Iron deficiency is common and can have harmful effects on the mother and her foetus. Anaemia, therefore, is always treated with iron supplements. However, the levels given vary widely and there is growing concern about the risks associated with overload. Since Fe can generate free radicals, and interact with other nutrients, assessment of supplementation in pregnant women is essential. Volunteers will be given two levels of Fe, within the range given clinically, or a placebo, and the effect on parameters such as oxidative stress, cardiovascular well-being, zinc and copper metabolism, will be measured. We will study treatment directly in patients with ileostoma, identifying the cause of GI upset. We will measure the effect on babies at term, on placental function and on expression of different genes in tissues in supplemented rats and in cultured cells, to elucidate the molecular basis of the changes and a rational basis for supplementation.
Iron deficiency during pregnancy is common and can cause harmful effects on the mother and her developing child. Consequently, supplementation with iron is recommended if a mother's iron levels are even slightly lower than recommended. The amount prescribed, however, varies widely and there is growing concern about the risks associated with excessive iron accumulation. This project, therefore, will examine the effect of two doses of iron supplements, given within the clinical range, on a variety of indicators of health and well being in pregnant women. Concurrently, we will study the effects of supplementation directly in humans and will test the mechanisms involved using cell culture and animal models.
We will identify the optimum levels of supplementation during pregnancy and will also determine the maximum safe level. Iron supplements have unpleasant side effects and our data will provide information why this should be the case. Supplementation will have effects on the metabolism of other nutrients in addition to iron, and our experiments will not only demonstrate which nutrients are affected but will also show the mechanisms of the interaction.
In order to prescribe sensible levels of iron, we need a clear understanding of the effect it has on the metabolism of other nutrients. For example, we have preliminary data, which suggest that increased iron levels decrease copper concentrations in the blood. What effect this may have on the developing foetus in not clear. Further, we know that iron is capable of generating free radicals, which may have local toxic effects on the gut lining.
At the molecular level, iron regulates the expression of many genes. Only some of these have been characterised. We will use modern techniques to identify new genes, to study how supplementation alters their expression and how they are regulated during pregnancy.
Surprisingly, supplementation rarely actually alters iron status of pregnant women. Why this is so is not clear. Our data will provide some explanations, probably relating to turnover of iron and associated micronutrients.
The main application will be in the field of public health. We will be able to provide rational guidelines for supplementation strategies and recommendations for safe levels of supplementation. We expect to recommend that women should take supplements much earlier in pregnancy than is currently the case and that lower levels should also be prescribed, especially in the UK, but possibly also in other European countries.