Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background

Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15.

Methods and Findings

Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0–2 years and BMI from 2–10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL- and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0–2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5–10), and were largely mediated by fat mass at age 15.

Conclusion

Changes in PI/BMI from 0–10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5–10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight.     

Genetic risk sum score comprised of common polygenic variation is associated with body mass index

Genome-wide association studies (GWAS) of body mass index (BMI) using large samples have yielded approximately a dozen robustly associated variants and implicated additional loci. Individually these variants have small effects and in aggregate explain a small proportion of the variance. As a result, replication attempts have limited power to achieve genome-wide significance, even with several thousand subjects. Since there is strong prior evidence for genetic influence on BMI for specific variants, alternative approaches to replication can be applied. Instead of testing individual loci sequentially, a genetic risk sum score (GRSS) summarizing the total number of risk alleles can be tested. In the current study, GRSS comprising 56 top variants catalogued from two large meta-analyses was tested for association with BMI in the Molecular Genetics of Schizophrenia controls (2,653 European-Americans, 973 African-Americans). After accounting for covariates known to influence BMI (ancestry, sex, age), GRSS was highly associated with BMI (p value = 3.19E−06) although explained a limited amount of the variance (0.66%). However, area under receiver operator criteria curve (AUC) estimates indicated that the GRSS and covariates significantly predicted overweight and obesity classification with maximum discriminative ability for predicting class III obesity (AUC = 0.697). The relative contributions of the individual loci to GRSS were examined post hoc and the results were not due to a few highly significant variants, but rather the result of numerous variants of small effect. This study provides evidence of the utility of a GRSS as an alternative approach to replication of common polygenic variation in complex traits.     

Age and body mass index associations with body segment parameters

Body segment parameters (BSPs) such as segment mass, center of mass, and radius of gyration are required in many ergonomic tools and biomechanical models to estimate injury risk, and quantify muscle and joint contact forces. Currently, the full effects of age and obesity have not been taken into account when predicting BSPs. The goal of this study is to quantify the impact of body mass index (BMI) and age on BSPs, in order to provide more representative measures necessary for modeling inputs. A whole body dual energy X-ray absorptiometry (DXA) scan was collected for 280 working men and women with a wide range of BMI and aged 21 to 70 years. Established DXA processing methods were used to determine in-vivo estimates of the mass, center of mass, and radius of gyration for the upper arm, forearm, torso, thigh, and shank for males and females. Regression models were used to determine if age and BMI terms, as well as their interactions, were associated with these BSPs. The variability in BSPs explained by BMI alone ranged from 4 to 51%, and age explained an additional 3–19%. Thus, BMI and age are significant correlates of BSPs, and need to be taken into account when predicting certain BSPs in order to obtain accurate and representative results in biomechanical models.     

Effects of gestational weight gain and body mass index on obstetric outcome

Abstract It is already known that maternal overweight, obesity, and morbid obesity are associated with adverse obstetric and neonatal outcomes. To assess the prevalence of overweight and obesity, and the impact of body mass index (BMI) on maternal and neonatal outcomes in Turkey. The study population consisted of 698 singleton pregnancies whose height and weight follow up were performed from the first trimester of pregnancy and whose deliveries were monitored in Trabzon, Turkey in July 2014–June 2015. The data obtained during the study were evaluated using SPSS 21 package program. The differences in variables were assessed by Chi-square-test for categorical data or by One-way Anova test for continuous data. The results were evaluated at a confidence interval of 95% and at a significance level of p?<?0.05. According to the BMI of the women in the study, 68.8% were in normal weight, 20.6% were overweight, 3.9% were obese, and the majority was in the 20–29 age group and 8–15.9?kg. The rate of cesarean, instrumental delivery, induction, episiotomy, late breastfeeding, low apgar (<7 at 5?min), neonatal intensive care unit admission requirement, the newborn at 4000?g or more in overweight (BMI 25–29.9) and obese (BMI?≥?30) pregnancies was higher and the first and second phases of labor were longer (p?<?0.05). The study showed that as the pre-pregnancy body mass index and gestational weight gain increased the rates of cesarean section and interventional delivery increased and the neonatal need for neonatal intensive care unit increased.     

