No outline received

Sexual health is an important component of physical and mental health. In the UK, rates of teenage pregnancy are among the highest in western Europe and sexually transmitted infections (STIs) such as chlamydia are common in teenagers and young adults. Sexual behaviour is a normal part of human development and it is crucial to understand the factors that influence sexual health and behaviour through this development process in adolescence to guide suitable public health interventions to improve sexual health.

The ALSPAC cohort is representative and extremely well characterised from before birth. The ALSPAC children are now teenagers, and this offers a unique opportunity to study adolescent sexual behaviour and adverse sexual health outcomes, including sexually transmitted infections. Sexual activity has been measured at age 11, 12, 13+, 15+ and factors affecting relationships between the individual and his/her environment have been measured across the life-course. We propose to repeat the sexual activity questionnaire at the age 17+ clinics and in addition, collect biological samples to test for current and past chlamydia and human papillomavirus (HPV) infection. These infections are common and important in terms of public health policy given the recent introduction of the National Chlamydia Screening Programme and imminent HPV vaccine introduction. Using this data, we will describe the sexual behaviour and prevalence and incidence of chlamdyia and HPV in teenagers, and identify risk factors for adverse sexual health outcomes. By doing so, we aim to identify potentially modifiable behaviours/ factors that can be used to develop sexual health interventions for young people.

Aims:

- To describe the sexual behaviour of ALSPAC participants attending the age 17+ clinics

- To establish the prevalence of current and past infection with chlamydia in ALSPAC participants attending the age 17+ clinics

- To establish the prevalence of current and past infection with HPV in ALSPAC participants attending the age 17+ clinics

- To measure associations between sexually transmitted infections with current and past sexual behaviour and other risk taking behaviours

- To establish early-life influences and predictors of adverse sexual health outcomes

Methods:

We propose to engage the cohort in the next round of clinics at age 17+ years. Participants attending the clinics will be invited to complete a computer assisted self-interview (CASI) on 'romantic relations' and other relevant risk behaviours, particularly substance use. The romantic relations questionnaire was first introduced at the age 11+ clinic and to maintain consistency between assessments we will retain this questionnaire. However, we will also assess whether further questions should be added, for example, to allow direct comparisons with NATSAL. Participants will be invited to give blood and first catch urine samples which will be used to test for active and past infection with chlamydia and HPV (see below). In addition, informed consent will also be sought to test stored samples collected in the age 15+ and 13+ clinics.

These data will be analysed to describe the age-specific sexual behaviour and the incidence and prevalence of HPV and chlamydia. We will then identify risk factors for HPV and/or chlamydia infection over life course and associations with other risk taking behaviours. Predictor variables from biological, individual, family, peer, social and cultural domains will be considered for inclusion in regression models.

No outline received

FAVOUR work package 4

Epidemiological investigations of impact of fruit and vegetables introductions at weaning on subsequent intake

Data analysis of existing longitudinal studies - ALSPAC, DONALD

Objectives Statistical analysis of fruit and vegetable eating in childhood in relation to early introduction of fruit and vegetables

Exploration of the relationship of socio-economic background to early feeding and later intake of fruit and vegetables

Description of work

ALSPAC: The Avon Longitudinal Study of Parents and Children (ALSPAC) was devised specifically to determine the ways in which the environment influences the health and development of the child (Golding et al,2001; http://www.alspac.bris.ac.uk/). Detailed information was collected regarding weaning practice and records of the child's food/drink intake were kept at repeated time points. During infancy, mothers completed questionnaires covering the age of introduction and types of weaning and family foods given to the child (at ages 6 and 15 months). Frequency of intake of fruit and vegetables was assessed by questionnaire at age 7 years. Preliminary analysis of this data has shown that children introduced to raw and home-cooked fruit and vegetables by 6 months of age ate fruit and vegetables more often at age 7 years than did those introduced to ready-prepared foods. More detailed food and drink record data were collected using 3d unweighed diaries from 750 to 1000 of the children at 4, 8, 18 months, 3.5, 5, 7 and 10 years. A complete range of foods and drinks consumed at each age is available as well as socio-economic background.

DONALD: The DONALD study is an ongoing open cohort study with about 40 new infants recruited every year. Currently there are 750 children and adolescents taking part. Dietary assessment has been conducted in the DONALD study as 3d weighed dietary records at ages 3, 6, 9, 12, 18, 24, 36 months. Food consumption is broken down to single food items including those from composite foods such as baby jars, and it is possible to distinguish between home prepared meals and commercial products at each age.For both studies, the diet records have been coded and analysed and information about food/drink and nutrient intakes including details of actual fruits and vegetables eaten is available. Children will be grouped according to fruit and vegetable weaning practice. Intakes of fruits, vegetables and other foods at each age up to 10 years will be investigated to determine the likely influence of these weaning behaviours. The socio-economic position of the families will be taken into consideration to determine the influence of these external factors on weaning practice. At each of the two cohorts a research nutritionist will be employed to carry out this work. The work will complement the results of the intervention study in work package 3.

