Children from deprived homes emerge from our schools with substantially lower levels of educational attainment. These educational deficits emerge early in children's lives, even before entry into school and widen throughout childhood.

But little is known about how family background affects education attainment. This project will consider the influences on children's skill development, in its broadest sense, focussing particularly on soft skills, and on attitudes to education amongst children from low-income backgrounds

To determine whether exposure to specific dietary factors in utero and infancy influences cognition.

Specific Hypotheses:

1) Suboptimum levels of specific nutrients such as folate and omega-3 fatty acids in utero lead to impaired neurodevelopment and low cognitive ability.

2) Polymorphisms in genes which metabolise nutrients are associated with neurodevelopment in infancy and can be used to infer causal relationships between specific nutrients and cognition.

3) Maternal genotype and corresponding offspring genotype, jointly determine neurodevelopment in infancy and childhood. Associations with maternal genotype, independent of offspring genotype, will support the role of the prenatal environment.

Neuroanatomical and neurophysiological studies show that brain development occurs most rapidly during fetal development and in infancy. Nutrition is probably the single greatest environmental influence both on the fetus and neonate, and plays a necessary role in the maturation and functional development of the central nervous system. Therefore a lack of any nutrient required for brain development may be related to neurodevelopmental diseases such as autism as well as influencing general cognition. Nutrients found to be lacking in the mothers' diet could, if shown to be related to brain development, be modified to prevent disease and ensure that the childs' cognitive ability is not impaired.

We plan to:

1) Genotype mothers and their offspring with respect to candidate polymorphisms which influence nutrient intake, metabolism, transport or cellular uptake.

2) Determine associations between the above maternal and infant polymorphisms and childhood cognition.

3) Stratifying by offspring genotype, determine associations between maternal genotype and offspring cognition.

4) Investigate whether the above polymorphisms are associated with cigarette smoking, socioeconomic status, reproductive factors and other potential confounders in the mothers, to confirm that developmental outcome associations with genotypes are not confounded.

Genotype analysis

Variation in genes which alter the availability of specific nutrients will be exploited in this project. Suitable candidate genes include those which are; a) associated with nutrient intake, such as the lactase gene, polymorphisms of which determine lactose intolerance and therefore intake of lactose b) involved in nutrient metabolism, for example there are several enzymes involved in the biosynthesis of the omega-3 fatty acid DHA from its' precursors in the diet including cycloxygenase (COX), lipoxygenase (LOX) and delta-5 desaturase, c) important in the transport and internalization of nutrients into target cells, such as the choline transporter (CHT1) gene. Genotyping of SNPs will be carried by K-Biosciences (http://www.kbioscience.co.uk).

Outcome measurements

The primary outcome will be the Wechsler Intelligence Scale for Children (WISC)-III, which is a UK measure of cognitive ability (IQ) measured at the focus clinic at age 8 1/2 (score available for 7188 children). Education is strongly influenced by political and social factors and is therefore less likely to be due to mothers' diet, however, educational scores will be secondary outcomes in this study as education is likely to be important in the pathway between cognition and later health. Additional outcome measures will be included in this project as they may provide insights into specific aspects of neurodevelopment that may be particularly sensitive to maternal dietary influences in-utero. The secondary outcomes are:

* Wechsler Objective Reading Dimensions (WORD) test and the Wechsler Objective Language Dimension (WOLD) Test - which measure reading and language respectively,

* Social Communication Disorders Checklist (SCDC), - measures social interaction and communication skills.

* Development and Well-Being Assessment (DAWBA) and the Strengths and Difficulties Questionaire (SDQ) - both designed to measure conduct problems, emotional behaviour and hyperactivity,

* School and hospital diagnosed learning difficulties - will pick up individuals with clinically diagnosed conditions.

* SATS test scores and GCSE results are included in the list of outcomes to determine whether dietary effects on cognition, are translated into school performance. We would only explore associations with this outcome where there was a positive association of a maternal dietary factor with cognitive ability. Thus, this would extend the primary analysis to provide an indication of whether the effect of maternal diet on cognition had an important effect on performance.

* Head circumference- this is a more crude measure of brain development than the other outcome measures proposed in this grant. However, it was measured at birth for all children in the ALSPAC study and as this is an indicator which relates specifically to in-utero development.

The large number of tests generated by having several outcomes will increase the possibility of false positive results. In order to guard against this we will:

* Undertake secondary analyses only when there is an indication to do so from the primary analyses (e.g. with school performance)

* Seek to replicate any positive results (with primary or secondary outcomes) in other cohort studies as described in the proposal.

