Historical Perspective

At one time, it was widely held by most physicians that the uterus afforded a protective environment for the fetus, and the placenta served as a protective shield from the external environment. This belief was questioned in 1941 by Dr. N.M. Gregg, an Australian physician, who observed a high incidence of birth defects in women who contracted German measles (rubella) during the first 3 months (first trimester) of pregnancy. The susceptibility of the developing fetus to medications became tragically evident when women who took thalidomide in the first trimester of pregnancy gave birth to infants with limb defects. Thalidomide, a sedative, was marketed in Europe and Canada in the 1950s and prescribed to pregnant women to treat morning sickness. Fortunately, it was not introduced in the United States because the U.S. Food and Drug Administration (FDA) was not convinced of its safety. It was later found that thalidomide caused infants to be born with missing limbs or short, flipper-like limbs, and the drug was subsequently banned worldwide. The FDA’s cautious approach probably prevented thousands of similar birth defects in this country.


Many medications and chemicals can cross the placenta and, depending on their properties, can attain varying levels in the embryo and fetus. If the fetus is exposed to certain medications and chemicals, or a virus such as rubella, these agents can cause abnormal cell formation and growth. Something that causes cellular damage or abnormal cell formation in the fetus is teratogenic, and the term teratogenesisrefers to the production of congenital malformations, such as cleft lip and abnormal limbs, from in utero exposure to a teratogen.

In the absence of clinical studies of drugs in pregnant women, much of our information about the risks of medications in pregnancy comes from animal testing, empirical evaluation, and collection of data from reported cases. Although animal studies are useful and provide some insight into the potential adverse effects in humans, they by no means guarantee that a drug found to be safe in animals is also safe for humans.

Since 1975, the FDA has required pharmaceutical companies to include in their labeling a section on the drug’s ability to cause birth defects and other effects on reproduction and pregnancy. Moreover, all medications must be classified under one of the five categories that the FDA assigned as risk factors for drugs in pregnancy (see table).

Risk categories for medications used in pregnancy
AControlled studies show no risk to humans.
BAnimal studies have revealed no evidence of harm to the fetus; however, there are no adequate and well-controlled studies in pregnant women.
CAnimal studies have shown an adverse effect, but there are no adequate and well-controlled studies in pregnant women. Therefore, the risk to humans cannot be ruled out.
DStudies or observations have demonstrated positive evidence of risk to the fetus. The benefits of therapy may outweigh the potential risks.
XStudies or observations demonstrated positive evidence of fetal abnormalities, and the use is contraindicated in women who are or may become pregnant.

Psychotropic Medications in Pregnancy

All psychotropic medications cross the placenta in varying degrees. If administered during pregnancy, particularly during the first trimester, there is risk of teratogenesis with certain medications. Lithium has been associated with cardiac defects, and Depakote (divalproex sodium), used in the treatment of bipolar disorder, has a 1%–2% risk of spina bifida (incomplete formation of the spinal cord); these medications are assigned to the high-risk Category D. The benzodiazepines used for treating sleep disorders, including Halcion (triazolam), Dalmane (flurazepam), Restoril (temazepam), ProSom (estazolam), and Doral (quazepam), are in Category X and contraindicated in pregnancy. Most psychotropic medications, however, are assigned to Category C and have not been observed to cause birth defects, but risks in humans have not been ruled out.

Psychotropic medications can also affect labor and delivery. The adverse side effects of these medications may complicate pregnancy or affect the infant. For example, infants born to mothers taking benzodiazepines (e.g., Valium) may undergo withdrawal symptoms shortly after birth. These newborns are often observed to be flaccid and slow to respond after delivery.

Medications should be avoided, if possible, during pregnancy. However, when medications are discontinued, symptoms frequently recur, worsening preexisting psychiatric conditions. The physician and patient often face the dilemma of restarting the medication or seeking a safer, but perhaps less effective, alternative treatment during pregnancy. Not treating the mental condition during pregnancy also has significant risks for the mother and the unborn infant.

Treatment Considerations

The decision to administer medication during pregnancy must be based on informed consent from the patient. The physician should inform the woman of the potential risks of the medication and offer safer alternative treatment options, which may not include medications. Ultimately, the benefits of therapy must outweigh any potential risks.

Patients should be referred to the pregnancy section of the handout for the medication they are taking. In addition, patients can learn more about medications in pregnancy and breastfeeding at the following Web sites:

Perinatology.com (www.perinatology.com/exposures/druglist.htm)
American Council for Drug Education (www.acde.org/parent/Pregnant.htm)
Organization of Teratology Information Services (www.otispregnancy.org)