one carbon metabolism


Early identification of high-risk pregnancies and targeted nutraceutical intervention to reduce the incidence of adverse pregnancy outcomes.

Executive Summary

Micronutrients such as folate and vitamin B12 are important for normal fetal growth and development. Currently, women are not routinely tested for these substances during early pregnancy. Such information may be useful in tailoring the correct dietary intake of micronutrients to reduce the risk of pregnancy complications. This study will determine if it is of benefit to test women’s nutrient status during early pregnancy and, on that basis, provided tailored nutrient intake to improve pregnancy outcome.

The simple process of transferring a single carbon unit to other molecules (i.e. the one-carbon metabolism [OCM] pathway) is one of the most important and defining processes that regulates human development. It provides the precursors for DNA synthesis, repair and methylation.  Folate and vitamin B12 are essential for the maintenance of OCM.  Folate deficiency causes DNA strand breaks, diminished DNA repair capacity and aberrant DNA methylation.  Despite the recognised importance of this pathway in fetal development, current obstetric practice does not include routine measurement of folate, vitamin B12 and homocysteine to diagnose impaired OCM and determine individual micronutrient requirements.  There is an unmet need for a stronger evidence-based framework to underpin practice and policy for assessing OCM status and dietary supplementation with one-carbon nutrients during the periconceptional period and throughout pregnancy.  Thus, the aims of this project are: to establish the clinical utility of measuring red cell and plasma folate, vitamin B12 and homocysteine in the first trimester to identify women at risk of adverse pregnancy outcomes (i.e. preterm birth, fetal growth restriction, congenital abnormalities, preeclampsia, miscarriage and stillbirth); and to establish whether or not the early identification of high-risk pregnancies and targeted nutraceutical treatment throughout gestation reduces the prevalence of adverse pregnancy outcomes. The study is a randomised controlled trial with sub-stratification of low and normal OCM status women within each arm.  The successful completion of this project will provide Level I clinical evidence of the efficacy of personalised nutraceutical supplementation based on screening of OCM status to reduce complications of pregnancy.