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Paracetamol during pregnancy linked to ADHD risk

Children of women who take paracetamol during pregnancy may be at higher risk of developing attention-deficit hyperactivity…

It’s too early to adjust recommendations for paracetamol use during pregnancy, experts say. Image from shutterstock.com

Children of women who take paracetamol during pregnancy may be at higher risk of developing attention-deficit hyperactivity disorder (ADHD), a new pilot-style study suggests. But experts warn this should not prompt a change in recommendations around paracetamol use.

Paracetamol is the most commonly used medication for pain and fever in Australia, including among pregnant women. Although it readily crosses the placenta, it is considered safe when taken at the recommended dose.

The study is published today in the journal JAMA Pediatrics, alongside an editorial which concludes the authors have made an “interesting observation” but it would be wrong for women and doctors to change their practices based on the findings.

The joint US-Danish research team, led by Zeyan Liew from the University of California, set out to test the hypothesis that paracetamol affected sex and other hormones which could impact on brain development and cause behavioural dysfunction.

The researchers studied 64,000 children and mothers from the Danish National Birth Cohort born between 1996 and 2002. The mothers described their paracetamol use, along with a list of other pain relievers, in three phone interviews during pregnancy and again after childbirth.

After the children turned seven, the researchers asked the parents to complete a questionnaire about any behavioural problems their child might have. The researchers also collected data about ADHD diagnoses and medication prescriptions from Danish registries.

More than half of the mothers (56%) reported using paracetamol during pregnancy.

Children of women who took paracetamol during pregnancy were 13% to 37% more likely to have a diagnosed hyperkinetic disorder (the European equivalent of ADHD), to be taking ADHD medication, or to have ADHD-like symptoms, compared with children of mothers who took none.

The researchers said the risk increased when the women used paracetamol in more than one trimester.

Caution required

Adjunct senior lecturer at Monash University George Halasz said the research was best described as a pilot study. “It’s so preliminary that I wouldn’t expect the findings to have any direct impact on anything else other than the formation of a substantial study,” he said.

“To have a policy and practice change on intervention during pregnancy, the onus is on the research to prove, within the realms of science, the high probability that there is a causative link. This doesn’t even go to the earlier level of an associative link.”

Dr Halasz said the idea of testing for ADHD risk factors was also a hornet’s nest because researchers still don’t know what caused the disorder, though some suggest it might have a genetic base.

“No one disputes that children have a whole range of behavioural and emotional problems that are linked to hyperactivity, but what is it still remains an open question.”

Clinical senior lecturer at Deakin University Michael Vagg said the JAMA Pediatrics study “may be a random finding which will go away when attempts to replicate it are made” and should not cause women to stop using paracetamol.

“We don’t have a firm idea exactly how paracetamol works, so the idea it could influence developing foetal brains in some way is not inherently implausible.

“There is, however, a huge amount of experience with paracetamol in pregnancy which has not previously suggested a link.”

Dr Vagg said expectant mothers should try to manage day-to-day pains with hot or cold packs, rest and pacing of activities before using medications.

But those with chronic pain problems who become pregnant should discuss their options with their GP or pain specialist, he said.

“There are health risks to mother and foetus associated with not treating headaches, backaches and fevers effectively during pregnancy, so changes to practice should not be made until the risk (if it is real) from paracetamol is more thoroughly understood.”

University of Western Sydney professor of midwifery Hannah Dahlen said there were many reasons women may take paracetamol that could make the outcome of ADHD an association, not a cause.

“For example, women who are anxious or stressed get more headaches and may take panadol for this, with the anxiety and stress being more of a causal factor than the paracetamol,” she said.

“It is unlikely that one environmental or genetic trigger is at play, with ADHD it is likely to be far more complex than being due to paracetamol use.

“Women tend to either take no drugs or use several during pregnancy so polypharmacy may be an issue.”

