No outline received

No outline received

The British 1958 birth cohort1 is based on all persons born in Britain during one week in March in 1958. Participants have been followed throughout their lives and biomedical information has been collected at various time points. Biological samples were collected from the cohort during medical examinations between Sept 2002 and March 2004. Funding for creation of a blood derived DNA bank was provided by the MRC (strategic project grant G0000934). Funding for creation of lymphoblastoid cell lines, cell line derived DNA extraction, banking and distribution was funded by the Wellcome Trust (grant no 068545).

DNA and cell line banks were created in the ALSPAC Laboratory. Blood derived DNA is available from 8018 individuals and has been used successfully in several genotyping studies.

Cell lines from 2288 individuals were created at ECCAC, Porton and a further 5239 in the ALSPAC laboratory. DNA has been extracted from all of these samples and has been organised into geographically representative subgroups of samples specifically for use as control samples in case control studies. Samples have been distributed to over 20 collaborators and were used as control samples by the Wellcome Trust Case Control Consortium2.

Further funding was obtained in 2006 for management of the cell line and DNA banks and distribution of samples (grant details). This funding will end on 31st August 2007 and we are therefore applying for additional funds to continue these functions.

Background: Domestic violence may start or increase in severity during pregnancy (Gazmararian et al 1996; Bowen et al, 2005). The main health effect specific to domestic violence during pregnancy is the threat to health and risk of death of the mother, foetus, or both, from trauma (El Kady et al, 2005; Pearlman et al, 1990). Domestic violence is also associated with depression, anxiety, insomnia, alcohol and drug abuse, and suicide attempts (Campbell 2002). However, the impact of domestic violence during pregnancy on the risk ofchild development has not been previously investigated to our knowledge. A recent study has reported, though, on the significant impact of postnatal domestic violence on child development, which, with postnatal depression, had a cumulative effect, leading to worse child outcome (Whitaker et al, 2006). There is increasing evidence that prenatal stress and major depression during pregnancy are associated with increased concentrations of corticotrophin releasing hormone (O'Keane et al, submitted); this increase in pituitary-adrenal activity may explain the association of domestic violence during pregnancy with poor obstetric outcomes (low birthweight and preterm pregnancy) . Domestic violence may therefore adversely affect child development independent of the effect of antenatal psychiatric morbidity or subsequent psychiatric morbidity, but any effects on child development may also be partly mediated by antenatal psychiatric morbidity.

The long term health outcomes for young people with different amounts of total body fat are unknown as most large scale studies examining the effects of childhood obesity have not used measures of body fat, but proxies such as body mass index (BMI). However, BMI may not indicate the level of central adiposity which is also associated with clustering of cardiovascular disease risk factors including dyslipidaemia, hypertension and insulin resistance. Clusters of risk factors are fairly stable characteristics that tend to track from adolescence to adulthood, hence the early identification of children who are likely to develop an elevated risk profile is of interest.1

Waist circumference has been recommended as a means of identifying young people at metabolic risk.2 Yet, there are several studies that indicate that waist circumference measurements have a similar performance to BMI in identifying dyslipidaemia and screening for the metabolic syndrome.3,4,5 These results are not unexpected, BMI and waist circumference are highly correlated.6

However, the waist to height ratio has been shown to more readily identify young people with adverse cardiovascular risk factors (cross-sectionally) when compared to BMI7 and may be an accurate indicator of change over time in fat distribution as it accounts for both waist circumference and height.8

Anecdotally there has been much interest expressed in the waist to height ratio by clinicians. Recent evidence suggests that the waist to height ratio, unlike BMI and waist circumference, does not require specification of sex or age and a ratio cut-point of 0.5 has been proposed as a simple means of indicating whether the amount of central adiposity is excessive in both children8 and adults.9 The concept of an increased waist girth relative to height may be easier to understand by patients and families compared to BMI percentiles, particularly if the message is 'keep your waist circumference to less than half your height'.8 However, to our knowledge use of the 0.5 ratio has not been validated at predicting metabolic risk in young people.

Aim: Examine the effectiveness of the waist to height ratio in identifying young people at risk of metabolic risk clustering.

No outline received

We are currently in the process of applying to the ESRC for a grant to fit longitudinal models to the repeated MFQ depression measures administered to both the mother (in child-based questionnaires) and to the child (in the clinic).

We feel that whether or not this grant is successful (we expect to hear by the autumn) it will be useful to have carried out some preliminary work using SDQ measures (47mn, 81mn, 9/11/13 years). These measures will avoid many of the methodogical problems expected when using the MFQ, and we anticipate the fifth of these measures to become available within the next few months.

Consequently we are proposing to fit a series of Longituginal Latent Class Analysis (LLCA) and Latent Class Growth Analysis (LCGA) models to these repeat measures, much in the same way as the recent asthma and bedwetting models and that this would stand up as a paper in it's own right.

This pilot study will compare hair-based toxicological assessment of cannabis exposure with self-reported use of cannabis over the same historical period amongst a purposive sample of 100 people selected to represent a range of cannabis exposure levels. Self-reported use will be assessed through completion of the assessment schedule currently incorporated in the 15+ ALSPAC Focus clinic (where hair samples are being collected and stored). For convenience, cannabis negative controls (10) will be sought amongst volunteers from the Department of Social Medicine. A further 90 individuals with a range of cannabis use levels from low (monthly or less) to high (daily) will be recruited through advertisements amongst students and users of community drugs projects with whom we have contacts. These sources have been successfully used in the past to recruit to focus groups; participants will be offered a £20 inconvenience fee and will be given assurances of complete confidentiality. Following completion of the questionnaire, an investigator will check participant responses. Participants will then provide a hair sample for toxicology. Assessments of use in the past 3 months provided by toxicology will be compared to those from self-report. Hair samples will be collected via the standard procedures used in ALSPAC.Colour of hair and use of any cosmetic treatments (e.g. perming or bleaching) will be recorded as these can influence toxicology results (though seldom to the point of producing false negatives).

Toxicological assessment will be undertaken at the TrichoTech laboratories in Cardiff. Quantitative assessment of cannabis content of the samples will be undertaken using gas chromatography/mass spectrometry. Cannabis dose exposure as inferred by the amounts and frequencies reported by questionnaire in the same participants will also be calculated and ranked. The two assessments will be compared using weighted Kappa scores to compare categorical assessments of dose/ consumption. Intraclass correlations also will be used to assess association between continuous measures of consumption. Based on a sample size of 100 and consideringthe percentage agreement for a binary outcome, for example "heavy" consumption defined as the top quintile of each distribution, we will be able to detect agreement between the two methods of 60% or more based on the width of the one-sided 95% confidence interval.[i]

High Kappa or correlation scores will be taken as evidence of low levels of reporting bias in the self-reported cannabis measures. Conversely, low agreement between self-report and toxicological assessment will be taken to suggest that the former may have been influenced by social desirability bias.

Results of this pilot study will be used to support funding applications (for example to the NIH and the MRC) for toxicological assessment of the full ALSPAC cohort based on samples collected at the 15+ Focus clinic and subsequently.

[i] Machin D, Campbell M, Fayers P, Pinol A. Sample size tables for clinical studies 2nd Ed. Blackwell, Oxford 1997.

(a) Aims of the project

To determine whether there is a causal association between:

1. low-to-moderate prenatal alcohol exposure
2. binge drinking during pregnancy
3. polymorphisms of the main alcohol metabolizing genes in mother and child

and birth weight, length at birth, head circumference at 8 months; growth at 7/8 years; and neurodevelopmental outcome through to age 11?