Does Acetaminophen use During Pregnancy Cause ADHD in Offspring?

May 18, 2020 | Stephen Faraone, Ph.D.

Many media outlets have reported on a study suggesting that mothers who use acetaminophen during pregnancy may put their unborn child at risk for ADHD.   Given that acetaminophen is used in many over-the-counter pain killers, correctly reporting such information is crucial.  As usual, rather than relying on one study, looking at the big picture using all available studies is best.  Because it is not possible to examine this issue with a randomized trial, we must rely on naturalistic studies.

One registry study (http://www.ncbi.nlm.nih.gov/pubmed/24566677) reported that fetal exposure to acetaminophen predicted an increased risk of ADHD with a risk ratio of 1.37.  The risk was dose-dependent in the sense that it increased with increased maternal use of acetaminophen.  Of particular note, the authors made sure that their results were not accounted for by potential confounds (e.g., maternal fever, inflammation and infection).  Similar results were reported by another group (http://www.ncbi.nlm.nih.gov/pubmed/25251831), which also showed that risk for ADHD was not predicted by maternal use of aspirin, antacids, or antibiotics.  But that study only found an increased risk at age 7 (risk ratio = 2.0) not at age 11.  In a Spanish study, (http://www.ncbi.nlm.nih.gov/pubmed/27353198), children exposed prenatally to acetaminophen were more likely to show symptoms of hyperactivity and impulsivity later in life.  The risk ratio was small (1.1) but it increased with the frequency of prenatal acetaminophen use by their mothers.

We can draw a few conclusions from these studies.  There does seem to be a weak, yet real, association between maternal use of acetaminophen while pregnant and subsequent ADHD or ADHD symptoms in the exposed child.  The association is weak in several ways: there are not many studies, they are all naturalistic and the risk ratios are small.   So mothers that have used acetaminophen during pregnancy and have an ADHD child should not conclude that their acetaminophen use caused their child’s ADHD.  On the other hand, pregnant women who are considering the use of acetaminophen for fever or pain should discuss other options with their physician.  As with many medical decisions, one must balance competing risks to make an informed decision.

Find more evidenced-based blogs at www.adhdinaduls.com.

What is Evidenced Based Medicine?

May 11, 2020 | Stephen Faraone, Ph.D.

What is Evidenced Based Medicine?

With the growth of the Internet, we are flooded with information about attention deficit hyperactivity disorder from many sources, most of which aim to provide useful and compelling “facts” about the disorder.   But, for the cautious reader, separating fact from opinion can be difficult when writers have not spelled out how they have come to decide that the information they present is factual.

My blogs several guidelines to reassure readers that the information they read about ADHD is up-to-date and dependable.  They are as follows:

Nearly all the information presented is based on peer-reviewed publications in the scientific literature about ADHD.  “Peer-reviewed” means that other scientists read the article and made suggestions for changes and approved that it was of sufficient quality for publication.  I say “nearly all” because in some cases I’ve used books or other information published by colleagues who have a reputation for high quality science.

When expressing certainty about putative facts, I am guided by the principles of evidenced based medicine, which recognizes that the degree to which we can be certain about the truth of scientific statements depends on several features of the scientific papers used to justify the statements such as the number of studies available and the quality of the individual studies.    For example, compare these two types of studies.   One study gives drug X to 10 ADHD patients and reports that 7 improved.   Another gave drug Y to 100 patients and a placebo to 100 other patients and used statistics to show that the rate of improvement was significantly greater in the drug treated group.  The second study is much better and much larger, so we should be more confident in its conclusions.  The rules of evidence are fairly complex and can be viewed at the Oxford Center for Evidenced Based Medicine (OCEBM; http://www.cebm.net/).

The evidenced-based approach incorporates two types of information: a) the quality of the evidence and b) the magnitude of the treatment effect.  The OCEBM levels of evidence quality are defined as follows (higher numbers are better:

1. Mechanism based reasoning. For example, some data suggest that oxidative stress leads to ADHD and we know that omega-3 fatty acids reduce oxidative stress.  So there is a reasonable mechanism whereby omega-3 therapy might help ADHD people.
2. Studies of one or a few people without a control group or studies that compare treated patients to those that were not treated in the past.
3. Non-randomized, controlled studies. In these studies the treatment group is compared to a group that receives a placebo treatment, which is a fake treatment not expected to work.   Non-randomized means that the comparison might be confounded by having placed different types of patients in the treatment and control groups.
4. Single randomized trial. This type of study is not confounded.
5. Systematic review and meta-analysis of randomized trials. This means that many randomized trials have been completed and someone has combined them to reach a more accurate conclusion.

It is possible to have high quality evidence proving that a treatment ‘works’ but the treatment might not work very well.  So it is important to consider the magnitude of the treatment effect, also called the “effect size” by statisticians.  For ADHD, it is easiest to think about ranking treatments on a ten point scale.   The stimulant medications have a quality rating of 5 and also have the strongest magnitude of effect, about 9 or 10.  Omega-3 fatty acid supplementation ‘works’ with a quality rating of 5, but the score for magnitude of effect is only 2 so it doesn’t work very well.  We have to take into account patient or parent preferences, comorbid conditions, prior response to treatment and other issues when choosing a treatment for a specific patient, but we can only use an evidenced-based approach when deciding which treatments are well supported as helpful for a disorder.