Tylenol causes ADHD and Behavior Disorders–Really?

Here’s a study that got a lot of attention yesterday.

I am sure the authors were proud of themselves. However they might have expected a big splash, such a popular diagnosis, Attention Deficit Disorder, Hyperactivity Disorder. everyone knows it, everyone is conscious of it.

And of course Tylenol is ubiquitous, used, as recommended by the Medical people in pregnancy to avoid any concerns about Non steroidals, that are a concern in later phases of pregnancy.

So the perfect storm, all you have to do is grind the numbers, show a small association between Tylenol (acetaminophen) and take a victory lap after you establish that acetaminophen in pregnancy creates a risk of Hyperactivity, Attention Deficit, Behavior disorders in children. Ignore the obvious problem that these are soft diagnostic entities, subject to a lot of debate and criticism.

So JAMA Pediatrics gets in the hands of the press. The audience is guaranteed–it’s about mothers and babies. THE CHILDREN.

And here come the media.

http://www.foxnews.com/health/2014/02/24/acetaminophen-use-during-pregnancy-tied-to-adhd-behavioral-problems-in-children/

So this article caught the attention of our chief resident at the place where I work, and he circulated it for our residency programs to review.

We do research so we have to know how to analyze research and design good research.

Here’s the important part of the report in the Journal JAMA Pediatrics

RESULTS More than half of all mothers reported acetaminophen use while pregnant. Children
whose mothers used acetaminophen during pregnancy were at higher risk for receiving a
hospital diagnosis of HKD (hazard ratio = 1.37; 95%CI, 1.19-1.59), use of ADHD medications
(hazard ratio = 1.29; 95%CI, 1.15-1.44), or having ADHD-like behaviors at age 7 years (risk
ratio = 1.13; 95%CI, 1.01-1.27). Stronger associations were observed with use in more than
1 trimester during pregnancy, and exposure response trends were found with increasing
frequency of acetaminophen use during gestation for all outcomes (ie, HKD diagnosis, ADHD
medication use, and ADHD-like behaviors; P trend < .001). Results did not appear to be
confounded by maternal inflammation, infection during pregnancy, the mother’s mental
health problems, or other potential confounders we evaluated.
CONCLUSIONS AND RELEVANCE Maternal acetaminophen use during pregnancy is associated
with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and
outcome are frequent, these results are of public health relevance but further investigations
are needed.

JAMA

Hazard Ratio is similar to Relative Risk or increase in the rate of the problem that is identified as the adverse effect and toxic end point.

In this case endpoint is diagnosis of ADHD or ADHD type behaviors at age 7.

That’s called a soft endpoint, since ADHD is a set of signs and symptoms subject to judgement.

The Hazard ratios were below 2, which is inadequate to establish proof of causation. The Hazard Ratio for behavior barely escaped 1.0 at 1.01 which would have meant that the confidence interval included ZERO. That means that one of the endpoints, behavior is so weak a correlation as to be a joke–get that. As for the other endpoint I can think of one major confounder not commented on, Tylenol use as a marker for more active medical user–higher level of medical awareness and hyper alertness, even, dare i mention it–anxiety and neurosis–now imagine that such a thing might impact ever so slightly the inclination of a mother to take a kid to the pediatrician and press for a diagnosis like ADHD. Maybe?

Their list of confounders doesn’t come close to describing all the confounders in a study like this. Endpoints, exposures, likelihood of Tylenol use by selection and the likelihood of diagnosis of ADHD as marked by increased rate of maternal Tylenol use in pregnancy.

I don’t know, but I do know that a Hazard Ratio of 1.13 for behavior is a small association and 1.37 for Hyper kinetic disorder is small and, if there is no double counting, the 1.29 Hazard Ratio for ADHD meds is small too. The confidence intervals are not too bad, but that is derivative of the size of the study, as is the p value, which goes with the confidence interval (CI).

You betcha the authors are right when thy suggest further study, even though these observational studies are always mostly just hypothesis generating, particularly in the range of small associations.

If the rate of ADHD was found to be 150 percent higher as compared to 29% or Hyperkinetic disorder was 150% or 200 % higher instead of 37 % then, in this kind of study the strength of evidence would be more impressive, even if not dispositive on the question.

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4 responses to “Tylenol causes ADHD and Behavior Disorders–Really?

  1. Wasn’t it the medical community that said Tylenol was safe and assured us that more hospitals used Tylenol than any other pain reliever (or was that a lie by Tylenol?)? Wasn’t it the pharmaceutical companies that combined acetaminophen with hundreds of prescription drugs (in some cases forcing one to take it when not wanted or needed?) and over the counter drugs? Now, they want to come back and say “Oh, sorry…….”
    The research is pretty iffy and I am always surprised by the tiny significance found but as long as it exceeds the magic “chance” value by even by wee bit, it’s considered big news.
    Maybe this can help get acetaminophen out of “combination” medicines and back to a stand-alone medication so we can take only what medicine we actually need? If so, the study could actually be of some value.

  2. Excellent article, John. Please post more informative analysis such as this.

    In addition to the obvious confounder you pointed out, I’d add that women who get headaches are more likely to consider a child to be “too active”. I still contend that ADHD is a symptom of children not getting to expend their energy in creative and unstructured ways. I know my own children will begin to exhibit “ADHD like behavior” whenever it rains several days in a row.

    • GH05T, Please do some of your own research before you go spouting off your ignorant theories about what ADHD really is as if you really know.

      Yes, of course most children need to play more, be outside more, be away from screens more and yes, all children can exhibit hyperactivity, inattentiveness and impulsivity. They wouldn’t be kids if they didn’t.
      But a psychologically assessed child who exhibits the above traits way more often and to a greater extreme than typical kids, is truly dealing with Attention Deficit Hyperactivity Disorder. It is very disingenuous to compare your kids with cabin fever to those children who struggle to get through each day of their lives.
      And ‘women who get headaches are more likely to consider a child to be “too active”‘??? What utter nonsense.

      • While there are children who have extreme difficulty in sitting still and concentrating, even the psychiatric community questions whether or not the current huge numbers of children being medicated are truly for an illness or just for convenience. While G’s comment is an over-simplification, today’s society reaches for a pill to fix virtually everything from baldness, to peeing too much to not being able to wake up happy every morning. Medication is the easy answer, just not always the right answer.

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