Abstract Background Active school transport (AST) can increase children’s and adolescents’ physical activity. The proportion of children and adolescents who engage in AST has declined internationally in recent decades. This study examines the prevalence, correlates, and perceived barriers to AST in the city of Leipzig, Germany. Methods The study sample includes 1070 participants, 364 children and 706 adolescents, aged between 6 and 18 years, as well as their parents. The parents as well as adolescents age 10 and above completed questionnaires concerning sociodemographic variables, means of transport/AST and perceived barriers to AST. The distance between home and school was calculated as the network distance from the home to school address using the Dijkstra algorithm. Based on these data, logistic models were fitted in a two-step variable selection process, using AST as the dependent variable. Results Approximately half of the children (59%) and adolescents (51%) engaged in AST. The prevalence of AST exhibited a negative correlation with age (Odds Ratio (OR) = 0.94, 95% confidence interval (CI) = 0.9–0.99, p = 0.015) and did not significantly differ by gender (children: ORgirls = 1.5, CI = 0.95–2.25, p = 0.075, adolescents: ORgirls = 1.01, CI = 0.75–1.37, p = 0.924). A high socioeconomic status was positively correlated to AST on the morning trip (OR = 1.7, CI 1.3–2.21, p < 0.01) but negatively on the afternoon trip (OR = 0.7, CI = 0.53–0.9, p < 0.01) in the summer. Common barriers for children (from their parents’ perspective) and for adolescents (from their own and their parents’ perspective) were distance and a heavy load to carry. The parents of adolescents did not perceive any other specific barriers as a serious impediment. Further significant barriers perceived by the younger children’s parents were adults giving a lift on the way to other errands, no other children to walk or cycle with, and too much traffic. Too much traffic was also a significant barrier for adolescents, as were taking too much time and bad weather conditions. Conclusions Future interventions promoting AST in an urban environment should be guided by the identified perceived barriers. Trial registration LIFE Child has been retrospectively registered with ClinicalTrials.gov (NCT02550236).

ZusammenfassungEs wurde viel darüber spekuliert, ob durch Schulschließungen, eingeschränkte soziale Kontakte und den Wegfall sportlicher Aktivitäten während der Covid-19-Pandemie die Adipositasepidemie im Kindesalter verstärkt werden würde. Deshalb haben wir die BMI-Verläufe während der 15 Jahre vor und während der Covid-19-Pandemie untersucht. Der Trend der BMI-Veränderungen (als delta-BMI-SDS) und die Anteile der Kinder, die Gewicht zunahmen bzw. verloren, zwischen 2005 und 2019 sowie entsprechend Daten von 2019 vor der Pandemie und von 2020 nach dem Einsetzen der ersten Pandemiemaßnahmen wurden bei mehr als 150 000 Kindern (ca. 10 000 in der pandemischen Phase) verglichen. Während der Covid-19-Pandemie fand sich eine substantielle Gewichtszunahme über alle Gewichtsklassen und Altersstufen hinweg. Die Änderung des mittleren BMI-SDS war wesentlich höher als in den Jahren zuvor. Ebenso stieg der Anteil der Kinder, die Gewicht zunahmen. Der Anteil der Kinder, die Gewicht über den Zeitraum verloren, nahm hingegen ab. Außerdem fanden wir ähnliche Trends, der zwar auf eine wesentlich schwächere aber doch stetige Gewichtszunahme hinweisen, bereits seit 2005. Es ist alarmierend, dass sowohl der langfristige Trend als auch die kurzfristigen, pandemie-bezogenen Effekte bei Kindern, die bereits übergewichtig oder adipös waren, am größten waren.Die Trends, die wir in mehreren Parametern der Gewichtsveränderung über einen Zeitraum von mehr als 15 Jahren beobachten konnten, weisen auf eine Zunahme des BMI-SDS. Besonders bei adipösen Kindern ist diese Dynamik ausgeprägt. Covid-19-bezogene Maßnahmen verstärken die Effekte und könnten damit die Adipositasepidemie im Kindesalter weiter eskalieren.

