The use of acetaminophen, the active ingredient in Tylenol, by pregnant women is associated with a greater risk of attention deficit / hyperactivity disorder in their children, according to research published in the current issue of JAMA Pediatrics. A Danish research team found that children of mothers who took acetaminophen while pregnant were 37 percent more likely to be diagnosed with hyperkinetic disorder and 29 percent more likely to be prescribed drugs for ADHD.
The editorial board of JAMA Pediatrics chose to downplay the study results, asserting that the correlations are "an interesting observed association, but too early to infer causality." However, as Dr. Daniel Kahn of UCLA told the LA Times, "We used to count a baby's ten fingers and ten toes and assume that any drug his mother took must have been safe." However, when considering taking drugs of any kind during pregnancy, Dr. Kahn advises, "The lowest exposure is always best, for any agent."
The comments from Dr. Kahn, who was not involved in the Danish study, highlight an important aspect of the research: drugs are considered safe for children in utero until proven otherwise, and the effects of drugs on developing babies may not be obvious until a large number of children are affected. The Danish researchers do not assert a binary situation, in which taking Tylenol once during pregnancy guarantees a child with an ADHD diagnosis -- after all, 56 percent of pregnant Danish women consume acetaminophen during pregnancy, a figure similar to the US -- but their data do show a statistically significant association between in utero exposure to acetaminophen and ADHD symptoms. The risk appears to be greatest when the drug is consumed during the second and third trimesters of pregnancy: an ADHD diagnosis was 63 percent more likely when the drug was taken during these two periods.
Although the official pose of JAMA Pediatrics is one of skepticism, the questions raised by the editorial board seem weak compared to the Danish study's strengths. For example, the editors comment that some of the mothers involved in the study could not remember their precise week of acetaminophen use. This statement does nothing to undermine the overall association between acetaminophen use during pregnancy and an ADHD diagnosis in the child, although it may make the precise trimester of greatest risk harder to pinpoint. Another remark by the editors is that some of the mothers in the study could not be included because they could not be reached by telephone; the editors assert that ADHD is a heritable disorder and that "dropout may be differential according to the ADHD status of the parents." Unfortunately, they give no scientific basis for either assertion.
Unlike the JAMA Pediatrics editors, the Danish team is able to cite prior research as the basis for their study. Specifically, Dr. Beate Ritz, one of the lead authors, notes that acetaminophen is known to cross the placenta, and that acetaminophen use during pregnancy has been linked in previous studies to undescended testicles in male offspring of those pregnancies. Research from Norway links in utero exposure to acetaminophen (known as paracetamol in Europe) to "substantially adverse developmental outcomes." "Pregnancy is such a sensitive period," Dr. Ritz tells the LA Times, "and the development of the fetal brain is so vulnerable to disruption."
Even those who view the Danish study with skepticism are compelled to admit that less drug use by pregnant women is less risky for their children. The Cleveland Clinic's Dr. Jeff Chapa tells USA Today, "We really should start looking at non-pharmacological ways to deal with pain."