An Unnecessary Risk

When a clinical trial excludes pregnant women, we have no idea how the drug or vaccine will affect their fetuses.

In Canada, research involving humans is primarily governed by guidelines set out in the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. These guidelines are currently being revised and the public consultation period ends March 1.

When the policy statement was published in 1998, it addressed a serious ethical problem of the day, namely the exclusion of women from research. The guidelines stipulated that “women shall not automatically be excluded from research solely on the basis of sex or reproductive capacity.” This directive had a salutary effect – the number of women research participants increased exponentially. However, problems with research involving women remain.

Frequently, women of reproductive capacity (including nuns, lesbians, heterosexual women with infertile male partners, and women who abstain from sexual activity) are required to use oral contraceptives as a condition of research participation. This is ethically offensive.

Another ethical problem is the common practice of excluding pregnant women from research. This can harm pregnant women and undermine fetal safety. For example, frequently there are no clinical trial data on which to base health care decisions about treatment or immunization. This can result in under-treatment or mistreatment, to the detriment of pregnant women and their fetuses.

It is common knowledge that social drugs like tobacco or alcohol and illicit drugs like marijuana are potentially harmful to your health. These drugs can also be harmful to developing fetuses if they are taken by pregnant women. Drugs taken during pregnancy can reach the fetus by crossing the placenta, resulting in miscarriage, pre-term labour and delivery, birth defects, or permanent disability that only become apparent later in the child’s life. For these reasons, women are strongly encouraged not to use such drugs when they are pregnant. But, what about the use of prescription or over-the-counter drugs?

Imagine, a woman with epilepsy who is taking Lamotragine (one of the newer anti-epileptic medications) becomes pregnant. Lamotragine is used extensively for pregnant women because it is thought to be safer than some of the older anti-epileptic drugs. But what if this drug is just as risky as the others? For a pregnant woman to have a healthy baby, she needs to be healthy herself. Does she continue, change, or stop her pre-pregnancy medication?

This is a tough decision, made all the more difficult by the level of uncertainty involved. While there are known benefits for the woman to continue with her prescription drug use, the potential harm to her fetus is unclear. The drug could be safe, or dangerous. Two to three per cent of all birth defects result from the use of drugs other than alcohol.

It is one thing for a woman to deny herself health benefits by discontinuing her medication when that medication is known to have a harmful effect on the fetus. It is quite a different matter for a woman to deny herself health benefits when there is no or only a slight benefit for her fetus.

And what about vaccination? Imagine a pregnant woman who wants to be inoculated against H1N1. Should she take the adjuvanted or the unadjuvanted vaccine ? The adjuvanted vaccine has less antigen (or killed virus) than the unadjuvanted one, so it is reasonable to think that the adjuvanted vaccine would be safer for pregnant women. Health Canada provided adjuvanted vaccine for the general population, but recommended the unadjuvanted one for pregnant women under 20 weeks. This recommendation was made despite the fact that there was no evidence that the adjuvanted vaccine was unsafe for pregnant women, as they had been excluded from research.

If we had knowledge about the effects of medications and vaccinations on developing fetuses, pregnant women could make informed choices about the trade offs. Since, however, pregnant women are typically excluded from clinical trials, new drugs or vaccines are usually not approved for use by them. Instead, pregnant women are advised “to consult a physician” before taking non-prescription medications or a vaccine. This is also why physicians frequently advise pregnant women to discontinue or alter prescription medications during their pregnancy, unless absolutely necessary for their health or that of their fetus.

If clinicians are to give their patients sound medical advice, they need good data. This means that the guidelines for research involving humans need to prohibit the routine exclusion of pregnant women. It is not enough to simply “take into account potential harms and benefits for the pregnant woman, and her embryo, fetus or infant.” This will neither prompt nor facilitate a change in the status quo which clearly harms pregnant women