Tylenol, pregnancy, and autism: What recent studies show and how to interpret the data

**Peter Attia** (0:11)
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Welcome to a special episode of The Drive everyone. If you've been following the headlines recently, you may have seen, of course, stories linking acetaminophen or Tylenol use during pregnancy to autism. Not surprisingly, those headlines have generated a lot of questions, a lot of controversy and a lot of confusion. I've heard about this a lot from every direction. My patients, listeners of the podcast, friends, family members, people writing in through the website. Basically, it's like I'm sure many people in the space, we've all been inundated by it. And the more I thought about it, the more I realized this was a great opportunity to, I think, maybe put forth a framework for how to think about these things critically. While we initially thought we would just do this in the newsletter last week, once we got into it, we realized, now this doesn't really lend itself to an article or even a short video. It really commands effectively the discipline of what we do in the AMAs, the Ask Me Anythings. Of course, unlike the normal AMAs, this is gonna be made available to everybody. So before we dive in though, I wanna kind of lay out some groundwork. We're gonna unpack some of the points in more detail that I'm gonna lay out below. But I also wanna make sure we're starting from a place of reference. I wanna start out with a few important observations. Okay, so the first is, autism rates have risen dramatically over the past generation. Now we're gonna talk about why that might be, but it's very important to state up front that there is unlikely to be a single cause. Why? Because complex conditions usually don't have simple explanations. This is true of obesity, despite what some people would have you believe, that it's just this one thing or just this one thing or whatever. But the reality of it is, complex conditions require multiple things typically. So anytime we look at a possible contributing factor, we need to kind of resist the temptation to assume it's the sole cause. Now that doesn't diminish the interest in identifying a bunch of potential causes. Okay, second point I wanna make here, and it's kind of weird that I have to make it, but I do, science is supposed to be apolitical. Unfortunately, that's not the case. And for reasons that I don't think I'm smart enough to understand, autism happens to be one of those examples. But so are many other topics we've discussed, like nutrition or protein, which has become remarkably political. My goal here is not to have a political debate, but rather to examine the evidence as carefully and objectively as I can. Third, we do need to realize something that I think is very hard to accept, and that is that as humans, we are not wired to think scientifically. I want to restate that, because it sounds condescending, but it's simply an observation of how we have evolved. We are not wired for critical and scientific thought. This is something I've written about, and we're going to actually link to a piece I wrote over 10 years ago that I think synthesizes that point really well. But again, it really comes down to the fact that we should understand that the scientific method and critical thought are human inventions. They're wonderful inventions, and I would argue they are the single most important invention our species has ever put forth. And without this, nothing else would exist. We'd still be living in caves. But that doesn't mean that it comes naturally, and it doesn't mean we're wired to do it. So just keep that in mind as you catch yourself, as I catch myself falling into non-scientific thought. We're gonna rely on a framework at some point during this discussion, which is very helpful when considering epidemiology, which is the branch of science we're gonna be talking primarily about today, and it's called the Bradford Hill criteria. These are nine principles that were laid out in the mid-60s to help us determine whether an observed observation is likely to be causal. So this framework looks at things like strength of association, consistency across multiple studies, biologic plausibility, temporality and things like that. They're not a checklist per se, but they provide a disciplined way to try to make sense of correlations and interpret which ones have a higher probability of being causal from those that don't. Another thing I want to point out is we're gonna be talking about medications, we're gonna be talking about pregnancy. And I think it should be obvious, and I'm sure anyone listening to this or watching this, who has gone through pregnancy, will understand that the bar is very high when we are talking about medications to be used during pregnancy. Most physicians, myself included, though I don't treat very many pregnant women, think about drugs and supplements very differently in the setting of pregnancy. Of course, because we are typically not treating patients with life-threatening conditions, our mantra is during pregnancy, women should basically stop all medications and supplements beyond the obvious ones, such as prenatal vitamins or hormones, such as thyroid hormone, which can be essential. But anything that's even in a gray area or probably okay, we tend to just avoid. Now, since the late 70s, the FDA has used a very simple letter system to classify drugs by their risk during pregnancy. These categories go by A, B, C, D, and X, and basically each letter refers to a level of evidence, mostly from animal and human studies, about the potential harm of the drug to the fetus. So for more than, I don't know, 35 years or so, this was the framework physicians relied on. About 10 years ago, the FDA replaced it by a framework that was called the Pregnancy and Lactation Labeling Rule, or the PLLR. The idea was to move away from single letters and instead provide a more descriptive guidance. And in theory, that's an improvement, but in practice, it's been kind of slow to roll out. And frankly, I'm a little guilty of generally thinking about it in the ABCDX category, and that's what I'm going to refer to a little bit. So I'm going to stick with that older category. And while it's imperfect, it's widely understood. It is still a clear framework. And I just want to share with you as we begin this, so you have a broad sense of how drugs fit into this. Okay. So category A means that there is no demonstrated risk in well-controlled human studies. Again, that's pretty unusual because that's a hard thing to do. And that's reflected in the proportion of total drugs and supplements out there that fit in this category. And it's somewhere between 2% and 5%. Okay. So what does that mean? That means that is completely safe. We have definitive evidence that women can take these things during pregnancy and obviously as reflected by the numbers, virtually nothing fits in that category. By the way, the examples I gave earlier of thyroid hormone and prenatal vitamins do fit in that category. Then you have Category B which says there's no evidence of risk in humans, but animal data might show signals in some studies. And so these are generally thought of as safe, but exercise caution basically, and this is 15 to 25%.