Tylenol Could Be Risky for Pregnant Women – A New Review of 25 Years of Research Finds Acetaminophen May Contribute to ADHD and Other Developmental Disorders in Children

Yves here. I must confess that one reason I am running this piece is that I have long and loudly maintained that acetaminophen, aka Tylenol, is too dangerous to be sold OTC. Less than 2x the recommended dose level is considered toxic. Mind you, its dangers have been known for decades. From a 2004 article:

Acetaminophen overdose is the leading cause for calls to Poison Control Centers (>100,000/year) and accounts for more than 56,000 emergency room visits, 2,600 hospitalizations, and an estimated 458 deaths due to acute liver failure each year. Data from the U.S. Acute Liver Failure Study Group registry of more than 700 patients with acute liver failure across the United States implicates acetaminophen poisoning in nearly 50% of all acute liver failure in this country. Available in many single or combination products, acetaminophen produces more than 1 billion US dollars in annual sales for Tylenol products alone. It is heavily marketed for its safety compared to nonsteroidal analgesics. By enabling self-diagnosis and treatment of minor aches and pains, its benefits are said by the Food and Drug Administration to outweigh its risks. It still must be asked: Is this amount of injury and death really acceptable for an over-the-counter pain reliever?

Acetaminophen also kills cats.

Now it turns out that acetaminophen, instead of much-maligned vaccines, could play a role in the rise of autism.

By Ann Z. Bauer, Postdoctoral Fellow in Epidemiology, University of Massachusetts Lowell. Originally published at The Conversation

The Big Idea

A mounting body of evidence shows that the use of acetaminophen – widely known by its brand name Tylenol – during pregnancy may pose risks to the fetus and to early childhood development. That was the conclusion of a new review study on which I was a lead author.

Acetaminophen, which has the chemical name paracetamol, is a go-to over-the-counter medication that is widely recommended by doctors to relieve pain and reduce fever.

Our study, based on an assessment of 25 years of research in the areas of human epidemiology, animal and in-vitro studies, concludes that prenatal acetaminophen exposure may increase the risks of reproductive organs developing improperly. We identified a heightened risk of neurodevelopmental disorders, primarily attention deficit hyperactivity disorder and related behaviors, but also autism spectrum disorder, as well as language delays and decreased IQ.

In our consensus statement – a broad agreement by our multidisciplinary international panel of experts – published in Nature Reviews Endocrinology in September 2021, 91 clinicians and researchers are calling for caution and additional research.

Why It Matters

Acetaminophen is an active ingredient in over 600 prescription and over-the-counter medications. It is used by more than 50% of pregnant women worldwide and at least 65% of pregnant women in the U.S. Research suggests that acetaminophen is an endocrine disruptor and may interfere with the hormones essential for healthy neurological and reproductive development.

Current guidance recommends acetaminophen as the pain reliever of choice during pregnancy, as other pain relievers such as ibuprofen and aspirin are not considered safe after midpregnancy.

Rates of reproductive disorders and neurodevelopmental disorders, such as ADHD and autism spectrum disorder, have been increasing over the last 40 years.

Over the same time period, the use of acetaminophen during pregnancy has gone up. We conclude that because acetaminophen is so commonly taken during pregnancy, if its use is responsible for even a small increase in individual risk, it could contribute substantially to these disorders in the overall population.

What Still Isn’t Known

It’s unethical to do experiments that could harm a human life, so to gain a better understanding of the direct effects of acetaminophen during pregnancy, we must rely on human observational and experimental studies to assess the possibility of causal connections. But to really get at these questions, we need human cohort studies that can precisely capture when and why acetaminophen is taken during pregnancy. Additionally, we would like to see research that gives us a better understanding of the biologic pathways.

Notably, acetaminophen is also the medication most commonly given to infants. More research is needed to determine whether this practice is safe for the developing brain.

What’s Next

The current near-ubiquitous use of acetaminophen during pregnancy is due in part to the widespread perception – even among doctors – that it has limited side effects and negligible risk. But a growing body of research suggests that the indiscriminate use of acetaminophen during pregnancy – especially for conditions such as chronic pain, low back pain and headaches – may be unwarranted and unsafe.

