The effect of comorbidities on diagnostic interval for lung cancer in England: a cohort study using electronic health record data.

BACKGROUND: Comorbid conditions may delay lung cancer diagnosis by placing demand on general practioners' time reducing the possibility of prompt cancer investigation ("competing demand conditions"), or by offering a plausible non-cancer explanation for signs/symptoms ("alternative explanation conditions"). METHOD: Patients in England born before 1955 and diagnosed with incident lung cancer between 1990 and 2019 were identified in the Clinical Practice Research Datalink and linked hospital admission and cancer registry data. Diagnostic interval was defined as time from first presentation in primary care with a relevant sign/symptom to the diagnosis date. 14 comorbidities were classified as ten "competing demand" and four "alternative explanation" conditions. Associations with diagnostic interval were investigated using multivariable linear regression models. RESULTS: Complete data were available for 11870 lung cancer patients. In adjusted analyses diagnostic interval was longer for patients with "alternative explanation" conditions, by 31 and 74 days in patients with one and ≥2 conditions respectively versus those with none. Number of "competing demand" conditions did not remain in the final adjusted regression model for diagnostic interval. CONCLUSIONS: Conditions offering alternative explanations for lung cancer symptoms are associated with increased diagnostic intervals. Clinical guidelines should incorporate the impact of alternative and competing causes upon delayed diagnosis.

The Pre-Implementation Phase of a Project Seeking to Deliver a Community-Based CVD Prevention Intervention (SPICES-Sussex): A Qualitative Study Exploring Views and Experience Relating to Intervention Development.

BACKGROUND.: Community-led health care interventions may be an effective way to tackle cardiovascular disease (CVD) risk factors, especially in materially deprived communities where health care resources are stretched and engagement with institutions is often low. To do so effectively and equitably, interventions might be developed alongside community members through community engagement. OBJECTIVES.: The aim of this project was to carry out stakeholder mapping and partnership identification and to understand the views, needs, experiences of community members who would be involved in later stages of a community-based CVD prevention intervention's development and implementation. METHODS.: Stakeholder mapping was carried out to identify research participants in three communities in Sussex, United Kingdom. A qualitative descriptive approach was taken during the analysis of focus groups and interviews with 47 participants. FINDINGS.: Three themes were highlighted related to intervention design (a) Management: the suitability of the intervention for the community, management of volunteers, and communication; (b) Logistics: the structure and design of the intervention; and (c) Sociocultural issues, the social and cultural expectations/experiences of participants and implementers. CONCLUSIONS.: Study participants were open and willing to engage in the planned community-based intervention, particularly in elements of co-design and community-led delivery. They also highlighted the importance of sociocultural factors. Based on the findings, we developed recommendations for intervention design which included (but were not limited to): (a) a focus on a bottom-up approach to intervention design, (b) the recruitment of skilled local volunteers, and (c) the importance of fun and simplicity.

Association between naturally occurring lithium in drinking water and suicide rates: systematic review and meta-analysis of ecological studies.

BACKGROUND: The prevalence of mental health conditions and national suicide rates are increasing in many countries. Lithium is widely and effectively used in pharmacological doses for the treatment and prevention of manic/depressive episodes, stabilising mood and reducing the risk of suicide. Since the 1990s, several ecological studies have tested the hypothesis that trace doses of naturally occurring lithium in drinking water may have a protective effect against suicide in the general population. AIMS: To synthesise the global evidence on the association between lithium levels in drinking water and suicide mortality rates. METHOD: The MEDLINE, Embase, Web of Science and PsycINFO databases were searched to identify eligible ecological studies published between 1 January 1946 and 10 September 2018. Standardised regression coefficients for total (i.e. both genders combined), male and female suicide mortality rates were extracted and pooled using random-effects meta-analysis. The study was registered with PROSPERO (CRD42016041375). RESULTS: The literature search identified 415 articles; of these, 15 ecological studies were included in the synthesis. The random-effects meta-analysis showed a consistent protective (or inverse) association between lithium levels/concentration in publicly available drinking water and total (pooled ß = -0.27, 95% CI -0.47 to -0.08; P = 0.006, I2 = 83.3%), male (pooled ß = -0.26, 95% CI -0.56 to 0.03; P = 0.08, I2 = 91.9%) and female (pooled ß = -0.13, 95% CI -0.24 to -0.02; P = 0.03, I2 = 28.5%) suicide mortality rates. A similar protective association was observed in the six studies included in the narrative synthesis, and subgroup meta-analyses based on the higher/lower suicide mortality rates and lithium levels/concentration. CONCLUSIONS: This synthesis of ecological studies, which are subject to the ecological fallacy/bias, supports the hypothesis that there is a protective (or inverse) association between lithium intakes from public drinking water and suicide mortality at the population level. Naturally occurring lithium in drinking water may have the potential to reduce the risk of suicide and may possibly help in mood stabilisation, particularly in populations with relatively high suicide rates and geographical areas with a greater range of lithium concentration in the drinking water. All the available evidence suggests that randomised community trials of lithium supplementation of the water supply might be a means of testing the hypothesis, particularly in communities (or settings) with demonstrated high prevalence of mental health conditions, violent criminal behaviour, chronic substance misuse and risk of suicide.

