3 levels in the mother and child. Our data provide additional evidence for the potentially harmful influence of POPs. Our data indicate that POPs influence pre- and postnatal 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 <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 <0.001). In males, alkaline phosphatase (p <0.001) is additionally significantly associated with CysC. Thyroid hormones show significant correlations only in multivariate analyses in females (p <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.

Concentrations of oligosaccharides in human milk and child growth.

BACKGROUND: The relationship between human milk oligosaccharides (HMO) and child growth has been investigated only insufficiently with ambiguous results. Therefore, this study examines potential influencing factors of HMO concentrations and how HMO are associated with child growth parameters. METHODS: Milk samples from the German LIFE Child cohort of healthy children were analyzed for 9 HMO. Putative associations with maternal and child cofactors and child height, head circumference and BMI between 3 months and 7 years of age were examined. Secretor status, defined as the presence of 2'-fucosyllactose, was investigated for associations with infant outcomes. RESULTS: Our population consisted of 21 (14.7%) non-secretor and 122 (85.3%) secretor mothers. Maternal age was significantly associated with higher 3'SL concentrations; gestational age was associated with LNT, 6'SL and LNFP-I. Pre-pregnancy BMI was negatively associated with LNnT only in non-secretors. The growth velocity of non-secretors' children was inversely associated with LNnT at 3 months to 1 year (R = 0.95 [0.90, 0.99], p = 0.014), 1 to 2 years (R = 0.80 [0.72, 0.88], p < 0.001) and 5 to 6 years (R = 0.71 [0.57, 0.87], p = 0.002). 2'FL was negatively associated with BMI consistently, reaching statistical significance at 3 months and 4 and 5 years. Children of non-secretors showed higher BMI at 3 months, 6 months, and 3, 6, and 7 years of age. CONCLUSION: We found that some associations between HMO and infant growth may extend beyond the infancy and breastfeeding periods. They highlight the importance of both maternal and infant parameters in the understanding of the underlying associations. TRIAL REGISTRATION: The study is registered with ClinicalTrial.gov: NCT02550236 .

Effect of physical activity and BMI SDS on bone metabolism in children and adolescents.

OBJECTIVE: Children with obesity are known to have reduced bone density and are at a higher risk for fractures. This may be caused by decreased physical activity or a metabolic phenomenon. In this study, we evaluated associations of physical activity with bone metabolism in children and adolescents with and without obesity. METHODS: Results from 574 visits of 397 subjects, 191 girls and 206 boys aged five to 18 years (mean: 11.7 ± 2.8) representing 180 children with (mean BMI SDS 2.5 ± 0.4) and 217 without obesity (mean BMI SDS 0.2 ± 1.0) from the LIFE Child study, a population-based cohort of children/adolescents with normal weight and with obesity were analyzed for the impact of their daily physical activity (MET/day, SenseWear Accelerometer) on serum SDS levels for bone formation (alkaline phosphatase, osteocalcin, procollagen type I N propeptide [P1NP]), bone resorption (beta-crosslaps), and calcium homeostasis (parathormone, OH-25-vitamin D) by a linear regression model adjusted for gender- and age-based differences. RESULTS: For male subjects, BMI SDS significantly influenced the association of physical activity to PTH, vitamin D, and beta-crosslaps SDS levels. A higher physical activity was accompanied by increased PTH but decreased vitamin D SDS levels in children with normal weight. In males with obesity, all levels remained unaltered. In females, BMI SDS significantly impacted the association of physical activity to PTH, vitamin D, P1NP, beta-crosslaps, and osteocalcin SDS levels. In females with obesity, higher physical activity was related to higher SDS levels of vitamin D, P1NP, and beta-crosslaps. In contrast, in normal weight females, only PTH SDS was higher. CONCLUSIONS: The effect of daily physical activity on bone metabolic markers and calciotropic hormones depends significantly on gender and BMI SDS. However, higher levels of physical activity were associated with increased bone turnover for female subjects with obesity only. Thus, motivating especially girls with obesity to be physically active may help improve their bone health.

Associations of prenatal exposure to phthalates and one phthalate substitute with anthropometric measures in early life: Results from the German LIFE Child cohort study.