In our consensus statement, we urge education of health professionals and pregnant women about the risks and benefits of acetaminophen use during pregnancy.

Based on our extensive review of the evidence – and the recognition that there are limited alternatives for the necessary treatment of high fever and severe pain – we recommend that pregnant women refrain from using acetaminophen unless it is medically recommended by a doctor. Women should also minimize risk to the fetus by using the lowest effective dose for the shortest possible time.

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52 comments

  1. PlutoniumKun

    There is also significant evidence that it alters the microbiome in unpredictable ways.

    I became interested in this some years ago when I had a chronic pain problem following an accident and experimented with different over the counter meds (doctors here are far less likely to prescribe painkillers than in most countries). I really didn’t like the effect most of them had on me – I fell back to old fashioned aspirin and sometimes Ibuprofen (which has its issues too) and eventually worked out other ways of addressing the particular pain problem I had (mostly yoga and lots of walking).

    I don’t know the situation in the US, but on this side of the Atlantic it is very widely used by doctors and so far as I’m aware, doctors are trained to see it as a safe and cheap backup for almost any form of pain (its often given in prescription form to patients seeking painkillers and unaware that they are just being given a stronger form of what they could buy OTC). Sometimes its given in a mix with Ibuprofen. A friend who is a doctors wife told me she was worried about just how much he took himself, she bought a pack almost every week for him.

    After doing my reading on this a few years ago, I decided that the majority of pains are better addressed by just living with them for as long as you can. I still take ibuprofen or others occasionally, but only when its really needed to get some relief or sleep.

    Reply
    1. Yves Smith Post author

      I was really annoyed when I was at the hospital that the staff insisted on giving me Tylenol, which I made them stop ASAP. One reason for them not being willing to administer anything else is that aspirin and NSAIDs are blood thinners, and they didn’t want to do anything to interfere with blood clotting.

      A NSAID we have here OTC which is not bad is naproxen. But yes, I don’t take them unless I have a bad headache (which fortunately I pretty much never get).

      My doctor now had me on a prescription NSAID because I’ve become very inflamed around the surgical sites. Nasty stuff. Really bothered my digestion (not just stomach….). I’ve stopped taking it.

      Reply
      1. PlutoniumKun

        I have very slight osteoarthritis in one hip after an accident. Usually here doctors say to take Ibuprofen for things like this when it flares up (for some reason – it may be related to the blood thinning issue – acetaminophinine is usually favoured here by hospital doctors while family doctors prefer Ibuprofen).

        My local doctor is great. When I was talking about this with him he told me take turmeric to keep inflammation down. Lots of foods have anti-inflammatory qualities and (maybe because of microbiome issues), its good to experiment with different ones to see if they help with long term chronic aches.

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        1. Terry Flynn

          You have a good doctor. Another route can be great but can be awful – gabapentin/pregabalin.Trouble is the overall effects are bimodal in both – there is a group for whom these meds are live savers. Another group experiences rapid increases in tolerance and addiction. The doctors still can’t predict which group you may fall into since “addictive behavior” is not a strong predictor. I can take or drop a benzodiazepine easily. Pregabalin? Nope. Docs still profoundly worried by these because they don’t know what’s going on.

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          1. SteveB

            Have been on pregabalin for 10 years for chronic nerve pain. Started to get many side effects. Alternative medicine MD asked me to let him try Ozone injections in the area
            of pain. Long story: Bottom line I was able to reduce the amount of pregabalin I was taking by 1/2. Still get Ozone injections every 2 weeks or so… He taught my wife (retired RN)
            how to give injections when we moved away…

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          2. Jason Boxman

            That’s impressive; Dropping a benzo destroyed me for years. In the United States at the time (and still?) no one took them seriously, so I had to taper myself. The proper way is switch to valium and step down, but I was stuck cutting a tablet into pieces. The day after a cut was always brutal. I’d lay in bed catatonic unable to even move or fully perceive the world.

            Not an experience I’d recommend.

            Reply
            1. Terry Flynn

              I have generalised anxiety disorder. Valium is my saviour. But I deliberately don’t allow my body to get used to it. I mess with dosage, days off etc. Often I have to anticipate bad days, good days. Doesn’t always work out. But generally I can do it. I’ve shown docs I can do this.

              This is why pregabalin was a nightmare. The manufacturer said it was “easier”. Nope. Thus the government reclassified it. Watching the prescribing stats was “interesting”! Most people on it in North Nottingham UK are at a single General Practice and are 99% likely ex-miners with terrible pain.

              Reply
        2. Eustachedesaintpierre

          PK – The best doctor we ever had was situated in Mullingar – a nice fella who was I believe back then the only Doc in the town who treated Travellers. He looked after Pam & visited her at home when he had the time, while also after she had gone craftily organised for me a drastic weekend cure for advanced feeling sorry for myself.

          BTW – FLCCC have just added turmeric & black cumin seed with honey to their prophylaxis protocol – the latter contains thymoquinone which appears to have much potential as an inflammatory & antioxidant while also appearing to work as a neutraliser of cytokines.

          Been around a bit as the seed was found in Nefertiti’s tomb.

          https://www.sciencedirect.com/topics/medicine-and-dentistry/thymoquinone

          Reply
          1. PlutoniumKun

            Thats interesting, I hadn’t heard about the black cumin seed effect.

            I’ll avoid my usual rant here about the failure of the science establishment to do really good long term studies on the use of specific foods as prophylactics against a wide range of conditions.

            The one thing that really impresses me is the evidence around sulforaphane – the main ‘active’ ingredient in broccoli. It has a remarkable range of positive effects, but is notoriously hard to keep stable, so its not easy to buy as a supplement. Brexit cut off my supply from France (for convoluted reasons). I grow lots of broccoli sprouts for my daily smoothie, but of course I’ve no direct means of knowing if its doing me good or not.

            Reply
      2. Susan the other

        I jus googled this again to be sure. Melatonin is a very effective anti inflammatory. They say it is at least partly due to its anti oxidant effects cleaning up free radicals, etc. And not so bad as a sleeping pill either.

        Reply
        1. Eustachedesaintpierre

          Yes, swapped melatonin for her prescribed quetiapine & for a while now she has been sleeping much better with the return of her dreams, so therefore I assume more REM.

          Reply
        1. t

          In the UK, when I was there, Paracetamol was OTC but you had to ask for it and could only by maybe 12. Canada the same. (Not that I bought it. I cannot tolerate it at all.)

          Reply
          1. CoryP

            Canada you can definitely buy 100+ pack sizes of APAP 500mg in a bottle with a “child-resistant” cap. Actually some of the bottles have this arthritis-friendly cap which now that I think about it cannot even pretend to be child-resistant….

            Oh and you can buy Tylenol #1s aka acetaminophen/caffeine/8mg codeine in bottles of 200 tablets but you have to ask for them at the pharmacy counter. Technically the pharmacist has to be involved in the sale. But in the opioid-addled town where I work, this basically involves the pharm assistant shouting “hey! This guy says he’s taken them before and doesn’t have any questions for you!” and the pharmacist goes “yep!” and goes back to the phone call, blister pack and Covid test they were trying to do simultaneously.

            (Man this profession is a joke right now…)
            /rant

            Reply
            1. Terry Flynn

              Twas same in UK till 10-15 years ago. Now although you can still buy it with caffeine or with codeine, the former has small amount of caffeine and the latter will virtually always get you a one-to-one inquisition from pharmacist as to why you need codeine too.

              (plus the 16 tablets per pack thing trumps all)

              Reply
    2. Terry Flynn

      The microbiome was brought up as potential reason for increase in autism here on NC a while back. Apologies I no longer have the reference but the appropriate site specific search can I’m sure find it. We have half as many bacteria as our parents etc….

      I certainly don’t discount analgesics but maybe we should keep in mind the argument NC pondered back then – that increasing amounts of processed foods were causing poorer microbiome and in turn increased autism. I’m the type to look for multiple effects…!

      Reply
      1. PlutoniumKun

        My Polish neighbours have an autistic boy and they swear by non-dairy and high fibre diets for him. They say the transformation in him when they changed his diet (following advice from a somewhat fringe doctor) was remarkable (they attribute it to microbiome improvements). They were saying he reverts back in behaviour when staying with his grandmother as she struggles to get the right food. They are both very level headed people so I’d be inclined to believe them.

        Reply
        1. Terry Flynn

          That sounds amazing. Please take this in the jokey way it is intended but does anything go wrong in your life?!

          My Irish Mum is completely crushing me in terms of things that are falling apart here in UK compared to Skerries (where she grew up before moving to UK) etc…

          Reply
          1. PlutoniumKun

            Skerries is a lovely town. It still feels like somewhere thats been a bit by-passed by the last few decades, but its all the nicer for it. My parents used to love going out there for lunch and a stroll by the harbour. A while back I brought two Japanese friends who live here for a daytrip out to walk the beach and they said it reminded them of small Japanese coastal towns and they immediately started asking about the cost of rents there.

            I’ve been having regular online chats with friends in the UK comparing notes on shops, etc. Ireland, like most of Europe is struggling a little with the HGV driver shortage, but there is no indication yet of any impact on supermarket shelves. One friend of mine is extremely upset now that M&S are cutting back their food range. She is a recent Irish citizen and I regularly berate her for buying M&S spreadable butter when she could be buying Kerrygold, but she hasn’t quite gotten the knack yet of letting butter soften naturally.

            Reply
  2. timbers

    I always take aspirin – never acetaminophen. Don’t mind saying one of the reasons being I enjoy drinking wine (too much sometimes) and I plan on having a healthy liver so I can continue to so so for many decades to come.

    Acetaminophen is not part of a plan to keep the liver healthy.

    Reply
  3. Scott 2

    I’ve been nursing a swollen knee for a few weeks (partially torn meniscus). I’ve tried 5 different OTC and prescription anti inflammatories and so far the best performer is good old-fashioned aspirin. A close second is topical indomecetrin which was OTC in Japan and Europe for decades, but now available in the US.

    Reply
  4. Great job!

    In my toxicology class in college I learned in great horrific detail the way one dies from an o.d. of acetaminophen. I also learned that acetaminophen has a very strong synergistic effect with alcohol (ethanol) that magnifies the toxicity to the liver when the compounds are present together. Very important information to know as a college student looking for a hangover cure. Suffice it to say that I’ve been personally aware of the risks and dangers of acetaminophen for years, especially taken while there may be alcohol in the system.

    Reply
  5. Terry Flynn

    Paracetamol is my goto painkiller but I am always very aware of how much I’ve taken. NSAIDS (aspirin/ibuprofen) give me chronic stomach pain and cause a bleed for my mother even in small amounts.

    What annoys me is that there is a perceived “choose your poison” dichotomy element here – liver or stomach problems. Via certain other ailments I learnt of other meds that were never invented as analgesics but like aspirin turned out to be wonder drugs with benefits in many areas. Thus I discovered amitriptyline – invented as an antidepressant but at SMALL sub-anti-depressant doses is well known to be amazing at dealing with non-specific pain, insomnia etc. Of course it is long off-patent so gets no attention but specialists in some areas love it.

    Reply
      1. Terry Flynn

        1. Please put into context how many KEY classes of drugs (like mood stabilisers essential to make bipolar sufferers be able to stay out of mental hospitals) DON’T have risks of dementia. (Hint – it isn’t many).

        2. Please put into context how many people would suffer such intolerable quality of life without these classes of drugs. Please also state if the dosage you’re advising of risking dementia is the “tiny dose” used for other things or the dose used for antidepressants. Since I already know most research was done when these “made money” I’m willing to bet the quality of the former is poor.

        3. Context generally. Medicine is so often a trade off. I’ve written the top book in a branch of patient trade offs. Glib point scoring annoys me. Please consider those who were ready to do something like evade security and jump off Sydney Harbour Bridge. Beats possible dementia 30 years later.

        Reply
    1. Utah

      I used to take amitriptyline for migraines. It worked great. Had to come off of it because it made my teeth grinding worse and I cracked a tooth, even at the lowest dose. If I didn’t have that problem I’d still take it as I had no other side effects and it helped so much.

      Reply
      1. Terry Flynn

        That’s interesting. If you feel willing to share, was this a night-time teeth grinding issue? I had no problem for about 10 years, then night-time sleep-walking started with no explanation other than the amitriptyline.

