Doctors weigh risks of drugs in pregnancy

Prescriptions: The stakes are high and information is scanty when an expectant woman needs medication.

Medicine & Science

April 12, 2004|By Erika Niedowski | Erika Niedowski,SUN STAFF

In the 1960s, women who used the drug thalidomide to relieve morning sickness learned a terrible truth: It could cause major malformations - including missing arms and legs - in their children.

Expectant mothers who took DES found out a decade later that the synthetic estrogen was linked to a rare type of vaginal cancer in their daughters.

Those being treated today with the acne medication Accutane are strongly warned not to become pregnant while taking it; it too can cause birth defects.

Now, researchers are questioning the safety of yet another drug - one commonly prescribed to halt pre-term labor.

Although studies of terbutaline offer only preliminary evidence that it could leave children at risk for learning and behavioral problems, the findings highlight an issue that physicians have pondered for decades: What drugs are safe for women carrying children?

"There's always concern about any medication we give to mom, and any potential long-term fetal side effects," said Dr. Mary Jo Johnson, a specialist in maternal-fetal medicine and chief of obstetrics at St. Joseph Medical Center.

"Most, if not all, drugs are not tested on pregnant women. [But] if, as obstetricians, we could only use FDA-approved drugs for pregnancy, we would have nothing to use."

Indeed, some medications, including antibiotics and antiseizure drugs, often have to be prescribed during pregnancy even when there's no body of scientific evidence showing they're safe, in the long run, for babies.

The alternative is leaving the mother's underlying illness or condition untreated - a measure that poses obvious dangers of its own.

"If a patient is in pain, we give painkillers. If a patient has an infection, we give antibiotics," said Dr. Helain Landy, interim chairwoman of obstetrics and gynecology at Georgetown University Hospital.

"We don't try and prescribe unless we feel we need to prescribe," she said. "Certainly, we're all very attuned to the mistakes that were made with DES and then with thalidomide. We have to be very cautious.

"I think you have to make an intelligent decision with your care provider, weighing the risks of the drug vs. what you're trying to treat."

The drug at issue now - terbutaline - is approved by the Food and Drug Administration only as an asthma treatment. But it's widely given to women in premature labor.

In 1997, the FDA issued a "Dear Colleague" letter cautioning doctors about prescribing the drug to pregnant women for prolonged periods. The agency said terbutaline had been proved effective only at staving off labor for 48 hours or less - and its effects on the fetus were largely unknown.

Starting with animals, a team of scientists at Duke University Medical Center set out to investigate. In February, the group reported in the Journal of Pharmacology and Experimental Therapeutics that terbutaline had chemically altered and damaged the brains of rat fetuses and could explain the higher incidence of cognitive problems in the offspring of women treated with the drug.

Last month, many of the same researchers followed up with a report in another journal that terbutaline might leave children's brains particularly vulnerable to the harmful effects of other chemicals, including pesticides.

They exposed rats first to terbutaline, then to a common insecticide called chlorpyrifos, which is used to combat agricultural pests and termites, among other things.

They found damage to the animals' brains in areas that controlled functions ranging from intelligence to mood, appetite and movement, said Theodore A. Slotkin, professor of pharmacology and cancer biology at Duke, who was involved with both studies.

"You could see the biochemical evidence of the damage early on," he said. "The functional and structural changes emerged or were evidenced in adolescence or adulthood."

Still, the findings are far from conclusive. And, for that reason, some clinicians are unwilling to write off a treatment that can help hold off premature birth - which itself is a serious risk to children.

"The problem with this research and with all the drugs - not just this one but all the drugs that are used in the arena of pre-term labor - is that the largest risk factor for abnormal neurological development is prematurity," said Dr. Frank Witter, director of labor and delivery at the Johns Hopkins Hospital.

"It's very difficult to take one study in isolation and say, `Gee, this is something we shouldn't use,'" he said. "You have to look at the totality of information that's available to us and, each time, reassess the balance of risk to benefit. And, at this point, the benefit still outweighs the risk."

Drug companies are almost universally unwilling to test their products on pregnant women because of liability concerns. Conforming to standard practice, terbutaline's manufacturer, aaiPharma, even notes in its package insert that the product is not approved and should not be used for pre-term labor.

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