The Arthritic Association is built upon the clear recommendations of Charles de Coti-Marsh for the use of diet, supplements and lifestyle for the amelioration of the symptoms of arthritis. The Home Treatment Programme includes recommendations of a diet of potassium-rich foods andincreased intake of fruit, nuts, vegetables and whole grains, low saturated fat intake, low sugar and salt intake, the use of supplements such as homeopathic Arnica, 'K' compound and Oil of Garlic and the advocation of a lifestyle that includes regular gentle exercise and adequate sleep.

However, as pointed out by the Association there is no evidence yet as to whether the use of such diets and/or treatments may prevent symptoms of arthritis and/or limb and other pain from actually occurring. We propose to use data collected in ALSPAC to assess whether there is any evidence to support such a hypothesis and also to investigate associations between the recommendations of the Home Treatment Programme upon ALSPAC parents with arthritis and parents and children with joint pain. In so doing, this investigation has the unique opportunity to examine these key factors by laying down foundations as to the pre-cursors of children developing arthritis in later life.

(No outline received).

Mother-baby bedsharing is associated with an increased risk of unexpected infant death, particularly for mothers who smoke or drink alcohol, but little is known of the potential beneficial effects of bedsharing (e.g. establishment or maintenance of breastfeeding), and recent US data has confirmed the beneficial effects of breastfeeding in reducing infant mortality. The Avon Longitudinal Study of Parents And Children (ALSPAC) has collected information on health, growth, development, medical, environmental and social factors from pregnancy to the present, in a cohort of 14,000 children born in 1991-2 and their families. Detailed information has been collected on sleep patterns, duration and place for the infants and their parents. Preliminary analysis of the data on sleep in infancy and childhood has shown that in the first 6 months 33-70% infants share a bedroom with their mother, and routine mother-baby bedsharing for night time sleep is common throughout infancy and early childhood, varying between 9% and 18%. Many factors (e.g. birthweight, breastfeeding), are associated with sleep patterns and duration, and, whilst short sleep duration in early infancy is associated with obesity in later childhood, breastfeeding (which is associated with bedsharing) may reduce the risk of obesity.

We will use complex statistical modelling techniques to analyse the data from ALSPAC children and families, to identify factors contributing to parents choices about bedsharing in infancy, together with any immediate or long term adverse consequences or benefits of bedsharing, room sharing or separate sleeping, for both children and mothers. The large size and completeness of the data from the ALSPAC cohort will allow us to take account of multiple psychological, medical, social and environmental factors that may have influenced decisions about infant care practices, and may themselves have been associated with potential benefits or adverse consequences (e.g. breastfeeding, maternal smoking, socio-economic deprivation, pacifier use).

Aims

• To use SNPs in linkage disequilibrium with IL-1RN*2 to genotype the 'Children in Focus' (CIF) cohort of the ALSPAC study.
• To test for association of the inferred IL-1RN*2 genotype with birth weight.

(No outline received).

Aim :To test for associations between habitual physical activity and executive function at age 11- the ALSPAC cohort provides a unique opportunity to test this hypothesis due to its combination of large sample size, good measures of habitual physical activity (accelerometry) and executive function, and key confounders.

Denervation of pelvic organs taking place at vaginal delivery results in subsequent reinnervation and wide-ranging gynaecological symptoms e.g. vulvodynia, dyspareunia, chronic pelvic pain, irritative bladder symptoms, rectal hypersensitivity, menorrhagia and dysmenorrhoea (1-12). All benign myometrial pathology e.g. endometriosis, adenomyosis, leiomyomata, etc. has specific neural abnormalities in the spectrum of denervation-reinnervation (4-7). Reinnervation, in several different patterns, has been described in every female pelvic organ often in association with a prior history of difficult vaginal delivery including premature, or prolonged, maternal voluntary efforts (8-12).

In nulliparous women, straining to achieve defaecation has been demonstrated to cause specific neurological lesions in different pelvic viscera (8, 9, 12), and this mechanism, operating at the endometrial-myometrial nerve plexus , has been proposed as a source of impaired placentation in nulliparous pre-eclampsia. intrauterine growth retardation, abruption, placenta accrete/percreta (13, 14).

The question arises: "Do nulliparous women with severe obstetric problems e.g. early-onset preeclampsia. IUGR, preterm delivery, abruption, etc. suffer subsequent gynaecological symptoms e.g. menorrhagia, dysmenorrhoea, chronic pelvic pain, that require specific medical and surgical interventions e.g. hysteroscopy, laparoscopy, hysterectomy, etc. within the subsequent 10 years".