While acetaminophen is generally regarded as one of the few painkillers safe for use during pregnancy, a new study suggests that the drug could be linked to autism and attention deficit hyperactivity disorder (ADHD). Conducted by researchers at the Center for Research in Environmental Epidemiology (CREAL) in Barcelona, Spain, the study was published in the International Journal of Epidemiology.
It’s estimated that approximately 65 percent of pregnant women in the US take acetaminophen – also known as paracetamol – during pregnancy. In 2010, the Centers for Disease Control and Prevention (CDC) found that acetaminophen use during the first trimester of pregnancy was not associated with an increased risk of major birth defects.
Interestingly, some studies have even found that acetaminophen may lower the risk of certain birth defects. A study conducted in 2014 however, found that pregnant women who took the painkiller during pregnancy were more likely to have offspring who showed symptoms and behaviours associated with ADHD.
Researchers from CREAL – including Claudia Avella-Garcia, the study’s lead author – set out to further investigate the possible link between acetaminophen and ADHD, as well as the drug’s potential to increase the risk of autism. Using questionnaires filled out by 2,644 expectant mothers, the researchers assessed whether the women had taken acetaminophen directly before, or during their pregnancy.
At 12 and 32 weeks into their pregnancy, the women were also asked how often they had taken the drug. Eighty-eight percent of the resulting children were assessed for neuropsychological development at 12 months of age, with 79.9 percent of children assessed again at age 5.
The Bayley Scales of Infant Development (BSID) was used to assess the children at one year, while the McCarthy Scales of Children’s Abilities (MCSA) and the Childhood Autism Spectrum Test (CAST) were used for the same purpose at 5 years. Women who took acetaminophen in the first 32 weeks of pregnancy gave birth to 43 percent of the total children assessed at one year of age, and 41 percent of those assessed at 5 years.
Attention impairments associated with autism and ADHD were 30 percent more likely in five-year-old children born to mothers who took the drug in early pregnancy, compared to those who did not. Hyperactivity and impulsivity were also more common in these children.
In addition, continuous exposure to acetaminophen was associated with children who performed more poorly on tests of visual speed processing. Male children in particular, were more likely to show clinical symptoms of autism if they were prenatally exposed to the drug. As autism is more common in boys than girls, this finding could potentially explain these gender differences.
“The male brain may be more vulnerable to harmful influences during early life,” said Avella-Garcia. “Our differing gender results suggest that androgenic endocrine disruption, to which male brains could be more sensitive, may explain the association.”
While it’s unclear which mechanisms may contribute to this increased risk of ADHD and autism, the researchers say that acetaminophen targets the cannabinoid receptors in the brain, which reduces pain but may also impair connections 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,” said Dr. Jordi Júlvez, a researcher at CREAL and a co-author on the study.
For now, expectant mothers are urged not to worry about the potential risks of taking the drug during pregnancy, as further studies must be conducted in order to verify the link. “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,” said Dr. James Cusack, director of science at the UK-based autism charity, Autistica. “The results presented are preliminary in their nature, and so should not concern families or pregnant women.”