There are two reports this month from a very long-running study in Aberdeen which has been looking at mothers with epilepsy taking anti-epileptic drugs (AEDs) and health outcomes in their children.

Malformations of the spine, skull and brain, called neural tube defects, are some of the commonest types of serious malformation seen in children born to mothers with epilepsy taking AEDs. Scientists believe that the AEDs somehow interfere with how the mother's body breaks down folic acid leading to the malformations.

Folic acid
Folic acid, also called folate, is a B-vitamin, found naturally in some foods like spinach, beans and peas and in meats, especially liver. Folic acid is needed by the body to produce new cells (such as blood cells) and maintain them. Eating enough folic acid is especially important during pregnancy, as not having enough can cause serious damage to the growing baby, including neural tube defects. Taking supplements of folic acid around the period of conception have been shown to prevent 50-70% of these cases.

Folic acid is processed in the body by a number of enzymes. One of the most significant is called MTHFR. The genes that form the blueprint for this enzyme are not exactly the same in everybody, leading to two different forms of the enzyme. Some people have only the normal form (called the C form), some people only the mutated form (called the T form) and some people have a mixture of the two. The C form works better than the T form. People with only the T form are more likely to get the conditions caused by not enough folic acid, including neural tube defects.

Study results
Researchers led by Dr John Dean at the University of Aberdeen wanted to see whether there was any link between the probability of a woman with epilepsy having a baby affected by her AEDs, and which versions of the folic acid breakdown genes she has.

The researchers included 200 women in the study who had had children while they were taking AEDs to control their epilepsy. They collected information about the health of each of the 337 children born, and did a gene test on the mother to characterise her folic acid breakdown genes . They also tested the father of each child and the child themselves for these genes, to see whether their genetic input made a difference.

Only one gene was found to correspond with rates of malformation: the mother's version of the MTHFR gene. Which version the father and the child had made no difference. Mothers who had only the T form of the MTHFR enzyme were 3-4 times more likely to have a child damaged by AEDs than women with only the C form, or with a mixture of C and T forms. These findings were published in the American Journal of Medical Genetics (Part A) in October.

Though the children's MTHFR genes didn't correspond to their likelihood of being damaged by AEDs, Dr Dean and his colleagues did find that the children physically and developmentally affected by AEDs were more likely to have mutations in two other genes which code for enzymes in folic acid breakdown, called MTR and MTRR. The reasons for this, and what it means, aren't yet clear.

In a separate report in the journal Seizure in September, the same research group analysed whether the type of epilepsy a woman has is associated with her MTHFR gene type. They found that women with idiopathic generalised epilepsy were more likely than the average to have only the T form of the gene, the type that predisposes to having children with serious malformations (in addition to the potential for damage caused by AEDs). Other folic acid genes had no effect. Again, it's not clear whether this gene is involved in causing epilepsy, or how it might do this.