A new study has found that paracetamol (aka acetaminophen; trade names include Tylenol and Panadol), which is used extensively during pregnancy, has a strong association with autism spectrum symptoms in boys and for both genders in relation to attention-related and hyperactivity symptoms.
The findings* were published this week in the International Journal of Epidemiology. This is the first study of its kind to report an independent association between the use of this drug in pregnancy and autism spectrum symptoms in children.
It is also the first study to report different effects on boys and girls. Comparing persistently to nonexposed children, the study has found an increase of 30 per cent in the risk of detriment to some attention functions, and an increase of two clinical symptoms of autism spectrum symptoms in boys. Boys also showed more autism spectrum symptoms when persistently exposed to paracetamol.
“Paracetamol could be harmful to neurodevelopment for several reasons,” said Co-author Dr. Jordi Júlvez, also a researcher at CREAL. “First of all, it relieves pain by acting on cannabinoid receptors in the brain.
Why boys are more likely to have autism
“Since these receptors normally help determine how neurons mature and connect with one another, paracetamol could alter these important processes. 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.”
There could also be an explanation for why boys are more likely to have autism spectrum symptoms: “The male brain may be more vulnerable to harmful influences during early life”, said Claudia Avella-Garcia. “Our differing gender results suggest that androgenic endocrine disruption, to which male brains could be more sensitive, may explain the association.”
The study concluded that the widespread exposure of infants to paracetamol in utero could increase the number of children with ADHD or autism spectrum symptoms. However, they stressed further studies should be conducted with more precise dosage measurements, and that the risks versus benefits of paracetamol use during pregnancy and early life should be assessed before treatment recommendations are made.
* Researchers in Spain recruited 2644 mother-child pairs in a birth cohort study during pregnancy. 88 per cent were evaluated when the child was one year old, and 79.9 per cent were evaluated when they were five years old. Mothers were asked about their use of paracetamol during pregnancy and the frequency of use was classified as never, sporadic, or persistent. Exact doses could not be noted due to mothers being unable to recall them exactly. 43 per cent of children evaluated at age one and 41 per cent assessed at age five were exposed to any paracetamol at some point during the first 32 weeks of pregnancy. When assessed at age five, exposed children were at higher risk of hyperactivity or impulsivity symptoms. Persistently exposed children in particular showed poorer performance on a computerised test measuring inattention, impulsivity and visual speed processing.
Abstract of Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms
Background: Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age.
Methods: This Spanish birth cohort study included 2644 mother-child pairs recruited during pregnancy. The proportion of liveborn participants evaluated at 1 and 5 years was 88.8% and 79.9%, respectively. Use of acetaminophen was evaluated prospectively in two structured interviews. Ever/never use and frequency of use (never, sporadic, persistent) were measured. Main neurodevelopment outcomes were assessed using Childhood Autism Spectrum Test (CAST), Conner’s Kiddie Continuous Performance Test (K-CPT) and ADHD-DSM-IV form list. Regression models were adjusted for social determinants and co-morbidities.
Results: Over 40% of mothers reported using acetaminophen. Ever-exposed offspring had higher risks of presenting more hyperactivity/impulsivity symptoms [incidence rate ratio (IRR) = 1.41, 95% confidence interval (CI) 1.01–1.98), K-CPT commission errors (IRR = 1.10, 1.03–1.17), and lower detectability scores (coefficient β = −0.75, −0.13–−0.02). CAST scores were increased in ever-exposed males (β = 0.63, 0.09–1.18). Increased effect sizes of risks by frequency of use were observed for hyperactivity/impulsivity symptoms (IRR = 2.01, 0.95–4.24) in all children, K-CPT commission errors (IRR = 1.32, 1.05–1.66) and detectability (β = −0.18, −0.36–0.00) in females, and CAST scores in males (β = 1.91, 0.44–3.38).
Conclusions: Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.
- Claudia B. Avella-Garcia, Jordi Julvez, Joan Fortuny, Cristina Rebordosa, Raquel García-Esteban, Isolina Riaño Galán, Adonina Tardónf, Clara L. Rodríguez-Bernal, Carmen Iñiguez, Ainara Andiarena, Loreto Santa-Marina, Jordi Sunyer. Acetaminophen Use in Pregnancy and Neurodevelopment: Attention Function and Autism Spectrum Symptoms. International Journal of Epidemiology, 2016 DOI: 10.1093/ije/dyv (open access)