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.
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2 thoughts on “Does Acetaminophen use During Pregnancy Cause ADHD in Offspring?”
To supplement professor Faraone’s post, a potential confounder in all these studies could be maternal ADHD. As ADHD has a strong genetic heritability, the genes which underlie ADHD in the mother, will when transmitted to the child increase the risk of ADHD in the child. As it is not unreasonable to believe that mothers with ADHD, ADHD-symptoms or ADHD-associated personality traits, have a lower threshold for taking acetaminophen during pregnancy, it would make it look like acetaminophen use is associated with offspring ADHD. An example of so-called genetic confounding.
However, in the first study described by professor Faraone (http://www.ncbi.nlm.nih.gov/pubmed/24566677), they do adjust for maternal psychiatric illnesses, though it is uncertain whether this also includes maternal ADHD, and they adjust for childhood behavior problems in the parents. Therefore, despite it being unclear whether the authors are able to adjust for maternal ADHD as an exact confoundER, much of the confoundING from maternal ADHD could be covered by the adjustments they were able to do, simply because ADHD is so tightly associated with other psychiatric disorders.
Furthermore, there is a cohort-based study utilizing sibling controls which investigated the effect of prenatal acetominophen exposure on offspring child development (https://www.ncbi.nlm.nih.gov/pubmed/24163279). In this study, as they use sibling controls who had not been exposed to acetaminophen during prenatal life, the genetic confounding should not be an issue. In addition, we assume siblings to share relatively similar upbringing environment. This study showed that prenatal use of acetaminophen was associated with traits associated with ADHD in the offspring. Together, it is reasonable to believe that maternal acetaminophen use during pregnancy increases the risk of offspring ADHD, and that this effect is not due to genetic confounding, nor different upbringing environments among those who were exposed to acetaminophen as compared to those that were not. However, as professor Faraone pointed out, this effect is weak.
Furthermore, maternal autoimmunity has been associated with offspring ADHD (https://www.ncbi.nlm.nih.gov/pubmed/26809250) and could perhaps lead to more acetaminophen use, for example for the pains of arthritis. Maternal autoimmunity could therefore be another potential confounder. Though, as we expect the sibling controls to have been exposed to relatively similar environments when in their mutual mother’s womb, this study to some degree suggests that maternal autoimmunity is not an likely underlying confounder. In line with this, in the studies described by professor Faraone, adjusting for fever, inflammation muscle and joint diseases, which could also be due to autoimmunity, did not eliminate the association between prenatal acetaminophen use and offspring ADHD.
By the way, if you are unsure what confounding really means, check out this website: