Study linking acetaminophen use to language delay is preliminary, experts say

Women who take acetaminophen early in pregnancy may increase their risk of having a child with language delay — but only if the child is a girl, a new study suggests¹. Experts warn that the findings are preliminary, however, and far from having clinical value.

Acetaminophen, commonly marketed as Tylenol in the United States, is a pain reliever and fever reducer that’s been in use for decades and is considered safe in recommended doses. In the past several years, researchers have been asking whether the medication has subtle side effects during pregnancy.

But the findings to date — including those from the new study — are inconclusive, experts say.

“Honestly, my reading of the literature is that we don’t know about the risk and benefits of acetaminophen; there are lots of different possible explanations for the [new] findings,” says Brian D’Onofrio, professor of psychological and brain sciences at Indiana University in Bloomington, who was not involved in the work.

The researchers found that daughters of women who reported having taken more than six tablets of acetaminophen during the first trimester of pregnancy have a sixfold increase in risk of language delay. (The researchers define language delay as speaking fewer than 50 words at 30 months old.)

They found the same link from measuring acetaminophen in the women’s urine: higher concentrations are tied to language delay — again, only in daughters.

Impaired language development can be an early sign of autism or general cognitive problems, and it can affect a child’s academic performance, says study investigator Shanna Swan, professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai in New York.

The results should be interpreted with caution, however, as they rely on fewer than 1,000 pregnant women, and only 133 women took more than six tablets of the drug in total. The study shows only an association between the medication and language delay, not a causal connection. And scientists can only guess at why acetaminophen might have a sex-specific effect on language.

In fact, the connection could be related to the conditions acetaminophen is used to treat rather than to the drug itself. For example, fever during pregnancy is thought to increase the risk of autism in the child.

“You get the medication because you have a certain problem,” D’Onofrio says. “It is plausible that the medication is actually just a red flag highlighting that there are other things going on.”

Girl talk:

Other studies have linked exposure to acetaminophen during gestation to low intelligence quotients, communication deficits, attention deficit hyperactivity disorder (ADHD) and autism². Most have relied on women’s recollections of their acetaminophen use while pregnant, which may be inaccurate.

The new study matched women’s reports with an objective measure: urine concentrations.

“What is so interesting is that the [two measures] are not inconsistent,” Swan says.

The researchers analyzed data from 754 pregnant women who enrolled in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study when they were 8 to 13 weeks pregnant. Nearly 60 percent of the participants reported taking acetaminophen between conception and enrollment in the study. The researchers also tested urine samples from 111 of the women.

When the children were 30 months old, their parents answered survey questions about the number of words their child spoke. Overall, the responses suggest that about 13 percent of boys and 4 percent of girls had language delay, similar to the rates in the general population.

The rate of language delay increased with exposure: Among the 133 women who took more than six acetaminophen tablets overall, 8.5 percent of their daughters showed language delay, compared with 1.3 percent of girls born to the 308 women who did not take acetaminophen.

The study found a statistically similar increase from analyzing urine concentrations. Girls born to women whose urinary acetaminophen level was in the top quartile were 10 times as likely to have language delay as daughters of women in the lowest quartile. The sixfold increase from the mothers’ reports may be more reliable because it is based on a larger number of women, Swan says.

In boys, exposure to acetaminophen had no statistically significant effect on language. The work appeared 10 January in European Psychiatry.

Hormone hypothesis:

One possible explanation for this effect is that language development is sensitive to the balance of testosterone and estrogen hormones. And acetaminophen is thought to lower circulating testosterone levels and increase estrogen, Swan says.

“We would expect sex differences from a hormonally active exposure,” she says.

Many factors are likely to influence any effects acetaminophen has on an embryo. In addition to the amount of medication, when during pregnancy it is taken matters.

Genetics might also play a role. People vary in their ability to break down and excrete acetaminophen, says Mady Hornig, associate professor epidemiology at the Columbia University, who was not involved in the study. “What that might do is lead to buildup of certain potentially toxic compounds. This needs to be explored.”

The study does not include genetic analysis. Experts say it is too soon to draw specific conclusions about the risk of acetaminophen during pregnancy. The bottom line, Hornig says, is not to take any medication without weighing the benefits against the potential risks.