Drugs Should Be Tested on Pregnant Women. It’s Unethical Not To.

Health and medicine explained.
July 24 2013 12:01 PM

Is It Safe to Take Medication While Pregnant?

It isn’t unethical to test drugs on pregnant women. It’s unethical not to.

Woman in hospital.
Excluding pregnant women from drug trials on the basis of safety may actually endanger a greater number of pregnant women.

Photo by Naomi Bassitt/Thinkstock

When we were planning our honeymoon this year (which at that stage was already a babymoon), we had our eye on Burma. A friend lived in Yangon, and the country looked interesting. But parts of Burma have malaria that is resistant to chloroquine, the preferred drug for treating and preventing the disease. I asked my doctor about other anti-malarial medication, and she said there wasn’t enough existing evidence about other drugs to confirm that they were safe for pregnant women.

We ended up choosing a malaria-free vacation destination instead and didn’t think anything more about it. But for pregnant women with chronic or newly acquired conditions, choices about whether to take medication and what kind can have real risks and consequences, and doctors are often in the dark about exactly what these repercussions are.

With more women getting pregnant later in life, pregnancies are often accompanied by chronic conditions such as diabetes, asthma, depression, and lupus. In fact, a recent article in the Drug and Therapeutics Bulletin noted that at least 10 percent of pregnant women in the United Kingdom have a chronic illness requiring medication, and at least 40 percent of pregnant women in the U.K. take a prescription drug during their pregnancy. In the United States, this statistic is even higher, with 64 percent of women taking a prescription medication during their pregnancy.

Indirect maternal deaths in the U.K.—those caused by a condition unrelated to but potentially aggravated by pregnancy—have almost doubled in the past 20 years. Some of these deaths may well be attributable to poor adherence to medication. Women who are expecting often take a cautious approach to drugs, especially because so little is known about their risks and benefits to their unborn child.

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Many of these risks remain unknown because pregnant women are a tricky cohort in which to test drugs. They are described as “therapeutic orphans” when it comes to clinical drug trials. Pharmaceutical companies are not willing to navigate the legal and ethical minefield of testing drugs on pregnant women, especially because pregnancy lasts only nine months, a short window in which the tests could pay off in additional sales. As a result, drugs are often prescribed to this population off-label, meaning that they haven’t been specifically approved for pregnant women. The editors of the Drug and Therapeutics Bulletin argue that not only is enrolling pregnant women into drug trials important, it’s unethical not to do so. The authors of a New England Journal of Medicine review of how pregnant women were treated during the H1N1 flu pandemic say such research “is not only permissible but also imperative.”

Pregnancy was not always off-limits when it came to medication. Before the 1960s the placenta was generally thought of as an impenetrable barrier, protecting the fetus from contaminants. However, after 10,000 children were born in the late 1950s and early 1960s with birth defects as a result of their mothers taking thalidomide, opinion swung in the other direction.

In 1977 the FDA excluded all women of childbearing potential from early phases of drug testing, a decision that was overruled only 20 years ago. The goal was to protect fetuses and pregnant women. The irony is, as an article in The Lancet points out, that the scale of the thalidomide tragedy could have been reduced had the drug been properly trialled.

The lack of drug testing has led pregnant women (and the doctors who treat them) to a conundrum. Either they risk ditching medications they need or they take drugs that haven’t been specifically tested on pregnant women and could pose an unknown danger. This occurred with anticonvulsant sodium valproate, which was found to be associated with an increased risk of impaired cognitive function among children whose mothers took the drug while pregnant.

On the other hand, studies have found that women who stop taking medications they need can be at serious risk, too. A study in the Journal of Allergy and Clinical Immunology found that 30 percent of women with asthma reduced or stopped their asthma medications in the first few months of pregnancy. A separate review reported that 6 percent of pregnant women with asthma are hospitalized for an acute attack. Furthermore, a third of asthmatics intended to stop or stopped taking inhaled corticosteroids during pregnancy, with 44 percent of asthmatic women revealing that they had concerns about the ways that asthma medication and asthma attacks would affect their baby.

Anne Drapkin Lyerly, associate director of the Center for Bioethics at the University of North Carolina, co-founded the Second Wave Initiative, a project that promotes the responsible inclusion of pregnant women in biomedical research. She recalls a case in which a woman with severe asthma was taken off her medication by her doctor. She presented to the emergency room with a severe asthma attack. Instead of treating her, hospital staff tried to reach her doctor. The woman died.

Lyerly and Ruth Faden, another founder of the Second Wave Initiative and the director of the John Hopkins Berman Institute of Bioethics, argue that pregnant women are often seen as just vessels, with their own health regarded as secondary to the health of their unborn child.

This is particularly true in the case of pregnant women who take antidepressants, which some research has found to have adverse outcomes for the baby when taken throughout pregnancy. However, the needs of the baby and the needs of the mother should not be mutually exclusive. “If a newborn has a mother who has crippling depression, the infant also suffers,” Faden says.

“The bottom line is that what we have is a really unfair circumstance. We don’t have as much evidence as we would like in medicine generally, but there is something profoundly wrong when we have one group in the population that has to be managed with far less evidence than anybody else,” Faden says.

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