BackgroundProfound 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.AimTo 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.MethodsThe ‘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.ResultsClose 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.DiscussionThis 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.

Puberty is a period of physical and psychological maturation, with long-term effects on health. During the 20(th) century, a secular trend towards earlier puberty occurred in association with improvements in nutrition. The worldwide pandemic of childhood obesity has renewed interest in the relationship between body composition in childhood and the timing and tempo of puberty. Limited evidence suggests that earlier puberty is associated with a tendency towards central fat deposition; therefore, pubertal status needs to be carefully considered in the categorization of childhood and adolescent overweight and obesity. In the other direction, rapid early weight gain is associated with advanced puberty in both sexes, and a clear association exists between increasing BMI and earlier pubertal development in girls. Evidence in boys is less clear, with the majority of studies showing obesity to be associated with earlier puberty and voice break, although a subgroup of boys with obesity exhibits late puberty, perhaps as a variation of constitutional delay in growth and puberty. The possible mechanisms linking adiposity with pubertal timing are numerous, but leptin, adipocytokines and gut peptides are central players. Other possible mediators include genetic variation and environmental factors such as endocrine disrupting chemicals. This Review presents current evidence on this topic, highlighting inconsistencies and opportunities for future research.

Metabolic syndrome (MetS) is recognized as an escalating major health risk in adults as well as in children and adolescents. Its prevalence ranges from 6 to 39% depending on the applied definition criteria. To date, there is no consensus on a MetS definition for children and adolescents. However, most authors agree on essential components such as glucose intolerance, central obesity, hypertension, and dyslipidemia; each representing a risk for cardiovascular disease. Recently, associations between MetS and non-alcoholic fatty liver disease, hyperuricemia, and sleep disturbances have emerged. Biomarkers like adipocytokines are a subject of current research as they are implicated in the pathogenesis of the MetS. Epigenetics and gestational programming, especially the role of microRNA, comprise a novel, rapidly developing and promising research focus on the topic of MetS. MicroRNAs are increasingly valued for potential roles in the diagnosis, stratification, and therapeutics of MetS. Early detection of risk factors, screening for metabolic disturbances, and the identification of new therapies are major aims to reduce morbidity and mortality related to MetS. Dietary modification and physical activity are currently the only adopted treatment approaches. Pharmacological therapies and bariatric surgery are still contradictory and, therefore, are only recommended in selected high-risk cases.

There is only small additional benefit in using WC measurements for routine pediatric care in addition to BMI for predicting metabolic risk. For all parameters, the relationship is strongest during midpuberty, emphasizing that among obese pubertal adolescents, anthropometric measures (BMI and WC) best predict cardiometabolic comorbidities. WtHR does not seem to be superior to BMI or WC in predicting metabolic or cardiovascular risk related to childhood obesity.

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10−6) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10−8, explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10−4) and adult height (N = 127 513; P = 1.45 × 10−5). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.