Pregnancy paracetamol use and the 'hyperactive behavioral phenotype' of autism

"Prenatal use of acetaminophen was associated with an increased risk of ASD [autism spectrum disorder] accompanied by hyperkinetic symptoms..., but not with other ASD cases."

I was rather interested to read that conclusion presented in the study by Zeyan Liew and colleagues [1] talking about how acetaminophen (or paracetamol as it is known here in Blighty) use during pregnancy might have some rather important connections to offspring outcomes specifically with autism and hyperkinetic symptoms in mind.

Interested not only because I've discussed other research talking about how we might need to be a little more cautious about how OTC pain relief such as paracetamol is used in certain circumstances with potential offspring outcomes in mind (see here and see here) but also because it makes reference to a quite specific effect to the "hyperactive behavioral phenotype" of autism. That hyperkinetic behavioural phenotype by the way, plugs into a growing body of peer-reviewed evidence talking about the over-representation of ADHD (attention-deficit hyperactivity disorder) symptoms in relation to [some] autism (see here).

Liew et al "followed 64,322 children and mothers enrolled in the Danish National Birth Cohort (DNBC; 1996–2002) for average 12.7 years to investigate whether acetaminophen use in pregnancy is associated with increased risk of ASD in the offspring." Details about paracetamol use during pregnancy were "collected prospectively from three computer-assisted telephone interviews" and offspring outcomes with labels like autism were compared. This follows a similar methodological template from some of this research team (see here).

Some 1.6% of children included in the analysis were eventually diagnosed with as ASD. Roughly a third of that 1.6% of children were also diagnosed with hyperkinetic disorders (which seems to tally with other independent data analysis [2]). Perhaps unsurprisingly, paracetamol use during pregnancy was pretty widespread in the cohort (~50%) but, despite this, authors detailed something of a potentially important relationship between pregnancy paracetamol use and offspring "ASD accompanied by hyperkinetic symptoms." That there also appeared to be a relationship between length of use of paracetamol and risk of offspring autism with hyperkinetic symptoms, seems to strengthen details of a possible association.

Accepting that this was a study plotting pregnancy medication use and offspring outcomes and hence findings need to be treated with a degree of caution (as with other studies on other medicines), set within the other research talking about paracetamol use during pregnancy I'm coming around the idea that more investigation is required in this area [3]. I could, once again, start talking about how pregnancy paracetamol use might link into childhood asthma symptoms [4] (albeit with some cautions attached [5]) and what that might mean for the behavioural 'associations' noted in some cases of asthma (see here) as a possible angle for future research. I would however temper such musings within the context of autism (see here); although the preliminary suggestion that prenatal exposure to certain drugs used to treat asthma might also affect risk of offspring autism is also interesting [6].

I do like that Liew and colleagues talked about the idea of a specific behavioural phenotype potentially linked to pregnancy paracetamol exposure as providing a guide for more targeted investigation and perhaps to some degree bypassing the need for the sweeping generalisations about 'all autism' (we've had enough of those down the years). I believe there is quite a bit of research traction in this area with the notion of the autisms (see here) in mind.

Music: Elvis Presley - If I Can Dream.

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[1] Liew Z. et al. Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood. Autism Research. 2015. Dec 21.

[2] Berenguer-Forner C. et al. Comorbidity of autism spectrum disorder and attention deficit with hyperactivity. A review study. Rev Neurol. 2015 Feb 25;60 Suppl 1:S37-43.

[3] de Fays L. et al. Use of paracetamol during pregnancy and child neurological development. Dev Med Child Neurol. 2015 Aug;57(8):718-24.

[4] Eyers S. et al. Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta-analysis. Clin Exp Allergy. 2011 Apr;41(4):482-9.

[5] Cheelo M. et al. Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis. Arch Dis Child. 2015 Jan;100(1):81-9.

[6] Gidaya NB. et al. In utero Exposure to β-2-Adrenergic Receptor Agonist Drugs and Risk for Autism Spectrum Disorders. Pediatrics. 2016. 6 Jan.

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Liew Z, Ritz B, Virk J, & Olsen J (2015). Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: A Danish national birth cohort study. Autism research : official journal of the International Society for Autism Research PMID: 26688372