A community health worker led approach to cardiovascular disease prevention in the UK-SPICES-Sussex (scaling-up packages of interventions for cardiovascular disease prevention in selected sites in Europe and Sub-saharan Africa): an implementation research project.

Background: This paper describes a UK-based study, SPICES-Sussex, which aimed to co-produce and implement a community-based cardiovascular disease (CVD) risk assessment and reduction intervention to support under-served populations at moderate risk of CVD. The objectives were to enhance stakeholder engagement; to implement the intervention in four research sites and to evaluate the use of Voluntary and Community and Social Enterprises (VCSE) and Community Health Worker (CHW) partnerships in health interventions. Methods: A type three hybrid implementation study design was used with mixed methods data. This paper represents the process evaluation of the implementation of the SPICES-Sussex Project. The evaluation was conducted using the RE-AIM framework. Results: Reach: 381 individuals took part in the risk profiling questionnaire and forty-one women, and five men participated in the coaching intervention. Effectiveness: quantitative results from intervention participants showed significant improvements in CVD behavioural risk factors across several measures. Qualitative data indicated high acceptability, with the holistic, personalised, and person-centred approach being valued by participants. Adoption: 50% of VCSEs approached took part in the SPICES programme, The CHWs felt empowered to deliver high-quality and mutually beneficial coaching within a strong project infrastructure that made use of VCSE partnerships. Implementation: Co-design meetings resulted in local adaptations being made to the intervention. 29 (63%) of participants completed the intervention. Practical issues concerned how to embed CHWs in a health service context, how to keep engaging participants, and tensions between research integrity and the needs and expectations of those in the voluntary sector. Maintenance: Several VCSEs expressed an interest in continuing the intervention after the end of the SPICES programme. Conclusion: Community-engagement approaches have the potential to have positively impact the health and wellbeing of certain groups. Furthermore, VCSEs and CHWs represent a significant untapped resource in the UK. However, more work needs to be done to understand how links between the sectors can be bridged to deliver evidence-based effective alternative preventative healthcare. Reaching vulnerable populations remains a challenge despite partnerships with VCSEs which are embedded in the community. By showing what went well and what did not, this project can guide future work in community engagement for health.

Disparities in the non-laboratory INTERHEART risk score and its components in selected countries of Europe and sub-Saharan Africa: analysis from the SPICES multi-country project.

Aims: Accurate prediction of a person's risk of cardiovascular disease (CVD) is vital to initiate appropriate intervention. The non-laboratory INTERHEART risk score (NL-IHRS) is among the tools to estimate future risk of CVD. However, measurement disparities of the tool across contexts are not well documented. Thus, we investigated variation in NL-IHRS and components in selected sub-Saharan African and European countries. Methods and results: We used data from a multi-country study involving 9309 participants, i.e. 4941 in Europe, 3371 in South Africa, and 997 in Uganda. Disparities in total NL-IHRS score, specific subcomponents, subcategories, and their contribution to the total score were investigated. The variation in the adjusted total and component scores was compared across contexts using analysis of variance. The adjusted mean NL-IHRS was higher in South Africa (10.2) and Europe (10.0) compared to Uganda (8.2), and the difference was statistically significant (P < 0.001). The prevalence and per cent contribution of diabetes mellitus and high blood pressure were lowest in Uganda. Score contribution of non-modifiable factors was lower in Uganda and South Africa, entailing 11.5% and 8.0% of the total score, respectively. Contribution of behavioural factors to the total score was highest in both sub-Saharan African countries. In particular, adjusted scores related to unhealthy dietary patterns were highest in South Africa (3.21) compared to Uganda (1.66) and Europe (1.09). Whereas, contribution of metabolic factors was highest in Europe (30.6%) compared with Uganda (20.8%) and South Africa (22.6%). Conclusion: The total risk score, subcomponents, categories, and their contribution to total score greatly vary across contexts, which could be due to disparities in risk burden and/or self-reporting bias in resource-limited settings. Therefore, primary preventive initiatives should identify risk factor burden across contexts and intervention activities need to be customized accordingly. Furthermore, contextualizing the risk assessment tool and evaluating its usefulness in different settings are recommended.