Genetic risk for earlier menarche also influences peripubertal body mass index

It is unclear whether earlier age at menarche is associated with higher body mass index (BMI) because they share a common genetic underpinning. We investigated the impact of single nucleotide polymorphisms (SNPs) influencing menarche timing on peripubertal BMI. For 556 Fels Longitudinal Study children (277 boys/279 girls) born 1928–1992, a genetic risk score (GRS₄₂) was computed as the sum of the number of risk alleles in 42 putative menarche SNPs. Serial BMI Z‐scores within ±6.99 years from each individual's age at peak height velocity (Age@PHV) were grouped into seven time points (?6 years, ?4 years, –2 years, Age@PHV, +2 years, +4years, and +6 years). Heritability of BMI ranged from 0.53 to 0.85 across the time points. The effect of GRS₄₂ on BMI Z‐scores at each time point was modeled using variance components‐based procedures. GRS₄₂ had a significant (P < 0.05) effect at every time point; an increase of one risk allele was associated with an increase of 0.03–0.08 BMI Z‐scores. A separate score (GRS₂₉) was computed that excluded 13 of the menarche SNPs previously documented to also influence adiposity; significant main effects were observed at Age@PHV+4 and +6 years. This finding supports a causal effect of advanced sexual development on post‐Age@PHV BMI. Significant positive GRS₄₂ (or GRS₂₉)‐by‐birth year interactions indicate that some genetic influences on BMI have amplified over the 20th century. This gene‐by‐environment interaction also suggests that children with a genetic predisposition to earlier sexual development might avoid elevated BMI through alteration of their nutritional environment. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Gestational weight gain and body mass index in children: results from three german cohort studies

Introduction

Previous studies suggested potential priming effects of gestational weight gain (GWG) on offspring’s body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear.

Methods

We combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring’s mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5–6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status.

Results

In adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m² of ‘real’ BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers.

Discussion

Increased GWG is likely to be associated with overweight in offspring of non-overweight mothers.     

Independent associations of TOMM40 and APOE variants with body mass index

The TOMM40‐APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 variants in Alzheimer's disease was suggested, comparative contribution of the TOMM40‐APOE variants in the regulation of body weight remains elusive. We examined additive effects of rs2075650 and rs157580 TOMM40 variants and rs429358 and rs7412 APOE variants coding the ε2/ε3/ε4 polymorphism on body mass index (BMI) in age‐aggregated and age‐stratified cohort‐specific and cohort‐pooled analysis of 27,863 Caucasians aged 20–100 years from seven longitudinal studies. Minor alleles of rs2075650, rs429358, and rs7412 were individually associated with BMI (β = ?1.29, p = 3.97 × 10^?9; β = ?1.38, p = 2.78 × 10^?10; and β = 0.58, p = 3.04 × 10^?2, respectively). Conditional analysis with rs2075650 and rs429358 identified independent BMI‐lowering associations for minor alleles (β = ?0.63, p = 3.99 × 10^?2 and β = ?0.94, p = 2.17 × 10^?3, respectively). Polygenic mega‐analysis identified additive effects of the rs2075650 and rs429358 heterozygotes (β = ?1.68, p = 3.00 × 10^?9), and the strongest BMI‐lowering association for the rs2075650 heterozygous and rs429358 minor allele homozygous carriers (β = ?4.11, p = 2.78 × 10^?3). Conditional analysis with four polymorphisms identified independent BMI‐lowering (rs2075650, rs157580, and rs429358) and BMI‐increasing (rs7412) associations of heterozygous genotypes with BMI. Age‐stratified conditional analysis revealed well‐powered support for a differential and independent association of the rs429358 heterozygote with BMI in younger and older individuals, β = 0.58, 95% confidence interval (CI) = ?1.18, 2.35, p = 5.18 × 10^?1 for 3,068 individuals aged ≤30 years and β = ?4.28, CI = ?5.65, ?2.92, p = 7.71 × 10^?10 for 6,052 individuals aged >80 years. TOMM40 and APOE variants are independently and additively associated with BMI. The APOE ε4‐coding rs429358 polymorphism is associated with BMI in older individuals but not in younger individuals.     

