Linda D. Voss

Contribution of Early Weight Gain to Childhood Overweight and Metabolic Health: A Longitudinal Study (EarlyBird 36)

BACKGROUND. Early weight gain (0–5 years) is thought to be an important contributor to childhood obesity and consequently metabolic risk. There is a scarcity of longitudinal studies in contemporary children reporting the impact of early weight gain on metabolic health. OBJECTIVE. We aimed to assess the impact of early weight gain on metabolic health at 9 years of age. METHOD. Two hundred thirty-three children (134 boys, 99 girls) with a gestational age of >37 weeks were assessed at birth, 5 years of age, and 9 years of age. Measures included weight SD scores at each time point and excess weight gained (Δ weight SD score) between them. The outcome measure included composite metabolic score (sum of internally derived z scores of insulin resistance, mean blood pressure, triglyceride level, and total cholesterol/high-density lipoprotein cholesterol ratio). RESULTS. Weight SD score increased by 0.29 SD score in girls and 0.26 SD score in boys from 0 to 5 years of age and by 0.03 SD score in girls and 0.11 SD score in boys from 5 to 9 years of age. Weight SD score correlated poorly to moderately before 5 years of age but strongly after 5 years of age. Birth weight SD score predicted (girls/boys) 2.4%/0% of the variability in composite metabolic score at 9 years of age. Adding Δ weight SD score (0–5 years old) contributed (girls/boys) 11.2%/7.0% to the score, and adding Δ weight SD score (5–9 years old) additionally contributed (girls/boys) 26.4%/16.5%. Importantly, once weight SD score at 9 years of age was known, predictive strength was changed little by adding Δ weight SD score. CONCLUSIONS. Most excess weight before puberty is gained before 5 years of age. Weight at 5 years of age bears little relation to birth weight but closely predicts weight at 9 years of age. Single measures of current weight are predictive of metabolic health, whereas weight gain within a specific period adds little. A single measure of weight at 5 years of age provides a pointer to future health for the individual. If metabolic status at 9 years of age means future risk, diabetes/cardiovascular prevention strategies might better focus on preschool-aged children, because the die seems to be largely cast by 5 years of age, and a healthy weight early in childhood may be maintained at least into puberty.

A Common Haplotype of the Glucokinase Gene Alters Fasting Glucose and Birth Weight: Association in Six Studies and Population-Genetics Analyses

Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance (P=10-9). rs3757840 was also highly significantly associated with fasting glucose (P=8x10-7), but haplotype analysis revealed that this is explained by linkage disequilibrium (r2=0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g) increase in offspring birth weight (P=.002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

Contribution of timetabled physical education to total physical activity in primary school children: cross sectional study.

A recent survey of children at primary schools in England found a marked decline in timetabled physical education between 1994 and 1999.1 Sport England expressed concern about the impact of competing priorities, such as numeracy and literacy, on curricular physical education and concluded that children from poorer backgrounds would be worst affected. We used accelerometers to measure the impact of timetabled physical education at school on overall physical activity in children. We monitored physical activity during waking hours for seven days using accelerometers (Manufacturing Technology, Fort Walton Beach, FL2) in 215 children (120 boys and 95 girls aged 7.0-10.5 (mean 9.0) years) from three schools with different sporting facilities and opportunity for physical education in the curriculum. School 1, a private preparatory school with some boarding pupils, had extensive facilities and 9.0 hours a week of physical education in the curriculum. School 2, a village school awarded Activemark gold status …

Physical activity at the government-recommended level and obesity-related health outcomes: a longitudinal study (Early Bird 37)

