Study Reveals Long-Term Use Of Paracetamol During Pregnancy Linked To ADHD In Children

However, there is no evidence of a cause-effect relationship.

Cover image via istockphoto via NY Post

A recent study has suggested that prolonged usage of acetaminophen during pregnancy has links to ADHD in children

Photo for illustration purposes only.

Image via Reuters/Regis Duvignau

Published in the latest issue of the journal Pediatrics, the Norwegian research investigates the maternal use of acetaminophen, also known as paracetamol, during pregnancy and of paternal use before pregnancy with attention-deficit/hyperactivity disorder (ADHD) in children.

The paper titled, 'Prenatal Exposure to Acetaminophen and Risk of ADHD' concluded that short-term usage of acetaminophen during pregnancy was negatively associated with ADHD in children. However, the same cannot be said for long-term usage.

"Long-term maternal use of acetaminophen during pregnancy was substantially associated with ADHD even after adjusting for indications of use, familial risk of ADHD, and other potential confounders," the paper's abstract states.

Findings from the research suggest that kids were twice as likely to be diagnosed with ADHD if their mothers used acetaminophen for 29 days or more during the term of their pregnancy

Here are some of the key findings from the research, based on the data compiled by the Norwegian Institute of Public Health:

• Women who used the drug during just one trimester was associated with 7% increased risk of having a child with ADHD;
• 22% increased risk for women who used acetaminophen in two trimesters;
• 27% increased risk for women who used acetaminophen in all three trimesters.
• Pregnant women who used acetaminophen for less than seven days were associated with a decreased risk (10% less likely) of ADHD in offspring.
• Women who used acetaminophen for fever and infections for 22 to 28 days, were more than six times more likely to have kids with ADHD than mothers who avoided the drug during pregnancy.

Photo for illustration purposes only.

Image via istockphoto via NY Post

"Surprisingly, adjusting for all the medical conditions related to acetaminophen use during pregnancy (e.g., infections and pain) and familial genetic risk for ADHD, children exposed to long-term use of acetaminophen use during pregnancy were more than two times more likely to have ADHD diagnosed by a specialist in a clinic," said lead study author Eivind Ystrom of the Norwegian Institute of Public Health and the University of Oslo, as reported by Reuters.

Ystrom told CNN that the risk of an ADHD diagnosis in a child was 220% higher, which is more than twice the expected risk, for pregnant women who used acetaminophen for 29 days or more.

The researcher also suggested that about 4% of the 114 744 children in the study would have an ADHD diagnosis by age 13.

The researchers have outlined three possible explanations on why long-term use of the drug during pregnancy has links to ADHD in chidren

First, neonatal exposure to acetaminophen changes the levels of brain-derived neurotropic factor in mice and results in altered behaviour, lowered fear responses, and reduced learning abilities in adulthood.

Second, acetaminophen could interfere with maternal hormones (such as thyroid hormones and sex hormones) that are related to fetal brain development.

Third, acetaminophen could interrupt brain development by induction of oxidative stress, leading to neuronal death.

Note: The information above was obtained from the published study.

Experts have opined that findings from the research cannot be used to prove that there is a definite connection between prenatal acetaminophen and ADHD

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Image via Investing Hope

A report by CNN cited experts who questioned the way in which a diagnosis of ADHD is assessed in the study.

Dr. Max Wiznitzer, co-chairman of the professional advisory board for the nonprofit Children and Adults with ADHD stressed that acetaminophen serves a practical purpose in pregnancy. He speculated that the group of mothers who takes pain medicine regularly may have some underlying condition - which may be associated with ADHD in the children, rather than the use of acetaminophen.

"Women should not be afraid of using acetaminophen, especially if it's their doctor's recommendation. The data here is not strong enough to support the conclusion," Wiznitzer concluded.

Others in the medical community have also pointed out that the study relied on a survey in which mothers self-reported the number of days they believed they had taken acetaminophen-containing products. It was also said that researchers failed to take into account the total dosage or the amount of acetaminophen taken by pregnant mothers in a single day.

It has been noted that the researchers have never claimed that there is a cause-effect relationship between acetaminophen and ADHD in children

"We do not provide definitive evidence for or against a causal relation between maternal use of acetaminophen and ADHD," the researchers concluded in the study, adding that longer term and more extensive studies are necessary to prove there is the association between the two. 

Dr. Mark Wolraich, professor of pediatrics at the University of Oklahoma Health Sciences Center, who wrote an accompanying editorial, said that the study identifies a possible association and not necessarily infer a causal relation.

"The authors are careful to point out that their results from a relational study cannot establish a causal relationship between prenatal acetaminophen exposures and ADHD in the offspring, but they do suggest the possibility and raise the need for further study and more cautious consideration of acetaminophen use during pregnancy," 
Wolraich said in the editorial.

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