Task 4.1 Assembly of dietary dataset covering weaning and later childhood diet Incorporate data from diet records from various timepoints covering nutrients and foods/drinks consumed. Create groups of subjects according to their fruit and vegetable weaning practice at 6 months.

Task 4.2. Linking of dietary dataset to socio-economic background variables. Compile socio-economic background data including educational level and age of mother, housing tenure, marital status and incorporate into dietary dataset

Task 4.3. Establishment of protocol for statistical analysis. Provide descriptive statistics of fruit and vegetable intakes at various ages and discuss with partners to establish protocol for the statistical analysis

Task 4.4. Statistical analysis. Determine amount of fruit eaten at each age in relation to eating raw fruit, home cooked, and ready-prepared fruit. Determine amount of vegetables at each age in relation to eating raw vegetables, home-cooked vegetables, and ready-prepared vegetables by 6 months.Investigate differences in nutrient intakes at each age according to type of fruit and vegetables introduced by 6 monthsInvestigate differences in other food/drinks consumed at each age according to type of fruit and vegetables introduced by 6 months

Task 4.5 Adjustment for socio-economic influences. Investigate the influence of socio-economic position on fruit and of vegetable eating at each age in relation to weaning practice.

Background:

Early life exposures have been hypothesised to affect subsequent levels of glucose and insulin. We aim to draw together all of the research done to date looking at this possible relationship in all normal populations in both children and adults.

Scientific hypothesis:

That there is an association between birthweight and subsequent levels of glucose and insulin.

Objectives:

To establish the difference in mean levels of fasting and post load glucose and insulin per one Kg increase in birthweight. We also wish to examine the effect of potential modifiers and confounders.

Methodology and planned statistical analyses:

The first stage is to identify all studies with published reports on the relationship between birthweight and subsequent levels of glucose and insulin in general populations of both children and adults. Investigators will be asked to provide data (preferably) or to carry out pre-defined analyses. Individual study data will be analysed with multiple logistic regression to obtain estimates for the differences in glucose and insulin that are associated with a 1 kg increase in birthweight, based on the full range of birthweights for each study. Models will be fitted without adjustment and then with additional adjustments for

* age and (if appropriate) gender

* for social class

* current body mass index

Analyses will also examine the effect of excluding subjects with

* birthweights greater than 4kg

* maternal diabetes.

The estimates will then be included in meta-analyses, carried out using fixed-effects modelling if there is not appreciable evidence of heterogeneity.

AIMS The aim of this proposal is to examine risk factors for developing psychosis-like symptoms (PLIKS) during late adolescence within a population-based birth cohort. Furthermore, we will examine factors affecting persistence of PLIKS throughout adolescence, and the pathways from developing PLIKS in early adolescence through to disorder (PLIKS with concurrent functional impairment) in late adolescence, focusing on both risk and protective factors that are likely to be operating along this trajectory. More specifically, the aims of this proposal are:

1) To carry out an interview-based assessment of PLIKS, along with measures of functional impairment, in order to determine the prevalence and distribution of sub-clinical PLIKS, and of PLIKS related disorder (PLIKS and concurrent functional impairment) in 17-year olds.

2) To investigate whether established risk factors for adult onset psychotic illness (maternal exposures during pregnancy, pregnancy and birth complications, social relationships during childhood and adolescence, social cognition, emotional experiences, cognitive ability, substance use, and genetic variation) alter risk of developing PLIKS at age 17, or impact upon persistence of symptoms (from assessment at age 12 through to age 17 assessment) or transition into PLIKS related disorder.

3) To further refine and increase the validity and positive predictive value of a self-rated questionnaire-based assessment of PLIKS by comparing self-reported responses to structured questions with observer ratings of PLIKS from a semi-structured interview

?SEQ CHAPTER h
1Our overall goal is to add a limited number of additional variables to our current data analyses using the ALSPAC data. We currently have information on the level of response to alcohol and demography at age 12-13, know the outcome regarding a limited number of alcohol-related variables at age 14-15, and have models of how the level of response to alcohol relates to alcoholic outcomes in teenagers and adults from several additional studies (the Collaborative Study on Genetics of Alcoholism, the San Diego Prospective Study adults, and the San Diego Prospective Study adolescents). However, to date none of these structural equation models have been tested in subjects in their early teens. Therefore, if several additional areas of data can be made available to us within the next week or so, we will be able to test whether aspects of the structural equation models generated in late teenagers and adults apply to the ALSPAC population using predictors from age 12-13. The published structural equation models have utilized both the MPlus approach and the AMOS programs as described in the references offered below. To carry out these analyses, we would be grateful for any of the following variables as an update to the data already supplied to us in June 2007.

