Obesity, leading to diseases such as diabetes and ultimately cardiovascular disease is an important public health issue. The current environment has been called “obesogenic” that is, it makes it easy for us to adopt a lifestyle of over-consumption of calories alongside low physical activity, increasing the risk of obesity. However, while lifestyle factors are undoubtedly important, there is evidence that an individual’s risk of obesity and associated diseases can be “programmed” in the womb. Specifically, if a woman is undernourished while pregnant, her baby may be born smaller than usual and have increased risk of Type II diabetes and cardiovascular disease (heart disease and stroke) as an adult.

Epidemiological studies have shown an association between low vitamin B12 intake in pregnant women and low birth weight babies, who goes on to have more ‘bad’ than ‘good’ fats in their blood, higher BMI, higher heart rate and greater risk of insulin resistance (pre-diabetes) as children. In addition, three studies in Indian populations suggest high folate intake, by mothers who have low intake of vitamin B12, is associated with low birth weight babies and increased fat mass and insulin resistance in those babies in childhood. This suggests the hypothesis that a pregnant woman’s dietary intake of vitamin B12, and the ratio of B12 to folate may influence her baby’s birthweight and risk of obesity, diabetes and cardiovascular disease when they grow up. We plan to investigate this hypothesis using the Avon Longitudinal Study of Parents and Children (ALSPAC).

ALSPAC has documented the health of 14,500 families in the Bristol area since 1990. Pregnant women were recruited into the study if their baby was due between April 1991 and December 1992. Detailed information has been collected on these women and their families using questionnaires, data extraction from routine information systems and research clinic visits. Information on folate and vitamin B12 intake in pregnancy (our “exposures of interest”) will come from a food frequency questionnaire completed by 10,851 women when they were 32 weeks pregnant, as well as questions on supplementation at 18 and 32 weeks of pregnancy.

We will examine three outcomes: 1. Birthweight: using information on birthweight and gestational age recorded from routine hospital data systems. 2. Childhood obesity: using height, weight and waist circumference measurements made at clinic visits when the child was 7, 11 and 16 years old. 3. Cardiovascular disease risk: we will examine a) the profile of fats in a blood sample taken when children were 15 years old, including total cholesterol, triglycerides, HDLc and LDLc, b) a measure of insulin resistance using blood glucose and insulin concentrations, and c) blood pressure recorded at the same clinic visit. These data are available in existing datasets.

We will use sophisticated statistical methods (Bayesian network analysis) to examine the association between our exposures of interest and the identified outcomes with adjustment for possible confounding factors such as socio-economic status and mother’s BMI. These methods will also account for the relationships between the outcomes in a way that has not been examined previously.

Our findings will be important because current advice to pregnant women recommends supplementation of their diet with folic acid. It may be that this should be updated to include a B12 supplement in women at risk of low intake of this vitamin (such as vegetarians). In addition, in some countries there is mandatory fortification of cereals with folate. If this results in a low ratio of B12 to folate in the general population, fortification may exacerbate the problem of childhood obesity, increase prevalence of diabetes and increase cardiovascular risk. Although our analysis will not provide a final answer to the question of whether there is a causal link between intake of these nutrients and risk of the conditions examined, it will suggest whether further research into this issue is worthwhile.