The influence of early nutrition and growth on body composition in childhood and early adult life.

There is increasing evidence that events early in life may 'programme' later body composition (BC) and health outcomes. The aim of the work presented in this thesis was to test the following hypotheses: (l) birthweight and growth in infancy programme specific components of BC in later life and therefore have differential effects on health outcomes (2) infant BC is differentially related to later BC, and is potentially involved in the programming process. These hypotheses were investigated in 2 cohorts (1) prospective follow-up during adolescence of subjects who had BC measurements during infancy (by stable isotope) as part of nutrition intervention studies (2) healthy children who participated in a BC reference study, with retrospective collection of early growth records. The main outcome was BC assessed by the four-component model. Secondary outcomes were cardiovascular risk factors (blood pressure, lipid profiles, and insulin resistance markers). 308 subjects aged 4.22-20.36 years were studied. Birthweight (regarded as a proxy for prenatal growth) was positively related to later height in both sexes, and positively associated with fat free mass (FFM) in boys. In contrast, postnatal growth during the first 6 months of life positively influenced later fat mass (FM) and central fat distribution, with a weaker effect on FFM. Whilst FM showed a consistent association with most cardiovascular risk factors except HDL-C, FFM showed a strong negative association with HDL-C, independent of FM and central fat distribution. In a smaller group (n=41), BC at 12 weeks of age showed no significant association with adolescent BC but SF during very early postnatal life (3 and 6 weeks) was related to later FFM and central fat distribution. Infant nutrition affected infant body composition, but I was unable to detect effects on later BC. Conclusion: I found differential effects of growth during different periods on later BC, measured using the 'gold standard' four-component model. The mechanism by which early growth 'programs' later BC possibly involves both prenatal and postnatal nutrition and warrants further investigation, since it could be useful in terms of designing effective early intervention to reduce obesity prevalence in childhood and adolescence. BC during adolescence has a differential impact on cardiovascular risk factors. Therefore, separate measurements of FM, FFM, and central fat distribution may offer more insight into the impact of body composition programming on health outcomes

Anthropometric Markers and Iron Status of 6–12-Year-Old Thai Children: Associations and Predictors

Introduction. Obesity may be associated with poor iron status. The objective of this study was to investigate the association between different indices of iron status and anthropometric measurements in Thai children. Materials and Methods. Anthropometry (weight, height, waist circumference (WC), and body composition assessed by bioelectrical impedance analysis) and iron indices were measured in 336 Thai children aged 6–12 years. Iron deficiency (ID) was defined using two or more of the following: (1) %transferrin saturation (%Tsat)  5 mg/L. Iron deficiency anaemia (IDA) was defined as haemoglobin 5 mg/L. Puberty and menarche were significant predictors of ID (puberty adjusted OR: 2.20, 95% CI: 0.43, 11.25; menarche adjusted OR: 6.11, 95% CI: 1.21, 30.94). Conclusion. Greater adiposity was associated with poorer iron status. However, SF may not be a good indicator of iron status in Thai children, particularly in those who are overweight/obese, whereas sTfR merits further investigation

Body-composition reference data for simple and reference techniques and a 4-component model: A new UK reference child

Background: A routine pediatric clinical assessment of body composition is increasingly recommended but has long been hampered by the following 2 factors: a lack of appropriate techniques and a lack of reference data with which to interpret individual measurements. Several techniques have become available, but reference data are needed. Objective: We aimed to provide body-composition reference data for use in clinical practice and research. Design: Body composition was measured by using a gold standard 4-component model, along with various widely used reference and bedside methods, in a large, representative sample of British children aged from 4 to ≥20 y. Measurements were made of anthropometric variables (weight, height, 4 skinfold thicknesses, and waist girth), dual-energy X-ray absorptiometry, body density, bioelectrical impedance, and total body water, and 4-component fat and fat-free masses were calculated. Reference charts and SD scores (SDSs) were constructed for each outcome by using the lambda-mu-sigma method. The same outcomes were generated for the fat-free mass index and fat mass index. Results: Body-composition growth charts and SDSs for 5-20 y were based on a final sample of 533 individuals. Correlations between SDSs by using different techniques were ≥0.68 for adiposity outcomes and ≥0.80 for fat-free mass outcomes. Conclusions: These comprehensive reference data for pediatric body composition can be used across a variety of techniques. Together with advances in measurement technologies, the data should greatly enhance the ability of clinicians to assess and monitor body composition in routine clinical practice and should facilitate the use of body-composition measurements in research studies. © 2012 American Society for Nutrition

Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings From the TOSCA Study

Research on tuberous sclerosis complex (TSC) to date has focused mainly on the physical manifestations of the disease. In contrast, the psychosocial impact of TSC has received far less attention. The aim of this study was therefore to examine the impact of TSC on health, quality of life (QoL), and psychosocial well-being of individuals with TSC and their families. Questionnaires with disease-specific questions on burden of illness (BOI) and validated QoL questionnaires were used. After completion of additional informed consent, we included 143 individuals who participated in the TOSCA (TuberOus SClerosis registry to increase disease Awareness) study. Our results highlighted the substantial burden of TSC on the personal lives of individuals with TSC and their families. Nearly half of the patients experienced negative progress in their education or career due to TSC (42.1%), as well as many of their caregivers (17.6% employed; 58.8% unemployed). Most caregivers (76.5%) indicated that TSC affected family life, and social and working relationships. Further, well-coordinated care was lacking: a smooth transition from pediatric to adult care was mentioned by only 36.8% of adult patients, and financial, social, and psychological support in 21.1, 0, and 7.9%, respectively. In addition, the moderate rates of pain/discomfort (35%) and anxiety/depression (43.4%) reported across all ages and levels of disease demonstrate the high BOI and low QoL in this vulnerable population

Catch-Up Growth Following Fetal Growth Restriction Promotes Rapid Restoration of Fat Mass but Without Metabolic Consequences at One Year of Age

BACKGROUND: Fetal growth restriction (FGR) followed by rapid weight gain during early life has been suggested to be the initial sequence promoting central adiposity and insulin resistance. However, the link between fetal and early postnatal growth and the associated anthropometric and metabolic changes have been poorly studied. METHODOLOGY/PRINCIPAL FINDINGS: Over the first year of post-natal life, changes in body mass index, skinfold thickness and hormonal concentrations were prospectively monitored in 94 infants in whom the fetal growth velocity had previously been measured using a repeated standardized procedure of ultrasound fetal measurements. 45 infants, thinner at birth, had experienced previous FGR (FGR+) regardless of birth weight. Growth pattern in the first four months of life was characterized by greater change in BMI z-score in FGR+ (+1.26+/-1.2 vs +0.58 +/-1.17 SD in FGR-) resulting in the restoration of BMI and of fat mass to values similar to FGR-, independently of caloric intakes. Growth velocity after 4 months was similar and BMI z-score and fat mass remained similar at 12 months of age. At both time-points, fetal growth velocity was an independent predictor of fat mass in FGR+. At one year, fasting insulin levels were not different but leptin was significantly higher in the FGR+ (4.43+/-1.41 vs 2.63+/-1 ng/ml in FGR-). CONCLUSION: Early catch-up growth is related to the fetal growth pattern itself, irrespective of birth weight, and is associated with higher insulin sensitivity and lower leptin levels after birth. Catch-up growth promotes the restoration of body size and fat stores without detrimental consequences at one year of age on body composition or metabolic profile. The higher leptin concentration at one year may reflect a positive energy balance in children who previously faced fetal growth restriction

Treatment Patterns and Use of Resources in Patients With Tuberous Sclerosis Complex: Insights From the TOSCA Registry

Tuberous Sclerosis Complex (TSC) is a rare autosomal-dominant disorder caused by mutations in the TSC1 or TSC2 genes. Patients with TSC may suffer from a wide range of clinical manifestations; however, the burden of TSC and its impact on healthcare resources needed for its management remain unknown. Besides, the use of resources might vary across countries depending on the country-specific clinical practice. The aim of this paper is to describe the use of TSC-related resources and treatment patterns within the TOSCA registry. A total of 2,214 patients with TSC from 31 countries were enrolled and had a follow-up of up to 5 years. A search was conducted to identify the variables containing both medical and non-medical resource use information within TOSCA. This search was performed both at the level of the core project as well as at the level of the research projects on epilepsy, subependymal giant cell astrocytoma (SEGA), lymphangioleiomyomatosis (LAM), and renal angiomyolipoma (rAML) taking into account the timepoints of the study, age groups, and countries. Data from the quality of life (QoL) research project were analyzed by type of visit and age at enrollment. Treatments varied greatly depending on the clinical manifestation, timepoint in the study, and age groups. GAB Aergics were the most prescribed drugs for epilepsy, and mTOR inhibitors are dramatically replacing surgery in patients with SEGA, despite current recommendations proposing both treatment options. mTOR inhibitors are also becoming common treatments in rAML and LAM patients. Forty-two out of the 143 patients (29.4%) who participated in the QoL research project reported inpatient stays over the last year. Data from non-medical resource use showed the critical impact of TSC on job status and capacity. Disability allowances were more common in children than adults (51.1% vs 38.2%). Psychological counseling, social services and social worker services were needed by <15% of the patients, regardless of age. The long-term nature, together with the variability in its clinical manifestations, makes TSC a complex and resource-demanding disease. The present study shows a comprehensive picture of the resource use implications of TSC

Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project.

BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters. RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions. CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters