Summary: A commonly used painkiller taken during pregnancy has been linked to a higher likelihood of autism spectrum symptoms and attention-related difficulties in exposed children.
New research indicates that prenatal exposure to paracetamol (acetaminophen) is associated with increased autism spectrum traits in boys and with attention and hyperactivity-related symptoms in both boys and girls.
The findings, published in the International Journal of Epidemiology, come from a large Spanish birth cohort and represent the first independent report describing an association between prenatal paracetamol use and later autism spectrum symptoms, with differing effects observed between boys and girls. Compared with children whose mothers did not use paracetamol during pregnancy, persistently exposed children showed about a 30% higher risk of impairment in some attention-related functions, and boys showed an increase in autism spectrum symptoms.
Researchers recruited 2,644 mother–child pairs during pregnancy and followed them through early childhood. Follow-up evaluations were completed for 88% of participants at age one and nearly 80% at age five. Mothers were asked about paracetamol use during pregnancy and responses were categorized as never, sporadic, or persistent use; precise dose information was not available because many mothers could not recall exact amounts. Around 43% of children assessed at age one and 41% assessed at age five had been exposed to paracetamol at some point during the first 32 weeks of gestation.
At the five-year assessment, children whose mothers reported any use of paracetamol during pregnancy were more likely to display hyperactivity or impulsivity symptoms. Children with persistent exposure performed worse on a computerized test that measures inattention, impulsivity and visual processing speed. Boys who experienced persistent prenatal exposure also showed a higher number of autism spectrum symptoms on the screening measure used.
Lead author Claudia Avella-Garcia, a researcher at CREAL (an ISGlobal allied centre in Barcelona), emphasized that the study measured symptoms rather than clinical diagnoses: “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.”
Co-author Dr. Jordi Júlvez, also at CREAL, outlined several plausible biological mechanisms that might explain the association. He noted that paracetamol acts, in part, on cannabinoid receptors in the brain, which play a role in how neurons mature and form connections; interference with these processes could alter neurodevelopment. Paracetamol might also influence immune development, create oxidative stress, or be directly toxic to fetuses that cannot metabolize the drug as effectively as adults.
The authors also considered why boys appeared more affected on autism screening: “The male brain may be more vulnerable to harmful influences during early life,” Avella-Garcia said. “Our differing gender results suggest that androgenic endocrine disruption, to which male brains could be more sensitive, may explain the association.”
The study concludes that widespread prenatal exposure to paracetamol could contribute to an increase in childhood attention problems and autism spectrum symptoms. The researchers caution that the findings do not prove causation and call for additional studies with more precise dose information and rigorous assessment of risks versus benefits before clinical recommendations about paracetamol use in pregnancy are changed.
Funding: The study received funding from the Instituto de Salud Carlos III, FIS-FEDER, the Spanish Ministry of Health, Generalitat de Catalunya-CIRIT, and the Miguel Servet Fellowship (Spanish Institute of Health Carlos III).
Source: Chloe Foster – Oxford University Press
Original research: The full open-access study is titled “Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms” by Claudia B. Avella-Garcia et al., published in the International Journal of Epidemiology (published online June 28, 2016).
Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms
Background: Acetaminophen is frequently used during pregnancy, yet population-based cohort evidence assessing a range of neuropsychological and behavioral outcomes has been limited. The investigators aimed to evaluate whether prenatal acetaminophen exposure is associated with neurodevelopmental outcomes at ages 1 and 5 years.
Methods: This Spanish birth cohort followed 2,644 mother–child pairs recruited during pregnancy, with 88.8% and 79.9% retained at 1- and 5-year assessments, respectively. Maternal acetaminophen use was recorded prospectively in structured interviews and categorized as never, sporadic, or persistent. Main outcomes included the Childhood Autism Spectrum Test (CAST), Conner’s Kiddie Continuous Performance Test (K-CPT) and an ADHD-DSM-IV symptom checklist. Analyses adjusted for social factors and comorbidities.
Results: More than 40% of mothers reported acetaminophen use. Ever-exposed children showed higher rates of hyperactivity/impulsivity symptoms (incidence rate ratio, IRR = 1.41), more K-CPT commission errors (IRR = 1.10) and lower detectability scores. CAST scores were elevated in ever-exposed males. Greater frequency of use was associated with larger effect sizes for hyperactivity/impulsivity, K-CPT errors and detectability, and with higher CAST scores in males.
Conclusions: Prenatal acetaminophen exposure was associated with more autism spectrum symptoms in males and with adverse attention-related outcomes in both sexes, with associations appearing to depend on exposure frequency. Further research with accurate dosage data and careful risk–benefit assessment is needed.
Citation: “Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms” by Claudia B. Avella-Garcia, Jordi Julvez, Joan Fortuny and colleagues. International Journal of Epidemiology. Published online June 28, 2016. doi:10.1093/ije/dyw115