The Dangerous Data Gap in Pregnancy Drug Research

Rachel Feltman: For Scientific AmericanIt is Science quickly, My name is Rachel Feltman.

The President of the United States recently claimed that the use of acetaminophen, commonly known by the brand name Tylenol, during pregnancy and early childhood may be linked to autism in children. But these claims are not supported by scientific evidence and highlight a much bigger problem: we know surprisingly little about the safety of medications during pregnancy.

For decades, pregnant women have been excluded from most clinical trials, leaving doctors and patients to make decisions with incomplete information. According to a recent study, between 80 and 90 percent of people take prescription medications during pregnancy, but less than 1 percent of clinical trials include them. The result is a health system that protects pregnant women Since research rather than through it.

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Here to explain why we’re missing this crucial data and what needs to change, Tanya Lewis, health desk editor at Scientific American.

Tanya, thank you so much for coming to chat with us.

Tanya Lewis: Yeah, thank you very much for having me.

Feltman: Pregnancy and medications have been in the news a lot lately, you know, mostly because of the alleged link between acetaminophen and autism in children. Before we get into everything you revealed in your recent article, could you give us a brief overview of these titles?

Louis: So yes, you may have heard that recently Donald Trump and his Secretary of Health held a press conference in which they announced that acetaminophen may be linked to autism in the child of a pregnant person taking the drug.

There is currently no good, high-quality evidence to support this link. It is based on correlations in poorly conducted studies and does not take into account the fact that, for example, Tylenol is often administered to treat infections, themselves associated with autism in some studies.

So there were a lot of confounding factors and variables that weren’t really mentioned at the press conference. And Tylenol is a medication that has been widely prescribed to children and pregnant people for, you know, decades and that, based on clinical evidence and studies, is generally safe in prescribed doses.

So this is obviously another case, I guess, of the administration going beyond the evidence and making a claim that doesn’t really back up in the data.

Feltman: Yes, and I think it struck a chord with people because the recommendations around medications and pregnancy are already so burdensome, so confusing, so restrictive.

I believe the president said something about pregnant women needing to “tough it out” instead of taking Tylenol. And given that Tylenol is the safe option for pain and fever relief during pregnancy, as opposed to ibuprofen, which has known real risks, it’s sparked a lot of conversations about the shortcomings of our evidence-based recommendations on medications during pregnancy, and you dove into that in a recent article.

Could you start by telling us where we are in terms of research on medications in pregnancy?

Louis: Yeah, absolutely. I mean, you hit the nail on the head here with the fact that even though Tylenol itself has been pretty well studied in pregnancy and is widely recommended because it’s sort of the only, quote, “safe” option for pain relief that’s not, you know, associated with known fetal malformations or anything like that, even if it’s true, the reality is that there just isn’t a huge amount of research on women pregnant women and medications because, by definition, many pregnant women have been left out or excluded from drug studies.

There are some historical reasons for this. It dates back to the days of thalidomide, a drug prescribed to treat morning sickness in Europe in the 1950s and 1960s. And that drug, as we know, was later found to cause horrible birth defects. And so, you know, rightly so, it kind of shook people up about the potential for negative effects of medications during pregnancy.

But as a result of all this experience, Congress decided to require more controlled studies of drugs, which was a good thing; I mean, they didn’t do that systematically for all drugs, so that was a good thing. The only downside was that they decided to classify pregnant women as “vulnerable” and therefore unable to give informed consent for these types of studies. And that meant that, in practice, they were completely excluded, and we know nothing – or very little – about many drugs used in pregnancy because they simply haven’t been studied in pregnancy.

Feltman: So what type of studies can researchers use to examine medications during pregnancy, and what are the gaps?

Louis: It’s true, so I mean, it’s something that we can and should study. I’ve spoken to a number of researchers and gynecologists who tell me there are ways to study drugs safely in pregnant women. For example, we often do what are called observational studies, in which we look at pregnant women who are already taking medications to treat a chronic illness like diabetes or heart disease, or even an infection like HIV. And these are medications that they can’t stop taking; these are, you know, life-saving medications. And we can study the effects, if any, on the fetus by observing these people.

