Pregnancy and Drug: Knowledge Gaps

by Food and Drug Administration (FDA)

(Page 2 of 3)

For now, what we have is a significant lack of adequate information on medications that sometimes must be used in pregnancy, such as antibiotics, and drugs to treat seizure disorders, hypertension, and psychiatric conditions, according to Sandra Kweder, M.D., co-chair of the FDA's Pregnancy Labeling Task Force. The FDA established the task force in 1996 to ensure pregnancy labeling of medical products is based on sound, scientific information.

More research has been done on hypertension, depression, and other conditions that commonly occur in women of childbearing age, but no areas could be considered well studied in pregnancy, Kweder says. "Hypertension is one of the number one problems women bring to pregnancy or develop during pregnancy," she says. "Yet the number of pregnant women who have been in clinical trials for hypertension is only several hundred."

This limits treatment options, says Stika. "We'll prescribe an older hypertension drug because its long history hasn't turned up serious safety concerns," she explains. "There may be other drugs that are more effective and better tolerated, but we don't use them because we don't know about their safety. Nor do we always know the appropriate dose for use in pregnancy."

Most people think that determining whether a drug causes birth defects is the major concern, but the knowledge gap doesn't stop there. "We also need more research on basic science and physiology in pregnancy," Stika says. There is a lot to be learned about how a pregnant woman's body changes from one trimester to the next, which can affect drug levels. Pharmacokinetic (PK) studies are needed to help determine accurate dosing, she adds. PK studies show how our bodies absorb, distribute, metabolize, and excrete drugs.

Pregnant women have increased blood volume, which forces the heart and kidneys to work harder. Drugs may be cleared through a pregnant woman's kidneys faster than normal. "In an effort to protect the baby, some doctors may err on the side of caution by giving pregnant women a lower dose than for non-pregnant patients," says the FDA's Kennedy. "But because of the physiological changes that occur in pregnancy, there may be times when pregnant women need a higher dose."

Making Treatment Decisions

So in the absence of adequate human studies, how do health-care professionals make decisions about drug treatment? "Generally, we use medicine when we have to and try to do the best we can," says Conover. "That means looking carefully at the data we do have."

Animal studies look for possible adverse reproductive effects in humans by giving animals higher doses of a drug. Experts also consider how a drug works and its likely effects, reported experiences with similar drugs, and adverse event reports.

Additionally, pregnancy registries have grown over the years. These registries follow women taking a certain drug until their pregnancy ends, allowing researchers to use the results to assess risks to mothers and their babies. According to a review of pregnancy registries published in the November/December 1999 issue of the Journal of the American Pharmaceutical Association, eight were recruiting patients as of October 1999, including the Antiepileptic Drug Pregnancy Registry run by Massachusetts General Hospital and the Organization of Teratology Information Services' (OTIS) Asthma Medications and Pregnancy Project.

The stage of pregnancy also influences clinical decisions. For example, after 24 weeks of pregnancy, the antibiotic tetracycline can cause permanent staining of a baby's teeth. And ACE (angiotensin converting enzyme) inhibitors, a group of drugs that treat high blood pressure, can damage a baby's kidneys in the second and third trimesters of pregnancy.

Depending on the risks, doctors may adapt treatment by switching a pregnant woman to a similar drug that is safer or prescribing medicine only during a certain portion of the pregnancy. "For example, if a depressed woman is taking lithium, she may be able to briefly discontinue the medication during the period of the baby's heart formation," Conover says. "Lithium use in pregnancy carries a small risk of fetal heart defects."

Revamping Pregnancy Labeling

Revamping pregnancy labeling is at the core of the FDA's efforts to better guide health-care professionals in making treatment decisions. Since 1975, the FDA has required drug labeling to include a subsection on a drug's ability to cause birth defects and other effects on reproduction and pregnancy. Products also must be classified under one of five letter categories — A, B, C, D, and X (see the chart "Current Categories for Drug Use in Pregnancy").

A public hearing in 1997 revealed that while this category system is a start, it's confusing and leads to oversimplification. "The letters imply a gradation of risk that doesn't necessarily exist," says the FDA's Kweder. People falsely assume that drugs labeled as category X pose the most risk in pregnancy and drugs labeled as A pose the least. But X reflects a benefit-risk judgment, and drugs in that category may be no more toxic than drugs called C or D.

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.