The Healthy Hearts Project: Development and evaluation of a website for cardiovascular risk assessment and visualisation and self-management through healthy lifestyle goal-setting.

Materially deprived communities in the UK have excess morbidity and mortality from cardiovascular disease (CVD) but are less likely to engage with formal care pathways. Community engagement and e-health may be more effective ways to promote risk-reducing lifestyle change. The "Healthy Hearts Project" website was designed for use by community health workers (CHWs) for cardiovascular risk assessment and lifestyle goal setting, or for independent use by community members. This paper describes the website's development and evaluation. The website was developed using interactive wire frame prototypes in a user-led approach. Qualitative evaluation of the completed website's usability and acceptability was conducted using the "Thinking Aloud" method in a purposive sample of 10 participants (one voluntary sector employee, three CHWs, two community members and four healthcare professionals). Thinking Aloud interview transcripts were thematically analysed using an inductive approach. A separate quantitative evaluation of usability and the effect of using the website on CVD knowledge and beliefs was conducted. A random sample of 134 participants, recruited using the online platform Prolific, completed the "Attitudes and Beliefs About Cardiovascular Disease" (ABCD) questionnaire before and after using the website, along with the System Usability Scale (SUS). Qualitative evaluation-Four key themes were identified: 1) Website functionality and design-participants generally found the website easy to use and understood the risk communication graphics and the feedback and goal-setting features,; 2) Inclusivity and representation-most participants considered the website inclusive of a range of users/cultures; 3) Language and comprehension-participants found the language used easy to understand but suggested reducing the amount of text; 4) Motivation and barriers to change-participants liked the personalized feedback and empowerment offered by goal-setting but commented on the need for self-motivation. Quantitative evaluation-The mean score across all domains of the ABCD questionnaire (from 2.99 to 3.11, p<0.001) and in the sub-domains relating to attitudes and beliefs around healthy eating and exercise increased after using the website. The mean(sd) score on the SUS was 77.5 (13.5). The website's usability was generally rated well by both quantitative and qualitative measures, and measures of CVD knowledge improved after use. A number of general recommendations for the design of eHealth behaviour change tools are made based on participants' suggestions to improve the website.

Association between Smokeless Tobacco Use and Waterpipe Smoking and the Risk of Lung Cancer: A Systematic Review and Meta-Analysis of Current Epidemiological Evidence.

BACKGROUND: Smokeless tobacco and waterpipes are used by hundreds of millions of people worldwide and consumption rates exceed that of cigarette smoking in much of South East Asia and parts of the Middle East. However, the cancer risks of these methods of tobacco consumption are less well-characterized than those of cigarette smoking. The objective of this study was to systematically review the epidemiological evidence on the association between smokeless tobacco use and waterpipe smoking and lung cancer risk. METHODS: The MEDLINE, EMBASE, Web of Science and OpenSIGLE databases were searched to identify eligible case-control and cohort studies (published before 1st December 2020 in any language) that adjusted for cigarette smoking or included non-cigarette smokers only. Summary odds ratio/relative risk estimates and confidence intervals were extracted, and pooled risk ratios (RRs) for lung cancer were calculated using random effects meta-analysis. RESULTS: The literature search identified 2,465 publications: of these, 26 studies including 6,903 lung cancer patients were included in the synthesis (20 studies of smokeless tobacco use, five of waterpipe smoking, one of both). Our results suggest that smokeless tobacco use is associated with an increased risk of lung cancer among non-cigarette smokers, and that betel quid tobacco may be particularly hazardous. The random effects meta-analysis showed that exclusive use of any type of smokeless tobacco (pooled RR = 1.53, 95%CI 1.09 - 2.14), betel quid chewing (pooled RR = 1.77, 95%CI 1.06 - 2.95), and waterpipe smoking (pooled RR = 3.25, 95%CI 2.01 - 5.25) were significantly associated with an increased risk of lung cancer. CONCLUSIONS: This meta-analysis of case-control/cohort studies supports the hypothesis that use of smokeless tobacco and waterpipe smoking is associated with increased risk of developing lung cancer. Considering the widespread and increasing use of smokeless tobacco in developing countries, and increasing prevalence of waterpipe smoking in almost all societies, these findings inform formulation of public health policy, legislation and tobacco control measures at national and international level to increase awareness and decrease the prevalence of smokeless tobacco use and waterpipe smoking.

