Paracetamol in pregnancy associated with ADHD and autism in children

Paracetamol, or acetaminophen, is very commonly used as an analgesic and antipyretic; it is one of the most prescribed drugs in the world. But a new study warns against its use during pregnancy: prenatal exposure to paracetamol has an average 20% higher risk for the child of developing symptoms characteristic of autism spectrum disorder or deficit disorder. attention with or without hyperactivity.

In many countries, paracetamol can be obtained from pharmacies without a prescription. But this analgesic has been talked about many times in recent years, due to the increase in cases of overdose. Beyond three grams per day, or in case of prolonged use, it can indeed cause serious liver complications. Faced with the increase in involuntary paracetamol poisoning, this drug has not been available in open access in France since January 2020; it must be given by the pharmacist, who must ensure that the appropriate dosage is recalled.

In 2016, a study published in the journal JAMA Pediatrics revealed that paracetamol taken during pregnancy could be associated with abnormal neurological development of the fetus. In particular, research suggested that paracetamol taken in the 2nd and 3rd trimester of pregnancy was linked to an increase in certain behavioral disorders in the child, such as hyperactivity. New work today supports this hypothesis.

Prenatal exposure that affects both girls and boys

This new study, conducted by the Barcelona Institute for Global Health (ISGlobal), involves more than 73,000 mother-child pairs, from six European cohorts. Depending on the cohort, 14% to 56% of mothers reported taking paracetamol during their pregnancy.

It turns out that children who were exposed to paracetamol before birth were 19% more likely to develop symptoms typical of autism spectrum disorder (ASD) than other children; they were also 21% more likely to develop symptoms of attention deficit disorder with or without hyperactivity (ADHD). The researchers also found that prenatal exposure to paracetamol generally affected girls and boys in the same way – although the associations observed were slightly stronger in boys.

Our results correct some of the weaknesses of previous meta-analyzes », Specifies Jordi Sunyer, researcher at ISGlobal and co-author of the study. This previous work had in particular been criticized for the heterogeneity of the criteria used. This is why the team considered this time larger cohorts, from several countries, while endeavoring to harmonize the definition of an exposure to paracetamol and the evaluation of the symptoms of the different disorders.

Exposure to paracetamol was assessed through questionnaires or maternal interviews; symptoms of ASD and ADHD were assessed between 4 and 12 years of age, using validated instruments (and confirmed by hospital diagnoses in one of the cohorts). In addition, several co-variables directly related to the mother were taken into account: age at childbirth, level of education, body mass index before pregnancy, alcohol, smoking, mental health problems during pregnancy, fever and infections during pregnancy, etc.

A drug to be taken in moderation

The team believes that the adverse effects of early exposure to paracetamol on neurological development may be due to several mechanisms: stimulation of the endocannabinoid system (responsible for maintaining cell homeostasis), a change in the level of neurotrophic factor derived from the brain (a protein essential for the development of the nervous system), oxidative stress due to immune activity induced by inflammation, changes in neurotransmission, or disruption of the endocrine system.

These results are rather worrying when we know that paracetamol was until now considered one of the safest drugs for pregnant women and their babies. According to several previous studies, it is estimated that 46 to 56% of pregnant women in developed countries use paracetamol as a pain reliever and / or fever reducer. Today, the link between paracetamol and behavioral problems is confirmed …

Still, Sunyer insists that these results should be interpreted with caution; paracetamol must not be definitively ruled out, but it must be used in moderation: ” We agree with previous recommendations stating that while paracetamol should not be withdrawn in pregnant women or children, it should only be used when necessary. “. In other words, common sense is essential.

At the same time, the team analyzed the exposure of children to paracetamol after birth (up to 18 months): it turns out that no association could be established between the use of this drug during childhood and symptoms of ASD. The researchers stress, however, that this conclusion requires additional studies, due to the heterogeneity of postnatal exposure to paracetamol among the different cohorts (which ranged from 6 to 92.8%).

Sources: European Journal of Epidemiology, S. Alemany et al.

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