Using the Medical Research Council framework for the development and evaluation of complex interventions in a theory-based infant feeding intervention to prevent childhood obesity:The baby milk intervention and trial

Introduction. We describe our experience of using the Medical Research Council framework on complex interventions to guide the development and evaluation of an intervention to prevent obesity by modifying infant feeding behaviours. Methods. We reviewed the epidemiological evidence on early life risk factors for obesity and interventions to prevent obesity in this age group. The review suggested prevention of excess weight gain in bottle-fed babies and appropriate weaning as intervention targets; hence we undertook systematic reviews to further our understanding of these behaviours. We chose theory and behaviour change techniques that demonstrated evidence of effectiveness in altering dietary behaviours. We subsequently developed intervention materials and evaluation tools and conducted qualitative studies with mothers (intervention recipients) and healthcare professionals (intervention deliverers) to refine them. We developed a questionnaire to assess maternal attitudes and feeding practices to understand the mechanism of any intervention effects. Conclusions. In addition to informing development of our specific intervention and evaluation materials, use of the Medical Research Council framework has helped to build a generalisable evidence base for early life nutritional interventions. However, the process is resource intensive and prolonged, and this should be taken into account by public health research funders. This trial is registered with ISRTCN: 20814693 Baby Milk Trial

Genetic Regulation of Puberty Timing in Humans.

Understanding the regulation of puberty timing has relevance to developmental and human biology and to the pathogenesis of various diseases. Recent large-scale genome-wide association studies on puberty timing and adult height, body mass index (BMI) and central body shape provide evidence for shared biological mechanisms that regulate these traits. There is a substantial genetic overlap between age at menarche in women and BMI, with almost invariable directional consistency with the epidemiological associations between earlier menarche and higher BMI. By contrast, the genetic loci identified for age at menarche are largely distinct from those identified for central body shape, while alleles that confer earlier menarche can be associated with taller or shorter adult height. The findings of population-based studies on age at menarche show increasing relevance for other studies of rare monogenic disorders and enrich our understanding of the mechanisms that regulate the timing of puberty and reproductive function.This work was supported by the MRC.This is the author accepted manuscript. The final version is available from Karger at http://www.karger.com/Article/Abstract/43102

Elucidating the genetic basis of social interaction and isolation.

The negative impacts of social isolation and loneliness on health are well documented. However, little is known about their possible biological determinants. In up to 452,302 UK Biobank study participants, we perform genome-wide association study analyses for loneliness and regular participation in social activities. We identify 15 genomic loci (P < 5 × 10-8) for loneliness, and demonstrate a likely causal association between adiposity and increased susceptibility to loneliness and depressive symptoms. Further loci were identified for regular attendance at a sports club or gym (N = 6 loci), pub or social club (N = 13) or religious group (N = 18). Across these traits there was strong enrichment for genes expressed in brain regions that control emotional expression and behaviour. We demonstrate aetiological mechanisms specific to each trait, in addition to identifying loci that are pleiotropic across multiple complex traits. Further study of these traits may identify novel modifiable risk factors associated with social withdrawal and isolation

Variability in the Heritability of Body Mass Index: A Systematic Review and Meta-Regression

Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24–0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (−0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (−0.04, P = 0.02), and with self reported versus measured BMI (−0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life

An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults.

BackgroundStudies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history.MethodsWe administered an anonymized, online survey to n = 2386 adults (n = 1183 autistic) aged 16-90 years of age. We employed Fisher's exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults.ResultsAutistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history.LimitationsOur sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships.ConclusionsAutistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep-and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep

An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults.

BackgroundStudies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history.MethodsWe administered an anonymized, online survey to n = 2386 adults (n = 1183 autistic) aged 16-90 years of age. We employed Fisher's exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults.ResultsAutistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history.LimitationsOur sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships.ConclusionsAutistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep-and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep

Serum Phthalate and Triclosan Levels Have Opposing Associations With Risk Factors for Gestational Diabetes Mellitus.

Certain phthalates and bisphenol A (BPA) have been associated with insulin resistance and type 2 diabetes in non-pregnant adults, but studies of gestational diabetes mellitus (GDM) have reported conflicting results for phthalates and no associations with BPA. Our aim was to investigate the relationship between maternal serum levels of phthalate metabolites and phenols at 10-17 weeks of gestation and glucose homeostasis at 28 weeks of gestation. 232 women aged ≥16 years without type 1 or 2 diabetes with singleton male pregnancies were recruited from a single UK maternity centre between 2001 and 2009 as part of a prospective observational study (Cambridge Baby Growth Study). Serum levels of 16 phthalate metabolites and 9 phenols (including BPA) were measured using liquid chromatography/tandem mass spectrometry. Oral glucose tolerance tests were performed at 28 weeks. 47/232 (20.3%) women had GDM. First-trimester triclosan (TCS) was inversely associated with incident GDM (adjusted odds ratio per log increase in concentration 0.54, 95% confidence interval 0.34-0.86, p = 0.010). Amongst women without GDM, first-trimester mono-(2-ethylhexyl) phthalate and mono(carboxyisooctyl) phthalate levels were positively associated with 120-min plasma glucose (adjusted β 0.268 and 0.183, p = 0.0002 and 0.010, respectively) in mid-pregnancy. No other monotonic associations were detected between phthalate or phenol levels and fasting or stimulated plasma glucose, β-cell function, insulin resistance, or 60-min disposition index. Our results support a glycaemia-raising effect of phthalates during pregnancy, consistent with findings in non-pregnant populations and suggest a possible protective effect of exposure to TCS against GDM