But we can also do studies on people who have given birth to two different children and who took the drug in one pregnancy but not the other, if it’s a drug like Tylenol, for example. There are these studies, and you can compare them, and you…everything else is pretty much the same between these individuals, except one was exposed to the drug and one wasn’t. So that’s one way to do it.

And then, of course, you know, in terms of clinical trials, these are the studies that are done before a drug is approved and some of these safety studies that take place, you know, before it even goes into a human clinical trial. We therefore study these drugs in animals; we only study them for safety reasons in a small population of people. And these studies can be done in non-pregnant people, and we can prove that a drug may be safe before we give it to a pregnant person, and we can then look for possible adverse effects in that population.

So there are definitely ways to study this. There have been studies – just to give some numbers, you know, less than 1% of clinical trials currently include pregnant women. So this is a huge gap in our knowledge, and as some of the researchers who spoke to me said, you know, we’re protecting pregnant women. Since do research instead of through research.

So we need to change this because it is very important to take care of both the health of the mother and the fetus. If you don’t treat an illness that is really dangerous or unhealthy for the mom, the baby will be affected too. So, you know, we have to treat the whole couple.

Feltman: Yeah, one thing that really stood out to me in your article were these estimates of how things would have played out if we had had sort of randomized clinical trials of drugs that were found to be dangerous to the fetus. Because, you know, I think there’s naturally this spectrum of fetuses that might be harmed in a clinical trial for us to be able to get this data, but people have thought about it and compared it to the actual harm that occurred. So could you tell us a little more about that?

Louis: Yeah, totally. I mean, if you think about thalidomide, for example, that drug caused birth defects in 10,000 or more children. So if there had been a clinical trial of thalidomide in, say, 200 people, 33 of those children would have had serious birth defects, but that would have prevented 8,000 birth defects in other children because we would have had that knowledge, and therefore, those pregnant women would not have taken this drug during their pregnancy. So we’re talking about studying these drugs in a small, controlled population of people who are knowingly consenting, knowing, you know, what the potential risks might be. And we hope this will save many more individuals and children from potential harm.

So it’s never easy to think about, you know, any type of harm to a fetus or a pregnant person. But by not studying these medications in these people, we are going blind and not giving pregnant women the evidence they need to make informed, safe choices during their pregnancy. And the reality is that [as many as] 80 to 90 percent of pregnant women take prescription medications during pregnancy. So it’s not like they’re not taking these medications – they’re just taking them without evidence, simply on the best advice of their doctors. And it’s no one’s fault. The reality is that there is not enough data to give people truly informed choices on most of these medications.

There are some medications now, I should say, that are well studied and pretty well known for their safety. SSRIs, which are antidepressants, are an example of a fairly well-studied medication in pregnant women. And many pregnant women with depression or, you know, other mental health conditions need these medications to function. This is not an optional choice here. We know that poor mental health is one of the leading causes of postpartum mortality. So this is a huge problem in the United States and other countries; we need to treat people who have these mental health problems. But it’s still a conversation that people need to have with their doctors, and if we can provide them with solid evidence and studies to support those decisions, then everyone is safer.

Feltman: Thank you very much for coming to talk to us about all this.

Louis: Yeah, thank you very much for having me. It was a pleasure.

Feltman: That’s all for today’s episode. We’ll be back on Monday with our weekly roundup of science news.

Science quickly is produced by me, Rachel Feltman, with Fonda Mwangi and Jeff DelViscio. This episode was edited by Alex Sugiura. Shayna Posses and Aaron Shattuck check in on our show. Our theme music was composed by Dominic Smith. Subscribe to Scientific American for more recent and in-depth scientific news.

For Scientific American, It’s Rachel Feltman. Have a great weekend!