Is maternal education level associated with diet in 10-year-old children?

OBJECTIVE: To examine the associations between maternal education level and diet in 10-year-old children. DESIGN: Three-day diet diaries (child completed with parental help) were collected. Height and weight were measured in research clinics. Maternal education level was derived from a questionnaire completed during pregnancy and classified into low, medium or high. One-way ANOVA was undertaken to compare maternal education groups for nutrient intakes and the Kruskal-Wallis test used for food consumption. SETTING: Avon Longitudinal Study of Parents and Children (ALSPAC), Bristol, UK. SUBJECTS: Children (n 7474) who provided dietary data at age 10 years. RESULTS: A large proportion (60 %) of the sample was classified as plausible reporters, with under-reporting accounting for 36 %. No clear differences were found for intakes of energy or macronutrients between maternal education groups for plausible reporters. However, there were marked differences in micronutrient intakes especially for vitamin C, retinol equivalents and folate, highlighting lower diet quality with lower maternal education level. Intakes of fruit and vegetables showed a positive gradient with increasing maternal education (57 % v. 79 % consumed fresh fruit in low and high educational groups, respectively). A trend towards higher intake in the lower educated group was shown for less healthy foods (meat pies P < 0·001; sausages, burgers and kebabs P < 0·001). CONCLUSIONS: The quality of children's diet at 10 years was related to maternal education level. Lower maternal education was associated with less healthy food choices that could be detrimental to health. Further research is needed to establish if these associations can be explained by other socio-economic factors.

Changing epidemiology and age-specific incidence of cutaneous malignant melanoma in England: An analysis of the national cancer registration data by age, gender and anatomical site, 1981-2018.

BACKGROUND: The incidence of cutaneous malignant melanoma, which is mostly attributable (86%) to UV radiation exposure, has been steadily increasing over the past four decades in predominantly fair-skinned populations. Although public health campaigns are increasing sun-protective behaviour in England, their effect on melanoma incidence is largely unknown. We conducted a retrospective population-based cohort study to examine whether there have been changes in the epidemiology of melanoma in England during the past four decades. METHODS: Individual level data for patients diagnosed with melanoma in England during 1981-2018 were obtained from the Office for National Statistics/Public Health England. Average annual incidence rates were calculated by three age categories (0-34, 35-64, 65+ years), gender and anatomical site during the seven five-year time periods (1981-85 to 2011-15) and the recent three-year period (2016-18). The percentage change in incidence was calculated as change in the average incidence rate from the first (1981-85) to the last time period (2016-18). The Average Annual Percentage Change (AAPC) was estimated using the slope of the linear trend line fitted to the incidence rates by year of diagnosis. FINDINGS: During the 38-year period (1981-2018), a total of 265,302 cases of melanoma (45.7% males, 54.3% females) were registered in England. The average annual number of cases increased from 837/year in 1981-85 to 6963/year in 2016-18 in males (+732%), and from 1609/year in 1981-85 to 6952/year in 2016-18 in females (+332%). In the young age-group (0-34 years), the average annual incidence rates initially increased from 1981-85 to 2001-05 and then stabilised during the recent period (2006-18). In the middle age group (35-64 years), the rates increased by +332% (AAPC, 10.4%) in males (from 5.6/100,000 in 1981-85 to 24.2/100,000 in 2016-18) and +185% (AAPC, 5.7%) in females (from 10.2/100,000 in 1981-85 to 29.1/100,000 in 2016-18); and in the old age-group (65+ years) the rates increased by +842% (AAPC, 25.7%) in males (from 9.6/100,000 in 1981-85 to 90.4/100,000 in 2016-18) and +381% (AAPC, 11.2%) in females (from 12.5/100,000 in 1981-85 to 60.1/100,000 in 2016-18). The largest increase in incidence in both males and females was observed for melanoma of the trunk (+817%, AAPC, 24.8% in males and +613%, AAPC, 18.3% in females), followed by melanoma of upper limb (+750%, AAPC, 22.9% in males and 518%, AAPC, 15.5% in females). INTERPRETATION: It appears that the incidence of melanoma among young people in England has stabilised (or levelled off) in recent decades, whereas it continues to increase substantially in older population. These findings suggest that public health campaigns targeted at children/adolescents/parents may be favourably influencing melanoma incidence. The steeper increase in incidence in males is consistent with their relatively greater sun exposure and poor sun-protective behaviour. All the available evidence suggests that the enormous increase in the melanoma of the trunk and upper limb, since the 1980s, is most likely due to increasing trend in intermittent high intensity recreational UV radiation exposure (e.g. sunbathing, holidaying in places with strong sunlight, indoor tanning). FUNDING: This work was supported by Brighton and Sussex Medical School (BSMS).

