4

There are apparently a bunch of law groups recruiting for potential class action lawsuits happening right now targeting medicines that contain acetaminophen, most notable Tylenol. The lawsuits allege that the use of acetaminophen products during pregnancy caused children to develop autism spectrum disorder. All of the lawsuits seem to be motivated by the Consensus statement 'Paracetamol use during pregnancy - a call for precautionary action.'

I've scanned through a bit of this paper. I have neither the time, access to the cited studies, nor the skillset to fully evaluate the paper's claims, but I'm always inherently skeptical of any "autism is caused by X" claims. The paper seems to be warning of a multitude of potential risks that add up to a potential for caution, not a 'Tylenol definitely causes autism' claim as the lawsuits seem to be implying. There also also a lot more emotionally weighted terms that would usually make me suspect bias if they showed up in a study, but I'm not sure how common that may be for a consensus statement.

In short, I'm not sure how much credibility I should be giving to the consensus statement in general, and in particular I want to know how much credibility the claim that acetaminophen leads to autism which the lawsuits seem to be implying is. How definitive are the real studies on this subject?

6
  • 1
    Perhaps the cited review article would be a good start. The highlights of the study seem pretty convincing.
    – user36020
    Commented Jan 22, 2023 at 18:38
  • 1
    And you think the doctors and researchers here behind the keyboards are in a better positions than the pesky lawyers and judges that will here the case? You're asking us to preempt the lawsuit that's going to decide the matter. Talk about current event!
    – pipe
    Commented Jan 22, 2023 at 19:25
  • 3
    The drive for the lawsuit is not the plausibility of the effect or the evidence but the wealth of the industry being sued. There isn't even a case for saying the industry continued to sell a potentially dangerous product as most of the papers are very recent. But that sort of reasoning never stopped lawyers.
    – matt_black
    Commented Jan 22, 2023 at 20:44
  • 2
    Some of the very recent papers propose a mechanism for the effect. But it involves metabolic defects commonly present in ASD so, logically, paracetamol might make ASD worse but it seems hard to blame it for causing ASD .
    – matt_black
    Commented Jan 22, 2023 at 20:45
  • 4
    If you'd summarize the outcome of this study, it would be unhealthy woman getting higher risk of babies with developmental disorders. I'm not saying it's impossible, but much more research is needed. There is no causation here (yet), just correlation. But this is how science work, we start with a big scope and narrow down to find any culprit if there is any.
    – Timmetje
    Commented Jan 23, 2023 at 9:48

1 Answer 1

16

Unless otherwise noted, quotes are taken from the associated review article.

Does acetaminophen use during pregnancy lead to children developing autism?

NO.

[acetaminophen] is one of the most commonly used medications globally. In the USA, [acetaminophen] is estimated to be used by up to 65% of pregnant women. Worldwide, more than 50% of pregnant women are estimated to use [acetaminophen]. [acetaminophen] has long been considered an option by regulatory bodies such as the FDA and EMA for use in pregnancy for pain and fever when used as directed, as NSAIDs are contraindicated for use in pregnant women in later pregnancy. Pharmacotherapy during pregnancy involves a benefit–risk assessment, in which there is a trade‐off between the potential benefits to the mother and fetus and possible risks to the fetus. The FDA has formerly given [acetaminophen] a ‘B’ rating for use in pregnancy in all three trimesters, meaning that animal studies have failed to demonstrate any risks of congenital birth defects from fetal exposure and that no adequate and well-controlled studies have been performed in pregnant women. In addition, the EMA has found epidemiological data inconclusive and that experimental data do not meet their standards.

Acetaminophen is a commonly used drug during pregnancy. There is no direct evidence that it is unsafe, and has been used for more than 150 years. The major professional body for obstetrics published the following statement in response to this review article:

A consensus statement that was recently published in the journal Nature Reviews Endocrinology claims that a growing body of research shows that prenatal exposure to paracetamol, or acetaminophen, may alter fetal development and increase the risks of neurodevelopmental, reproductive, and urogenital disorders.

ACOG and obstetrician-gynecologists across the country have always identified acetaminophen as one of the only safe pain relievers for pregnant individuals during pregnancy. This consensus statement, and studies that have been conducted in the past, show no clear evidence that proves a direct relationship between the prudent use of acetaminophen during any trimester and fetal developmental issues.

Neurodevelopmental disorders, in particular, are multifactorial and very difficult to associate with a singular cause. The brain does not stop developing until at least 15 months of age, which leaves room for children to be exposed to a number of factors that could potentially lead to these issues.

