What Do Data and Science Tell Us About Advising Women on Tylenol and Pregnancy?

Ashish Jha: 00:00:05

Hey, everybody. Ashish Jha here from a sunny, but somewhat cooler day in Providence, Rhode Island, excited to be back for a another episode of a moment in health, the podcast where we talk about one data point, discuss one study, and then answer one question. And let's jump right into it. The data point I want to talk about today is two thirds, about 65% that's the proportion of pregnant women who report taking Tylenol or acetaminophen at some point during pregnancy. Many of you know Tylenol in pregnancy has been in the news, and so looking through the data again, there's some range. Some studies suggest 50% some say maybe it's up to 70% but about two thirds is where it is. And I have to tell you that I was actually a little surprised at this number, that it was that low, because over a nine month period, or let's say, seven months, when women are aware of their pregnancy, only about two thirds of women reportedly end up taking Tylenol. What we also know is that the alternative pain medicine, or medicine for fever, ibuprofen, is largely contraindicated or advised against, certainly as you get beyond 20 weeks of pregnancy, and so in the last three and a half, four months of pregnancy, Obstetricians and Gynecologists as well as family practitioners largely recommend that women take Tylenol for pain, for fever, for other things. And again, the data point is two thirds. About two thirds of women report taking Tylenol at some point during pregnancy.

Ashish Jha: 00:01:38

Okay, now let's move on to the study of the week, and the study of the week remains with the same theme. The study is entitled, acetaminophen use during pregnancy and children's risk of autism, ADHD and intellectual disability. This is a 2024 study published in the Journal of the American Medical Association, or JAMA, really the best study to date, looking at the relationship between Tylenol use or acetaminophen use during pregnancy and health outcomes for children. This is a study that comes from Sweden, about two and a half million children, followed from 1995 through 2019 so followed for about 25 years or or about 25 years of data, and what they found was essentially the bottom line, no real Association. They initially saw a very tiny increased risk of autism, ADHD, other challenges in a matched control, but then to deal with what's called unobserved confounding, and I'll explain that more in a second. They looked at sibling controls. And when you look at sibling control, so pregnant woman who uses Tylenol for when she's pregnant with one child but doesn't when she's pregnant with another child, basically finds no association whatsoever between Tylenol use and ADHD, autism or any intellectual disability. The reason why the sibling part of this analysis is so important is that we know people are different, and there's always, whenever you're doing something that's not a randomized trial, you always worry about confounding. You always worry about, what am I not measuring that might be different between women who use tylenol and women who don't. Sibling studies are great because it's the same woman just in different pregnancies. And this study, the best study to date, I think, provides the strongest bit of evidence that there really is no link between Tylenol use and autism, ADHD or intellectual disability. Last point on this is there have been smaller studies, I would argue, less well done studies that seem to suggest that maybe there is a tiny

Ashish Jha: 00:03:49

link. But again, barring the definitive study, which would be a large randomized control trial, we are left with population based cohorts. And this is the best population based cohort coming out of Sweden, which tends to have fabulous data for their population. And what you see is no meaningful association between Tylenol use and either autism, ADHD or intellectual disability. So that paper from 2024 is indeed your study of the week. You

Ashish Jha: 00:04:18

You all right. And now for the question of the week, and for the question of the week, I have a very special guest, Dr Elizabeth Langen, who's a professor of obstetrics at the University of Michigan. Elizabeth, thank you so much for joining us. Thanks for having me. So my question for you is, you know, is thinking about data and evidence and guidance during pregnancy. You take care of pregnant women, and you are asked to advise them all the time on what medicines they can take, what is safe, what is not safe, given that so few drugs have been explicit. At least studied during pregnancy. How do you think about giving that advice? What approach do you take? How do you pull in evidence when we don't often have really good, rigorous, randomized trials among pregnant women?