Influences on child fruit and vegetable intake: sociodemographic, parental and child factors in a longitudinal cohort study.

OBJECTIVE: To examine the sociodemographic, parental and child factors that predict fruit and vegetable consumption in 7-year-old children. DESIGN: Diet was assessed using three 1d unweighed food diaries. The child's daily fruit and vegetable consumption was calculated by summing the weight of each type of fruit, fruit juice and vegetable consumed. The various others factors measured were assessed by a questionnaire at different time points. SETTING: The Avon Longitudinal Study of Parents and Children (ALSPAC). SUBJECTS: A total of 7285 children aged 7 years residing in the south-west of England during 1999-2000. RESULTS: Median daily fruit and vegetable consumption (201 g) was below the recommendations for this age group (320 g). Girls ate more fruit and vegetables per unit energy (30.3 g/MJ) than boys (26.7 g/MJ; P =< 0.001). The predictors of fruit and vegetable consumption were mostly similar. Fruit and vegetable consumption was associated with maternal consumption, maternal education status and parental rules about serving fruit/vegetables every day, food expenditure per person and whether the child was choosy about food. Vegetable consumption was also associated with the other characteristics of the child, such as whether the child enjoyed food and whether the child tried a variety of foods. CONCLUSIONS: Children are not eating recommended amounts of fruit and vegetables, particularly boys. Consumption of fruit and vegetables appears to be influenced by parental rules about daily consumption and parental consumption and by the child's choosiness. Parent's actions could influence this. These findings may prove useful for those planning healthy eating campaigns for children.

Diet throughout childhood and age at menarche in a contemporary cohort of British girls.

OBJECTIVE: To investigate associations between dietary intakes throughout childhood and age at menarche, a possible indicator of future risk of disease, in a contemporary cohort of British girls. DESIGN: Diet was assessed by FFQ at 3 and 7 years of age, and by a 3 d unweighed food diary at 10 years. Age at menarche was categorised as before or after 12 years 8 months, a point close to the median age in this cohort. SETTING: Bristol, South-West England. SUBJECTS: Girls (n 3298) participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher energy intakes at 10 years were positively associated with the early occurrence of menarche, but this association was removed on adjusting for body size. Total and animal protein intakes at 3 and 7 years were positively associated with age at menarche ≤12 years 8 months (adjusted OR for a 1 sd increase in protein at 7 years: 1·14 (95 % CI 1·04, 1·26)). Higher PUFA intakes at 3 and 7 years were also positively associated with early occurrence of menarche. Meat intake at 3 and 7 years was strongly positively associated with reaching menarche by 12 years 8 months (OR for menarche in the highest v. lowest category of meat consumption at 7 years: 1·75 (95 % CI 1·25, 2·44)). CONCLUSIONS: These data suggest that higher intakes of protein and meat in early to mid-childhood may lead to earlier menarche. This may have implications for the lifetime risk of breast cancer and osteoporosis.

Dental X-Rays and the Risk of Thyroid Cancer and Meningioma: A Systematic Review and Meta-Analysis of Current Epidemiological Evidence.

