In the last week of September 2021, a group of more than 90 doctors and researchers published a call to action, cautioning against the liberal use of Tylenol (acetaminophen) during pregnancy. The studies suggested that exposure to the drug could increase the risk of a baby having neurodevelopmental, reproductive and urogenital disorders.
The authors added, however, that Tylenol has long been considered one of the few safer options to treat pain in pregnancy, since Advil (ibuprofen) and opioids are considered riskier. They pointed out that, in some cases, a woman’s condition (fever and pain, for example) could be worse for her fetus than exposure to Tylenol. Until the research is more clear, talk to your doctor before taking Tylenol while pregnant and take the lowest possible dose for the shortest time period.
Definitive advice on the use of medications during pregnancy is hard to come by. Researchers generally won’t enroll pregnant people in clinical trials because, as Lauren Demosthenes, MD, an OB-GYN with Babyscripts, says, “When a drug comes out, they’re not going to say, ‘’Let’s experiment with this on pregnant women all the time.’” Physicians and patients must piece together information from animal and pharmacological studies and data gathered after the drug is approved.
For years, the Food and Drug Administration (FDA) supported a simple categorization strategy. It labeled each drug A, B, C, D or X, based on how safe it was thought to be, in descending order, for a fetus. Over time, doctors noted that while the system was easy-to-use, its simplicity could at times be misleading. Rankings often had more to do with how long a drug has been on the market than how safe it was during pregnancy.
In 2014, the FDA rolled out a new strategy. Now each drug’s label is required to list findings (or lack thereof) from clinical trials, animal studies and more in a specialized format, allowing doctors and patients to weigh the information together for themselves. Physicians say that while the new strategy can’t be interpreted as quickly as the previous letter-based categories, it better supports the doctor-patient shared decision-making process.
“Even though there used to be categories, the process has always been the same. So even if a drug was in one of the in-between categories, it’s still required that you just sit down and have a conversation about it,” says Demosthenes.
Nicole Derish, MD, who runs a private psychiatry practice specializing in working with perinatal, child and adolescent patients, explains that the decision is more complicated than avoiding any drug that can raise the risk to a fetus. “You have the risk of being exposed to the medication versus the risk of being exposed to [an] untreated illness. Just because a medication has some risk doesn’t mean it’s not the safest option for a pregnant woman and their baby,” she says. “Every woman I’ve ever treated – every single one – says, ‘Well, I don’t care. It’s nine months. I can white-knuckle it. I just want what’s best for my baby. I don’t care if my life is miserable.’ I have to say, ‘No, no. I hear you, but this is what’s good for the baby. What’s good for you is good for the baby.”
History of Drugs in Pregnancy
Pregnant people have good reason to be wary of using medications in pregnancy. In the 1950s, thalidomide was prescribed to expecting mothers for a variety of ailments, from morning sickness to pneumonia. About five years later, researchers made the connection between fetal exposure to the drug and birth defects that left about 10,000 babies with deformities in limbs, ears and other organs. The FDA never approved thalidomide despite incredible pressures from manufacturers (and the fact that most European countries were using it widely). As a result, very few babies were harmed in America. Even so, his tragedy led to increased scrutiny on drug approvals, and thalidomide is still the classic example of why a strong, independent FDA is crucial for everyone’s safety.
Thalidomide Is not the only regulatory catastrophe for drugs in pregnancy. DES (diethylstilbestrol), which was developed before thalidomide and used in pregnancy for years after, resulted in less visible but more insidious effects on growing fetuses. DES, which was prescribed until 1971 to prevent preterm births, is now known to have caused elevated risks of cancer, infertility and more, not only to one generation, but even to their children and grandchildren. (See our sister website and member organization, DES Action, for more information.)
Even though the FDA removed DES’s approval for use in pregnancy, similar drugs have taken its place. (See our article on Makena.)
New Labeling Guidelines
The FDA gradually phased out the letter-naming program,which ended in June 2020. Drug labels now must list available information under several consistent headings.
Pregnancy Risks Label
Under Section 8.1 of the drug label, the drug must have four headings.
The first is Pregnancy Exposure Register: Here, the drugmaker lists whether there is a registry where doctors must report outcomes in pregnant patients using the drug, and where to find it. Derish says, “You have to report any potential adverse reaction, even if you think it’s still unrelated, like, [for instance, if] somebody starts the medication and they start to get more mosquito bites. That goes on the registry. So one of the ways that these medications collect data is just by being on the market.”
The next section is Risk Summary. This is the crux of the label’s information. Here, the manufacturer lists what’s known about whether the drug can cross the placental barrier and if animal studies or human studies have identified any risks to the fetus. If data is unavailable, the company states this explicitly. This section also contains background information, such as how likely a baby is to be born with a birth defect in the general population and how likely they are to be born with a birth defect if the disease the drug addresses goes untreated during their mother’s pregnancy.
For example, if “the baseline rate [for a particular birth defect] is 1% of the general population, [research on a drug may indicate that using it in pregnancy] might raise the rate to 2%. And that is a big increase, right? From 1 to 2[%],” says Derish. “But even with that medication, 98% of the time, your baby’s going to be fine.”
The third section is Clinical Considerations, which lists information about dose adjustments during pregnancy or breastfeeding, and risks to the mother and the fetus.
