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 teratogenesis
refers 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
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|
|A||Controlled studies show no risk to humans.|
|B||Animal studies have revealed no evidence of harm to the fetus; however, there are no adequate and well-controlled studies in pregnant women.|
|C||Animal 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.|
|D||Studies or observations have demonstrated positive evidence of risk to the fetus. The benefits of therapy may outweigh the potential risks.|
|X||Studies 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),
and ProSom (estazolam), 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.
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
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:
American Council for Drug Education (www.acde.org/parent/Pregnant.htm)
Organization of Teratology Information Specialists (www.otispregnancy.org)