Background: Exposure to moderate-to-high doses of ionizing radiation is the only established environmental risk factor for thyroid cancer and brain and central nervous system tumors. Considering the high lifetime prevalence and frequency of exposure to dental X-rays, the most common source of diagnostic radiation exposure in the general population, even a small associated increase in cancer risk would be of considerable public health importance. With the objective to inform clinical practice and guidelines, we synthesized the current epidemiological evidence on the association between dental X-rays and the risk of thyroid cancer, meningioma, and other cancers of the head and neck region. Methods: The Medline, Embase, and Web of Science databases were searched to identify eligible studies. Summary odds ratio/relative risk estimates and confidence intervals were extracted, and pooled risk ratios (RRs) for each cancer were calculated using random effects meta-analysis. Results: The literature search identified 5537 publications; of these, 26 studies including 10,868 cancer patients were included in the synthesis. The random effects meta-analyses, based on seven studies of thyroid cancer (six case/control, one cohort) and eight studies of meningioma (all case/control), showed that multiple (or repeated) exposures to dental X-rays were significantly associated with an increased risk of thyroid cancer (pooled RR = 1.87 [95% confidence interval, CI 1.11-3.15]) and meningioma (pooled RR = 1.53 [CI 1.26-1.85]). There was no association with glioma, and there were too few studies of other cancers of the head and neck region to conduct a meaningful meta-analysis. Conclusions: Based on a meta-analysis of retrospective case/control studies, these findings provide some support to the hypothesis that multiple (or repeated) exposures to dental X-rays may be associated with an increased risk of thyroid cancer and meningioma. These studies did not include individual organ doses and ages at exposure, and are subject to recall bias and other limitations. Furthermore, the thyroid exposure has decreased dramatically over time from the use of thyroid shields and improved technology/equipment. Prospective studies, based on dental X-ray records and patient follow-up, are needed to test the hypothesis further and clarify the possible cancer risk associated with dental radiography, as although the risk at the individual level, particularly with improved technology/equipment, is likely to be very low, the proportion of the population exposed is high. Considering that about one-third of the general population in developed countries is routinely exposed to one or more dental X-rays per year, these findings manifest the need to reduce diagnostic radiation exposure as much as possible.

Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study.

BACKGROUND: Seafood is the predominant source of omega-3 fatty acids, which are essential for optimum neural development. However, in the USA, women are advised to limit their seafood intake during pregnancy to 340 g per week. We used the Avon Longitudinal Study of Parents and Children (ALSPAC) to assess the possible benefits and hazards to a child's development of different levels of maternal seafood intake during pregnancy. METHODS: 11,875 pregnant women completed a food frequency questionnaire assessing seafood consumption at 32 weeks' gestation. Multivariable logistic regression models including 28 potential confounders assessing social disadvantage, perinatal, and dietary items were used to compare developmental, behavioural, and cognitive outcomes of the children from age 6 months to 8 years in women consuming none, some (1-340 g per week), and >340 g per week. FINDINGS: After adjustment, maternal seafood intake during pregnancy of less than 340 g per week was associated with increased risk of their children being in the lowest quartile for verbal intelligence quotient (IQ) (no seafood consumption, odds ratio [OR] 1.48, 95% CI 1.16-1.90; some, 1.09, 0.92-1.29; overall trend, p=0.004), compared with mothers who consumed more than 340 g per week. Low maternal seafood intake was also associated with increased risk of suboptimum outcomes for prosocial behaviour, fine motor, communication, and social development scores. For each outcome measure, the lower the intake of seafood during pregnancy, the higher the risk of suboptimum developmental outcome. INTERPRETATION: Maternal seafood consumption of less than 340 g per week in pregnancy did not protect children from adverse outcomes; rather, we recorded beneficial effects on child development with maternal seafood intakes of more than 340 g per week, suggesting that advice to limit seafood consumption could actually be detrimental. These results show that risks from the loss of nutrients were greater than the risks of harm from exposure to trace contaminants in 340 g seafood eaten weekly.

Insulin-like growth factor-I and growth in height, leg length, and trunk length between ages 5 and 10 years.

OBJECTIVE: IGF-I, a major regulator of childhood growth, is also associated with the risk of several cancers in adult life. Adult height and particularly leg length are also associated with cancer risk. Prepubertal growth is more in leg than trunk length, and it has been suggested that leg length might be a biomarker of childhood IGF-I. However, there is little information on the association between childhood IGF-I and subsequent leg and trunk growth. In this study, we investigated the association of IGF-I measured at 5 and 7-8 yr with growth in height and the components of height (leg and trunk length) from 5 yr to 9-10 yr. PARTICIPANTS: A total of 675 children participated in the Avon Longitudinal Study of Parents and Children. RESULTS: IGF-I was strongly positively associated with growth in height in both sexes. Among boys, IGF-I was strongly associated with subsequent growth in both leg and trunk length, but there was no evidence that IGF-I was more strongly associated with one component of growth than the other. Among girls, IGF-I was strongly positively associated with growth in trunk but not leg length, although there was only weak evidence that these two associations differed in strength (P = 0.058). CONCLUSIONS: These results support the contention that the associations between height and cancer may be mediated by variation in childhood IGF-I. However, they provide no evidence to support the hypothesis that leg length is a better biomarker of childhood IGF-I levels than trunk length.

