What you need to know about medication safety in pregnancy

When a patient inquires about a particular drug, it is important to gather the following information:

• When did she take the medication?
• Why did she take it?
• For how long did she take the medication?
• Did she take other medications, or any substances of abuse, at the same time?

A number of sources of information about potential teratogens are available.^3-5 These include national computerized databases that are accessible on the Web:

• National Library of Medicine (https://sis.nlm.nih.gov/enviro.html)
• pregnancy exposure registries (www.fda.gov/womens/registries/default.htm)
• Reproductive Toxicology Center (https://reprotox.org) (access requires a paid subscription)
• LactMed, National Library of Medicine guide to drug safety in lactation (https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT)
• Organization of Teratology Information Specialists (OTIS) (www.otispregnancy.org).

The last source (OTIS) consolidates teratology information nationwide and reports it by state or region. It also publishes a host of fact sheets on various drugs that may be useful to dispense to the patient during counseling. In addition, many teratogen information services or poison control centers (often at children’s hospitals) are available throughout the United States to serve specific geographic areas. And teratogen registries at pharmaceutical companies may provide limited information about newer medications.

The Physician’s Desk Reference (PDR) is a common source of information about the use of prescription drugs in pregnancy.³ But be aware that, to avoid liability, pharmaceutical manufacturers do not encourage use of their drugs during pregnancy unless the benefit clearly outweighs the risk. It would be unrealistic for them to market a medication for specific use during pregnancy because it would require considerable time and cost, and raise ethical objections, to conduct research in a vulnerable population that is limited in number.

Effects of agents used more than 40 years ago were reported by the Collaborative Perinatal Project or the Boston Collaborative Drug Surveillance Program.⁶ Those findings are often inconclusive, reflect bias in study designs, and do not help a clinician evaluate current medications or those less commonly prescribed during pregnancy.

The risks and experience associated with new drugs are usually not well explored in regard to pregnancy. As a result, older medications are more likely to be prescribed as maintenance therapy during gestation for the simple reason that they have a larger body of information regarding their effects. These older drugs may no longer be preferred once the patient delivers.

Most drugs are not teratogens

The TABLE lists adverse effects in the human fetus known to arise from exposure to specific drugs. The information comes largely from the Reprotox database, which was reviewed as recently as 2006, describes human data only, and is reported by first trimester (anomalies, abortion) and the second and third trimesters (fetal growth restriction, stillbirth, low birth weight, preterm delivery, immediate neonatal problems).⁷ Typical dosages of most drugs are not anticipated to increase the risk of congenital anomalies.

Most human data come from small series or case reports. Although these types of studies are helpful, they tend to be biased or reflect the pregnancy’s background risk of birth defects rather than the risk posed by a specific drug. In addition, case reports of malformation after prenatal exposure to a certain drug may involve exposures to other agents and a lack of uniformity of abnormalities, making the association between adverse effects and a single agent unlikely. Dissimilarities in the dosage and route of delivery also limit interpretation. for example, short-term intravenous or sublingual administration of a drug may pose a different risk than taking that medication orally or vaginally, in a lower dose, for a longer period, or at a different period of gestation.

Randomized controlled trials of drugs are rare during pregnancy, as are prospective cohort investigations. Because a control population is often impossible to identify, it becomes difficult to separate any heightened risk identified during use of the medication from the underlying disease. When the gravida has significant medical problems, it is important to assess the potential risk of a drug—or its omission—in her as well as her fetus. The lowest effective dose is preferred, but keep in mind that inadequate treatment may lead to minimal benefit and potentially greater risk to the pregnancy.

When reviewing or planning maintenance drug therapy, follow the same principles as you would in a nonpregnant patient. Be familiar with more than one medication for each disorder. Also be aware that some drugs may need to be prescribed at a higher dose or greater frequency to attain a therapeutic concentration in the expanded intravascular volume of pregnancy. In addition, side effects such as nausea, fatigue, and gastrointestinal disturbance may mimic symptoms arising from physiologic changes of pregnancy.

Assessing the risks associated with over-the-counter medications and natural food products is even harder. The PDR for Nonprescription Drugs, Dietary Supplements, and Herbs⁸ contains little or no information about the reproductive hazards of most of these products. Many agents contain multiple ingredients, both active and inactive, thereby complicating counseling about their risks during pregnancy. Although the recommended dosage is usually low, many product labels do not specify what it should be.