MILLIONS of women may be susceptible to miscarriage or having children with birth defects as a result of carrying genes for a common enzyme deficiency, research on mice suggests.
The enzyme neutralises free radicals, reactive chemicals that damage cells. So if human studies confirm the link, it may be possible to prevent some miscarriages and birth defects by reducing the levels of free radicals circulating in women’s bodies-by giving them antioxidants, for instance.
Miscarriage is thought to occur in at least 15 per cent of pregnancies. Many factors have been implicated as possible causes (see Table). But usually, doctors have few clues of the cause when individual women miscarry.
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Peter Wells and his colleagues at the University of Toronto have now thrown fresh light on the problem by studying mice producing low levels of an enzyme called G6PD. This helps maintain levels of glutathione, a peptide that detoxifies free radicals. Wells suspected that G6PD deficiency might pose a particular risk to developing embryos, which lack many of the other enzymes that protect against free radicals.
Female mice carrying two defective copies of the gene for G6PD had litters only half as large as normal when mated with males that also carried the defect. They also saw three times as many pups die during the period between birth and weaning. Further breeding experiments confirmed that it was the genes passed on to the fetus that determined the risk-fetuses able to produce G6PD tended to survive, even in the wombs of enzyme-deficient females.
Although rodents tend to reabsorb their embryos instead of aborting them, Wells believes the factors involved are relevant to human miscarriage and birth defects. “It’s a matter of urgency now to take these studies forward in humans,” agrees Lesley Regan, a specialist in miscarriage at St Mary’s Hospital in London.
About 400 million people, or nearly 7 per cent of the world’s population, have G6PD deficiency. But in some populations from Africa, Asia and the Mediterranean, the rate is as high as 65 per cent. The condition is thought to have been selected for in these populations because the mutation helps resist malaria. Like sickle-cell disease, which also protects against malaria, G6PD deficiency can cause anaemia.
Wells’s research also suggests that women who carry genes for the enzyme deficiency and who take a commonly prescribed anticonvulsive drug may face a particularly high risk. Because the drug phenytoin boosts levels of circulating free radicals, his team gave it to some of their experimental animals. This further increased the number of fetuses lost.
Barbara Hales, a pharmacologist at McGill University in Montreal, says this makes studies of pregnant women taking phenytoin, and other drugs that boost levels of circulating free radicals, a high priority. Wells is already planning to conduct a study of women taking phenytoin.
If the link with G6PD deficiency holds up, avoiding drugs like phenytoin may not be the only action women with the condition can do to minimise the risk of miscarriage. They might be treated with a precursor to the enzyme, or given antioxidants that help neutralise free radicals. But Wells sounds a note of caution: “If you get the dose too high, it might do more harm than good.”