August 16, 2013
By David Martin
|Carl Weiner, M.D.|
One of the most notorious prescription drug debacles in recent history involved the German-developed medication thalidomide. Doctors in Europe first prescribed thalidomide in the late 1950s to treat anxiety, insomnia and, in pregnant women, morning sickness. Thalidomide was withdrawn from the market in the early 1960s when doctors discovered that it caused devastating birth defects. About 10,000 children around the world were born with major malformations because their mothers had taken the drug during early pregnancy.
In the wake of the disaster, the U.S. Food and Drug Administration (FDA) created a "Pregnancy Risk Factor" grading system for medications. Drugs now receive one of five grades — A, B, C, D or X — based on what's known about the risk they pose to a developing fetus. These grades are typically assigned when the drug is first released onto the market.
The system has limits. Two-thirds of all drugs sold in the United States are classified as Category C. The FDA says drugs in this category should be taken if the benefits outweigh the risk — a not particularly helpful recommendation.
In addition to carrying vague warnings, drugs can be slow to find their way into Category X, considered to be the most potentially harmful (thalidomide is Category X). For example, this past spring, the FDA advised that pregnant women should not take the anti-seizure medication valproic acid. But obstetricians have been warning of the dangers of valproic acid for years.
"We've known for decades that this drug causes birth defects," says Carl Weiner, M.D., an obstetrician and expert in maternal-fetal medicine. "We know that there are other drugs that we can use in pregnancy that have a better safety profile from the standpoint of the fetus, but they might not be as effective in controlling the mother's seizures."
Weiner, professor and the Kermit E. Krantz Chair in Gynecology & Obstetrics at the University of Kansas School of Medicine, says the use of medication during pregnancy is a neglected area of research. Only a few drugs are tested on pregnant women. In fact, in 1977, the FDA excluded all women of childbearing age from early phases of clinical trials. The decision was overruled in 1993. Still, much of the knowledge of a drug's impact on pregnancy — and pregnancy's impact on a drug — is derived from animal tests, epidemiological studies and registries of women who take medication and volunteer to provide information during and after their pregnancies.
"The art of medicine is based on relative risk, and it's no different if we're talking about a pregnant woman," Weiner says. "Because this information has been hard to come by, because it was poorly distilled for use, physicians frequently tell women, ‘Stop all your medicine.' But the truth is, many of those medicines were needed and stopping them posed a risk to the mother and the pregnancy."
Weiner has worked to educate physicians about medication use pregnant and breast-feeding patients. He is the co-author of a textbook, "Drugs for Pregnant and Lactating Women," about to enter its fourth edition.
Between updates, Weiner began to think about taking the material in the textbook and making it accessible to a wider audience. He found a professional lay medical writer, Kate Rope, who helped him translate the updated information into an affordable book for patients. The book, "The Complete Guide to Medications During Pregnancy and Breastfeeding," was published this past April.
The A-to-Z directory starts with acarbose and ends with zolpidem. Each entry describes how the drug works, how it affects the mother and her baby, its safety while breastfeeding, any reasons for avoiding it, the potential interactions and a "bottom line" assessment. The guide, for instance, notes that acetaminophen is the "pain reliever of choice in the first trimester if one must be used."
Weiner hopes that women will use guide as a springboard for a discussion with their health care providers. "A book is frozen in time," he says. "New information comes out all the time. But they could use what we are providing them as a starting point to question whether a particular drug was safe for them."
One challenge for Weiner and other obstetricians is that women of childbearing age are more likely to be taking medication than they were in the past. "We live in a far more medicated society than we did 20, 30 years ago," Weiner says.
For instance, one in 10 Americans now takes an antidepressant medication. Drugs that target the neurotransmitters related to mood have been associated with birth defects and behavioral abnormalities. But untreated depression poses risks, as well. "A woman who cannot function because of the depth of her depression needs medication," Weiner says. "She's not going to help her fetus if she's sick."
In fact, very few medications are considered perfectly safe. Less than 1 percent fall into Category A ("possibility of fetal harm appears remote"). With the rest, women and their health care providers need to work to find a balance between the perceived risk and benefit.
Weiner acknowledges the ambiguity can be frustrating. "We have a tendency to think in black and white terms," he says. "At least in my profession, black and white is the rarity. We have a lot of gray."
One sure way to improve the outcomes of pregnancies is to plan for them. Weiner wishes that more women made a conscious decision to get pregnant. With an unplanned pregnancy, the fetus is more likely to be exposed to drugs and environmental toxins that have adverse effects.
An unplanned pregnancy is also a missed opportunity for preconception care, which has been shown to improve a woman's chances having a having a healthy baby. Weiner would be happy if he met more new patients before the pregnancy has begun.
"If we were proactive, we could really change a lot," he says.
Dr. Weiner discussed breast-feeding with other guests on the KCUR-FM program "Central Standard" on Aug. 15. A podcast of the program is avaialable at this site.