A recent study by the Barcelona Institute of Global Health (ISGlobal) has analyzed the association between prenatal exposure to paracetamol and the development of symptoms of attention deficit hyperactivity disorder (ADHD) and spectrum disorders autism (ASD) in boys and girls.
The epidemiological study, which looked at 73,991 children from six different European cohorts, found that children exposed to paracetamol prenatally were 19% more likely to develop symptoms of ASD and 21% more likely to develop symptoms of ADHD than those not exposed.
We spoke to Sílvia Alemany, the first author of the study, to learn about how they work with such large amounts of data and what the possible effects of paracetamol consumption are.
More than 70,000 samples from six different cohorts seems like a challenge… What problems did you face when analyzing the data?
Yes, it is a challenge to work with data from different cohorts, as it involves coordinating with various groups and doing prior work to explore the available information. And then, the study variables must be harmonized as much as possible so that they are all comparable and the study can be done.
In addition, the use of data from some cohorts can also have an economic cost. However, in our case we were able to access the six different European cohorts for free because the collaborators have been very cooperative and generous and have been involved with the project from the very beginning.
“We have been able to work with a very wide sample and generate new results”
Why is it important to do this type of meta-analysis?
It is important to do meta-analysis, like ours, when there are several studies testing the same hypothesis in independent samples. What we are looking for is to gain statistical power and to jointly analyze data that has been collected under different conditions to see a global effect.
The fact that the overall analysis, after harmonizing the data, is consistent with previous results indicates that the association is robust. When we test the association excluding one cohort, and we repeat the analysis by excluding another cohort, and so on, and we always find the same result, that means this final result does not depend on the inclusion of a particular cohort. This reinforces the robustness of the association.
Looking at the results and knowing that paracetamol consumption is widespread (and specifically among pregnant women), do you think action should be taken to reduce it?
What emerges from our results is that if paracetamol is being consumed when it is not strictly necessary, perhaps its consumption should be decreased and with it, the likelihood of developing certain neurodevelopmental problems in the future. I believe that the use of paracetamol during pregnancy, which is a very sensitive stage of development, should be more closely monitored and the risk / benefit balance assessed in each case given the scientific evidence we have.
“Our role is to analyze and interpret the partnership with rigor and transparency and then communicate the results as well as we can.”
At the neurological level, how does paracetamol affect development? Is it known if its consumption also has effects on adult life?
It is not yet established how paracetamol consumption acts in neurodevelopment. However, there are several proposed mechanisms that lead us to think that it is biologically plausible that exposure to this drug can cause long-term changes in the brain:
- There is evidence that paracetamol can cross the placenta and enter the fetal bloodstream.
- Several studies indicate that paracetamol may cause changes in the endocannabinoid system, relevant to neurodevelopment, and also in some neurotransmitters. Interestingly, in animal models an association has been observed between paracetamol and lower levels of brain factors in a region of the brain particularly relevant in attention deficit / hyperactivity disorder (ADHD) such as the striatal nucleus, involved in control of movements and cognitive processes.
- Other authors point out that the metabolic capacity of paracetamol may be impaired in pregnant women and people with autism spectrum disorders. If these metabolic pathways of paracetamol were saturated, the ability of cellular detoxification could deteriorate and lead to oxidative stress processes that have been linked to neurodevelopmental disorders.
Alemany, S., Avella-García, C., Liew, Z. et al. Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts. Eur J Epidemiol (2021).