Detection of risk factors for obesity in early childhood with quantile regression methods for longitudinal data

This article compares and discusses three different statistical methods for investigating risk factors for overweight and obesity in early childhood by means of the LISA study, a recent German birth cohort study with 3097 children. Since the definition of overweight and obesity is typically based on upper quantiles (90% and 97%) of the age specific body mass index (BMI) distribution, our aim was to model the influence of risk factors and age on these quantiles while as far as possible taking the longitudinal data structure into account. The following statistical regression models were chosen: additive mixed models, generalized additive models for location, scale and shape (GAMLSS), and distribution free quantile regression models. The methods were compared empirically by cross-validation and for the data at hand no model could be rated superior. Motivated by previous studies we explored whether there is an age-specific skewness of the BMI distribution. The investigated data does not suggest such an effect, even after adjusting for risk factors. Concerning risk factors, our results mainly confirm results obtained in previous studies. From a methodological point of view, we conclude that GAMLSS and distribution free quantile regression are promising approaches for longitudinal quantile regression, requiring, however, further extensions to fully account for longitudinal data structures

Temporal Changes in Total Serum Immunoglobulin E Levels in East German Children and the Effect of Potential Predictors

Background: Elevated total serum immunoglobulin E (IgE) levels are a prominent feature of allergic and parasitic diseases. An epidemiologic study was conducted in East German children to describe trends in the development of total serum IgE levels and analyze the impact of potential determinants. Methods: The study consisted of three cross-sectional surveys in 1992-1993, 1995-1996 and 1998-1999 and was conducted in three areas of the former German Democratic Republic. In total, 8,051 questionnaires were completed by the parents of children aged 5-14 years, supplying information on allergic symptoms and potential risk factors. A total of 5,918 measurements of total serum IgE and specific IgE to 5 common aeroallergens were available from 4,353 schoolchildren. Generalized estimating equations were applied to data from all children and stratified for atopic and nonatopic children to identify trends and estimate the effect of potential determinants on total IgE. Results: Total serum IgE levels decreased significantly with a linear trend in East German schoolchildren between 1992 and 1999, the effect being stronger in nonatopic children. The following factors were associated with lower total serum IgE levels: female gender, living in a household with fewer than 4 people, no history of helminth infestation, younger age group (5-7 years), no parental allergy and high socioeconomic status. No association was seen for `smoking at home' and close contact to pets. Conclusion: Total serum IgE declined parallel to helminth infestation; however, the latter explained the decrease only in part. Furthermore, total IgE developed in an opposite direction to specific IgE, indicating that it has determinants other than allergic sensitization. Copyright (C) 2011 S. Karger AG, Base

Associations between BMI and the FTO Gene Are Age Dependent: Results from the GINI and LISA Birth Cohort Studies up to Age 6 Years

Objective: The association between polymorphisms in intron 1 of the fat mass and obesity associated gene (FTO) and obesity-related traits is one of the most robust associations reported for complex traits and is established both in adults and children. However, little is known about the longitudinal dynamics of these polymorphisms on body mass index (BMI), overweight, and obesity. Methods: This study is based on the 2,732 full-term neonates of the German GINI-plus and LISA-plus birth cohorts, for whom genotyping data on the FTO variants rs1558902 (T>A) or rs9935401 (G>A) were available. Children were followed from birth up to age 6 years. Up to 9 anthropometric measurements of BMI were obtained. Fractional-Polynomial-Generalized-Estimation-Equation modeling was used to assess developmental trends and their potential dependence on genotype status. Results: We observed no evidence for BMI differences between genotypes of both variants for the first 3 years of life. However, from age 3 years onwards, we noted a higher BMI for the homozygous minor alleles carriers in comparison to the other two genotype groups. However, evidence for statistical significance was reached from the age of 4 years onwards. Conclusions: This is one of the first studies investigating in detail the development of BMI depending on FTO genotype between birth and the age of 6 years in a birth cohort not selected for the phenotype studied. We observed that the association between BMI and FTO genotype evolves gradually and becomes descriptively detectable from the age of 3 years onwards