        The shrink implied that long – term use in some people could cause trouble but he was also very well versed in insomnia and my “pain auto-immune issue” had settled by then so moving to another mental health drug (but again at a dose WELL below its “psychological dose”) gave me equally good protection against insomnia and the auto-immune issue, although reappearing with a suspected covid infection, has not been serious/frequent enough to seek help. So I’m ok.

        Reply
  6. Anon

    Tylenol can also cause vertigo. Published research has proven that. Yet most doctors are totally unaware of Tylenol’s side effects.

    I have a chronic illness that causes severe daily headaches and constant vertigo. I am allergic to aspirin and can’t tolerate NSAIDs. I take Tylenol only when the pain becomes excruciating but I know that I will have increased vertigo as a result and am more likely to suffer from a fall.

    Reply
  7. Arakawa

    Worth looking into whether this explains the anecdotal observed link between giving a childhood vaccine and developmental regression. Suppose the vaccine causes a fever, the fever is medicated with a large dose of Tylenol, the Tylenol produces brain damage. Parents know something caused the damage, but assume the ‘ordinary’ Tylenol couldn’t be the culprit.

    Reply
      1. Arakawa

        I’m requested to pay money for the PDF which means I can’t verify your claim.

        If you are going to dismiss vaccines as a cause of autism, you have to find and present some alternative explanation for the developmental regression some parents observe besides “it’s all in your head, our statistics don’t show it”. Otherwise, what is the use of your statistics, exactly?

        Reply
  8. petal

    For a long time, when I was bored and my brain wouldn’t shut off, my scientist brain would think about and wonder what might have increased in use/availability along with the rise of autism(was it forever chemicals, drugs, other things?), and it occurred to me that tylenol did. I remembered the tons of commercials that were on tv when I was a kid that targeted pregnant women, and how the commercials said it was “the #1 pain killer given to pregnant women” and women giving birth/new moms or whatever and was “completely safe”. There was a big push during this period to give tylenol to pregnant women. Does anyone else remember this(would have been on tv during late 80s, 90s, 00s)? I’m so glad that this possible association is being looked at.

    Reply
  9. Joe Well

    All the more shocking that acetaminophen and other pills are sold loose in bottles in North America rather than in blister packs like in many (most?) other countries.

    Reply
    1. Terry Flynn

      In UK you used to be able to buy them in large quantities in a bottle (100 tablets?) but the law was changed. Now you cannot buy more than two packets of 16 tablets (which must be in blister packs) of painkillers at a time.

      Recently I learnt that this is 32 tablets in total, no matter what the painkiller. So don’t try to buy 32 paracetamol plus 32 ibuprofen etc. I was shopping for mum (paracetamol) and dad (ibuprofen) and was told to put two of the 4 packs back.

      Co-codamol (paracetamol + codeine) law also changed. The strength of codeine allowed OTC was radically reduced. Pregabalin was moved to a Class C drug meaning it must be initiated only by certain doctors. It had become the street drug of choice in Nottingham.

      Reply
  10. Carla

    Took acetaminophen probably 50 years ago for a headache and it did ZERO. Have stuck with aspirin ever since with no regrets. Fortunately, I don’t have to take it often. Saw research in last coupla years stating that Tylenol was no better at pain relief. Will try to find link & post.

    Reply
      1. Terry Flynn

        Hmmm. As I say elsewhere in the thread, I treat paracetamol with respect. I am on an MAOI antidepressant and the only two times I got a bad food reaction making me consider hospital were after eating “western” foods that werent meant to include soy (the one no-no for me). So I look carefully.

        The almost identical rates of mistakes in north america and UK concerning meds that contain paracetamol is what I’d politely call a “red flag” given that that name has VASTLY different recognition factors. Plus the structure – scary risk, a one in a million risk (without reference to whether it is EACH factor or overall) just confirms my (yes anecdotal) experience with The Conversation.

        I and my boss vowed NEVER to publish there again after an editor clearly wanted us to “fit a predefined story”. It’s like the Guardian – they syndicate Ben Goldacre after looking bad over MMR but then he’s gone. Why? Plus check the conflicts of interest. I LOLLED straightaway.

