Which Meds are Safe When You’re Pregnant? Science Wants to Find Out
Sarah Mancoll was 22 years old when she noticed a bald spot on the back of her head. A dermatologist confirmed that it was alopecia aerata, an autoimmune disorder that causes hair loss.
Of 213 new drugs approved from 2003 to 2012, only five percent included any data from pregnant women.
She successfully treated the condition with corticosteroid shots for nearly 10 years. Then Mancoll and her husband began thinking about starting a family. Would the shots be safe for her while pregnant? For the fetus? What about breastfeeding?
Mancoll consulted her primary care physician, her dermatologist, even a pediatrician. Without clinical data, no one could give her a definitive answer, so she stopped treatment to be "on the safe side." By the time her son was born, she'd lost at least half her hair. She returned to her Washington, D.C., public policy job two months later entirely bald—and without either eyebrows or eyelashes.
After having two more children in quick succession, Mancoll recently resumed the shots but didn't forget her experience. Today, she is an advocate for including more pregnant and lactating women in clinical studies so they can have more information about therapies than she did.
"I live a very privileged life, and I'll do just fine with or without hair, but it's not just about me," Mancoll said. "It's about a huge population of women who are being disenfranchised…They're invisible."
About 4 million women give birth each year in the United States, and many face medical conditions, from hypertension and diabetes to psychiatric disorders. A 2011 study showed that most women reported taking at least one medication while pregnant between 1976 and 2008. But for decades, pregnant and lactating women have been largely excluded from clinical drug studies that rigorously test medications for safety and effectiveness.
An estimated 98 percent of government-approved drug treatments between 2000 and 2010 had insufficient data to determine risk to the fetus, and close to 75 percent had no human pregnancy data at all. All told, of 213 new pharmaceuticals approved from 2003 to 2012, only five percent included any data from pregnant women.
But recent developments suggest that could be changing. Amid widespread concerns about increased maternal mortality rates, women's health advocates, physicians, and researchers are sensing and encouraging a cultural shift toward protecting women through responsible research instead of from research.
"The question is not whether to do research with pregnant women, but how," Anne Drapkin Lyerly, professor and associate director of the Center for Bioethics at the University of North Carolina at Chapel Hill, wrote last year in an op-ed. "These advances are essential. It is well past time—and it is morally imperative—for research to benefit pregnant women."
"In excluding pregnant women from drug trials to protect them from experimentation, we subject them to uncontrolled experimentation."
To that end, the American College of Obstetricians and Gynecologists' Committee on Ethics acknowledged that research trials need to be better designed so they don't "inappropriately constrain the reproductive choices of study participants or unnecessarily exclude pregnant women." A federal task force also called for significantly expanded research and the removal of regulatory barriers that make it difficult for pregnant and lactating women to participate in research.
Several months ago, a government change to a regulation known as the Common Rule took effect, removing pregnant women as a "vulnerable population" in need of special protections -- a designation that had made it more difficult to enroll them in clinical drug studies. And just last week, the U.S. Food and Drug Administration (FDA) issued new draft guidances for industry on when and how to include pregnant and lactating women in clinical trials.
Inclusion is better than the absence of data on their treatment, said Catherine Spong, former chair of the federal task force.
"It's a paradox," said Spong, professor of obstetrics and gynecology and chief of maternal fetal medicine at University of Texas Southwestern Medical Center. "There is a desire to protect women and fetuses from harm, which is translated to a reluctance to include them in research. By excluding them, the evidence for their care is limited."
Jacqueline Wolf, a professor of the history of medicine at Ohio University, agreed.
"In excluding pregnant women from drug trials to protect them from experimentation, we subject them to uncontrolled experimentation," she said. "We give them the medication without doing any research, and that's dangerous."
Women, of course, don't stop getting sick or having chronic medical conditions just because they are pregnant or breastfeeding, and conditions during pregnancy can affect a baby's health later in life. Evidence-based data is important for other reasons, too.
Pregnancy can dramatically change a woman's physiology, affecting how drugs act on her body and how her body acts or reacts to drugs. For instance, pregnant bodies can more quickly clear out medications such as glyburide, used during diabetes in pregnancy to stabilize high blood-sugar levels, which can be toxic to the fetus and harmful to women. That means a regular dose of the drug may not be enough to control blood sugar and prevent poor outcomes.
Pregnant patients also may be reluctant to take needed drugs for underlying conditions (and doctors may be hesitant to prescribe them), which in turn can cause more harm to the woman and fetus than had they been treated. For example, women who have severe asthma attacks while pregnant are at a higher risk of having low-birthweight babies, and pregnant women with uncontrolled diabetes in early pregnancy have more than four times the risk of birth defects.
Current clinical trials involving pregnant women are assessing treatments for obstructive sleep apnea, postpartum hemorrhage, lupus, and diabetes.
For Kate O'Brien, taking medication during her pregnancy was a matter of life and death. A freelance video producer who lives in New Jersey, O'Brien was diagnosed with tuberculosis in 2015 after she became pregnant with her second child, a boy. Even as she signed hospital consent forms, she had no idea if the treatment would harm him.
"It's a really awful experience," said O'Brien, who now is active with We are TB, an advocacy and support network. "All they had to tell me about the medication was just that women have been taking it for a really long time all over the world. That was the best they could do."
More and more doctors, researchers and women's health organizations and advocates are calling that unacceptable.
By indicating that filling current knowledge gaps is "a critical public health need," the FDA is signaling its support for advancing research with pregnant women, said Lyerly, also co-founder of the Second Wave Initiative, which promotes fair representation of the health interests of pregnant women in biomedical research and policies. "It's a very important shift."