Background/Objectives There is a concern that measures aiming to limit a further spread of COVID-19, e.g., school closures and social distancing, cause an aggravation of the childhood obesity epidemic. Therefore, we compared BMI trends during the 15 years before and during the COVID-19 pandemic. Subjects/Methods To assess the change in weight dynamics during the first months of COVID-19, we compared the trends of 3-month change in BMI-SDS (ΔBMI-SDS) and the proportions of children showing a high positive (HPC) or high negative (HNC) weight change between 2005 and 2019 and the respective changes from 2019 (pre-pandemic) to 2020 (after the onset of anti-pandemic measures) in more than 150,000 children (9689 during the pandemic period). The period of 3 months corresponds approximately to the first lockdown period in Germany. Results During the COVID-19 pandemic, we found a substantial weight gain across all weight and age groups, reflected by an increase in the 3-month change in BMI-SDS ( β = 0.05, p < 0.001), an increase in the proportion of children showing HPC (OR = 1.4, p < 0.001), and a decrease in the proportion of children showing HNC (OR = 0.7, p < 0.001). Besides, we found the same trends since 2005 on a low but stable level with a yearly increase of ΔBMI-SDS by β = 0.001 ( p < 0.001), the odds of HPC increased by OR high_pos = 1.01 ( p < 0.001), and the odds of HNC decreased by OR high_neg = 0.99 ( p < 0.001). These rather small effects accumulated to β = 0.02, OR high_pos = 1.14, and OR high_pos = 0.85 over the whole period 2005–2019. Alarmingly, both the long-term and the short-term effects were most pronounced in the obese subgroup. Conclusions There are positive dynamics in different measures of weight change, indicating a positive trend in weight gain patterns, especially within the group of children with obesity. These dynamics are likely to be escalated by COVID-19-related measures. Thus, they may lead to a significant further aggravation of the childhood obesity pandemic.

Introduction: The thyroid parafollicular hormone calcitonin (CT) shows particularly high blood levels in early childhood, a period of high bone turnover, which decrease with increasing age. Data about the physiological role of CT during infancy, childhood, and adolescence are contradictory or lacking. Objective: We hypothesize that CT demonstrates age-related correlations with parameters of bone growth and turnover as well as with parameters of calcium homeostasis. Methods: 5,410 measurements of anthropometric data and venous blood samples were collected from 2,636 participants of the LIFE Child study, aged 2 months–18 years. Univariate correlations and multiple regression analysis were performed between serum CT and anthropometric indicators (height standard deviation scores [SDS] and BMI-SDS), markers of calcium (Ca) homeostasis (Ca, parathyroid hormone, 25-OH vitamin D, and phosphate [P]), bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin), and bone resorption (β-CrossLaps). Results: CT was significantly associated with Ca (β = 0.26, p < 0.05) and P1NP/100 (β = 0.005, p < 0.05) in children aged 2 months–1.1 years. These relations were independent of age and sex and could not be confirmed in children aged 1.1–8 years. Independent of age, sex, puberty, P, and height SDS CT showed a significant positive relation to Ca (β = 0.26; p < 0.001) in children aged 8–18 years. Conclusions: Our findings suggest a unique association between CT and Ca in periods of rapid bone growth and point to a possible involvement of CT in promoting bone formation during the first year of life.

BACKGROUND:There is only limited information on serum reference ranges of calcitonin (CT) in infants, children and adolescents. This gap hampers valid diagnostics in patients with multiple endocrine neoplasia type 2 (MEN 2) and planned prophylactic thyroidectomy. In addition, age-dependent reference ranges for CT are necessary to define a cure in medullary thyroid carcinoma (MTC). We asked whether the reference ranges for CT levels were age- and gender-dependent in the serum of a pediatric cohort.METHODS:A total of 6090 serum samples of 2639 subjects of the LIFE-Child cohort aged between 1 month and 17.9 years were analyzed by the CT electrochemiluminescence immunoassay (ECLIA). Reference intervals were estimated using the LMS method. For clinical validation the serum of 28 patients (61 samples) with MEN 2 and 106 patients (136 samples) with thyroid diseases were analyzed.RESULTS:CT levels showed a clear age- and gender-dependence with significantly higher values in boys (p<0.01). An accelerated decline of CT levels from newborn to children at the age of 4 and 5 years was observed for both sexes. A cure for MTC was demonstrated in 71% of MEN 2 patients after thyroidectomy, whereas 5 patients remained suspicious for micrometastasis or relapse. Only 1.5% of our patients with thyroid diseases revealed increased CT levels.CONCLUSIONS:This is the largest study to establish novel pediatric reference ranges from the CT values of healthy subjects. It allows a precise laboratory monitoring of CT in pediatric patients with MEN 2. Thyroid diseases did not have a relevant influence on CT levels in our pediatric cohort.