        Reply
  11. marieann

    I take a fair bit of Acetaminophen. I have arthritis in almost all of my joints, I also have chronic sinus headaches. I am also on Celebrex daily so I don’t ever take any other NSAIDs. I never come close to the maximum 4 grams recommended daily

    I am always cognizant when buying other OTC’s to make sure I check the ingredients.I have found acetaminophen in many otc products eg: cough syrup, sinus meds, sleep aids.

    If one were to buy any the above listed it would be easy to overdose on tylenol without being aware of it.

    I think this is an overlooked danger of being able to buy otc’s without assistance from medical personnel

    Reply
  12. CoryP

    Just read the whole review. This will definitely inform my practice. It’s fascinating but also oh my god, the scale of this problem…

    I had always assumed forever chemicals, plastics and pesticides/herbicides were the reason we as a species are getting increasingly weird in terms of neurological and sexual development and function…

    Reply
  13. Jason Boxman

    Thanks for posting about this over the years! I had no idea, and I’ve sworn off acetaminophen ever since. If I can’t spell it, I probably shouldn’t be taking it anyway.

    Reply
  14. boz

    Before I had children of my own, I remember over hearing a colleague who was regularly on the phone to someone (husband? Nanny? Not sure) about her young son. I remember his name, but all I heard was “calpol” this and “calpol” that and “calpol” the other thing.

    Now I have children, I understand what calpol is.

    When nurses on the maternity ward endorse something, you listen to them.

    https://www.theguardian.com/lifeandstyle/2019/jun/04/why-parents-are-addicted-to-calpol

    Reply
    1. Conrad Schumacher

      Here in NZ calpol is known as Pamol and is the ubiquitous panacea for infants. We frequently dosed all three of our children with it when they were little.

      I suspect it will be viewed as this era’s laudanum in a generation or so.

      Reply
  15. rowlf

    One of my aunts, a retired surgical nurse of the Nurse Ratched mold, has had Tylenol as one of her hot-button issues for the last three decades, frequently stating that it was evil and needed to be removed from use. Unfortunately I haven’t had a chance yet to find the basis for her viewpoint.

    After so many years of findings like this I wonder how well the medicines rolled out in the last year will age.

    Reply
  16. Darius

    Tylenol does nothing for me. If I’ve overdone it or have a bad cold, I’ll take naproxen a couple hours before bed. Usually does the trick. I also use aspirin since I take it anyway for my heart.

    However, when my daughter was an infant, baby Tylenol worked wonders for teething pain and other crises. We were always careful to use it sparingly. But that’s just us.

    Reply
  17. great-aunt REIT

    The illicitness of a substance, pharmaceutical or otherwise, the desire for control does not correlate to toxicity. It is social convention. Acetaminophen in vivo was first practiced in German in the late 19th-century. In 1914 Munich one brand began being marketed as “TOGAL, THE SOVEREIGN PAIN RELIEVER” – the less said about that the better. Common remedies are cultural markers both within the privacy of the hearth and frequently transmitted between social groups in folk tradition.1943 Stateside, acetaminophen was first combined with hydrocodone out of wartime necessity. Acetaminophen production in Munich then came to an abrupt halt in the same air campaign as diesel engines.

    The cultural ubiquity of acetaminophen in the industrial west cannot be understated. We have blister seals because some mad man poisoned acetaminophen in Chicago. Doctors having the same cognitive basis and marketed-to upbringing as everyone else, would need to witness catastrophic consequences during pregnancy given pregnancy is fraught with peril; the embryo would cause deadly hemorrhaging but for a mother’s adequate immune system.

    Reply
    1. EarlyGray

      Until a nurse friend of mine told me the same thing, Panadol (the equivalent as far as I can tell for Tylenol in Ireland) was my go-to for hangovers, to which I was very susceptible. It’s scary to think of how much damage I may have done over the years

      Reply
  18. Bart Hansen

    We raised our three kids some 40 years ago, and I recall a big scare about Reyes Syndrome which was associated with aspirin. That must have had an effect to increase the use of both acetaminophen and NSAIDS for children. At that time the word ‘autism’ was not commonly used. The big scare for new parents was SIDS.

    Reply

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