Booties on the ground

In his excellent review of Annie Murphy Paul's new book, Origins: How the Nine Months Before Birth Shape the Rest of Our Lives in the New York Times Book Review on Sunday, physician/author Dr. Jerome Groopman wrote:

Of necessity, research on fetal development involves observing pregnant women in their daily lives; no one would purposefully have one group eat in a possibly risky way or be exposed to a potentially dangerous substance, and compare outcomes with an unperturbed control group. We have, at best, only correlations between a mother’s lifestyle and her child’s future health, not clear causation.

And, in "The Case Against Breast-Feeding," Hanna Rosin's 2009 article in The Atlantic, she wrote, "An ideal study would randomly divide a group of mothers, tell one half to breast-feed and the other not to, and then measure the outcomes. But researchers cannot ethically tell mothers what to feed their babies."

Really? Why not? Both Groopman and Rosin are writing about how vulnerable observational studies are to being tainted by hidden variables. Controlled trials are a better system for testing what works and what doesn't.

But if I am reading their statements correctly, Groopman and Rosin are saying that we cannot even think about practicing actual, rigorous science if babies and fetuses are involved.

Building up a body of "evidence-based medicine" around a segment of the population that is exempted from clinical trials — depending entirely on observational research, that is — seems unwise to me. We don't need to wonder what a worst-case scenario involving babies would look like;  we have the 50-year-old thalidomide catastrophe as a demonstration. Thousands of children around the world were born with deformed limbs after their mothers took the drug.

Subjecting drugs and behaviors that can affect unborn children to standard scientific trials that include pregnant women might save the population from potentially massive damage from those behaviors, and from the drugs once they are put on the market. This is especially true now that we suspect the experience in the womb has a huge influence on the course of an individual's life — the subject of Paul's book, Origins.

Now I understand why the medical ethicist Ruth Macklin, writing in The Lancet last winter, called for the inclusion of pregnant women in drug trials, and retaining women who get pregnant in such trials. Conventional wisdom seems to have rendered the concept so unthinkable that a call for change is necessary.

What do you think about including pregnant women in clinical trials? I would love to read your comments.

Pregnant women and drug trials

Should pregnant women participate in trials to discover the effectiveness and potential side effects of new drugs?

This is a controversial topic, because participating in drug tests exposes pregnant women and their babies to possible harm.

Ruth Macklin, an ethicist writing in The Lancet, makes a compelling case for enrolling pregnant women in drug research and retaining women in studies if they become pregnant.Pregnant Graffiti

After all, once approved, drugs go on the market, where doctors will prescribe them to many people across the board, including pregnant women in potentially large numbers, Macklin notes. If researchers haven't had a chance to see the effects of a particular drug on pregnant women and their fetuses, then drugs that cause damage might injure large numbers of people before an alarm is sounded.

We don't have to imagine such an event. Thalidomide, a multi-purpose drug introduced in Europe in 1957, was prescribed for morning sickness for pregnant women. It took four years for researchers to realize and then prove that the drug was causing devastating birth defects. More than 10,000 babies in 46 countries whose mothers had taken thalidomide were born with deformed, often truncated limbs.

"Had the drug been tested in very few women in a ... clinical trial, the mutagenic effect would more likely have been discovered and the number of babies born with deformities would have been much smaller," Macklin writes.

Various governmental bodies, including the U.S. Food and Drug Administration, have gone back and forth on whether to test drugs on pregnant women since it became known that drugs can cross the placenta and affect babies.

HIV-AIDS has forced the issue because not only will pregnant women likely take the drugs that are being developed to combat the fatal disease, but clinical trials also present an opportunity for infected women to obtain potentially life-saving treatment that has not been approved for general use. It is "essential" to include infected pregnant women in these trials, Macklin writes.

The Microbicide Trials Network, based at the University of Pittsburgh and Magee-Womens Research Institute in Pittsburgh, which is working to develop new treatments for HIV-AIDS, is doing just that. In a drug study now under way, MTN is retaining women who become pregnant, and is enrolling pregnant women as well, including healthy, HIV-negative pregnant women, Macklin writes.

However, researchers who enroll pregnant women in studies must "ensure that the informed consent process meets the highest standards," so the women who choose to participate in trials understand the risks to them and their fetuses, Macklin writes.

Image from "Pregnant Graffiti" by Petteri Sulonen