Acetaminophen During Pregnancy Doesn’t Raise Risk of Autism, ADHD, Study Finds

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  • A new study showed acetaminophen during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability.
  • Despite prior findings that advised against acetaminophen, experts said it is safe to use and the best option for pregnancy pain and fever relief.
  • There are numerous genetic and environmental factors that impact a child’s risk of neurodevelopmental disorders.

Using acetaminophen during pregnancy was not linked with drastically increased children’s risk of autism, ADHD, or intellectual disability in sibling control analysis, according to a new study.

The findings were published April 9 in JAMA.

Researchers wanted to understand if there are risks of using acetaminophen sold under the brand name Tylenol in the U.S. during pregnancy.

Understanding risks of pain relievers during pregnancy

Co-senior author of the study, Renee M. Gardner PhD, a researcher at the Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden, told Healthline, that they wanted to study this subject after a group of researchers stated in the medical journal Nature Reviews Endocrinology that women should be cautioned against using acetaminophen during pregnancy over concerns that it could disrupt the nervous system of the developing fetus and influence hormone signaling.

“There was a strong response to that statement, including a number of letters published in the same journal disputing the conclusions and pointing out that such ‘calls for action’ run the risk of adding anxiety and guilt among pregnant women,” Gardner told Healthline. “We knew that this fear and anxiety must also be affecting many expectant parents across the world, and we also knew that there were some substantial limitations to the existing studies that examined the relationship between [acetaminophen] and neurodevelopmental disorders.”

As a result, they decided to use Swedish data to study the question of whether acetaminophen use was robustly associated with risks for neurodevelopmental conditions like autism and ADHD, while addressing limitations of previous studies.

Brian Lee PhD, Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, Pennsylvania, co-senior author, explained the methodology behind the study.

“We first aimed to replicate the same sorts of a

ssociations that other researchers had reported between acetaminophen use in pregnancy and children’s neurodevelopmental outcomes such as autism and ADHD, and then we aimed to understand if those associations were also apparent in analyses when we controlled for different indications of acetaminophen use and when we compared full siblings,” said Lee.

Finding the actual risk of taking acetaminophen during pregnancy

Researchers were able to gather data on acetaminophen use during pregnancy from two sources.

During prenatal care, women were asked by their attending midwives if they regularly take medications or supplements. Women were prompted at different points throughout their prenatal care to report on medication use, including at the first visit.

The second source of data was a register of drug prescriptions that is kept in Sweden. Acetaminophen is available over the counter as is the case in the U.S. However, if a physician recommends taking the drug, it is also possible to obtain the medication as a prescription so that it is available at a lower cost to the patient.

The researchers compared children whose mothers had reported acetaminophen use during pregnancy or who obtained a prescription for use during pregnancy with children with no reported maternal use. They were able to follow children up for clinical diagnoses of autism, ADHD, and intellectual disability using a register of all specialist (and inpatient) care in Sweden.

“When we compare children in the greater Swedish population, we saw the exact same sorts of associations that have been reported in other populations, with about a 26% increased risk of autism associated with acetaminophen use,” Lee stated. “However, when we controlled for different indications of acetaminophen use in the mother in our models, this risk was attenuated down to a 5-7% increased risk for each of the neurodevelopmental outcomes that we were interested in studying.”

In addition, the researchers compared siblings who were exposed to acetaminophen during pregnancy to those that were not exposed.

“This sort of analysis helps us to control for genetics. Since other studies have shown that women with a higher genetic liability for neurodevelopmental disorders like ADHD are more likely to report taking acetaminophen during pregnancy as well as to suffer from indications for use of pain-relievers during pregnancy, we felt that it was extremely important to understand this component,” Lee noted.

For example, a mother who suffers from relatively frequent mild to moderate headaches may not end up seeking care or being treated by a specialist. In this case, they can capture data on indications for acetaminophen use.

“By comparing siblings born to the same mother, we can control for many indications as well as early life environmental factors that might influence the relationship that we are studying. When we compared the full siblings, we saw no difference in risk between the exposed siblings and the unexposed siblings,” said Lee.

What the study found

Results showed no link between acetaminophen use during pregnancy and children’s risk of autism, ADHD, or intellectual disability in sibling control analysis.

“This is a very well done, methodologically rigorous study,” Blake Turner, PhD, assistant professor of clinical social science in the department of psychiatry at Columbia University Vagelos College of Physicians and Surgeons. “The sibling control design effectively adjusts for many potential confounders that could plausibly be responsible for a spurious association between acetaminophen use during pregnancy and risk of autism in offspring.”

Turner continued: “Interestingly, even in the models without sibling control, the elevated odds for offspring autism were quite small, though were statistically significant because of the huge population sample. The fact that these modest associations disappeared in the sibling analysis provides convincing evidence that the associations documented in earlier research were due to unadjusted confounding.”

Turner was not involved in the study.

How to manage fever and pain during pregnancy

Despite previous claims that recommended avoiding acetaminophen, experts said it is safe to use and the best option for pregnancy pain and fever relief. Additionally, they recommend avoiding aspirin and ibuprofen.

“The weight of the evidence suggests that, relative to other options, acetaminophen is probably the safest analgesic for women who are pregnant,” said Turner. “The FDA advises against the use of aspirin and NSAIDs like ibuprofen or naproxen sodium because of potential fetal kidney damage.”

This new study suggests that acetaminophen is safe with respect to autism spectrum disorder (ASD).

“There is some evidence that links [acetaminophen] use during pregnancy to offspring ADHD,” Turner stated. “However, one needs to consider the risks of the conditions for which acetaminophen is taken. Prolonged maternal fever during pregnancy is itself a risk factor for autism in offspring.”

One past study found a strong effect on ASD for untreated maternal fever, but no effect when treated with a fever reducer.

Experts note that pain can also affect maternal mental health, which can also be a risk factor for child mental health problems. Therefore judicious use of acetaminophen for these indications seems appropriate, Turner noted.

Takeaway

Acetaminophen during pregnancy was not linked with children’s risk of autism, ADHD, or intellectual disability in sibling control analysis, a new study showed.

While prior research recommended avoiding acetaminophen during pregnancy, experts said it is safe to use and the best option for pain and fever relief.

A child’s risk of developing autism, ADHD and intellectual disabilities are also attributable to various genetic and environmental factors.

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