Regulation of early human growth: impact on long-term health

Growth and development are central characteristics of childhood. Deviations from normal growth can indicate serious health challenges. The adverse impact of early growth faltering and malnutrition on later health has long been known. In contrast, the impact of rapid early weight and body fat gain on programming of later disease risk have only recently received increased attention. Numerous observational studies related diet in early childhood and rapid early growth to the risk of later obesity and associated disorders. Causality was confirmed in a large, double-blind randomised trial testing the ‘Early Protein Hypothesis'. In this trial we found that attenuation of protein supply in infancy normalized early growth and markedly reduced obesity prevalence in early school age. These results indicate the need to describe and analyse growth patterns and their regulation through diet in more detail and to characterize the underlying metabolic and epigenetic mechanisms, given the potential major relevance for public health and policy. Better understanding of growth patterns and their regulation could have major benefits for the promotion of public health, consumer-orientated nutrition recommendations, and the development of improved food products for specific target populations.</jats:p

Influence of FADS Polymorphisms on Tracking of Serum Glycerophospholipid Fatty Acid Concentrations and Percentage Composition in Children

Tracking of fatty acid (FA) contribution to plasma or serum lipids over time was shown in children and adults. However, the potential role of FADS gene variants has not been investigated. Serum GP FA composition of 331 children aged 2 and 6 years, participating in an ongoing birth cohort study, was analyzed. Correlation coefficients were estimated to describe FA tracking over 4 years and to assess the influence of FADS variants on tracking. We found low to moderate tracking (r = 0.12-0.49) of FA compositions and concentration between 2 and 6 years. Concentration changes of total monounsaturated FA and total saturated FA over time correlated closely (r = 0.79) but percentage values were unrelated (r = -0.02). Tracking for n-6 long chain polyunsaturated fatty acid (LC-PUFA) concentrations was lower in subjects homozygous for the major allele of FADS variants and higher in carriers of at least one minor allele, whereas for total n-3 LC-PUFA concentrations and compositions this was vice versa. For individual n-3 PUFA inconsistent results were found. Serum GP FA composition shows low to moderate tracking over 4 years with a higher tracking for LC-PUFA metabolites than for their precursor FA. Serum PUFA levels and their tracking seem to be more influenced by lipid and lipoprotein metabolism than by FA specific pathways

Influence of FADS Polymorphisms on Tracking of Serum Glycerophospholipid Fatty Acid Concentrations and Percentage Composition in Children

BACKGROUND: Tracking of fatty acid (FA) contribution to plasma or serum lipids over time was shown in children and adults. However, the potential role of FADS gene variants has not been investigated. METHODS AND PRINCIPAL FINDINGS: Serum GP FA composition of 331 children aged 2 and 6 years, participating in an ongoing birth cohort study, was analyzed. Correlation coefficients were estimated to describe FA tracking over 4 years and to assess the influence of FADS variants on tracking. We found low to moderate tracking (r = 0.12-0.49) of FA compositions and concentration between 2 and 6 years. Concentration changes of total monounsaturated FA and total saturated FA over time correlated closely (r = 0.79) but percentage values were unrelated (r = -0.02). Tracking for n-6 long chain polyunsaturated fatty acid (LC-PUFA) concentrations was lower in subjects homozygous for the major allele of FADS variants and higher in carriers of at least one minor allele, whereas for total n-3 LC-PUFA concentrations and compositions this was vice versa. For individual n-3 PUFA inconsistent results were found. CONCLUSIONS AND SIGNIFICANCE: Serum GP FA composition shows low to moderate tracking over 4 years with a higher tracking for LC-PUFA metabolites than for their precursor FA. Serum PUFA levels and their tracking seem to be more influenced by lipid and lipoprotein metabolism than by FA specific pathways

Prenatal and Postnatal Tobacco Exposure and Behavioral Problems in 10-Year-Old Children: Results from the GINI-plus Prospective Birth Cohort Study

BACKGROUND: Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear. OBJECTIVE: We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally. METHODS: We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as &quot;normal,&quot; &quot;borderline,&quot; or &quot;abnormal&quot; according to the subscales &quot;emotional symptoms,&quot; &quot;conduct problems,&quot; &quot;hyperactivity/inattention,&quot; &quot;peer-relationship problems,&quot; and a total difficulties score. Smoke exposure and further covariates were assessed using parent questionnaires. RESULTS: Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age. Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9-1.9). These results could not be explained by confounding by parental education, father&#39;s employment, child&#39;s time spent in front of computer or television screen, being a single father or mother, or mother&#39;s age. CONCLUSIONS: Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children. Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important