Acetaminophen, long the mainstay of a pregnant woman’s pain-relief arsenal, has been linked to behavioral problems in children born to mothers who used it during pregnancy.

Research published today by the journal JAMA Pediatrics found that a woman’s use of acetaminophen at 18 and 32 weeks of pregnancy was associated with greater odds that when the resulting child was 7 years old, his or her mother would report a range of problematic behaviors.

Compared to women who reported no acetaminophen use at 18 weeks of pregnancy, those who took the medication at that point of gestation were 42 percent more likely to report hyperactivity and 31 percent more likely to report conduct problems in the children they bore.

Women who took acetaminophen at 32 weeks of pregnancy were 29 percent more likely than women who did not to report emotional difficulties in their child at age 7. Children born to mothers who took acetaminophen late in their pregnancy were 46 percent more likely to experience a wide range of behavioral difficulties than were children born to moms who took no acetaminophen at that point.

Finding a link between acetaminophen use during pregnancy and an outcome affecting the child is no proof that acetaminophen is the cause of the outcome. But the authors contend that the study results do heighten concerns that fetal exposure to acetaminophen can give rise to neurodevelopmental problems.

Several epidemiological studies have linked acetaminophen use during pregnancy to ADHD-like behaviors in the child. Research performed on mice has suggested that the medication alters brain development by disrupting hormonal function in the developing fetus. And several other mechanisms of injury have been suggested.

The authors of the study took several steps to reduce confusion in interpretation of the study’s findings, and to strengthen evidence of a causal link between acetaminophen and poor neurodevelopmental outcomes in children exposed before birth.

They looked for a link between a child’s behavioral problems at age 7 and his or her mother’s postnatal acetaminophen use, and found none. They looked for a link between a child’s behavioral problems at age 7 and acetaminophen use by the mother’s partner during pregnancy. Again, they found no association.

The emerging picture, then, points more strongly to a developing fetus’ exposure to acetaminophen as a possible causative factor. The authors wrote that the new findings add to those of a 2013 study that compared adverse behavioral outcomes in siblings as a function of a mother’s acetaminophen use during pregnancy. Collectively, the two suggest that “unmeasured familial factors” — socioeconomic differences, or a mother’s attitudes toward medication use — are not the actual cause of a child’s behavioral problems.

The new research also sought to take account of the possibility that women who passed on a genetic propensity to hyperactivity or impulsive, inattentive behaviors might also be more likely to use acetaminophen during pregnancy. In a subset of participating mothers, researchers looked for a passel of common genetic variations linked to ADHD-like behaviors. They failed to discern a pattern of increased medication-taking by women who were carriers of genetic variations linked to behavioral problems.

Finally, the authors of the study acted to avoid a common problem with research that links adverse pregnancy outcomes to certain medications: that women whose children have some identifiable problem are more likely to recall taking medications during pregnancy. The current study asked women when they were pregnant about their medication use, and then — seven years after her child’s birth — asked her to assess her child’s emotional and social well-being and report a range of problematic behaviors.

The new study reflects the experience of 7,796 mothers who gave birth to a baby in 1991 and 1992 in the county once known as Avon, England.

Acetaminophen has long been seen as safe for use by pregnant women, and more than half of pregnant women in the United States and Europe are thought to use it during pregnancy. In this study population, 53 percent of women reported use of acetaminophen at 18 weeks, and 42 percent reported acetaminophen use at 32 weeks.

As a fever reducer, acetaminophen is considered a bulwark against a more immediate threat to a developing fetus. The authors cautioned that pregnant women and their physicians should carefully weigh any potential harm to offspring against the risks of not treating fever or pain in the mother.

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©2016 Los Angeles Times