When Pregnant Women Need Medicine, They Encounter A Void
A few years ago, almost every aspect of Rosanne Mottola's life was governed by the feeling in her gut. Literally.
"I experienced extreme urgency to have to use the bathroom. Pain. Bleeding," says Mottola, who has ulcerative colitis. "A lot of times I would go the whole day without eating," she says, so that she wouldn't have to rush to the bathroom so often.
When her disease acted up, it was painful and exhausting. The steroid treatment made it hard to sleep, and she put on so much weight that she'd get what she calls "chipmunk cheeks."
"So it was not easy," says Mottola, who is 31 and lives in Staten Island, N.Y.
Then, right before her wedding, it got worse. The doctors said she had two options: Get her large intestine removed and replaced with a colostomy bag, or try a mix of two drugs that might or might not work. She chose the drug combo.
"And it did the trick," says Mottola. "It gave me back a quality of life."
So for a while, Mottola got on with her life with no stress. And then she got pregnant.
One of the drugs Mottola was taking, a chemotherapy drug called 6-mercaptopurine, has shown some signs it could cause problems including birth defects and preterm birth. The other, the immune system suppressant infliximab, hadn't been studied enough in humans to know what would happen.
"It made me extremely nervous," says Mottola. "I must have had four conversations with my doctor. I kept calling him. I said, 'Are you sure that I can do this? Are you sure this is safe? Are you sure that the baby won't be affected?' "
Her obstetrician wanted more information. A pediatrician basically said, "No way, you cannot breast-feed on those drugs." And Mottola worried that the fetus might absorb some of the medication, potentially making it harder for the baby to fight off infections once he was born.
But her gastroenterologist, who had worked with patients like Mottola and was up to date on the research, reassured her that it would be fine. So in the end, she decided to stick with it.
"At the end of the day, I had a very healthy pregnancy. I probably felt the best I've ever felt since my diagnosis," she says.
And these days, her 1 1/2-year-old son is up to all sorts of things.
"Oh, my gosh, climbing, talking. He's very inquisitive, loves reading books. He's healthy, he's thriving, and it was the right call," she says.
Even though things worked out for Mottola and her family, the doubt that she and her husband experienced during the pregnancy is not a happy place for expecting parents.
And unfortunately, Mottola is not alone. The CDC estimates that 70 percent of pregnant women in the U.S. take at least one prescription drug — whether it's for something like colitis or diabetes, or just allergies.
And a lot of them are stuck in the same spot as Mottola, wondering if the drugs they need might do any harm, says Maggie Little, a bioethicist at Georgetown University.
"There's actually shockingly little that we know about how to treat illness during pregnancy," she says.
Little says there are only about a dozen medications in the U.S. that are approved as safe during pregnancy. For people who want to know more about the safety of the medication they're taking, the CDC suggests two resources — MotherToBaby, which is run by the Organization of Teratology Information Specialists, and LactMed, which is run out of the National Institutes of Health.
But the CDC acknowledges that as pregnant women aren't usually included in drug safety studies, we know very little about the effects of most medication on pregnancy. Little says this means a lot of drugs go to market without any information on how they act in pregnant women.
"Hundreds of medicines are responsibly and importantly used during pregnancy, because pregnant women get ill and ill women get pregnant," Little says. "The point is, we need to get more information on how to use those drugs during pregnancy to make sure they're the most effective and the safest for use during that time."
That's why she's working with a group of researchers to figure out how to get more information in a responsible way. "We are looking at finding ethical pathways to doing the needed research with pregnant women," says Little.
There's an understandable squeamishness toward the idea of testing medications on pregnant women.
For one, there's no way for a fetus to consent to a drug trial. Secondly, researchers, academic institutions and pharmaceutical companies are really afraid of what could go wrong.
There's one worst-case scenario that runs through almost everyone's minds.
"They don't want to be the next thalidomide," says Little.
Decades ago, after pregnant women took thalidomide to relieve nausea, thousands of babies were born with birth defects, including arms and legs that looked like flippers. The drug had caused the defects. That jolted people into a fear of mixing medications and pregnancy that continues today.
Drug companies and universities are understandably wary that testing medications in pregnant women could end up causing birth defects. But Little and her colleagues argue that the thalidomide tragedy is exactly why drugs need to be tested in that way.
"If we had done early and safe studies on thalidomide, we would have found out before it got to market that pregnant women shouldn't take it," she says. "So, the lesson of thalidomide is actually: Do safe and early studies on drugs around pregnancy, and we'll avoid those tragedies."
Instead, she says, people in the scientific community tend to run in the other direction — an attitude that can have repercussions.
In 2006, for example, researchers found that women who took certain ACE inhibitors for high blood pressure early in their pregnancy were more likely to have babies with heart and nervous system problems. The medication had been on the market for decades. Before that study, it was considered problematic to take ACE inhibitors during the second and third trimesters, but OK during the first. After the 2006 study, the FDA issued a safety alert reiterating the risk of taking ACE inhibitors during pregnancy.
In other cases, medicines don't necessarily do harm, but they don't help women in pregnancy. Studies on the effectiveness of a diabetes drug and the widely used antibiotic amoxicillin found they didn't work as well in pregnant women because the women's bodies filtered out the drugs more quickly. The patients likely needed higher doses to have any impact on the disease.
"There can almost be a Catch-22," says Little. "Until we do the research, we don't know what the risk to the fetus is, and if we don't know what the risk to the fetus is, how can we ethically do the research?"
But the U.S. has managed to solve that dilemma when it comes to testing medications in children, whose bodies work differently from those of adults. Congress gave incentives to pharmaceutical companies to test drugs in children. As a result, there have been more studies conducted in children in the past five years than in the previous 30 years combined, according to the U.S. Food and Drug Administration. Those studies have resulted in pediatric information on the labels of more than 80 drugs. Ibuprofen is one example. Recent studies on infants resulted in safe over-the-counter dose information on ibuprofen labels for babies as young as 6 months.
But there hasn't been the same support for testing medications in pregnancy, though there is a bill in Congress that would take a step toward addressing the knowledge gap.
So in the meantime, it's up to enterprising researchers, like Dr. Uma Mahadevan, to slowly fill the void of information.
"What mom wants to be on medication that hasn't been studied in pregnancy?" says Mahadevan, a gastroenterologist at the University of California, San Francisco.
A lot of her patients have health issues like Rosanne Mottola's. Sometimes, after consulting with another doctor, they'd quit their medications entirely, thinking it would be better for the pregnancy. But if their disease acts up, Mahadevan says, their options are "really ugly," like taking steroids or even having surgery while pregnant.
"These are all much more high-risk things than the medication that they were on before," she says.
To help counter the uncertainty, Mahadevan and her colleagues tracked about 1,500 women with inflammatory bowel disease to find out if two classes of common medications were safe. "There is no increase in birth defects, and that's very clear and everyone agrees on that," she says.
And that may turn out to be true in many cases — that a healthy mom on medication is ultimately better for the fetus.
It's a bit like the warning flight attendants give on an airplane, Little says. "If there's a reduction of oxygen in the plane, reach for your own mask first. When you're pregnant with a serious illness, you first have to treat your illness. That is helping your baby."
But until there's more thorough research on medication taken during pregnancy, there will always be an element of uncertainty — and for many women, says Little, that uncertainty is agonizing.
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