The Risks (and Rewards) of Pills and Pregnancy

Any pregnant woman who has ever cracked open a medicine cabinet is familiar with the warnings against using nearly every kind of medication, including those sold over the counter, from the moment of conception onward. Yet each year in the U.S., some 500,000 pregnant women battle psychiatric illness, cancer, autoimmune disease, influenza and other conditions that require treatment. Leaving aside for a moment the issue of whether the benefits of certain drugs outweigh the risks to the baby, what is the appropriate dosage for a mom-to-be? Given the shifts in her metabolism, how much she should take is often anyone’s guess.

In the event of an anthrax scare, for example, the American College of Obstetricians and Gynecologists recommends that pregnant women take amoxicillin. But an obstetrics researcher in Seattle recently concluded there’s no way to give a pregnant woman enough of the antibiotic to be effective. Kidney function is so revved up during pregnancy that even in high doses, amoxicillin is excreted before it can work its magic. Think of it as trying to fill a bathtub with the drain open, suggests Jason Umans, an internist and maternal-fetal pharmacologist at Georgetown University. “In emergencies, you always hear, ‘Treat the pregnant women first!'” he says. “The joke should be ‘Yeah, how?'” (See how the FDA classifies drugs and their effects on pregnancy.)

To start formulating an answer, an élite group of some 30 doctors, ethicists, scientists and government officials gathered in Washington this spring to launch a movement they’re calling the Second Wave of clinical research. (The first happened in the early ’90s, when studies began to include large numbers of women.) A conclave of maternal-health advocates is now pushing for better information on how drugs affect pregnant women.

A recently as 20 years ago, some in the medical community were still using the male body as their research prototype and extrapolating for women. The approach, as summarized by Anne Drapkin Lyerly, an obstetrician and bioethicist at Duke University, was “If you happen to have boobs and a uterus, then we’ll adjust things.”

Because drugmakers now include women and, thanks to a 2003 law, children in appropriate drug studies, Second Wave organizers are hoping to push federal agencies to gather more data on pregnant women — what they’re taking and with what effects — and draw more blood samples so doctors can prescribe an effective dosage rather than winging it.

“Everyone thinks, Oh, my God, research on pregnant women! All kinds of ethical flags go up,” says Ruth Faden, director of the Berman Institute of Bioethics at Johns Hopkins University. “We don’t have to start with high drama.” There’s enough “low-hanging fruit,” she says, “that we could keep lots of medical researchers busy for a long time.”

Chronic illnesses like depression, diabetes and hypertension don’t magically disappear during pregnancy. And as women delay childbearing, more moms-to-be are struggling with cancer. So it’s hardly surprising that two-thirds of women take up to five drugs over the course of their pregnancy and labor. Yet only a dozen prescription drugs are approved for use by the U.S. Food and Drug Administration (FDA) during pregnancy, and they’re all pregnancy-related: drugs for inducing labor, for example, or epidural anesthesia. Which means patients with many common conditions face an excruciating dilemma: decline medication whose effects on a fetus may be largely unknown or take it and worry about the consequences.

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Some women who choose the latter approach have been asked to sign a raft of release forms so doctors don’t get sued if problems arise. Patty Sosnader, who received a diagnosis of Hodgkin’s disease at the end of her first trimester, rejected her doctor’s advice to abort and had to petition a hospital ethics board — and undergo psychiatric evaluation — in order to get the medications she sought. “It was very frustrating,” says Sosnader, 45, a logistics manager for Procter & Gamble in Worcester, Pa. “Everyone had their own opinion about what I should do, but there were no facts to support any of it.” (See how the FDA classifies drugs and their effects on pregnancy.)

Her son, whom doctors delivered five weeks early to spare him an additional round of chemotherapy, is now in fifth grade and is “just a regular boy” who plays football and in-line hockey and has a yen for adventure novels, says his mom, who just celebrated her 10th year cancer-free.

At the other end of the attitude spectrum are women like Diane Mello, who was newly pregnant when she learned she had melanoma in 2004. The 21-year-old from New Jersey underwent surgery but took a pass on chemo. Spooked by the lack of data on pregnant women, she chose her baby’s health over her own and died when her daughter was 9 months old.

Second Wavers know the idea of pharmaceutical research on pregnant women is a moral, not to mention legal, minefield, which is why they advocate starting small by analyzing the amount of medication circulating in the bloodstream of pregnant women who are already taking prescription drugs out of necessity. A program launched in 2004 by the National Institutes of Health (NIH) is doing a few studies of this kind in four cities — Galveston, Texas; Pittsburgh, Pa.; Seattle; and D.C. — where flyers placed in obstetricians’ offices seek pregnant women taking prescription drugs who are willing to stay in a hospital for at least 12 hours hooked up to an IV, ideally once a trimester. It takes a mighty altruistic person to volunteer for that. So far, fewer than 500 women have taken part in the studies.

Researchers could substantially broaden their data pool by piggybacking on the NIH-funded National Children’s Study, which is enrolling 100,000 women who are or plan to become pregnant, with the goal of tracking the development of children from before birth to adulthood. Tack on some questions and blood draws and suddenly you’ve captured a huge number of potential subjects. But expanding the study costs money. Second Wavers like Georgetown bioethicist Maggie Little have begun searching for members of Congress who are willing to take up their cause. “This issue could make somebody on the Hill a hero,” she says.

In the meantime, the FDA has proposed a massive overhaul of the guidance it gives on drug use by pregnant women. Prompted by a spate of birth defects caused by thalidomide, the notorious morning-sickness drug, the agency since 1979 has classified drugs in one of five pregnancy-related categories, with A being the safest and X being the least necessary (like Accutane, an acne treatment associated with birth defects). Category B has pretty positive safety data, and D encompasses chemotherapy and other drugs whose benefits may outweigh the risks to the fetus. And then there’s Category C, which covers the mushy middle. Karen Feibus, who oversees the FDA’s maternal-health team in the Office of New Drugs, estimates that this category contains nearly 70% of all drugs. In terms of safety data, “they can be very different, but many people think that a C is a C is a C,” she says.

That’s why the FDA is moving toward ditching these broadly defined categories in favor of a more narrative, evidence-based summary of what’s known about an individual drug and its effect on pregnant and nursing women. “People are very uncomfortable with shades of gray,” Feibus says, “and pregnancy is all gray.” Of course, Second Wavers are hoping that won’t always be the case.

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