Influence of Genetics on Vitamin Metabolism in Pregnant Women

A number of genetic polymorphisms influence human folate, vitamin B12 and related micronutrient levels. Vitamin B12 and folate levels in pregnancy have been linked to birth defects including neural tube defects, orofacial clefts, and congenital heart disease. Additionally, related analytes, such as homocysteine, may be related to birth defects and pregnancy complications. The behavior of maternal serum micronutrients and related analytes throughout human pregnancy is not well described. In this study, we aim to characterize the patterns of micronutrient status during pregnancy. We plan to perform biochemical analyses on serial blood samples collected from 500 pregnant women at five intervals spanning early pregnancy and the post partum period. We will also characterize neonatal micronutrient status using a specimen of umbilical cord blood. These blood specimens, as well as buccal swab specimens collected from the fathers, will also be evaluated to measure the influence of genetic variants on metabolite levels. The major outcomes measured will be longitudinal maternal micronutrient levels and aggregate alleel frequencies among family triads. Comparisons will be made between the presence of genetic variants, biochemical parameters, and clinical phenotype. At a later date we also plan to study the same metabolic and genetic parameters in a large cohort of healthy individuals. Characterizing these biochemical and genetic variants should provide insight into the metabolic processes of normal and complicated pregnancies.

• Eligible participants will be women of Irish origin (older than 18) presenting for prenatal care to the Coombe Women's Hospital, Dublin, Republic of Ireland. Non-Irish women (a small proportion of the population) will be excluded because the prevalence of genetic polymorphisms can vary greatly among different populations; we already have an estimate of the distribution of this genotype in the Irish women. Members of the only minority group native to Ireland, the Travelers, will not be excluded. While culturally distinct, the Travelers are genetically similar to the majority population. Women with multiple pregnancy (more than one fetus) and users of IV drugs will be excluded. Women will be asked for permission to obtain a cord blood sample from the infant at delivery. Women will be asked to assist with recruitment of their partners (father of the fetus), who will be included if they consent.