Paracetamol during pregnancy did not increase the risk of RAS and ADHD in children
A population-based study by Swedish scientists using a sibling-adjusted statistical model has found that taking paracetamol during pregnancy does not increase the risk of autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and mental retardation in children. The authors of the paper, published in The Journal of the American Medical Association, believe that the positive associations seen in previous studies may have been due to confounding and confounding factors.
The US Food and Drug Administration and the European Medicines Agency believe that taking paracetamol poses minimal risk during pregnancy. However, a consensus statement from an international group of scientists and clinicians published in 2021 recommends, among other precautions, that pregnant women should "discontinue paracetamol unless its use is medically indicated" because of the potential risk of developmental disorders such as RAS and ADHD.
However, in studies where such associations have been observed, there may be confounding and confounding of risk factors. For example, paracetamol may have been used because of some health disorder, such as an infection, fever, migraine or pain caused by an autoimmune disease. All of these indications for the use of the drug may be independent risk factors for neurodevelopmental disorders and thus lead to false associations. In addition, confounding with parental health and genetics is likely, as disorders of nervous system development are largely hereditarily mediated.
A research team led by Brian Lee from Karolinska Institute investigated the association between paracetamol intake during pregnancy and the risk of children developing RAS, ADHD and mental retardation among nearly 2.5 million children, of whom 185909 were exposed to paracetamol. This analysis included prospectively collected antenatal data and prescription records to reflect medication use, clinical diagnoses related to nervous system development, and sibling data.
Intrauterine exposure to paracetamol was more common among children born to parents of lower socioeconomic status, higher body mass index in early pregnancy, those who smoked during pregnancy, and those diagnosed with any mental illness, neurodevelopmental disorders. During the follow-up period, with a mean duration of 13.4 years, 188929 children developed at least one neurodevelopmental disorder: 68584 had RAS, 146386 had ADHD, and 24554 had mental retardation. The mean age of diagnosis was 11.6 years for RAS, 12.2 years for ADHD, and 8.2 years for mental retardation.
The primary analysis showed that intrauterine exposure to paracetamol resulted in a non-significant increase in the risk of developing neurodevelopmental disorders. However, in sibling-adjusted models, intrauterine exposure to paracetamol was not associated with an increased risk of developing RAS, ADHD or mental retardation. The modelling results showed that even if paracetamol use had been significantly underestimated, this measurement error was unlikely to have led to the null associations observed when compared with control drugs. In addition, sensitivity analyses showed that the results were consistent regardless of the data source used to determine medication use, stratification by age group at birth, or the method of handling missing data.
Similar results showed similar group comparisons when analysing intake of other non-steroidal anti-inflammatory drugs, with aspirin even reducing the statistical risk of neurodevelopmental disorders. Additional analyses showed no dose-response type relationship for paracetamol.
These findings, obtained on a large cohort of children, contradict the conventional wisdom that paracetamol during pregnancy alone may increase the risk of neurodevelopmental disorders in children. The scientists are confident that the adverse effect of paracetamol may reach zero in further confounding analyses.