The list of medications that women shouldn’t take in pregnancy keeps getting longer.

Earlier this month, the Food and Drug Administration strengthened warnings that expectant mothers who take topiramate (brand name Topamax), for migraines or to control seizures, have an increased risk of giving birth to babies with cleft lips or cleft palates.

Last month, the FDA advised doctors that babies whose mothers took antipsychotic drugs such as Haldol, Zyprexa, Seroquel and Abilify, could suffer withdrawal symptoms such as agitation and difficulty breathing and feeding for hours or days after birth. It also warned that terbutaline, an asthma drug also used to halt preterm labor, should not be used by pregnant women due to the potential for maternal heart problems or death.

Also last month, the Centers for Disease Control and Prevention warned that taking pain relievers containing opioids, such as Vicodin, OxyContin and Tylenol with codeine just before or in early pregnancy increased the risk of congenital heart defects, glaucoma and other problems.

Ever since the 1960s when thalidomide, a sleep aid and morning-sickness drug, was linked to more than 10,000 babies born with missing or shrunken limbs, it has been known that medications a pregnant woman takes can cross the placenta and affect her unborn child.

But determining what the impact might be for tens of thousands of medications is a Herculean task. The labels on most medicines have little or no information on how they might affect the mother or the fetus, other than advising to check with her doctor. Physicians are often baffled too, since conclusive data on safety in pregnancy don’t exist for the majority of prescription medications.

There is not much more known about the safety of over-the-counter drugs. Most experts believe that acetaminophen (Tylenol) is safe to use in all trimesters. But many advise pregnant women not to take aspirin, ibuprofen and some other nonsteroidal anti-inflammatory drugs (NSAIDs), particularly in the third trimester, due to the potential for excess bleeding and other labor complications.

Meanwhile, small studies have linked pseudoephedrine, a common ingredient in decongestants and other cold remedies, with a higher risk of gastroschisis, in which the baby’s intestines grow outside the abdominal wall. Antacids are generally safe, although sodium bicarbonate is absorbed into the bloodstream and can raise a woman’s sodium level.
There’s so little safety information because it is considered unethical to expose pregnant women and unborn babies to potential risks in randomized-controlled clinical trials used to test drug safety.

Yet millions of pregnant women take medications. Studies show that 64% use at least one prescription drug during pregnancy and, on average, women use three to five.
Experts agree that chronic conditions such as asthma, epilepsy, high blood pressure and depression can’t go untreated for nine months without posing risks to both mothers and fetuses. For example, if a mother has a severe asthma attack or prolonged seizure, the fetus could be starved for oxygen; untreated hypertension in a mother could stunt her baby’s growth or cause preterm labor.

So doctors must carefully weigh the benefits of a medication to both mother and baby against the often uncertain risk that it might interfere with fetal development. Many of the most serious medication risks occur when a baby’s vital organs are forming in the first trimester, often before a women knows she’s pregnant.

To manage the uncertainty, the FDA in 1979 set up a system rating drugs’ safety in pregnancy based on what data exist. Very few drugs are in category A, meaning that there are large, well-controlled studies demonstrating safety for human fetuses. Those in category B are believed safe but have less evidence.

More than 60% of drugs are in category C, with no information on the risk to humans. Drugs in category D have been shown to pose some harm to human fetuses, but the potential benefits may outweigh to risks. Drugs in category X have either such a clear risk of harm or so little benefit to pregnant women that there is no justification for their use.

The FDA is also drafting new guidelines to help drug makers find ways to include pregnant women in clinical trials. “Pregnant women get sick, and sick women get pregnant. This is a reality,” says Dr. Feibus.

In the meantime, the FDA has encouraged drug companies and other groups to set up registries to monitor how pregnant women who do opt to take prescription medications and their babies fare. More than 40 such registries are up and running, and some have alerted the FDA to some dangers drugs pose to fetal development.

In some cases, mothers and doctors can opt for a substitute medication for the condition that’s thought to pose less risk. There is a wide variety of antidepressants, for example, with different associated risks. The popular category called serotonin-reuptake inhibitors (SSRIs) is generally considered safe, although some studies have linked a few of them to a higher risk of congenital heart defects when taken in the first trimester, and infants suffering withdrawal symptoms such as irritability and seizures for more than a week after birth.

All this information creates some hard choices for mothers-to-be and their health-care providers. Sarah Lieberman Weisz, 36, of Chicago, who takes Wellbutrin, a category C drug for depression, talked it over with her midwife before her first pregnancy. Even though several other antidepressants are considered to be safer during pregnancy, Ms. Weisz had tried others and was reluctant to switch.

They found some small-scale studies showing no adverse effects on human fetuses, and no large studies contradicting them. “To me, that was enough. We decided that the risk of switching and suffering more depression or new side effects was greater than a possible risk to the baby,” says Ms. Weisz, who had a healthy baby boy in 21 months ago and a healthy, baby girl last month.

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