Why pregnant women deserve drug trials

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It’s easy to gloss over health care disparities until they start really affecting you or your loved ones. When I became pregnant this summer, I discovered the dearth of information available about drug safety during pregnancy. (I wrote a little about it in this Slate article published in July.) Women who rely on medication get pregnant—for instance, one in eight pregnant women takes antidepressants, which could pose serious risks, as I’ve discussed elsewhere—and pregnant women develop complications that require medicine. Yet the only drugs that have been approved by the FDA for use during pregnancy are for gestation- or birth-related problems, not for conditions like depression, hypertension or infection. And if you ask two obstetricians for their opinions about a drug’s safety, they’ll sometimes give you two different answers, as I discovered when I looked into taking Sudafed for a nasty cold I had this fall.

Certainly, it seems unethical to expose a fetus to a potentially dangerous drug in a clinical trial—after all, it cannot consent. But isn’t it worse to expose a fetus to a drug without any safety data at all, and outside the structured trial setting, where there is no patient monitoring? Yes, clinical trials in pregnant women could be dangerous. But not having them is even more so, given that pregnant women have to take drugs anyway—and without any knowledge of how they might affect them or their unborn children. Remember the sedative thalidomide, which caused pregnant women to give birth to babies with missing limbs in the 1950s, and DES, a drug prescribed to prevent miscarriages that increased the risk that female babies would develop rare vaginal cancers? Might we have avoided these disasters, or at least lessened their magnitude, if thalidomide and DES had been tested in controlled clinical trials in pregnant women first?

Thankfully, we haven’t had any major disasters like these in decades, but the government still makes drug recommendations based on little data. Take flu shots: The CDC has been telling pregnant women to get seasonal flu shots since the 1960s, but the first randomized, prospective trial testing the vaccine on pregnant women and their babies was not completed until 2008—and it was comprised of just 340 subjects in Bangladesh. (Luckily, the trial suggests that flu shots are safe, although it only tracked the health of the babies for 24 weeks after birth.) For decades, then, the FDA’s recommendations and assurances about flu shots were not based on clinical trial evidence, but retrospective data, which is often flawed. “The agency said, ‘there’s so much risk, we won’t put you in a trial—but as soon as it’s approved in a different population, we’ll give it to you,’” explains Francoise Baylis, a bioethicist at the Dalhousie University in Canada. (Not that the FDA is entirely to blame—drug companies certainly have little interest in testing their compounds in pregnant women, a small population that could pose them serious liability risks.)

I struggled over the decision to get a flu shot myself. For one thing, last year in an article in the Atlantic, veteran science journalists Shannon Brownlee and Jeanne Lenzer raised questions over whether the vaccine actually works. And although pregnant women who catch the flu in the first half of their pregnancy are at an increased risk of giving birth to children who develop schizophrenia, given the timing of my pregnancy, I was at low risk for getting the flu then anyway—and I know from conversations with Caltech biologist Paul Patterson that there is a possibility that the vaccine itself confers this same increased risk. (For more about the link between prenatal infections, vaccines and mental illness, check out this feature I wrote in Scientific American MIND in 2008.) On the other hand, I also know that it could be dangerous to get sick in my third trimester, when I will be at an increased risk for serious respiratory problems. In the end, I decided to get the flu shot once I reached the halfway point in my pregnancy, when I felt the potential schizophrenia risk was minimal, and the shot could still (possibly) protect me towards the end of my pregnancy. Still, my decision was a gamble based on a lot of incomplete information.

It’s not just flu shots, though: pregnant women are taking more medicines than ever now, as they’re having babies later in life—when they tend to be on more drugs—and medical breakthroughs have made some pregnancies possible for the very first time. “We have people with cystic fibrosis who never in decades past would survive long enough to consider pregnancy, who are now living well into middle age and beyond,” says Ruth Faden, executive director of the Johns Hopkins Berman Institute of Bioethics. These women typically need to take medications throughout their pregnancy, yet no one knows their effects.

So what’s the solution? There isn’t a perfect one, but Baylis and Faden argue that there should be trials designed to test drugs in pregnant women who are going to be taking them no matter what. That way, structures are at least in place to collect data and look for adverse events. As for new experimental drugs, Baylis recommends incorporating pregnant women into later-stage trials, once the drugs have been shown to be safe and effective for other adults. “Instead of thinking of research as a risky activity,” she says, “we need to think of the continued off-label use of drugs [during pregnancy] as the risky activity.”

Citations:

Zaman, K., Roy, E., Arifeen, S., Rahman, M., Raqib, R., Wilson, E., Omer, S., Shahid, N., Breiman, R., & Steinhoff, M. (2008). Effectiveness of Maternal Influenza Immunization in Mothers and Infants New England Journal of Medicine, 359 (15), 1555-1564 DOI: 10.1056/NEJMoa0708630

Brown, A. (2005). Prenatal Infection as a Risk Factor for Schizophrenia Schizophrenia Bulletin, 32 (2), 200-202 DOI: 10.1093/schbul/sbj052

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