Exposure to phthalates is widespread and especially early life stages represent a critical window of exposure. In the present study, we investigated the effect of prenatal exposure to phthalates on birth outcomes and weight development in early life. In 130 mother-child pairs, we estimated the association of concentrations of 13 phthalates in spot-urine samples collected during pregnancy and birth outcomes and weight gain in the first two years of life using robust linear regression. High molecular weight phthalates were inversely associated with birth weight in girls but not in boys. Thus, prenatal exposure to phthalates may affect birth weight in a sex-specific manner.

Motor skills in relation to body-mass index, physical activity, TV-watching, and socioeconomic status in German four-to-17-year-old children.

BACKGROUND: The present study describes motor skills in a large sample of German children and adolescents and investigates associations with age, gender, body-mass index, physical activity, television time, and socioeconomic status. METHODS: 2,106 children (1076 boys, 1030 girls) aged 4 to 17 years performed five different motor tests for strength (pushups, standing long jump), coordination (backward balancing, jumping side-to-side) and flexibility (forward bend) within the framework of the LIFE Child study (Leipzig, Germany). Anthropometric parameters were assessed through standardized measurement. Data on physical activity, television time, and socioeconomic status were collected via questionnaires. Linear regression analyses were applied to assess relations. RESULTS: Strength and coordination performance were higher in older than in younger children. While boys showed a higher performance in strengths tests than girls, girls performed better in flexibility and coordination during precision tasks (backward balancing). In terms of coordination under time constraint (jumping side-to-side), both genders produced similar results. Lower body-mass index, higher physical activity, and higher socioeconomic status were significantly related to better motor skills. Longer television times were significantly associated with lower performance in long jump. CONCLUSIONS: The present findings are similar to data collected at the beginning of the century, indicating that motor skills have hardly changed in recent years. The findings furthermore suggest that children from lower social strata, children with higher body weight, and children who move little have a higher risk of developing insufficient motor skills and should therefore be given special support.

COVID-19 pandemic and families' utilization of well-child clinics and pediatric practices attendance in Germany.

OBJECTIVE: The COVID-19 pandemic and the measures implemented to stop the pandemic had a broad impact on our daily lives. Besides work and social life, health care is affected on many levels. In particular, there is concern that attendance in health care programs will drop or hospital admissions will be delayed due to COVID-19-related anxieties, especially in children. Therefore, we compared the number of weekly visits to 78 German pediatric institutions between 2019 and 2020. RESULTS: We found no significant differences during the first 10 weeks of the year. However, and importantly, from April, the weekly number of visits was more than 35% lower in 2020 than in 2019 (p = 0.005). In conclusion, the COVID-19 pandemic seems to relate to families´ utilization of outpatient well-child clinics and pediatric practice attendance in Germany.

Atopic diseases in children and adolescents are associated with behavioural difficulties.

BACKGROUND: Atopic diseases and behavioural difficulties in children have both been on the rise in recent decades. This study seeks to assess associations between atopic diseases and behavioural difficulties, examining the differences considering child age and how behavioural difficulties were reported (via self-report or parent-report). METHODS: Data on behavioural difficulties, assessed through the Strengths and Difficulties Questionnaire (SDQ), and on atopic diseases, assessed through the participant's medical history, were available for 2701 study participants aged 3 to 18 years. Associations between atopic diseases and behavioural difficulties were evaluated using linear regression analyses. We split the study sample into two groups. I: 3-to 10-year-olds/parent-reported SDQ (n = 1764), II: 11- to 18-year-olds/parent-reported SDQ (n = 937) and self-reported SDQ (n = 915). All analyses were adjusted for age, gender, and socioeconomic status. RESULTS: In younger children, atopic dermatitis was strongly associated with higher total difficulties scores, more emotional problems and conduct problems, and more symptoms of hyperactivity/inattention. Parents reported higher total difficulties scores, more emotional problems, and more peer-relationship problems for adolescents with bronchial asthma and other allergies, whereas the adolescents themselves reported more peer relationship problems. CONCLUSION: In younger children, atopic dermatitis is associated with internalizing and externalizing problems. In adolescents, bronchial asthma and other allergies are associated with a greater level of internalizing problems only. The findings further suggest that parents of adolescents are more likely to perceive associations between atopic diseases and behavioural difficulties than the adolescents themselves.

Longitudinal analysis of axial length growth in a German cohort of healthy children and adolescents.

