This is a story about good intentions causing possible harm.
Drug companies have historically excluded pregnant women from medication trials to prevent harm to the fetus. Even when research may not involve giving medication, investigators have avoided research in pregnant women because of legal risk, ethical concerns, and the hormonal and physiological complexities of pregnancy.
Unfortunately, the unwillingness to include pregnant and breastfeeding women in clinical research trials has led to a worrisome lack of data about safety and long-term outcomes of medication exposure, in pregnancy and through breast milk.
As a perinatal psychiatrist, I often hear questions from patients on the safety of medications in pregnancy and breast milk. Of course all women want a healthy pregnancy and the assurance of a healthy baby. If something goes wrong—as it does with three percent of healthy pregnancies even when the mother isn't taking prescription medication—no woman wants to worry whether it is the result of something she did.
Still, in the United States, 70 percent of women take at least one prescription medication beyond a prenatal vitamin in pregnancy. An estimated 25 million take four or more prescription medications during pregnancy. Although over-the-counter and herbal remedies are commonly taken in pregnancy and considered "safer," they are less regulated by the Food and Drug Administration than prescription medications. Broadly, prescription and non-prescription pills lack information on risk or optimal dosing for pregnant women.
The risk of medication exposure to a fetus in utero must be weighed against the risk of an untreated illness in pregnancy, one that may be detrimental to the fetus as well as the mother.
For women who choose to breastfeed, as recommended by the U.S. Surgeon General, it is important to know which medications are transferred in the breast milk and how they affect the child long-term. Research on breast milk transfer of medications and long-term outcomes is even more limited than data on medication exposure in pregnancy. Although tests such as milkscreen assess the presence of alcohol in the milk, the accuracy of such over-the-counter tests remains in question.
For these reasons, research needs the participation of pregnant women, women who are breastfeeding, and women seeking to get pregnant. Yes, this stance is controversial.
What has always been evident is that pregnant women are not immune from illness—pregnant women get sick, and sick women get pregnant.
The current global fear over the Zika virus presents a very real and timely case study: Should pregnant women who have been exposed to the disease take a drug if that drug would minimize or prevent the risk of microcephaly, a condition linked to fetal exposure to the virus? To inform effective treatment for any woman who might encounter the virus in the future, it would be best to observe all women who are known to have it—while also observing the long-term development of their children.
Clearly the study of Zika is more complex than the study of better-characterized illnesses such as depression and diabetes, given that 80 percent of those stricken with Zika may not have symptoms, and the test to identify it is most useful only in the first week. Long-term, structured observation of the women and their offspring might aid us in minimizing risk to the fetus and optimizing wellness for mother and baby in the future. Similar observation and follow-up will be important to determine the outcomes of a Zika vaccine for pregnant women.
The risk of medication exposure to a fetus in utero is a significant concern. But it must be weighed against the risk of an untreated illness in pregnancy, one that may be detrimental to the fetus as well as the mother.
Visualizing a pregnant woman as a guinea pig for research may be disconcerting. But a woman who commits suicide because she didn't have her antidepressant, or seizes because she doesn't have her anti-epileptic medications, or experiences a life-threatening asthma attack because the steroid inhaler is withheld—these are scenarios that might arise if we deny certain medications to a woman during pregnancy.
Often women enter pregnancy with chronic conditions such as asthma, seizure disorder, or diabetes, which require continued treatment. For such illnesses, lack of treatment in pregnancy is detrimental to the health of the mother and the baby. In severe illnesses, lack of treatment can be the difference between life and death. Whether the onset of an illness is prior to pregnancy or during, a pregnant woman is advised to take a prescription medication only when the benefits of treatment outweighs the known risks of the medication or the untreated illness.
Most medication labels direct the pregnant or breastfeeding woman to visit her doctor and determine whether or not she should medicate during pregnancy. Because of the limited research, physicians often feel ill equipped to provide data that balances the risks and benefits of treatments in pregnancy. Additionally, women are bombarded by misinformation on the Internet and find it difficult to balance the risks and benefits of medication in pregnancy.
Fortunately, there is progress.
For the past 35 years, medications have required a pregnancy label of A, B, C, D, or X. The category A suggests a low risk during pregnancy, while X suggests the medication may cause fetal malformation when used during pregnancy. Categories B through D represent graduating levels of risk, more often determined by studies in animals.
That pregnancy categorization, though, was too simple and misleading, classifying some drugs in safer categories despite a lack research on the drugs' effects in human pregnancy. Because of the limited research in human pregnancy and medication exposure, it had proven difficult for physicians to lead patients through choices about the reproductive safety of various medications.
As of June 2015, the old FDA pregnancy categories of ABCDX became obsolete with the emergence of the Pregnancy and Lactation Labeling Rule. The PLLR will require findings from both animal and human testing, as well as the severity and incidence of adverse fetal outcomes and clinical considerations for dosing the medication during pregnancy.
A pregnant woman should not agree to be a subject in a study without proper consideration, of course. Fortunately, there are now pregnancy exposure registries that collect information to help women and health-care providers learn more about the safety of medication in pregnancy. Women who enroll in the study have chosen to continue medication treatment and are not given medication as part of the research protocol. Exposure registries or observational research studies in pregnancy follow women through pregnancy and postpartum. These studies are designed to evaluate pregnant women and infant outcomes.
For women who—with the help of their physician—decide that the benefit of medication outweighs the risk, monitoring should be mandatory. This monitoring can assess how well the medication controls the symptoms of the illness across pregnancy, how much is transferred to the baby, and long-term outcomes for exposed children. Observational assessments and developmental exams should be the required protocol for every pharmaceutical company bringing a new drug to market for an illness that a pregnant woman might experience.
She and her baby have a right to know.