Link between folic acid supplementation in pregnancy, DNA methylation and birth weight in newborn babies

This state-of-the-art 'epigenetic' study, from scientists at Keele and Nottingham Universities together with doctors at University Hospital of North Staffordshire and Derby Children's Hospital, led by Professor William Farrell, Professor of Human Genomics, Institute for Science and Technology in Medicine at the University of Keele, and funded by the World Cancer Research Fund, showed that the levels of a critical metabolite of folic acid, homocysteine, in the blood of newborn babies is linked to modifications of their DNA (DNA methylation) in key genes and that such modifications might be used to predict birth weight.

Supplementation with the vitamin, folic acid during pregnancy is known to reduce the risk of neural tube defects such as spina bifida. It also protects against low birth weight, which has numerous short- and long-term consequences. It has been suggested that folic acid, though its metabolism to chemicals such as homocysteine, might secure these clinical effects via DNA methylation.

Researchers in the Fetal Epigenomics Group examined the relationship between folic acid supplementation and its metabolites on DNA methylation in human blood from the umbilical cord, using a state-of-the-art 'microarray' techniques which simultaneously examines methylation at 27,578 sites in the DNA.

Professor Farrell said: "It has been known for many years that folic acid supplementation is essential for women during pregnancy to reduce the risk of neural tube defects and low birth weight delivery. However, we had little idea as to how this worked. This study is the first to suggest that methylation of particular genes in the baby's DNA may be the key to unlocking the secret of the action of folic acid. "

"Now we have identified which genes might be the link between folic acid and birth weight, we have opened the door to research that may allow doctors to predict the likelihood of low birth weight with greater certainty. Furthermore, it sheds light on the underlying causes of low birth weight and offers the potential to intervene earlier to prevent poor pregnancy outcomes such as premature delivery and pregnancy loss."

The work, some of which was published recently in the scientific journal Epigenetics, illustrates the potential of DNA methylation 'microarray' technology to identify a new generation of clinical markers that will have a major impact, not only on the development of new therapeutic agents, but also on the way we manage a wide range of medical scenarios.

The Fetal Epigenomics Group comprises Professor Anthony Fryer, Keele Professor of Clinical Biochemistry, University Research Institute of Science and Technology in Medicine/University Hospital of North Staffordshire, Dr Richard Emes, Associate Professor in Bioinformatics, School of Veterinary Medicine and Science; University of Nottingham, Dr Khaled Ismail, Consultant and Senior Lecturer in Obstetrics and Gynaecology, Keele Research Institute for Science and Technology in Medicine/University Hospital of North Staffordshire, Dr Kim Haworth, Keele Research Institute of Science and Technology in Medicine, Dr Charles Mein, Barts and the London School of Medicine and Dentistry; Genome Centre, Dr William Carroll, Consultant Paediatrician, Derbyshire Children's Hospital, and Professor Farrel.