PURPOSE: To generate continuous growth curves for axial length (AL) in German children. We hypothesise that percentile curves of AL can be used as a predictive measure of myopia. METHODS: In this longitudinal and cross-sectional LIFE Child Study, children's non-cycloplegic refraction data was collected using the Zeiss i.Profiler plus while AL was measured using the Haag-Streit Lenstar. Reference growth curves were estimated as a continuous non-parametric function of age. RESULTS: Data from 4511 visits of 1965 participants (1021 boys and 944 girls) between 3 and 18 years of age were analysed. For all ages and percentiles, the estimated AL was higher in boys than girls. AL differences between boys and girls were most pronounced in the 98th percentile at 3 years of age, being 0.93 mm longer eyes in boys. This difference decreased to 0.21 mm at 18 years of age. While the lower percentiles of AL reach their final value around age 13, the 50th percentile was still increasing by 0.05 mm per year until the end of the observation period. While, in general, children with longer eyes are more likely to develop myopia, this relationship is weaker between the ages of 5 and 8. CONCLUSION: The LIFE Child Study data provides European AL data. In both Germany and China, AL has comparable growth rates when the baseline ALs are compared as percentiles. Thus, percentile curves of AL can be used as a predictive measure for the likelihood of developing as well as the progression of myopia.

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.

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.

Speaking Voice in Children and Adolescents: Normative Data and Associations with BMI, Tanner Stage, and Singing Activity.

OBJECTIVES: The aim of this study was to establish normative data concerning the speaking voice of children and adolescents for clinical diagnostics. STUDY DESIGN: Population-based mixed cross-sectional and longitudinal childhood cohort study. METHODS: Normative data measuring the speaking voice profile of 1352 male and 1274 female participants aged 6 to 17 years were collected. To evaluate the voice range, five different intensity levels as the quietest voicing speaking voice (Level I), conversational voice (Level II), classroom voice (Level III), shouting voice (Level IV), and again the quietest speaking voice (Level V) were investigated. Multivariable analyses were performed to describe the effects of body mass index, Tanner stage, and singing activity on the outcome variables. RESULTS: A clear distinction in frequencies and sound pressure levels between the five different voice levels can be found in both genders. In females the mean fundamental frequency of the conversational voice lowers from 223.3 to 205.8 Hz. In male participants it lowers from 223.3 to 102.3 Hz. The most substantial decrease in the fundamental frequency of the speaking voice in boys occurs at 13.5 years. Girls show an almost continuous decline in their fundamental frequency. Only the Tanner stage showed significant positive relationships with the grade of lowering of the fundamental frequency in both sexes. CONCLUSIONS: It was shown that the investigation of the speaking voice using predefined intensity-levels represents a feasible examination for children and adolescents. This study provides reference data on the range and age-adjusted normative values of the speaking voice.

Cystatin C serum levels in healthy children are related to age, gender, and pubertal stage.

BACKGROUND: This study aims to establish age- and gender-specific cystatin C (CysC) reference values for healthy infants, children, and adolescents and to relate them to pubertal stage, height, weight, and body mass index (BMI). METHODS: Serum CysC and creatinine levels of 6217 fasting, morning venous blood samples from 2803 healthy participants of the LIFE Child study (age 3 months to 18 years) were analyzed by an immunoassay. Recruitment started in 2011; 1636 participants provided at least one follow-up measurement. Percentiles for CysC were calculated. Age- and gender-related effects of height, weight, BMI, and puberty status were assessed through linear regression models. RESULTS: Over the first 2 years of life, median CysC levels decrease depending on height (ß = - 0.010 mg/l/cm, p < 0.001) and weight (ß = - 0.033 mg/l/kg, p < 0.001) from 1.06 to 0.88 mg/l for males and from 1.04 to 0.87 mg/l for females. Following the second year of age, the levels remain stable for eight years. From 11 to 14 years of age, there is an increase of median CysC levels in males to 0.98 mg/l and a decrease in females to 0.86 mg/l. The change is associated with puberty (ß = 0.105 mg/l/Tanner stage, p < 0.001 in males and ß = - 0.093 mg/l/Tanner stage, p < 0.01 in females) and in males with height (ß = 0.003 mg/l/cm, p < 0.001). CONCLUSIONS: CysC levels depend on age, gender, and height, especially during infancy and puberty. We recommend the use of age- and gender-specific reference values for CysC serum levels for estimating kidney function in clinical practice.