One of the major weaknesses of the study was the exclusion of 28,254 women because they missed one or more telephone calls, Prof Dahlen said. The inability of many women (28%) to remember when paracetamol was taken during their pregnancy also reduced accuracy.

Prof Dahlen said the fact that half the women in the study used paracetamol during pregnancy suggests “we may be getting complacent about its use”.

“Bottom line is, if you don’t really need a medication in pregnancy then don’t take it. Never presume any drug is completely safe in pregnancy,” she said.

Join the conversation

28 Comments sorted by

    1. Michael Vagg

      Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health

      In reply to Sue Ieraci

      Absolutely Sue. It's always a concern with large epidemiological studies like this that seem to throw up associations which need to be very carefully interpreted. There were a number of really significant shortcomings with their data (for example, nearly 30% of those who took paracetamol couldn't remember when in the pregnancy they took it) and the possible association can have several equally plausible explanations which don't involve paracetamol having a direct effect on ADHD risk.

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  1. Robin Bell

    Research Academic Public Health, at University of Newcastle

    Agree with you Sue. In addition, given the responses of many mothers to even small risks of harm (a credit to them, not a criticism), early puiblication of pilot studies with weak associations may be more harmful than the paracetamol.

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  2. Victor Jones

    Freelance

    Statistical associations are legit.
    Fair statement was made by one of the researchers - avoid paracetemol for minor issues.

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    1. Sue Ieraci

      Public hospital clinician

      In reply to Victor Jones

      ''Statistical associations are legit"? What do you mean by ''legit'', Victor Jones?

      If we consider every association as equivalent to causation, then we would have to avoid smart phones, organically grown foods, air travel, consumption of multi-vitamins - all of these things have increased during the time that ASD diagnoses have risen. Statistical associations are everywhere - they are not the same as causation.

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    2. Victor Jones

      Freelance

      In reply to Sue Ieraci

      No, you deal with the evidence at hand and assume caution.
      Its actually possible that although the confidence interval of the statistical analysis found a 30+% increased risk of ADHD, the reality might be 230+%.
      Correlations work both ways - there may be no actual correlation, or there might be a much stronger correlation.

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  3. Danny Hoardern

    Analyst Programmer

    "This doesn’t even go to the earlier level of an associative link."

    Could it be that the stress involved with the pain has more to do with "ADHD risk" than paracetamol?

    The brain of someone with ADHD has fewer nerve connections in the prefontal cortex[1]. Stress[2] and sugar[3-4] both prune neural connections.

    1. ABC Kids on Speed Episode 1 33m:55s
    2. http://www.sciencedaily.com/releases/2012/08/120812151659.htm
    3. http://www.brisbanetimes.com.au/lifestyle/diet-and-fitness/sugar-can-make-you-dumb-us-scientists-warn-20120516-1ypox.html
    4. https://www.aan.com/PressRoom/Home/PressRelease/1100

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  4. Sharon Potocnik

    HR Officer

    There is no causal link between full fat dairy and cardiovascular disease or obesity yet plenty of authorities seem fine about making recommendations around that. The "don't worry until there is proof" approach just sounds like trying to protect the profit margins of the paracetamol suppliers to me. I'm sure there are good reasons to resort to painkillers from time to time, but over 50% use it....amazing/alarming statistic.

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    1. Sue Ieraci

      Public hospital clinician

      In reply to Sharon Potocnik

      There it is - an example of what can happen with wide reporting of speculative results from a single study

      The fact that a bit over half of pregnant women use at least one dose of a very benign pain-killer at some stage over the nine months of their pregancy is neither amazing nor alarrming.

      I suspect close to 100% of pregnant women ride or drive in cars - another practice that has utility without 0% risk.

      Much has been made of the toxicity of paracetamol in overdose or chronic over-use. In comparison to this huge everyday use, paracetamol use is very benign.

