Research Programme.The aim of his project is to:

1)Increase the strength of causal inference regarding associations between modifiable maternal exposures (medication and supplement use, diet, smoking, alcohol consumption, physical activity) and offspring obesity, psychological health and cognitive function.

2) Formally compare these associations in a cohort from LMIC (Brazil) and one from HIC (Britain).

I (under the supervision of Professors Davey Smith, Victora, Lawlor, and Drs Lewis and Matijasevich) will implement this utilising:

1) Maternal and child data collected prospectively in the ALSPAC cohort in Britain and Pelotas cohort in Brazil.

2) Using two methods that can provide more robust causal inference regarding effects of maternal intrauterine effects that can be obtained from conventional observational epidemiology approaches11.

a. Comparison of maternal behaviour-offspring outcome associations to paternal behaviour-offspring outcomes. The idea behind this approach is that specific maternal intrauterine effects should result in stronger associations between maternal behaviour-offspring outcome and paternal behaviour-offspring outcome. I have used this approach once in my PhD work12 and would like to develop this relatively novel approach, including more sophisticated statistical modelling (e.g. to account for possible non-paternity further).

b. Use of genetic variants that are related to maternal modifiable exposures as instrumental variables to determine the causal effect of the maternal modifiable exposure. Mendelian randomisation has been proposed as one way of overcoming confounding by utilising the random allocation of alleles from parent to offspring13. Certain genetic variants can be found to affect behaviours e.g. LCT genotype and lactose-containing foods14. Genetic variants such as these can be used as instrumental variables for maternal behaviours, and provide a means for testing an unconfounded and unbiased association with components of offspring health.

ALSPAC. ALSPAC data that would be required for this proposed outline include maternal and paternal questionnaire data on health and behaviours during pregnancy (medication and supplement use, diet, smoking, alcohol) and clinic data in the children relating to size and obesity (BMI, body fat, lean mass, trunk fat etc) as well as psychological measures (depression, anxiety, cognitive function). In addition, genetic data from the DNA samples that are currently being collected in both mothers and children would be required.Pelotas cohort, Brazil.One of the largest and longest running birth cohorts in the developing world, this cohort consists of 5914 infants born in 1982 in the Brazilian city of Pelotas. Follow-up assessments (in varying numbers of children) have been carried out at varying stages of development ranging from at birth, infancy and childhood (age ranges from less than 1 year to 5 years), adolescence (12 to 19 years) and young adulthood (22 to 24 years). A wide range of information is available, including family socioeconomic position, maternal characteristics, maternal health and behaviours in pregnancy, infant perinatal data, environmental factors, infant nutrition, as well as physical and psychological measures in infancy, childhood and adolescence. Similar data is also available in another Pelotas cohort initiated in 1993.DNA samples will be collected in a planned follow up study in 2008.Existing collaborations between ALSPAC and Pelotas.There is enormous potential (given the similarity of design and measurements in the two studies) for scientifically valuable collaborations between these two cohorts, and the two scientific directors (Davey Smith and Victora) are eager to facilitate and support such collaboration. With an award by the Wellcome Trust for Dr Alicia Matijasevich, who works with Professor Victora on the Pelotas cohort to spend six months in Bristol on a project comparing socioeconomic differentials of maternal and childhood outcomes between the two cohorts. I intend to build upon this work in the current proposal and further strengthen collaborations between the two cohorts.