Even after double-checking for possible confounding factors, a new study from JAMA Pediatrics confirms that women who use acetaminophen while pregnant are more likely to have children with behavioral or emotional problems in early and middle childhood.

The researchers set out to find if this previously made claim could have been hiding other factors; perhaps there were other social, genetic or environmental factors at play. But the results showed, even after measuring partner acetaminophen use and post-natal maternal acetaminophen use, prenatal acetaminophen use is still associated with emotional and behavioral difficulties.

They examined more than 14,000 babies born between 1991 and 1992 in England and their mothers. The participants filled out questionnaires about their and their partners’ general health and painkiller usage. Researchers then compared this data with the health records of the mothers and their children. They were asked to fill out the questionnaires at 18 and 32 weeks of pregnancy and again when their children were about 5.

When the children were 7 years old, the researchers assessed children's behavioral and emotional states using the 10-point Strengths and Difficulties Questionnaire, which measures emotional symptoms, conduct problems, hyperactivity symptoms, peer relationship problems and prosocial behavior.

About 5 percent of the children studied ended up with behavioral problems. More than half of mothers used acetaminophen when they were pregnant (more women took it earlier in the pregnancy than later).

The health and drug use questionnaire, combined with the behavioral assessment of the children, showed a correlation between early-pregnancy acetaminophen use and conduct problems of the resultant children. But later-pregnancy use of the drug showed more of a correlation with emotional problems in the kids.

“Given that there is active brain development and growth during the third trimester, this finding could indicate that there are developmental periods when the brain is more sensitive to acetaminophen exposure,” the study authors wrote, though they called for further research to ascertain the exact mechanism by which this could take place.

The babies born to women who had taken the drug at 18 and 32 weeks were at a 1.42 and 1.31 times greater risk of developing conduct issues and hyperactivity problems, respectively, by age 7. The children born to women who took acetaminophen at 32 weeks were at 1.29 and 1.42 times risk of emotional problems and total difficulties, respectively.

The same associations were not found when testing for a correlation between those problems and maternal post-natal use of acetaminophen and partner use. (About 89 percent of mothers used the drug after the babies’ births and about 84 percent of their partners took it.)

These findings could be in contradiction with current widespread practice among pregnant women and their physicians’ recommendations—about 50 percent (more in the EU, less in the U.S.) of pregnant women use acetaminophen while pregnant as a first-choice painkiller. The authors of the study cautioned, however, that the necessity of treating maternal fever or pain during pregnancy is also important, and the benefits of using acetaminophen to treat those issues during pregnancy should be weighed against the potential risks for the fetuses.