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    2. Sharon Potocnik

      HR Officer

      In reply to Sue Ieraci

      I'm amazed because I didn't know that before and the statistic was no where near the figure I would have guessed and I'm alarmed that so many people resort to painkillers and I wonder how many doses could have been avoided with alternative approaches such as drinking water etc. I am just an average person expressing an opinion or do we all have to be "qualified" to contribute to the conversation?

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    3. Sue Ieraci

      Public hospital clinician

      In reply to Sharon Potocnik

      Clearly we don't ''all have to be "qualified" to contribute to the conversation'' - many personal opinions are posted here.

      People with some knowledge in the area don't appear to be banned from disagreeing, however.

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  5. Nathalie Martinek

    logged in via Twitter

    The title to this article is completely misleading and if this is all anyone reads, then it has just created a myth that is akin to MMR vaccine linked to autism risk, which we know is false.

    It was stated in the article:

    'After the children turned seven, the researchers asked the parents to complete a questionnaire about any behavioural problems their child might have. The researchers also collected data about ADHD diagnoses and medication prescriptions from Danish registries.'

    Now if you…

    Read more
  6. Evelyn Haskins

    retired

    While this doesn't surprise me one bit, there is another possible explanation to consider.

    And that is the personality/behaviour of women who take paracetamol.
    They just MIGHT be the sort of women who resport readily to medication for minor issues, and therefore be more likely to not only seelk medical treatment for a childy perceove as a behaviour problem. Then of course they might very well be the sort of person who percieves problems where other moths might just see it as a 'stage' their child is going through.

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    1. Sue Ieraci

      Public hospital clinician

      In reply to Evelyn Haskins

      Wow. Ms Haskins - have you found the same association in tea-drinkers?

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  7. Evelyn Haskins

    retired

    > There are health risks to mother and foetus associated with not treating headaches, backaches and fevers effectively during pregnancy, so changes to practice should not be made until the risk (if it is real) from paracetamol is more thoroughly understood.”>

    On the other hand I do not agree with this. There are other treatment for pain and fevers. Statistically were are told that paracetamol works *no better than* bathing in tepid water for fever reduction.
    (Paracetamol: An evidence summary on possible harm from reducing fever
    Author: Dr Peter Silberberg; Dr Dan Ewald)

    Headaches frequently respond to water and/or salt intake (or both!)

    Surely it is sensible them to at least suggest that in pregnacy paracetmol should be a last resort rhathe than a substance the women can by at teh supermarket and take willy-nilly!

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    1. Sue Ieraci

      Public hospital clinician

      In reply to Evelyn Haskins

      Ms Haskins recommends ''water and/or salt intake'' for headache.

      One can acquire water intoxication or hypertension with over-use or acute overdose of either of these substances - available at the supermarket and able to be taken willy-nilly!

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    2. Evelyn Haskins

      retired

      In reply to Sue Ieraci

      Well, I get my water from the tank, via a pump, piping and tap.

      Would you have warnings on all taps to beware of an over-dose of water? Or is is only bottled water than people run the risk of over-dosing on?

      However, having lived in the tropics I can assure you that salt depletion is a very significant contribution to severe headaches.

      We humans lose SO much salt in our sweat that depletion of the electrolytes in the body can have serious consequences. Sodium is the main electrolye lost through sweating but magnesium is also at risk.

      The old cuppa tea, a Bex and a good lie down used to be recommended. But a glass of water, with a pinch of plain cooking salt and a short lie down works as well, as well as more safely.

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    3. Sue Ieraci

      Public hospital clinician

      In reply to Evelyn Haskins

      I fear you have missed my point, Ms Haskins. A cuppa with a glass off water and two 500 mg paracetamol and a short lie down is just as safe as the pinch of salt.

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    4. Evelyn Haskins

      retired

      In reply to Sue Ieraci

      I suppose that you also missed my point.

      Sodim, usually provoded in the diet my NaCl, is a necessary nutirent.

      As a doctor I am sure that you know the risks of hyponatremia, the causes and effects.