Association of puberty timing with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND:Emerging studies have investigated the association between puberty timing, particularly age at menarche (AAM), and type 2 diabetes. However, whether this association is independent of adiposity is unclear. We aimed to systematically review published evidence on the association between puberty timing and type 2 diabetes (T2D) or impaired glucose tolerance (IGT), with and without adjustment for adiposity, and to estimate the potential contribution of puberty timing to the burden of T2D in the United Kingdom (UK). METHODS AND FINDINGS:We searched PubMed, Medline, and Embase databases for publications until February 2019 on the timing of any secondary sexual characteristic in boys or girls in relation to T2D/IGT. Inverse-variance-weighted random-effects meta-analysis was used to pool reported estimates, and meta-regression was used to explore sources of heterogeneity. Twenty-eight observational studies were identified. All assessed AAM in women (combined N = 1,228,306); only 1 study additionally included men. In models without adjustment for adult adiposity, T2D/IGT risk was lower per year later AAM (relative risk [RR] = 0.91, 95% CI 0.89-0.93, p < 0.001, 11 estimates, n = 833,529, I2 = 85.4%) and higher for early versus later menarche (RR = 1.39, 95% CI 1.25-1.55, p < 0.001, 23 estimates, n = 1,185,444, I2 = 87.8%). Associations were weaker but still evident in models adjusted for adiposity (AAM: RR = 0.97 per year, 95% CI 0.95-0.98, p < 0.001, 12 estimates, n = 852,268, I2 = 51.8%; early menarche: RR = 1.19, 95% CI 1.11-1.28, p < 0.001, 21 estimates, n = 890,583, I2 = 68.1%). Associations were stronger among white than Asian women, and in populations with earlier average AAM. The estimated population attributable risk of T2D in white UK women due to early menarche unadjusted and adjusted for adiposity was 12.6% (95% CI 11.0-14.3) and 5.1% (95% CI 3.6-6.7), respectively. Findings in this study are limited by residual and unmeasured confounding, and self-reported AAM. CONCLUSIONS:Earlier AAM is consistently associated with higher T2D/IGT risk, independent of adiposity. More importantly, this research has identified that a substantial proportion of T2D in women is related to early menarche, which would be expected to increase in light of global secular trends towards earlier puberty timing. These findings highlight the need to identify the underlying mechanisms linking early menarche to T2D/IGT risk

A novel school-based intervention to improve nutrition knowledge in children: cluster randomised controlled trial.

BACKGROUND: Improving nutrition knowledge among children may help them to make healthier food choices. The aim of this study was to assess the effectiveness and acceptability of a novel educational intervention to increase nutrition knowledge among primary school children. METHODS: We developed a card game 'Top Grub' and a 'healthy eating' curriculum for use in primary schools. Thirty-eight state primary schools comprising 2519 children in years 5 and 6 (aged 9-11 years) were recruited in a pragmatic cluster randomised controlled trial. The main outcome measures were change in nutrition knowledge scores, attitudes to healthy eating and acceptability of the intervention by children and teachers. RESULTS: Twelve intervention and 13 control schools (comprising 1133 children) completed the trial. The main reason for non-completion was time pressure of the school curriculum. Mean total nutrition knowledge score increased by 1.1 in intervention (baseline to follow-up: 28.3 to 29.2) and 0.3 in control schools (27.3 to 27.6). Total nutrition knowledge score at follow-up, adjusted for baseline score, deprivation, and school size, was higher in intervention than in control schools (mean difference = 1.1; 95% CI: 0.05 to 2.16; p = 0.042). At follow-up, more children in the intervention schools said they 'are currently eating a healthy diet' (39.6%) or 'would try to eat a healthy diet' (35.7%) than in control schools (34.4% and 31.7% respectively; chi-square test p < 0.001). Most children (75.5%) enjoyed playing the game and teachers considered it a useful resource. CONCLUSIONS: The 'Top Grub' card game facilitated the enjoyable delivery of nutrition education in a sample of UK primary school age children. Further studies should determine whether improvements in nutrition knowledge are sustained and lead to changes in dietary behaviour.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (β' = 0.078 (0.024-0.133); p = 0.005), head circumference (β' = 0.060 (0.012-0.107); p = 0.02), body mass index (β' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (β' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM