Halfway through her third pregnancy, Liz Diament, a 33-year-old art curator from Silver Spring, MD, developed an itchy rash all over her body. When she visited a dermatologist and asked him to look at the rash, he whipped out a handheld device and tapped on some keys. "Oh, well," he said, "The drug I thought would help most is a C, so we'll have to talk about that."
Diament's doctor was referring to a five-letter rating system established almost 30 years ago by the Food and Drug Administration (FDA) to help doctors determine whether a drug poses a risk to a fetus. Category C means that no studies have been done, or that animal studies have shown a risk to the fetus but because there haven't been follow-up studies in humans, "risk cannot be ruled out."
Diament decided to forgo the drug, and luckily, the rash eventually went away. Many women, however, have no choice but to take medications during their pregnancy to treat chronic conditions (such as asthma or epilepsy), pregnancy-related bacterial infections, or severe allergies, says Sheila Weiss Smith, Ph.D., an associate professor at the University of Maryland's School of Pharmacy.
The average woman will take three prescription drugs during pregnancy, according to Smith. Most of what is known about the safety of these medications in pregnant women is based on animal studies, which aren't necessarily predictive of what will happen in humans, says Gideon Koren, M.D., director of Motherisk, a research and consulting service based at the Hospital for Sick Children in Toronto, that tracks the effects of drugs during pregnancy and breastfeeding. More often than not, the safety of a drug during pregnancy is based on both a degree of guesswork and a hope that it won't harm the fetus.
The Trouble With Testing
Over the last decade, many obstetricians and researchers have grown frustrated with the lack of data available on drugs that are often used in pregnancy. At a meeting in Washington, D.C., convened by the FDA and the National Institutes of Health (NIH) on the proper dosing of drugs during pregnancy, some researchers complained that drug companies call doctors to find out about available data on the safety of a drug on a fetus, but don't conduct enough of their own studies.
"We want to get the data but are leery of doing studies," says Bert Spilker, M.D., Ph.D., former senior vice president of scientific and regulatory affairs at Pharmaceutical Research and Manufacturers of America (PHRMA). "We don't want to put women at risk unnecessarily," explains Dr. Spilker. "What we think is reasonable is that we collect data on pregnant women taking a drug and put the information on the package label so that women can talk to their doctors and make an informed choice."
Doctors involved in both research and advocacy efforts say the significance of having up-to-date, easily accessible information on the safety of drugs during pregnancy cannot be overstated. At the FDA/NIH meeting, participants listened to a report of a young woman who stopped taking her asthma medication while pregnant and subsequently died of an asthma attack before the baby was born. "Without information, many women simply refuse to take the drugs, not realizing the harm they can cause themselves and their baby," says Marietta Anthony, vice president for women's health research at the Arizona Health Sciences Center."
A Role for the Government
To meet this need for information, the government has stepped in with multiple efforts and agencies. For example, the FDA awarded two research grants -- unusual for the agency -- to university medical centers to study the effects of blood pressure drugs commonly used in pregnancy. In addition, the Centers for Disease Control and Prevention (CDC) launched the National Center on Birth Defects and Developmental Disabilities to study causes of fetal defects, including the effects of drugs during pregnancy, according to the center's founding director, Jose Cordero, M.D. And the Council on Family Health, a nonprofit organization that works with the pharmaceutical industry, teamed up with the FDA to launch a public awareness campaign to educate women on the safe use of medications and supplements before, during, and after pregnancy.
Even more important, the FDA has been working to do away with the current rating system and instead provide much more detailed information on what is known about a drug's effect on a fetus or a breastfed newborn. But Dianne Kennedy, the FDA’s MedWatch director, cautions it could take several years before any proposal for reform becomes policy.
While the proposal may change somewhat as it goes through the review process, Kennedy says drug companies will likely have to expand the section on each label about what is known of a drug's effects during pregnancy and breastfeeding. It would include references to all available studies as well as specific instructions for doctors, such as waiting until after the first trimester (when most of the fetal organs are formed) before using certain drugs.
The FDA is also proposing guidelines that would require companies to provide periodic reports on positive and negative experiences in women who are pregnant or breastfeeding. "In the past, we've waited for companies to issue spontaneous reports of bad outcomes," says Sandra Kweder, M.D., deputy director of the FDA’s office of New Drugs. "This rule would require a proactive approach."
What We Know Now
The FDA's plan is commendable, but at least ten million babies will be born before the proposed regulations make it off the drawing board. Until then, there is already information that's available to help women and their doctors make decisions on what drugs to take during pregnancy, the proper dosage, and when to take them.
Sources such as Motherisk, the Organization of Teratology Information Services (a network of groups that monitor the effects of substances on the fetus), the FDA, and the CDC will provide information to pregnant women or their doctors. These organizations often have knowledge of current research from government studies, as well as from smaller studies conducted by private obstetricians who observe how patients and their newborns respond to medications taken during pregnancy.
While data has been slowly accumulating for years, many researchers say that studies on pregnant women with AIDS helped push research along on many other drugs. According to the CDC, many anti-retroviral drugs given during pregnancy and intravenously at delivery now prevent the perinatal transmission of the virus.
In the past, says Dr. Spilker, most physicians tended to take a conservative approach and caution women who were on long-term medications to stop taking their drugs during pregnancy. Today these women can usually work with their obstetricians and specialists to develop a treatment plan to maintain the health of both baby and mother. Under the advice of several doctors, Jean Halbauer, 37, of Valhalla, NY, changed epilepsy medications or drug dosages during each of her three pregnancies, and is now the proud mother of three healthy young children.
The Need for Research
Drugs for chronic conditions during pregnancy have gotten a great deal of attention, but the truth is that information is needed on nearly every drug, says Smith. That's because about half of all pregnancies are unplanned, which means that a woman may be pregnant and taking almost any medication during the early weeks before she learns that she's pregnant.
Also essential is information on exactly what doses of a drug are necessary during pregnancy, says Nancy Green, M.D., medical director of the March of Dimes. Dr. Green says that many doctors are inclined to reduce the dose of a drug during pregnancy to lower the chance of harm to the baby. But changes in blood flow and hormone levels may actually mean that a dose has to be increased during pregnancy to remain effective. More research on basic physiology in pregnancy is needed, according to Catherine Stika, M.D., associate professor of obstetrics and gynecology at Northwestern University in Chicago. Dr. Stika says there is much to be learned about how a woman's body changes from one trimester to the next, which can affect how pregnant women absorb, metabolize, and excrete each drug.
Having good data empowers women to get the treatment they need, says Dr. Green. Case in point: The FDA switched an asthma drug, the Pulmicort Turbuhaler, from category C ("risk cannot be ruled out") to category B ("no evidence of risk in humans") after data on more than 2,000 women who had used it during pregnancy showed that the drug did not increase the risk of birth defects.
The switch was important news to Debbi Fernandez, a social worker from New York City who was thinking about trying to conceive her first baby and had recently begun using the Pulmicort Turbuhaler. "The drug has been so effective that I can run up a full flight of stairs to the train without wheezing," says Fernandez. "My doctor was already recommending that I stay on it, and the fact that there are published studies to back that up makes me feel so much more confident about staying on the drug."
Before taking any drug -- prescription or over-the-counter -- talk to your doctor. The times to be most cautious about medication are during the first trimester of pregnancy (when organs are being formed) and during the last two weeks, when final development in utero takes place, according to Donald Sullivan, Ph.D., associate professor of pharmacy practice at Ohio Northern University and author of The Expectant Mother's Guide to Prescription and Nonprescription Drugs, Vitamins, Home Remedies, and Herbal Products (Macmillan). Listed below are drugs your doctor may recommend to treat specific conditions during pregnancy.
Acetaminophen, the active ingredient in Tylenol, is the drug of choice for treating headache and fever during pregnancy, says Gideon Koren, M.D., director of Motherisk, a research and consulting center on the safety of drugs in pregnancy. Aspirin is never recommended in pregnancy.
Cough and Cold
Even if you've used over-the-counter products during a previous pregnancy, check with your doctor before taking anything, as information may have changed, advises Dr. Koren. It's also important to see a doctor because a persistent cold may actually be an infection that requires an antibiotic. To treat a stuffy nose, Sullivan recommends a short-acting nasal spray for a few days, as only two percent of the drug is absorbed in the body. Be sure to check with your doc first.
Asthma and Allergies
Many asthma drugs have been shown to be safe in pregnancy, especially inhaled medications, which are less likely to reach the baby, says Michael Schatz, M.D., chief of allergy at Kaiser Permanente in San Diego. For allergy relief, Benadryl appears safe for occasional use, although it may make you drowsy, says Sullivan.
If you have a preexisting skin condition, check with your dermatologist before continuing to use any product during pregnancy. The acne medication Accutane, for example, can cause severe birth defects. To alleviate the itching that can be common during pregnancy, use a moisturizer that does not contain any medication or try soaking the affected area in an oatmeal bath.
About 20 percent of reproductive-age women are diagnosed as being clinically depressed, says Dr. Koren. And up to 15 percent of women will become depressed during pregnancy. Antidepressants in the selective serotonin reuptake inhibitor family (such as Prozac, Zoloft, and Paxil) are considered generally safe during pregnancy, though most is known about Prozac, according to Sullivan.
Fortunately, both the government and advocacy groups are taking major steps to learn more about the effects of medications during pregnancy and to do a better job of disseminating the information that is already available to pregnant women and their doctors. You can become an advocate for your own health by seeking out this information before taking prescription or over-the-counter drugs during pregnancy.
Francesca Lunzer Kritz is a freelance writer.