Aims:

Grounded in evolutionary life history theory (Mace and Sear, 2005), the proposed research will examine the wider rearing environment of British children as a determinant of social and physical development trajectories, using the Avon Longitudinal Study of Parents and Children cohort (ALSPAC - children born in 1991/92). A previous study on this cohort has already identified a distinction in the impact of informal friend or kin-based care vs. paid care in determining cognitive outcomes by age 7 (Gregg et al., 2005) The proposed research takes a broader focus considering a wider range of development outcomes, over a longer period, and crucially will involve a more precise categorisation of contact with kin and investments by kin, informed by evolutionary demography. Outcome variables will include childhood malaise, growth, cognitive development and pubertal timing. ALSPAC provides an unusually detailed dataset to consider these questions, providing regular time-varying data on a wide range of relevant variables. Accordingly, multivariate multilevel models for change (Singer and Willet, 2003) will be utilised to gain a uniquely sophisticated longitudinal analysis of the role of contact with kin in childhood well-being.

The project would be two genetic association studies assessing the effects of variations in two genes (BDNF and ACE) on normal variation in cognitive function in ALSPAC. This would be an extension of our previous, successful collaboration in which we have investigated the effects of SNPs in the COMT, 5HTTP and MAOA genes (Barnett et al 2007). Analyses are hypothesis-driven (see below). Outcome measures would be cognitive scores from ages 8 (attention and IQ) and ten years (working memory). Genotype data would be required for the ACE and BDNF genes, which we understand has already been completed in the cohort.

Brain-derived neurotrophic factor (BDNF) is one of the group of neurotrophins which affect cell survival, axonal and dendritic growth and synaptic plasticity among dopaminergic and other neurons (Bath and Lee 2006). The BDNF gene on 11p13 contains a common Val-Met substitution at codon 66. The Met allele is associated with smaller hippocampal volume (Pezawas et al 2004; Szeszko et al 2005) and better memory (Egan et al 2003; Hariri et al 2003; Dempster et al 2005; Tan et al 2005; Ho et al 2006) but not attention, processing speed, language or planning abilities (Ho et al 2006). The relative rarity of Met/Met homozygotes (about 4% of the US population, (Shimizu et al 2004)) means that the cognitive status of Met/Met individuals is effectively unknown. There have been no studies, to our knowledge, of the effect of BDNF genotype on children's cognitive function, despite the obvious importance of BDNF in neurodevelopment.

Angiotension-converting enzyme (ACE) is a central enzyme of the renin-angiotensin system (RAS) and is primarily involved in blood pressure regulation. It is widely distributed throughout the brain, and particularly associated with cerebral blood vessels, and astrocytes of the periventricular nuclei. Raised RAS activity through elevated ACE is thought to impair cellular metabolism (Williams et al 2000) and amplify free radical and pro-inflammatory responses (Harding et al 2005). ACE may therefore play a role in neurodevelopmental progress and subsequent cognitive development (Harding et al 2005) as well as late-life cognitive decline (Amouyel et al 1996). This hypothesis is supported by demonstrations that ACE inhibitors improve cognitive function (Amenta et al 2002; Tzourio et al 2003).

The ACE gene on 17p23 contains a 287bp insertion/deletion polymorphism in intron 16. Both tissue and circulating ACE levels are higher in individuals with two copies of the deletion allele (Tiret et al 1992). The insertion allele appears to confer a slightly increased risk for Alzheimer's disease (Narain et al 2000) while the deletion allele has been repeatedly associated with increased risk for age-related cognitive impairment and dementia (Amouyel et al 1996; Palumbo et al 1999; Bartres-Faz et al 2000; Richard et al 2000; Stewart et al 2004). Deletion allele carriers are reported to show greater cognitive impairment in moderate and severe traumatic brain injury (Ariza et al 2006), less improvement after shunt surgery in normal pressure hydrocephalus (del Mar Matarin et al 2005), and reduced cognitive impairment in alcoholism (Bartres-Faz et al 2002). However three epidemiological studies have found no associations between ACE genotype and normal cognitive ageing (Visscher et al 2003, Frederiksen et al 2003, Yip et al 2002). Two studies have investigated the effects of ACE genotype on cognitive function in children (Gao et al 2006, Harding et al 2005). Both studies were negative, however both were limited by sample size and by the relatively crude cognitive measure they employed.