Research with pregnant women can be done ethically, Lyerly said, whether by systematically collecting data from those already taking medications or enrolling pregnant women in studies of drugs or vaccines in development.
Current clinical trials involving pregnant women are assessing treatments for obstructive sleep apnea, postpartum hemorrhage, lupus, and diabetes. Notable trials in development target malaria and HIV prevention in pregnancy.
"It clearly is doable to do this research, and test trials are important to provide evidence for treatment," Spong said. "If we don't have that evidence, we aren't making the best educated decisions for women."
A startup aims to make medicines in space
Story by Big Think
On June 12, a SpaceX Falcon 9 rocket deployed 72 small satellites for customers — including the world’s first space factory.
The challenge: In 2019, pharma giant Merck revealed that an experiment on the International Space Station had shown how to make its blockbuster cancer drug Keytruda more stable. That meant it could now be administered via a shot rather than through an IV infusion.
The key to the discovery was the fact that particles behave differently when freed from the force of gravity — seeing how its drug crystalized in microgravity helped Merck figure out how to tweak its manufacturing process on Earth to produce the more stable version.
Microgravity research could potentially lead to many more discoveries like this one, or even the development of brand-new drugs, but ISS astronauts only have so much time for commercial experiments.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth.”-- Will Bruey.
The only options for accessing microgravity (or free fall) outside of orbit, meanwhile, are parabolic airplane flights and drop towers, and those are only useful for experiments that require less than a minute in microgravity — Merck’s ISS experiment took 18 days.
The idea: In 2021, California startup Varda Space Industries announced its intention to build the world’s first space factory, to manufacture not only pharmaceuticals but other products that could benefit from being made in microgravity, such as semiconductors and fiber optic cables.
This factory would consist of a commercial satellite platform attached to two Varda-made modules. One module would contain equipment capable of autonomously manufacturing a product. The other would be a reentry capsule to bring the finished goods back to Earth.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth,” said CEO Will Bruey, who’d previously developed and flown spacecraft for SpaceX.
“We have a team stacked with aerospace talent in the prime of their careers, focused on getting working hardware to orbit as quickly as possible,” he continued.
“[Pharmaceuticals] are the most valuable chemicals per unit mass. And they also have a large market on Earth.” -- Will Bruey, CEO of Varda Space.
What’s new? At the time, Varda said it planned to launch its first space factory in 2023, and, in what feels like a first for a space startup, it has actually hit that ambitious launch schedule.
“We have ACQUISITION OF SIGNAL,” the startup tweeted soon after the Falcon 9 launch on June 12. “The world’s first space factory’s solar panels have found the sun and it’s beginning to de-tumble.”
During the satellite’s first week in space, Varda will focus on testing its systems to make sure everything works as hoped. The second week will be dedicated to heating and cooling the old HIV-AIDS drug ritonavir repeatedly to study how its particles crystalize in microgravity.
After about a month in space, Varda will attempt to bring its first space factory back to Earth, sending it through the atmosphere at hypersonic speeds and then using a parachute system to safely land at the Department of Defense’s Utah Test and Training Range.
Looking ahead: Ultimately, Varda’s space factories could end up serving dual purposes as manufacturing facilities and hypersonic testbeds — the Air Force has already awarded the startup a contract to use its next reentry capsule to test hardware for hypersonic missiles.
But as for manufacturing other types of goods, Varda plans to stick with drugs for now.
“[Pharmaceuticals] are the most valuable chemicals per unit mass,” Bruey told CNN. “And they also have a large market on Earth.”
“You’re not going to see Varda do anything other than pharmaceuticals for the next minimum of six, seven years,” added Delian Asparouhov, Varda’s co-founder and president.
Genes that protect health with Dr. Nir Barzilai
In today’s podcast episode, I talk with Nir Barzilai, a geroscientist, which means he studies the biology of aging. Barzilai directs the Institute for Aging Research at the Albert Einstein College of Medicine.
My first question for Dr. Barzilai was: why do we age? And is there anything to be done about it? His answers were encouraging. We can’t live forever, but we have some control over the process, as he argues in his book, Age Later.
Dr. Barzilai told me that centenarians differ from the rest of us because they have unique gene mutations that help them stay healthy longer. For most of us, the words “gene mutations” spell trouble - we associate these words with cancer or neurodegenerative diseases, but apparently not all mutations are bad.
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Centenarians may have essentially won the genetic lottery, but that doesn’t mean the rest of us are predestined to have a specific lifespan and health span, or the amount of time spent living productively and enjoyably. “Aging is a mother of all diseases,” Dr. Barzilai told me. And as a disease, it can be targeted by therapeutics. Dr. Barzilai’s team is already running clinical trials on such therapeutics — and the results are promising.
More about Dr. Barzilai: He is scientific director of AFAR, American Federation for Aging Research. As part of his work, Dr. Barzilai studies families of centenarians and their genetics to learn how the rest of us can learn and benefit from their super-aging. He also organizing a clinical trial to test a specific drug that may slow aging.
Show Links
Age Later: Health Span, Life Span, and the New Science of Longevity https://www.amazon.com/Age-Later-Healthiest-Sharpest-Centenarians/dp/1250230853
American Federation for Aging Research https://www.afar.org
https://www.afar.org/nir-barzilai
https://www.einsteinmed.edu/faculty/484/nir-barzilai/
Metformin as a Tool to Target Aging
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943638/
Benefits of Metformin in Attenuating the Hallmarks of Aging https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347426/
The Longevity Genes Project https://www.einsteinmed.edu/centers/aging/longevity-genes-project/
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.