Background: In the UK and USA, government guidelines for childhood physical activity have been set (⩾60 min/day at ⩾3 metabolic equivalents of thermogenesis (METs)), and body mass index (BMI) chosen as the outcome measure. Aim: To determine the extent to which physical activity at the government-recommended intensity is associated with change in body mass/fat and metabolic health in pre-pubertal children. Methods: Non-intervention longitudinal study of 113 boys and 99 girls (born 1995/96) recruited from 54 schools. Physical activity (Actigraph accelerometers), changes in body mass (raw and age/gender-standardised BMI), fatness (skin-fold thickness and waist circumference) and metabolic status (insulin resistance, triglycerides, cholesterol/HDL ratio and blood pressure – separately and as a composite metabolic z score) were measured on four annual occasions (5, 6, 7 and 8 years). Results: Mean physical activity did not change over time in either sex. Averaging the 7-day recordings from four time points rather than one increased the reliability of characterising a child’s activity from 71% to 90%. Some 42% of boys and 11% of girls met the guideline. There were no associations between physical activity and changes in any measurement of body mass or fatness over time in either sex (eg, BMI standard deviation scores: r = −0.02, p = 0.76). However, there was a small to moderate inverse association between physical activity and change in composite metabolic score (r = −0.19, p<0.01). Mixed effects modelling showed that the improvement in metabolic score among the more active compared to the less active children was linear with time (−0.08 z scores/year, p = 0.001). Conclusions: In children, physical activity above the government-recommended intensity of 3 METs is associated with a progressive improvement in metabolic health but not with a change in BMI or fatness. Girls habitually undertake less physical activity than boys, questioning whether girls in particular should be encouraged to do more, or the recommendations adjusted for girls.

Bullying in school: are short pupils at risk? Questionnaire study in a cohort

Bullying is still prevalent in schools and is clearly stressful for victims. 1 2 It may also have undesirable consequences for bullies, with antisocial behaviour persisting into adulthood. Victims are generally reported to be weaker than the bullies. 2 3 This would suggest that very short pupils are more likely to be victims and less likely to be the aggressors. The Wessex growth study allowed us to examine the prevalence of bullying, as experienced or perpetrated by pupils of different heights. Ninety two short normal adolescents who had been below the third centile for height at school entry4 and 117 controls matched for age and sex completed a bullying questionnaire, derived from work by Whitney and Smith.5 There were no refusals or any significant differences in sex or social class between the groups. Mean age (range) was 14.7 (13.4-15.7) years. Mean height SD scores were: short pupils −1.90 (−3.53 to −0.01), controls 0.31 (−1.41 …

A new stress-related syndrome of growth failure and hyperphagia in children, associated with reversibility of growth-hormone insufficiency

BACKGROUND Growth failure without organic aetiology but associated with behavioural disturbance and psychosocial stress has been termed psychosocial short stature. This condition is not a valid diagnostic entity, but encompasses failure to thrive, stunting secondary to chronic malnutrition, and idiopathic hypopituitarism. Some children show spontaneous catch-up growth when removed from the source of stress, without further treatment, but until now precise definition of this subgroup for the purpose of clinical identification has not been possible. METHODS Hospital-referred children with growth failure unrelated to organic pathology, who came from stressful homes, were compared with children of short-normal stature identified from an epidemiological survey (n = 31). Growth-hormone dynamics were studied in the hospital group by a combination of diurnal profiles and provocation tests. The tests were repeated after a hospital stay of 3 weeks away from familial stress. Standard behavioural measures were obtained from home and school. FINDINGS In a distinctive subgroup (n = 29), growth-hormone insufficiency was associated with characteristic behavioural features, especially hyperphagia and polydipsia, and a normal body-mass index. When the children were removed from their stressful home circumstances, growth-hormone insufficiency spontaneously resolved only in formerly hyperphagic subjects. 74% of the non-hyperphagic cases (n = 23) were anorexic, with a low body-mass index and normal growth-hormone responses to provocation tests. INTERPRETATION We present explicit behavioural and developmental criteria by which the novel syndrome of hyperphagic short stature may be recognised clinically. Such children have a capacity for spontaneous recovery of growth-hormone production on removal from or reduction of stress. Discriminant and predictive validity of the core symptoms are demonstrated. Preliminary familial studies indicate a possible genetic predisposition.

Poor growth in school entrants as an index of organic disease: the Wessex growth study.

