Acetaminophen is one of the very few painkillers considered generally safe to use during pregnancy. A new study, however, suggests it may not be so safe after all, after identifying a link between prenatal exposure to the drug and symptoms of autism and attention deficit hyperactivity disorder.
The study - led by researchers from the Center for Research in Environmental Epidemiology (CREAL) in Barcelona, Spain - is published in the International Journal of Epidemiology.
Also known as paracetamol, acetaminophen is one of the most commonly used over-the-counter medications during pregnancy. Around 65 percent of expectant mothers in the United States use the drug.
All pregnant women should seek medical advice before taking any medications, but for most mothers-to-be, acetaminophen use is deemed safe. A 2010 study from the Centers for Disease Control and Prevention (CDC) found no increased risk of major birth defects with use of acetaminophen in the first trimester of pregnancy, and some studies have even suggested it may lower the risk of birth defects.
However, there has been some evidence that acetaminophen use during pregnancy may interfere with the brain development of offspring. In 2014, a study published in JAMA Pediatrics found that expectant mothers who used acetaminophen were more likely to have children with behaviors associated with attention deficit hyperactivity disorder (ADHD).
Assessing the link between acetaminophen and ADHD, autism
For this latest study, lead author Claudia Avella-Garcia, a researcher at CREAL, and colleagues set out to further investigate the association between acetaminophen use in pregnancy and ADHD among offspring, as well as determine whether there might be a link with autism.
The team enrolled 2,644 expectant mothers to their study. At 12 and 32 weeks of pregnancy, the women completed a questionnaire, in which they were asked whether they had used acetaminophen in the month prior to becoming pregnant or during their pregnancy.
The women were also asked how often they had used the drug, though the exact doses used could not be assessed, due to mothers being unable to recall them.
The neuropsychological development of 88 percent of the women's offspring was assessed at the age of 1 year, while 79.9 percent were assessed at the age of 5 years.
At 1 year, the children's neuropsychological development was evaluated using the Bayley Scales of Infant Development (BSID), while a number of tests - including the McCarthy Scales of Children's Abilities (MCSA) and the Childhood Autism Spectrum Test (CAST) - were used for evaluation at 5 years.
Prenatal acetaminophen exposure linked to autism symptoms in boys
The researchers found that 43 percent of the children assessed at the age of 1 and 41 percent of those assessed at age 5 were born to mothers who used acetaminophen in the first 32 weeks of pregnancy.
Compared with children born to mothers who did not take acetaminophen during pregnancy, the researchers found that those whose mothers used acetaminophen in the first 32 weeks of pregnancy were 30 percent more likely at age 5 to have attention impairments, often found in children with autism or ADHD.
Children prenatally exposed to acetaminophen were also more likely to have symptoms of hyperactivity or impulsivity at the age of 5. Those who had been persistently exposed to the drug performed worse on tests of attention, impulsivity, and visual speed processing.
Furthermore, the researchers found boys with prenatal acetaminophen exposure were more likely to have clinical symptoms of autism than non-exposed boys, and the incidence of such symptoms increased with persistent exposure to the drug.
This finding, the team says, could explain why boys are much more likely to develop autism than girls.
"The male brain may be more vulnerable to harmful influences during early life," says Avella-Garcia. "Our differing gender results suggest that androgenic endocrine disruption, to which male brains could be more sensitive, may explain the association."
Overall, the researchers say their findings indicate that children exposed to acetaminophen in the womb may be at greater risk of symptoms of autism or ADHD.
"[...] although we measured symptoms and not diagnoses, an increase in the number of symptoms that a child has, can affect him or her, even if they are not severe enough to warrant a clinical diagnosis of a neurodevelopmental disorder."
'Expectant mothers should not be concerned'
While the researchers are unable to pinpoint the exact mechanisms by which prenatal acetaminophen exposure may be linked to autism or ADHD, they note that the drug alleviates pain by targeting cannabinoid receptors in the brain, which has the potential to reduce connectivity between nerve cells.
"It can also affect the development of the immune system, or be directly toxic to some fetuses that may not have the same capacity as an adult to metabolize this drug, or by creating oxidative stress," says study co-author Dr. Jordi Júlvez, also a researcher at CREAL.
The researchers conclude that further studies are needed to gain a better understanding of how acetaminophen may affect fetal brain development.
The findings are likely to worry expectant mothers, but Dr. James Cusack, director of science at Autistica - a U.K. autism charity - insists women should not be concerned about taking the drug during pregnancy.
"This paper does not provide sufficient evidence to support the claim that there is a strong association between paracetamol use and the presentation of symptoms of autism," he told The Independent. "The results presented are preliminary in their nature, and so should not concern families or pregnant women."
"As the authors correctly state, more research, with careful control for other factors is required to understand whether a link exists at all."