Obesity is underestimated using body mass index and waist-hip ratio in long-term adult survivors of childhood cancer

Objective

Obesity, represented by high body mass index (BMI), is a major complication after treatment for childhood cancer. However, it has been shown that high total fat percentage and low lean body mass are more reliable predictors of cardiovascular morbidity. In this study longitudinal changes of BMI and body composition, as well as the value of BMI and waist-hip ratio representing obesity, were evaluated in adult childhood cancer survivors.

Methods

Data from 410 survivors who had visited the late effects clinic twice were analyzed. Median follow-up time was 16 years (interquartile range 11–21) and time between visits was 3.2 years (2.9–3.6). BMI was measured and body composition was assessed by dual X-ray absorptiometry (DXA, Lunar Prodigy; available twice in 182 survivors). Data were compared with healthy Dutch references and calculated as standard deviation scores (SDS). BMI, waist-hip ratio and total fat percentage were evaluated cross-sectionally in 422 survivors, in who at least one DXA scan was assessed.

Results

BMI was significantly higher in women, without significant change over time. In men BMI changed significantly with time (ΔSDS = 0.19, P<0.001). Percentage fat was significantly higher than references in all survivors, with the highest SDS after cranial radiotherapy (CRT) (mean SDS 1.73 in men, 1.48 in women, P<0.001). Only in men, increase in total fat percentage was significantly higher than references (ΔSDS = 0.22, P<0.001). Using total fat percentage as the gold standard, 65% of female and 42% of male survivors were misclassified as non-obese using BMI. Misclassification of obesity using waist-hip ratio was 40% in women and 24% in men.

Conclusions

Sixteen years after treatment for childhood cancer, the increase in BMI and total fat percentage was significantly greater than expected, especially after CRT. This is important as we could show that obesity was grossly underestimated using BMI and waist-hip ratio.     

Breast cancer risk and the interaction between adolescent body size and weight gain in later life: A case-control study

BackgroundWhile the breast cancer risk associated with increasing adult BMI in postmenopausal women can be explained by increases in concentrations of endogenous estrogens the biologic mechanisms behind the inverse association between adolescent BMI and breast cancer risk are still a subject of controversial debate.MethodsWe investigated the association of breast cancer with body size and changes in body size across life time estimated by age-specific BMI Z scores and changes in BMI Z scores from teenage years to middle age in an age-matched population-based case-control study of 2994 Australian women. Logistic regression adjusted for the matching factor age and further potential confounders was used.ResultsAdolescent body leanness in postmenopausal women and excess adult weight gain in all study participants were associated with an increased breast cancer risk with an odds ratio [95% confidence interval] of 1.29 [1.08,1.54] and 1.31 [1.09,1.59], respectively. Interaction analyses restricted to postmenopausal women revealed an increased risk of breast cancer in those who were lean during adolescence and gained excess weight during adulthood (odds ratio [95% confidence interval]: 1.52 [1.19,1.95]) but not in women who were lean during adolescence and did not gain excess weight during adulthood (1.20 [0.97,1.48]) and not in women who were not lean during adolescence and but gained excess weight during adulthood (1.10 [0.95,1.27]) compared to postmenopausal women who were neither lean during adolescence nor gained excess weight.ConclusionIn postmenopausal women adolescent leanness was only associated with increased breast cancer risk when excess weight was gained during adulthood.