OBJECTIVE--To establish whether poor height or height velocity, assessed during the year of school entry, might identify children with previously undiagnosed organic disease. DESIGN--Observation of a total population and their case controls. SETTING--Community base. SUBJECTS--All 14,346 children in two health districts entering school during two consecutive years were screened for height by school nurses, and those whose height lay below the 3rd centile according to Tanner and Whitehouse standards (n = 180) were identified. After excluding 32 with known organic disease, five from ethnic minorities, and three who refused to take part, the remaining 140 short normal children were matched with 140 age and sex matched controls of average height (10th-90th centile) and their height velocities over 12 months measured. MAIN OUTCOME MEASURES--Height, height velocity, previously diagnosed organic disease, and organic disease diagnosed as a result of blood tests and specialist examination. RESULTS--Twenty five of the 180 short children (14%) were already known to have chronic organic disease which could explain their poor growth. Blood tests and specialist examination revealed a further seven with organic disease, which was acquired rather than congenital in three, and a second cause of short stature in one with known organic disease. These eight conditions had been missed at the school entry medical examination. The shorter the child, the more likely an underlying organic disorder, with seven of the 12 children whose heights were more than 3 standard deviations below the mean having some organic disease. Height velocity measured over 12 months, however, did not distinguish short normal children from those with disease or from their matched controls. CONCLUSIONS--Height, but not height velocity, is a useful index for identifying unrecognised organic disease at school entry. The shorter the stature the greater the prevalence of organic disease. The frequency of newly diagnosed remediable disease in this study (1 in 3-4000) is similar to that of neonatal hypothyroidism, which is routinely screened for. Routine investigation of all very short school entrants is recommended.

The reliability of height measurement (the Wessex Growth Study).

The two major components of reliability are accuracy and reproducibility. Three studies of the reliability of height measurement in children are reported. In the first, a standard metre rod was used to spot check the accuracy of installation of 230 measuring instruments in one health district in Wessex, UK. The readings obtained ranged from 90.0 to 108.5 cm and showed the urgent need for the positioning of instruments to be regularly checked. In a second study, to examine the reproducibility of height measurement, two experienced observers measured 10 young children (106.0 to 152.0 cm), three times on five instruments of different design. The observations were blind and in random order. The estimated standard deviation for a single height measurement was generally in the range 0.2-0.3 cm. Over 95% of the variance was attributable to the child, very little to the instrument or observer. Finally, the conditions of the second study were modified to examine the effect on reproducibility of non-blind and non-randomised measurements, as usually occurs in the clinic. A lower but inevitably false estimate of the error was obtained. It is recommended that the error of height measurement, appropriately established and expressed in simple terms, be stated in every published growth study.

The reliability of height and height velocity in the assessment of growth (the Wessex Growth Study)

Both biochemical and auxological measurements can be used to assess growth. Quality control in routinely reported in laboratory studies, but the reproducibility of height measurements, and the height velocity data derived from them, is seldom considered. We have previously established our error and in this report we examine its implications for the screening of short children and subsequent monitoring of their growth. The 95% confidence interval for height for a 5 year old observed to be on the 3rd centile for height, spanned the 2nd-4th centile. However, the confidence interval for a 12 month height velocity appropriate to such a child spanned the 8th-52nd centiles, the lower limit pathological and the upper more than satisfactory. A single height velocity even over 12 months therefore lacks the precision to provide a reliable index of current growth in short children. Furthermore, serial height velocity calculations on a cohort of 78 short normal children showed no significant correlation from year to year, suggesting that velocity is also unable to predict future growth. Although the proportion of this cohort of short children lying beneath the 25th centile for velocity remained constant from year to year, the identity of the individuals comprising that proportion changed, a phenomenon which could be largely accounted for by the random error associated with height velocity. Our data suggest that, by the time a trend in abnormal velocity is reliably established, a deviation from the height centiles is clearly evident. Although velocity charts are attractive in concept, they seem to be no more discriminating than height charts in practice, and may be clinically deceptive unless interpreted with great care.

Age Before Stage: Insulin Resistance Rises Before the Onset of Puberty: A 9-year longitudinal study (EarlyBird 26)

OBJECTIVE Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1. RESEARCH DESIGN AND METHODS The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5–14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units/L). RESULTS IR rose progressively from age 7 years, 3–4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P < 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels. CONCLUSIONS IR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important.