Cholesterol is an essential morphogenetic cofactor in developmental pathways that pattern the central nervous system during gastrulation and early embryogenesis. Adequate cholesterol is also an essential substrate for the rapid growth of neural tissues in the embryo and for synthesizing pregnancy-related steroid hormones. These critical morphogenetic events begin at embryonic day 14, prior to the establishment of a blood-brain barrier or feto-placental circulation, indicating that the embryo's early requirements may depend on uptake from the maternal circulation. Mothers with abnormally low levels of either total serum cholesterol or any essential lipoprotein fraction during the peri-conceptional period may be unable to supply the developing embryo with adequate cholesterol during this critical phase, resulting in pregnancy loss or the birth of infants with microcephaly and/or neuro-developmental disorders.

Specifically, we predict that mothers whose earliest prenatal total serum cholesterol value is within the lowest 5% of the study cohort will have an excess rate of pregnancy loss and an excess rate of microcephaly and of developmental delay in their offspring. The ALSPAC cohort is ideal for testing this hypothesis, because the number of study participants and the comprehensive pre-and post-natal data obtained from them permit an unbiased, carefully adjusted evaluation of the study hypothesis.

(No outline received).

The children in the ALSPAC cohort are now entering secondary school. The work already done in establishing the dataset means that there is now a unique opportunity to study in robust, quantitative and ground-breaking terms a number of crucial issues in the educational development of UK children. These studies will have important scientific benefits and implications for current and future Government policy. However, it is necessary to move quickly if the opportunity of putting the appropriate questions to the right individuals at the right times is not to be lost.

Other data collection will be occurring in ALSPAC through this phase, particularly in the fields of psychiatry and medicine and the investments made by related funding councils and others provide a platform for investments in educational research using ALSPAC.

A particular focus of the secondary school data collection in ALSPAC will be the motivation, engagement and attainments of pupils. Data collection will also concentrate on the impact on these aspects of development of family, school, policy and wider social factors. Planned reforms to the British education system for 14-19 year olds can be monitored by their impacts on this cohort of children. Social class differences in the process of engagement, choice and attainment of pupils can also be examined and quantified.

(No proposal form received).

(No outline received).

Specific aims of this research are to a) examine the long-term effects of prenatal anxiety on dimensional and diagnostic measures of psychopathology in early adolescence; b) assess the role of the HPA axis underlying the links between prenatal anxiety on adolescent psychopathology and stress vulnerability; c) test competing hypotheses concerning the processes by which prenatal anxiety has direct, mediated or moderated effects on adolescent psychopathology; and d) test the hypothesis that the effects of prenatal anxiety/stress on behavioral/emotional problems in early adolescence are moderated by genetic risk.

This project will investigate how well parents and health professionals can identify developmental problems in preschool children, using the ALSPAC study, a total birth cohort of 14,138 children born in 1991-2.

We will test whether parents are the first to identify impairments in their children and whether questionnaires can be an effective method of selecting children for further professional assessment in the pre-school period.

The overall aim of this grant was to create a Lymphoblastoid Cell Line (LCL) collection from children and parents participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). The study has collected data on a scale and with a richness unprecedented in the field of epidemiological study and the generation of the cell line bank would provide material for further genetic, gene expression and metabolomic research.

Development of the resource initially involved establishing a cell culture facility with robotic cell maintenance systems, development of a bespoke Laboratory Information Management System (LIMS) and development of protocols for the transformation and growth of LCLs. Once these systems were in place LCL production would become a routine laboratory procedure enabling cell lines to be produced from all cohort members who consented to cell line production.