Acetaminophen during pregnancy linked to autism? Maybe. – GWC Mag

I’ve been asked several times about the veracity of the claims that taking acetaminophen during pregnancy was linked to autism and other neurodevelopmental disorders. I do get tired of all the claims about what causes autism, especially when it comes to vaccines.

However, in this case, there seems to be some quality evidence that consuming analgesics, like acetaminophen, may be linked to an increased risk of autism.

Let’s look at some of the best data which may support this claim.

What is acetaminophen?

Acetaminophen (trade name Tylenol in the USA and Panadol in other countries), also known as paracetamol, is a medication that is used to treat fever and mild-to-moderate pain. Although it is the first-line treatment for pain and fever, it is inferior to non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen. However, NSAIDs have significant anti-coagulant activity, which acetaminophen lacks.

Acetaminophen during pregnancy and autism research

Several papers have been published on the relationship between consuming acetaminophen during pregnancy and autism spectrum disorders in children. Reviewing all of them would be beyond the patience of most readers, but lucky for us, there are several high-quality systematic reviews and meta-analyses that have examined the link, and, as my regular readers know, I consider systematic reviews to be at the pinnacle of the hierarchy of biomedical research.

In a paper published on 1 August 2018 in the respected American Journal of Epidemiology, the researchers examined seven studies that included 132,738 mother-child pairs, of which 61,601 were exposed to acetaminophen during pregnancy. Individuals were followed for three to 11 years, depending on the study, using questionnaires, interviews, and self-reports on medication use.

The researchers found that the risk ratio for autism spectrum disorder for mothers who took acetaminophen during pregnancy was 1.19 (95% CI: 1.14, 1.25; I2 = 14%). In other words, there was about a 19% additional risk for a diagnosis of autism.

But what does this study tell us:

1. The study relied upon memory and self-reporting for acetaminophen use. They did not measure blood levels, or some other objective measurement, of acetaminophen levels.
2. Although the study attempted to adjust for confounders, it is not possible to determine all of them.
3. This meta-analysis may be able to show correlation, but it does not provide us with causation.
4. It does not provide any biologically plausible mechanism that could establish a link between acetaminophen use during pregnancy and autism.

Another systematic review, published on 18 July 2022, seems to support the correlation between acetaminophen and autism spectrum disorder. Moreover, another NIH-sponsored study has indicated a link between acetaminophen use during pregnancy and autism (along with ADHD).

And another review, published on 13 July 2022, stated that “it can be concluded without any reasonable doubt that oxidative stress puts some babies and children at risk of paracetamol-induced neurodevelopmental injury, and that postnatal exposure to paracetamol in those susceptible babies and children is responsible for many if not most cases of ASD.” The conclusion doesn’t follow the careful statements that most scientists use, nevertheless, it seems that they have also found a link.

In one final review, published in October 2021 in the European Journal of Epidemiology, the researchers also confirmed a correlation between acetaminophen use during pregnancy and autism. Their results indicated that children prenatally exposed to acetaminophen were 19% more likely to subsequently have borderline or clinical autism spectrum disorder.

There are also some studies that try to explain the mechanism for a possible link:

• In a study published on 15 October 2021 in the International Journal of Molecular Science, the authors claim that metabolites of acetaminophen may have a biochemical effect on the developing fetal brain.
• In another study published on 6 April 2021 in Behavioural Brain Research, the researchers examined the effect of acetaminophen use in rats and showed lower glutathione levels in pups. This may show the mechanism between acetaminophen use and autism.

Summary

I went into this article thinking that this was just another “everything, including the kitchen sink, causes autism.” Those of us who have fought against the “vaccines cause autism” trope (vaccines are not linked to autism) are skeptical of every claim that something causes autism.

But a review of numerous systematic reviews and meta-analyses seems to show a small, but statistically significant, increase in the risk of autism in children whose mothers took acetaminophen during pregnancy. I even tried to cherry-pick a systematic review that disputed this link, and I couldn’t find one.

I think further research is necessary. We need more information like whether there is a dose-response relationship, or what the mechanism is.

But for now, I think we have some evidence, possibly of moderate strength, that supports the link. If you are pregnant, maybe you should consider limiting the use of acetaminophen.

However, there may be a confounder that may make the consumption of Tylenol merely coincidental. There is a growing body of evidence that pregnant mothers who contract a pathogen during pregnancy run a higher risk of autism in their children. Of course, many of these pregnant women might take Tylenol when they are sick.

I think more research is necessary, but at this point in time, it seems that there is a correlation between taking acetaminophen and an increased risk of autism in the child.

Citations

• Alemany S, Avella-García C, Liew Z, García-Esteban R, Inoue K, Cadman T, López-Vicente M, González L, Riaño Galán I, Andiarena A, Casas M, Margetaki K, Strandberg-Larsen K, Lawlor DA, El Marroun H, Tiemeier H, Iñiguez C, Tardón A, Santa-Marina L, Júlvez J, Porta D, Chatzi L, Sunyer J. 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 Oct;36(10):993-1004. doi: 10.1007/s10654-021-00754-4. Epub 2021 May 28. PMID: 34046850; PMCID: PMC8542535.
• Bührer C, Endesfelder S, Scheuer T, Schmitz T. Paracetamol (Acetaminophen) and the Developing Brain. Int J Mol Sci. 2021 Oct 15;22(20):11156. doi: 10.3390/ijms222011156. PMID: 34681816; PMCID: PMC8540524.
• Khan FY, Kabiraj G, Ahmed MA, Adam M, Mannuru SP, Ramesh V, Shahzad A, Chaduvula P, Khan S. A Systematic Review of the Link Between Autism Spectrum Disorder and Acetaminophen: A Mystery to Resolve. Cureus. 2022 Jul 18;14(7):e26995. doi: 10.7759/cureus.26995. PMID: 35989852; PMCID: PMC9385573.
• Masarwa R, Levine H, Gorelik E, Reif S, Perlman A, Matok I. Prenatal Exposure to Acetaminophen and Risk for Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies. Am J Epidemiol. 2018 Aug 1;187(8):1817-1827. doi: 10.1093/aje/kwy086. PMID: 29688261.
• Patel E, Jones Iii JP 3rd, Bono-Lunn D, Kuchibhatla M, Palkar A, Cendejas Hernandez J, Sarafian JT, Lawton VG, Anderson LG, Konsoula Z, Reissner KJ, Parker W. The safety of pediatric use of paracetamol (acetaminophen): a narrative review of direct and indirect evidence. Minerva Pediatr (Torino). 2022 Jul 13. doi: 10.23736/S2724-5276.22.06932-4. Epub ahead of print. PMID: 35822581.
• Rigobello C, Klein RM, Debiasi JD, Ursini LG, Michelin AP, Matsumoto AK, Barbosa DS, Moreira EG. Perinatal exposure to paracetamol: Dose and sex-dependent effects in behaviour and brain’s oxidative stress markers in progeny. Behav Brain Res. 2021 Jun 25;408:113294. doi: 10.1016/j.bbr.2021.113294. Epub 2021 Apr 6. PMID: 33836167.

Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!

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