Associations of size at birth and dual-energy X-ray absorptiometry measures of lean and fat mass at 9 to 10 y of age.

BACKGROUND: Birth weight has been positively associated with risk of overweight in later life. However, little information exists on how weight and length at birth are associated with subsequent lean and total body fat. OBJECTIVE: We investigated the association between weight and length at birth and body composition and fat distribution in childhood. DESIGN: Body composition was measured by using dual-energy X-ray absorptiometry in 9-10-y-old subjects (n = 3006 boys and 3080 girls). Weight and length at birth were measured or taken from hospital records. RESULTS: Birth weight was positively associated with both lean body mass (LBM) and total body fat at 9-10 y of age in both sexes. LBM rose by 320 g per 1-SD increase in birth weight (P < 0.001), and total body fat rose by 2.5% (P = 0.001), but birth weight was unassociated with the fat-to-lean mass ratio (FLR). Ponderal index (PI) at birth (ie, weight/length3) was positively associated with LBM, total body fat, and the FLR in both sexes; the FLR increased by 2.7% in boys (P = 0.021) and by 5.0% in girls per 1-SD increase in PI (P < 0.001). Weight and length at birth did not predict central adiposity; although trunk fat had a strong positive association with PI at birth, this association disappeared after adjustment for total body fat. CONCLUSIONS: Higher PI at birth is associated with both higher fat and lean mass in childhood but also with an increase in the FLR. PI at birth is a better predictor of subsequent adiposity than is birth weight.

Cross-sectional associations of diet and insulin-like growth factor levels in 7- to 8-year-old children.

BACKGROUND: The insulin-like growth factors (IGF) are polypeptide hormones which are associated with several adult diseases including cancer and coronary heart disease. The dietary determinants of circulating levels of components of the IGF system are of interest, as these may mediate some of the effects of diet on later health. However, few studies have examined the relationship between diet and IGF levels in children. OBJECTIVE: To investigate associations between diet and IGF-I and IGFBP-3 levels in 7- to 8-year-old children. METHODS: This study used subjects participating in the Avon Longitudinal Study of Parents and Children. Diet was assessed using a 3-day unweighed food diary. Confounding variables considered were maternal education, housing tenure, birthweight, and body mass index. RESULTS: Complete information on dietary intakes, IGF levels, and all confounding variables were available for 521 children (287 boys). IGF-I was positively associated with intakes of protein, magnesium, zinc, calcium, potassium, and phosphorus, and IGFBP-3 was positively associated with energy. The IGF-I/IGFBP-3 ratio was positively associated with intakes of protein, zinc, and phosphorus. There was some evidence that the dietary determinants of the IGF system differed between the sexes. None of the foods examined were strongly associated with IGF levels, in particular, there was no association with red meat or vegetable intake. CONCLUSION: These data suggest that the IGF axis in children is affected by diet. This may provide a mechanism whereby childhood diet could have a long-term effect on risk of chronic disease.

Relationship between birthweight and blood lipid concentrations in later life: evidence from the existing literature.

BACKGROUND: It has been suggested that there is a link between fetal growth and chronic diseases later in life. Several studies have shown a negative association between birthweight and cardiovascular diseases, as well as cardiovascular disease risk factors, such as blood pressure and type 2 diabetes. Far fewer studies have focused on the association between size at birth and blood lipid concentrations. We have conducted a qualitative assessment of the direction and consistency of the relationship between size at birth and blood lipid concentrations to see whether the suggested relationship between intrauterine growth and cardiovascular diseases is mediated by lipid metabolism. METHODS: A literature search covering the period January 1966 to January 2003 was performed using Medline, Embase, and Web of Science. All papers written in English and reporting the relationship between size at birth and lipid levels in humans were assessed. Bibliographies were searched for further publications. RESULTS: From an initial screen of 1198 references, 39 papers were included involving 28 578 individuals. There was no consistent relationship between size at birth and blood lipid levels; the one exception being triglyceride concentration, which showed statistically significant negative or U-shaped, but not positive, relationships with birthweight. CONCLUSION: This review does not strongly support a link between birthweight and blood lipid levels in later life. However, the research in this area is limited and in order to make any definitive conclusions, longitudinal studies with sufficient power, data, and prospective follow-up are needed.

