New Scientist
December 3, 2005


By Alison Motluk

Doctors treating a woman at risk of having a premature baby may
inadvertently be affecting her future grandchildren as well. A study
in guinea pigs suggests that a drug commonly given to pregnant women
to help their babies mature enough to survive can also affect the
brains and behaviour of their grandchildren too. The finding raises a
difficult dilemma for doctors, for while the drug undoubtedly saves
lives, its side effects could last for generations.

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).

Copyright 2005