The authors are not recommending anything counter to what is already done by obstetrician-gynecologists when prescribing acetaminophen for a given clinical condition. ACOG’s clinical guidance remains the same and physicians should not change clinical practice until definitive prospective research is done. Most importantly, patients should not be frightened away from the many benefits of acetaminophen. However, as always, any medication taken during pregnancy should be used only as needed, in moderation, and after the pregnant patient has consulted with their doctor.

Does the review article actually say anything inconsistent with this professional statement?

NO.

Acetaminophen is an interesting drug - it is very unlikely that it would, if discovered today, be an over-the-counter medication. The mechanism of action is broad and not well-understood, it has a number of fairly serious side effects, and the therapeutic range (the range between the dose that helps do what it's supposed to do and a toxic dose) is narrow, which is a particular risk for people who take it regularly. There are very real reasons to be concerned that it might be a risk.

The review article summarizes the summarizes studies about these risks:

Another study has demonstrated reduced AGD in boys exposed to the combination of [acetaminophen] and NSAIDs during pregnancy, suggesting a potential additive effect as exposure to [acetaminophen] alone did not result in a significant difference in AGD. Similar additivity with other analgesics has been seen for cryptorchidism, where the association is strongest among mothers using more than one analgesic during pregnancy. Moreover, exposure to [acetaminophen] for >2 weeks increased the risk of cryptorchidism. Most associations for cryptorchidism are seen following long-term [acetaminophen] exposure (>2 weeks) during late first to early second trimester, which is consistent with the critical time windows for development. Thus, these data suggest that the timing and duration of maternal [acetaminophen] use are critical factors and that short-term [acetaminophen] use might be of limited risk.

There may be a correlation between taking acetaminophen and some physical developmental disorders, with long-term exposure during critical stages of fetal development.

The relationships between prenatal [acetaminophen] exposure and adverse neurodevelopmental outcomes have been investigated in 29 observational studies in 14 cohorts including over 220,000 mother–child pairs from different parts of the world [...] Effect sizes were generally modest but because exposure is widespread, even a small effect size could translate into a large number of affected children. [...] In many of these studies, associations were weak for short-term exposure suggesting that short-term use might be of limited risk. As with reproductive and urogenital outcomes, exposure timing is important, as the highest risk seemed to occur from exposure during the second and third trimesters of pregnancy (with some exceptions).

There may be a correlation between taking acetaminophen and some neurological developmental disorders, with long-term exposure during critical stages of fetal development.

The authors note the potential confounding effects that make these studies difficult, and which are very difficult to resolve when the treatment (acetaminophen) is so widespread. They also reference in passing some experimental results that are generally unconvincing, as if or how they'd translate to clinical practice is unknown, and I will omit for brevity. This review article does not reference any causal evidence for a link between acetaminophen and neurological disorders (which does not exist at this time), only correlative evidence and mechanistic speculation.

The specific guidence suggested by the authors of this review is as follows:

We recommend that women be counselled prior to or early in pregnancy with the following guidance:

  • Pregnant women should forego [acetaminophen] use unless medically indicated.
  • Pregnant women should consult with their physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis.
  • Pregnant women should minimize risk by using the lowest effective [acetaminophen] dose for the shortest possible time.

This is very similar to the guidance in place for obstetrics for the last 50 or so years. In short, there are potential risks with long-term acetaminophen treatment, and you should not take medications while pregnant without discussing it with your obstetrician.

Why are lawyers recruiting for class action lawsuits?

I have no idea.

I don't think this is by any means an easily winnable case, based on what we know right now medically. Perhaps we will learn more in the future and the link will be stronger. Perhaps the medical evidence doesn't matter and the expectation is that a jury will side with crying mothers. Tylenol is made by Johnson & Johnson, which is a massive deep-pocketed conglomerate, so there's money to be made if they can win (or settle). I can't predict the future of this case and won't try.

2
  • 2
    Regarding Why are lawyers recruiting for class action lawsuits? Money. What else? Commented Jan 25, 2023 at 23:24
  • 1
    @DavidHammen - the money side is complicated: J&J is being sued over cancer from talc in baby powder, and if you can get a large jury award for anything else at just the right time (award before J&J goes into Chapter 11, but with an appeal timed for afterwards) then you may get to be high up the list of creditors
    – Henry
    Commented Feb 1, 2023 at 16:06

You must log in to answer this question.

Not the answer you're looking for? Browse other questions tagged .