Maternal macronutrient and energy intakes in pregnancy and offspring intake at 10 y: exploring parental comparisons and prenatal effects.

BACKGROUND: High maternal dietary intakes in pregnancy may lead to increased fetal growth and program neuroendocrine pathways that result in greater appetite, energy intake, and adiposity in offspring later in life. Few prospective dietary studies have explored this relation. OBJECTIVE: The objective was to assess associations of maternal dietary intake in pregnancy and maternal and paternal dietary intake postnatally with child dietary intake and adiposity. DESIGN: Dietary intakes of energy, protein, total fat, and carbohydrate were assessed prospectively in mothers during pregnancy, in mothers and their partners at 47 mo postnatally, and in children at 10 y (n = 5717 mother-child pairs prenatally, 5593 mother-child pairs postnatally, and 3009 father-child pairs). Child body composition was assessed at 9 and 11 y (n = 5725). RESULTS: Maternal dietary intakes of protein, fat (when adjusted for energy intake), and carbohydrate in pregnancy were positively associated with child dietary intakes of the same nutrients, and these associations were greater than those observed for paternal dietary intake, which was not strongly associated with offspring diet. Associations of maternal prenatal-offspring intakes were stronger than those of maternal postnatal-offspring intakes for protein and fat. Greater child energy and macronutrient intakes were only associated with greater adiposity in children when adjusted for potential energy underreporting. Maternal diet during pregnancy was not associated with offspring adiposity or lean mass. CONCLUSION: The stronger prenatal maternal associations with child dietary intake, particularly protein and fat, compared with both paternal intake associations and maternal postnatal intake associations provide some evidence for in utero programming of offspring appetite by maternal intake during pregnancy.

Infancy weight gain predicts childhood body fat and age at menarche in girls.

CONTEXT: Rapid postnatal weight gain has been associated with subsequent increased childhood adiposity. However, the contribution of rapid weight gain during specific infancy periods is not clear. OBJECTIVE: We aimed to determine which periods of infancy weight gain are related to childhood adiposity and also to age at menarche in UK girls. DESIGN, SETTING, AND PARTICIPANTS: A total of 2715 girls from a prospective UK birth cohort study participated in the study. MAIN OUTCOME MEASURES: Routinely measured weights and lengths at ages 2, 9, and 19 months were extracted from the local child health computer database. Body composition was assessed by dual-energy x-ray absorptiometry at age 10 yr, and age at menarche was assessed by questionnaire (categorized into three groups: <12.0, 12.0-13.0, and >13.0 yr). RESULTS: Faster early infancy weight gain between 0 and 2 months and also 2 to 9 months were associated with increased body fat mass relative to lean mass at age 10 yr and also with earlier age at menarche. Each +1 unit gain in weight sd score between 0 and 9 months was associated with an odds ratio (95% confidence interval) = 1.48 (1.27-1.60) for overweight (body mass index > 85th centile) at 10 yr, and 1.34 (1.21-1.49) for menarche at less than 12 yr. In contrast, subsequent weight gain between 9 and 19 months was not associated with later adiposity or age at menarche. CONCLUSIONS: In developed settings, rapid weight gain during the first 9 months of life is a risk factor for both increased childhood adiposity and early menarche in girls.

Dietary energy density affects fat mass in early adolescence and is not modified by FTO variants.

BACKGROUND: Dietary energy density (DED) does not have a simple linear relationship to fat mass in children, which suggests that some children are more susceptible than others to the effects of DED. Children with the FTO (rs9939609) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised. We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants. METHODS AND FINDINGS: We carried out a prospective analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Diet was assessed at age 10 y using 3-day diet diaries. DED (kJ/g) was calculated excluding drinks. Children were genotyped for the FTO (rs9939609) variant. Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner. There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y (beta = 0.005, p = 0.51), suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35+/-0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16+/-0.06 kg more fat mass at age 13 y, after controlling for misreporting of energy intake, gender, puberty, overweight status at 10 y, maternal education, TV watching, and physical activity. CONCLUSIONS: This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity, encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain.