Babies normally spend 40 weeks in the womb, but some can survive even if they are born 15 or 16 weeks early. However, their lungs lack enough of a substance called a surfactant to breathe unassisted. So since the 1970s, doctors have been injecting women at risk of having a very premature baby with synthetic glucocorticoid drugs, such as betamethasone, which hasten the development of a fetus's lungs.
A single dose cuts the death rate of such babies by up to 40 per cent. Because doctors think the drug works best when given within a week of birth, a baby who is not as premature as expected may be exposed to repeated doses. "Eleven courses of glucocorticoid is not unheard of," says fetal physiology specialist Stephen Matthews at the University of Toronto, Canada.
Now Matthews and his team have found alarming side effects of the drug in guinea pigs, which have similar placentas to humans and give birth to similarly mature offspring. They gave guinea pigs the equivalent of three injections of betamethasone, and compared them to a group given either three injections of saline, or nothing at all. Offspring of cavies given the drug showed some abnormalities compared with the other groups, such as hyperactivity. Human babies whose mothers are given multiple doses of betamethasone also show signs of hyperactivity, as well as growing more slowly.
But the drug affected the next generation of guinea pigs too. When affected female offspring were mated with normal males, their young also had physiological and behavioural abnormalities. Male 25-day-old pups, the grandchildren of the pregnant guinea pig given the drug, showed little interest in exploring a new environment, while females were hyperactive and made strange vocalisations, says Matthews.
John Newnham of the University of Western Australia in Perth, a specialist in the treatment of premature babies, says the findings are "terrifying beyond comprehension". The good news, he says, is that the side effects might not happen after one dose of the drug. A study earlier this year looking at 31-year-olds whose mothers had been given just one dose found no major effects. Matthews, who presented his findings to a conference on the developmental origins of health and disease in Toronto last month, suspects the drug, especially in repeated doses, may cause subtle epigenetic changes in the fetus, altering how its DNA is expressed. Such changes are known to be passed down the generations (New Scientist, 9 August 2003, p 3).