Pregnancy and Clinical Research

In the 1990s, amidst reports that women were underrepresented in clinical research, a key issue in science policy was whether women’s health interests were being adequately addressed. In response, the federal government established the Women’s Health Initiative to prioritize attention to women’s health needs and commissioned the Institute of Medicine to study the ethical and legal issues of including women in clinical studies. Much progress ensued: today, a majority of participants in clinical research are women. But one group has been left behind: pregnant women. Although the 1994 IOM report recommended pregnant women be “presumed eligible for participation in clinical studies,” many researchers and institutional review boards still regard pregnancy as a near-automatic cause for exclusion. Such resistance, understandably connected to concern for fetal well-being, comes at tremendous cost to both women and fetuses. As obstetricians well know, pregnant women often face serious medical needs. Chronic hypertension and diabetes each complicate nearly 40,000 pregnancies annually in the United States; psychiatric illness complicates an estimated 500,000 pregnancies; and cancer and autoimmune disease commonly occur with pregnancy. In fact, two-thirds of women take four to five medications during pregnancy. Yet only a dozen medications are approved by the Food and Drug Administration for use during pregnancy, and all are for gestationor birth-related issues like anesthesia or nausea. Any medicine taken to treat illness during pregnancy is used without data to guide effective and safe dosing. Pregnancy, it turns out, is an off-label condition. Given that pregnancy often changes the activity of drugs in dramatic ways, this is a problem. Recent studies reveal that pregnant women metabolize certain drugs such as amoxicillin so quickly that the drug cannot achieve therapeutic levels at usual doses. Other studies suggest that pregnancy alters drug metabolism in unpredictable ways. Further, with no data to reassure them, patients and providers sometimes halt medications—a decision that can present far greater risks than the possible risks of continuing them. Untreated depression in pregnant women, for instance, not only harms the woman but carries risks of prematurity, growth restriction, and postnatal complications for the fetus. Women suboptimally treated for asthma have worse pregnancy outcomes than those who control it with medication. And when a woman dies from cancer after pregnancy, neonatal health concerns are one thing, the wrenching implications of life without a mother quite another. Nor is the problem limited to wealthy nations. The treatment of malaria, for instance, which is responsible for up to 10,000 maternal and 200,000 infant deaths annually, relies on postmarketing surveillance for the safety and efficacy of antimalarials for drug-resistant disease. If we are to treat pregnant women’s illnesses effectively— something crucial to the health of both pregnant women and the children they bear—we must study medications in pregnant women. Certainly, guidelines for research in pregnancy must include safeguards and—as with any research involving those with a limited or absent capacity for consent, such as children—added protections for fetal interests. But mention of children is an important reminder: the pediatrics community has persuasively argued the need to conduct responsible research with children. Children are not just short adults— and pregnant women are not just women with big bellies. Some needed steps are straightforward, such as increased funding for research. Others will be more complicated: addressing liability concerns and developing guidance for IRBs, including, most critically, a framework for managing and limiting risk-benefit trade-offs between woman and fetus. Taking these steps will be challenging, but doing any less compromises fetal safety and relegates pregnant women to second-class medical treatment. Pregnancy and Clinical Research