BACKGROUND:The dynamics of body-mass index (BMI) in children from birth to adolescence are unclear, and whether susceptibility for the development of sustained obesity occurs at a specific age in children is important to determine. METHODS:To assess the age at onset of obesity, we performed prospective and retrospective analyses of the course of BMI over time in a population-based sample of 51,505 children for whom sequential anthropometric data were available during childhood (0 to 14 years of age) and adolescence (15 to 18 years of age). In addition, we assessed the dynamics of annual BMI increments, defined as the change in BMI standard-deviation score per year, during childhood in 34,196 children. RESULTS:In retrospective analyses, we found that most of the adolescents with normal weight had always had a normal weight throughout childhood. Approximately half (53%) of the obese adolescents had been overweight or obese from 5 years of age onward, and the BMI standard-deviation score further increased with age. In prospective analyses, we found that almost 90% of the children who were obese at 3 years of age were overweight or obese in adolescence. Among the adolescents who were obese, the greatest acceleration in annual BMI increments had occurred between 2 and 6 years of age, with a further rise in BMI percentile thereafter. High acceleration in annual BMI increments during the preschool years (but not during the school years) was associated with a risk of overweight or obesity in adolescence that was 1.4 times as high as the risk among children who had had stable BMI. The rate of overweight or obesity in adolescence was higher among children who had been large for gestational age at birth (43.7%) than among those who had been at an appropriate weight for gestational age (28.4%) or small for gestational age (27.2%), which corresponded to a risk of adolescent obesity that was 1.55 times as high among those who had been large for gestational age as among the other groups. CONCLUSIONS:Among obese adolescents, the most rapid weight gain had occurred between 2 and 6 years of age; most children who were obese at that age were obese in adolescence. (Funded by the German Research Council for the Clinical Research Center "Obesity Mechanisms" and others; ClinicalTrials.gov number, NCT03072537 .).

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

OBJECTIVE:To assess the frequency of incidental findings (IFs) in the population-based "Leipzig Research Centre for Civilization Diseases (LIFE) Child Study" within 1 year. METHODS:From July 2011 to June 2012, 969 children participated in the study. The IFs were analysed with respect to age, gender, type of examination and clinical action taken. RESULTS:The IFs were detected in 63 participants (6.5%), including five children who presented with two IFs simultaneously. Eleven children received a new, hence previously unknown, clinical diagnosis. Alternatively, 18 IFs could not be confirmed or were of a transient and self-limiting condition. The frequency of IFs varied widely depending on the type of examination, but did not differ by gender. CONCLUSION:Although IFs were common events, there was no finding with a profound clinical impact on the subject's life. Our current IF management protocol may be useful in creating management plans for other cohort studies.

Background Profound knowledge about child growth, development, health, and disease in contemporary children and adolescents is still rare. Epidemiological studies together with new powerful research technologies present exciting opportunities to the elucidation of risk factor-outcome associations with potentially major consequences for prevention, diagnosis and treatment. Aim To conduct a unique prospective longitudinal cohort study in order to assess how environmental, metabolic and genetic factors affect growth, development and health from fetal life to adulthood. Methods The ‘Leipzig Research Centre for Civilization Diseases (LIFE) Child Study’ focuses on two main research objectives: (1) monitoring of normal growth, development and health; (2) non-communicable diseases such as childhood obesity and its co-morbidities, atopy and mental health problems. Detailed assessments will be conducted alongside long-term storage of biological samples in 2,000 pregnant women and more than 10,000 children and their families. Results Close coordination and engagement of a multidisciplinary team in the LIFE Child study successfully established procedures and systems for balancing many competing study and ethical needs. Full participant recruitment and complete data collection started in July 2011. Early data indicate a high acceptance rate of the study program, successful recruitment strategies and the establishment of a representative cohort for the population of Leipzig. A series of subprojects are ongoing, and analyses and publications are on their way. Discussion This paper addresses key elements in the design and implementation of the new prospective longitudinal cohort study LIFE Child. Given the recognized need for long-term data on adverse effects on health and protective factors, our study data collection should provide magnificent opportunities to examine complex interactions that govern the emergence of non-communicable diseases.