Elizabeth Langen: 00:05:16

It's an excellent question, and honestly, it's something that I have to talk with patients about every day, because I think there is this natural instinct to say, I'm pregnant now so I cannot consume anything, take any medication in any way, expose this fetus to something that might potentially be harmful. I have patients come to me all the time and say, Gosh, I was on this list of medications that was controlling my chronic medical problem, and even my other doctor told me I needed to stop all these things because now I'm pregnant, and what if something happens to the baby. And while I very much appreciate that concern that both pregnant people as well as their care teams have when I think about somebody who's pregnant, I always think about the balance of exposing the pregnant person and their fetus to uncontrolled disease versus exposing the pregnant person and their fetus to a medication or treatment for that disease. And I cannot magically make the pregnant person not have whatever disease it is that they have, be it depression or lupus or diabetes, whatever it is they have. That is who they are when they start their pregnancy, and I have to either expose them and their fetus to uncontrolled disease or expose them to medication. So that is kind of the risk benefit that I'm balancing. And when I think about medications, there are some that clearly and consistently in multiple studies show very high risk of very similar abnormalities or adverse outcomes to a fetus. And so it's quite clear to us that these medications are of high risk because the data is overwhelming and consistent, and when that's the case, we find alternatives. You know, a common example is if we give a certain type of blood thinner in the very beginning of pregnancy, we know that can cause harm to a fetus because it's been shown over and over again. The pattern of anomalies is consistent and it there's just not a lot of ambiguity there. But we know if

Elizabeth Langen: 00:07:18

we switch to a different type of blood thinner, which is harder to take, it's injectable, it's not as pleasant, but we know if we switch, we can avoid those complications for the fetus. So we will sometimes jump through some hoops to try to get people on medications that are safer for the fetus in pregnancy. But I know that if somebody needs a blood thinner, and I don't give it to them, a blood clot that forms in the mom's lung or on the mom's heart and compromises her health is also going to compromise the health of that fetus, because if mom can't breathe, the fetus can't breathe, if mom's diabetes is out of control, the fetus is exposed to high amount of sugar. So it's not just a matter of what will this medicine do, but it's what will happen if we don't give the mom the medicine

Ashish Jha: 00:07:58

that is a fabulous framework and so incredibly helpful in that context. When you hear, and you know, I'm happy to talk specifically about what your sense is about Tylenol and pregnancy, presumably, when my wife was pregnant, we were basically told, she was told after the second trimester not to take ibuprofen, and really when she needed it for a fever or for pain, to rely on Tylenol. My sense is that is pretty standard advice. How do you think about overturning that? What is the level of evidence you'd like to see? What would make you go, ooh, now we have a real concern. We have to start weighing risks and benefits very, very differently. What is the kind of evidence that you'd you'd want to see generated to get to that real switch in guidance?

Elizabeth Langen: 00:08:46

Yeah, that's an excellent question, and sort of the question I wish people were asking, because that would put a lot of more money and funding and efforts into research about all kinds of different things that affect pregnant people. And I think that is where I would like to see efforts go, rather than simply scaring people to avoid medications. But the data that I would have to see would be, you know, studies that were done prospectively, because a lot of the studies rely on women remembering whether or not they took a Tylenol in pregnancy. And if you know, if you happen to have a bad backache or a cold and had a high fever and took a Tylenol once or twice five years ago, and now your child is totally fine. You might not remember that detail, but gosh, if your child had an adverse outcome and you're trying to find some explanation, you might hang on to that memory a little bit more firmly and recall taking the Tylenol where someone else might not. So these retrospective studies that rely on people's memories feel very uncertain to me. The other problem with a lot of these studies is there's we don't really know why the person took the Tylenol if someone has a really high fever and infection, that type of inflammation in somebody's body, we know is not great for a pregnancy, and that's not accounted for in a lot of this data. So I would. Seen some perspective studies where people going forward put down how much Tylenol they do or don't take, what the indication for it was, how long they took it, and then really systematically following these children forward, so we can know that this is harmful. But the data that exists right now, there have been some associations. Certainly no causal studies have been done there. There are some associations that are inconsistent. They are small, and again, don't account for recall bias or why the Tylenol was given. And so letting someone have a really high fever, I know is dangerous. Taking

Elizabeth Langen: 00:10:35

Tylenol, I don't really have anything clearly to show me that that's harmful. So I'm going to treat someone and make sure they don't have a high fever. That's putting them and their fetus in game in jeopardy.