The final section is Data, which lists more detailed information about the studies supporting the clinical guidelines.
Common Medicines: What’s Known
According to the Centers for Disease Control and Prevention (CDC), 70% of women say they take at least one prescription drug while pregnant.
There are some drugs, explains Demosthenes, like the acne drug Accutane (isotretinoin), that are known to be dangerous to a fetus. “There are certain medicines that even [have] requirements. You are asked to sign a form to say you understand the risk and you commit to being on birth control and [will] do everything you can not to get pregnant,” she says. “If you’re a teenager and you [are prescribed] Accutane, they will want you to be on some kind of contraception if sexually active.”
Some other drugs that are contraindicated before and during pregnancy in most instances are:
Methotrexate (Trexall): This rheumatoid arthritis drug blocks the action of folic acid, a crucial component to a fetus’ development.
Leflunomide (Arava): This is an immunosuppressant used to treat rheumatoid arthritis. It takes some time to leave your system, so physicians suggest getting a blood test first and stopping about a month before trying to conceive. Studies have shown an increased risk of miscarriage, and mixed results on birth defects.
Non-steroidal anti-inflammatory drugs (NSAIDS): The FDA recommended using Tylenol instead of non-steroidal anti-inflammatory drugs (NSAIDS), because NSAIDs, like Advil, can cause kidney problems in the fetus.
Most drugs fall into gray areas. Some of the most common questions, according to both doctors, are about psychiatric medications.
Stimulants in Pregnancy
Heather has been taking the attention deficit hyperactivity disorder (ADHD) medication Adderall since her late 20s. She’s now 36 and pregnant. When her physician said she needed to stop taking the drug during pregnancy, she was offered an alternative, but decided to forgo it. It’s been a struggle, she says, to get through her day and her work, but she’s managing with the help of counseling and meditation. The CDC states that stimulants used to treat ADHD may increase the risk of certain birth defects of the limbs and digestive system, though the organization maintains that the risk remains small.
SSRIs (selective serotonin reuptake inhibitors) in Pregnancy
“We actually have a ton of data on SSRIs (selective serotonin reuptake inhibitors) and pregnancy, the most common antidepressant, in pregnancy. And it’s very robust,” says Derish. “They’re very safe. They’re very well-tolerated.”
Untreated mental illness can be dangerous. Health Affairs published a study in October 2021 showing that women with mental health disorders had more expensive deliveries ($458 higher) and were 50% more likely to experience severe complications while giving birth, than others. Those with stress or trauma-related disorders had the most expensive deliveries. Those with untreated depression are more likely to experience preterm birth and have babies with low birth weights. This risk is especially high among Black women.
Pregnancy comes with a lot of stress and physical changes. If she diagnoses a mother with new depression during her pregnancy, “I try as hard as I can to try a nonpharmacological intervention. Protecting sleep is a very big one,” Derish says. But sometimes an SSRI makes more sense. For some, medications are more effective. For others, lifestyle changes during pregnancy aren’t practical. “I can recommend yoga. If I have a single mom who has three other kids, it’s not that yoga hasn’t occurred to her, it’s just [that] it’s not going to happen for her because she’s already so taxed.”
Benzodiazepines in Pregnancy
“Benzodiazepines are a little bit more iffy [than SSRIs],” explains Derish, because they’re more likely to cross the placental barrier, meaning that your baby can be exposed to and hurt by them. She adds that, in many cases, untreated anxiety is a bigger risk to the fetus. “We have a lot of data showing that women that have very high levels of anxiety have more complications of pregnancy and poorer outcomes.” Untreated anxiety during pregnancy has been linked to increased risk of preterm birth, for example.
Derish explains that that’s one of the benefits of the new labeling system. It allows for doctors and physicians to weigh the risks of untreated conditions versus those of exposures to their treatments, rather than just identifying some drugs as safe and others as dangerous.
MotherToBaby.com offers a series of factsheets on commonly used medications like ACE (angiotensin-converting-enzyme) inhibitors, proton pump inhibitors and statins in pregnancy. The FDA also maintains a searchable database with drug labels and pregnancy information.
In addition to talking with your physician about any medications you’re prescribed, you should also tell your doctor about any supplements or herbal remedies you’re using . Many of these are safe during pregnancy, but some do come with the risk of complications. For example, ginger may interact with other medicines you’re taking to increase the risk of bleeding.
Most herbal supplements have not been well-studied in pregnancy. Additionally, many supplements contain different combinations of ingredients that make it difficult to compare one brand to another. Bring any herbal supplements you use with you to the doctor to review the ingredients.
“Just because it’s ‘natural’ and it’s over-the-counter doesn’t necessarily mean that it would be advised to take in pregnancy,” says Demosthenes.
You should always discuss the risks and benefits of your medications and supplements with your healthcare provider, but during pregnancy is an especially important time to do so. The new labeling system ensures that you’re able to have an open conversation regarding what is and isn’t known about anything you may expose yourself or your fetus to.
“Everybody has an opinion of what pregnant women should do… So you really need to believe, at the end of the day, you can make good choices and you have to surround yourself with a team that you trust and that trusts you,” says Derish. “That way, when a relative or friend says, ‘You shouldn’t be taking that in pregnancy,’ you can definitively say, ‘My OB-GYN says I should, and I’m going to listen to them because they’re my doctor.’ ”