      I have yet to hear on anybody dying of the effects of paracetamol deficiency.

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    5. Ian Darby

      Academic/Researcher at RMIT University

      In reply to Evelyn Haskins

      Most of us are at little/no risk of being sodium deficient. We're designed very well for retaining it when we need to. I always find my headaches that I blame on dehydration don't respond to water - but do respond to paracetamol.
      I also fear if we don't stop talking about water and paracetamol we will stir (or perhaps shake) the homeopathy trolls from their slumber......

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    6. Evelyn Haskins

      retired

      In reply to Ian Darby

      Ian, it was when living in Kununurra -- a erage dily femperatures about 49 degrees C that I discovered that water left me feeling bloated but did nothing for the headaches. Then I remmebrbered by Grandfather's 'cure" -- a pinch of salt in the glass or water. It works like magic. It also works like magic for that light-headed, I think I'm about to faint feeling that you get when uyoue been out in the sun. Not to mention the morning after the night before -- provided that the headache is from a surfiet of good wine. Bad wines and orange juice leave you with recalcitrant headaches.
      And it probably wouldn't wok for a headache being caused by a bad fall or injury.

      On the other hand I've never known pacetamol to work either -- but then placebos tend to not work for me.

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    7. Sue Ieraci

      Public hospital clinician

      In reply to Evelyn Haskins

      ''Could you PLEASE stop referring to me as Ms!''

      I apologise, Mr Haskins - I thought ''Evelyn'' was conventionally a female name.

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    8. Sue Ieraci

      Public hospital clinician

      In reply to Evelyn Haskins

      I do indeed know the causes and effects of hyponatraemia. There are different types, depending on the total body water - so-called hypovolaemic, euvolaemic and hypervolaemic hyponatraemia. Hypovolaemic hypnonatraemia can occur with diuretics or severe vomiting and diarrhoea, euvolaemic can occur in SIADH secondary to malignancies, some medications, and hypervolaemic hyponatraemia -with expanded fluid volume, occurs in conditions of low protein like cirrhosis.

      Hyponatraemia is generally only seen after sweating if a large amount of clear water is taken very quickly. That's why sports drinks were first developed.

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    9. Evelyn Haskins

      retired

      In reply to Sue Ieraci

      Mrs Haskins, or Evelyn. Evelyn is both a male and famale name.

      But I am neither a manuscript, myultiple sclerosus, a frustrates spinster, sour divorcee nor lesbain.

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    10. Evelyn Haskins

      retired

      In reply to Sue Ieraci

      > That's why sports drinks were first developed.>

      Thanks, Doctor Ieraci :-)

      I KNEW you'd agree with me when you understood what I was talking about ;-)

      Ioriginally found relief with 'Staminade" (the first 'sports drink' on the marker, but them found the flavour and sugar in it unpleasant do changes to simple salt. Cheaper and nicer that commercial sports drinks :-)

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    11. Sue Ieraci

      Public hospital clinician

      In reply to Evelyn Haskins

      Nice try, but I was talking about massive plain water replacement after massive sweating - not expats sweating in the tropics.

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  8. Evelyn Haskins

    retired

    I've just seen this. Which gives more detail than the article here, and might help people make up her own minds as to whether or not the possible risk is worth the possible gain of taking paracetamol during pregnancy.

    Of course we ALL know that one research paper does not a swallow make -- the possible alternative reasons for the findings would need to be investigated as well as further studies that show the same correlations.

    http://www.sciencedaily.com/releases/2014/02/140225101656.htm
    “Use of acetaminophen during pregnancy linked to ADHD in children, researchers say”

    Journal Reference:
    Zeyan Liew, Beate Ritz, Cristina Rebordosa, Pei-Chen Lee, Jørn Olsen. Acetaminophen Use During Pregnancy, Behavioral Problems, and Hyperkinetic Disorders. JAMA Pediatrics, 2014;
    DOI: 10.1001/jamapediatrics.2013.4914

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