Ashish Jha: 00:10:45

Great last question for you related to this. So what would you advise pregnant women around the country right now, who might see this report? Worry about, can they take Tylenol safely? What's your advice to them? Who should they get the information from? Should they be talking to their doctor? How would you how would you advise people right now, I'm sure you're getting phone calls from family and friends. Yeah, what's the advice you're

Elizabeth Langen: 00:11:08

giving? Absolutely well. I mean, the standard advice, which I think all of us want to say, is talk to your healthcare team, right? Because your healthcare team understands why you need the Tylenol. What the benefit is going to be for you as an individual, and whether or not this theoretical risk that may or may not exist is worth it in the balance of risk and benefits for you as a person. So just like exposure to anything that might be toxic, you want to minimize that for all of us at every stage of life, we always want to minimize our toxin and drug exposure. We should all be using the least amount for the shortest duration of medications, and that's true in pregnancy, but to really help you balance risk and benefit of any type of medication use in pregnancy, you should talk to the person who knows you and your health history and what's happening with you, and not any generic statements that you might find on the internet.

Ashish Jha: 00:11:56

Awesome. Dr Lange, Elizabeth Lange, thank you so much. That was really helpful. Great framing. And I appreciate you getting on on short notice. That was a fantastic

Elizabeth Langen: 00:12:04

conversation. Oh my gosh, my pleasure. Thanks for having me. I appreciate you reaching

Ashish Jha: 00:12:14

out. And there you have it, another episode of a moment in health where we talked about one data point, 65% that's the proportion of women who recall taking Tylenol during their pregnancy, though, I suspect the number is probably much higher than that, given that Tylenol is ubiquitous and generally considered safe during pregnancy. Then we talked about one study, a study of two and a half million kids over 25 years in Sweden, showing no link between Tylenol use during pregnancy and autism or other similar outcomes. And then we talked to an absolutely fabulous obstetrician from the University of Michigan, Dr Elizabeth Langan, and asked her how she thinks about this. And to me, the question, the way I set it up was, you know, there just haven't been that many studies looking specifically at drugs in pregnancy, and yet, she is advised to advise women all the time on what to take, what not to take, how to manage pregnancy. And I thought she laid out an absolutely awesome framework where she made the point that during pregnancy, you want to lay out both the risks of uncontrolled disease, somebody has diabetes, somebody has depression, not treating those things is bad for the mom. It's also bad for the fetus. It's also bad for the baby. Treating them with drugs is helpful for the mom. It may or may not be bad for the baby, and it just depends. Just depends on what the evidence is. And then she talked about that risk benefit, that conversation, and then also the importance of, if you're going to make a recommendation against using a certain medicine in pregnancy, the kind of evidence you want to see. You want to see prospectively collected data. You want to see consistently the same bad outcomes showing up over and over again. And based on her framework, to me, and I'm not an obstetrician, but I read the evidence, there is nothing like that for Tylenol and pregnancy. And so it strikes me that what we saw coming out of the administration is

Ashish Jha: 00:14:19

wildly irresponsible. It doesn't rise to the level of evidence that you'd want before you make a recommendation for women not to use Tylenol, and combine that with the Swedish study, combine that with how much women really use tylenol because they don't have a good alternative, and the answer right now is yes, go talk to your doctor, get advice from your doctor, but boy, it is hard for me to see On what basis we should be recommending that women avoid Tylenol during pregnancy. So anyway, that's a sort of summary of this episode. Thank you so much for joining us. We'll be back again next week with another episode of a moment in health where we're gonna talk about one data point, discuss a study and answer a question. Have a good week, everybody. You. You.