Why the Swedish Sibling Study May Give the Wrong Message

What the study did

A large Swedish study analyzed data on 2.48 million children born between 1995 and 2019. The researchers compared siblings:

• One pregnancy where the mother took Tylenol (acetaminophen).

• Another pregnancy where she did not.

They reported no difference in autism, ADHD, or intellectual disability between exposed and unexposed siblings. Based on this, the authors concluded there was “no real link” between Tylenol use in pregnancy and these conditions (Ahlqvist et al., 2024).

Why that can be misleading

Tylenol may not increase autism risk directly. The concern is that the harm happens indirectly:

• Acetaminophen metabolism can reduce glutathione (GSH), the body’s main antioxidant (Kaplowitz, 2004).

• Glutathione is essential for maintaining the folate cycle and methylation, which support DNA synthesis and brain development (James et al., 2004).

• If a mother has low glutathione and folate reserves, Tylenol may push these levels even lower → increasing risk for the baby’s neurodevelopment.

• If a mother has adequate glutathione and folate, Tylenol may cause little or no measurable harm.

This means the risk is not the same for all pregnancies — it depends on the mother’s biology at the time.

Why the sibling comparison hides this

Sibling studies assume the mother’s internal biology is unchanged across pregnancies. But this is rarely true. Between pregnancies, a woman’s:

• Diet and prenatal supplement use,

• Stress, sleep, or illness,

• Liver and kidney function,

• Exposure to toxins or infections

can all change.

So in one pregnancy, she may have strong protection (high folate and glutathione). In another, she may be vulnerable (low levels). When the study averages outcomes across siblings, the risk in vulnerable pregnancies gets washed out. This creates the illusion that Tylenol is harmless.

That is why it is misleading — and potentially dangerous — to interpret the Swedish sibling study as proving Tylenol is safe in pregnancy.

What we really need to know

Future studies should measure:

• Maternal glutathione levels during pregnancy.

• Folate and related methylation markers.

• Dose and timing of Tylenol use.

Only then can researchers fairly test whether Tylenol interacts with these biological factors to increase risk. Until then, the conclusion of “no risk” is premature.

✅ Take-home message
The Swedish sibling study is important, but it misses a key point: Tylenol’s risk may depend on whether the mom has enough glutathione and folate during pregnancy. Because those levels change, comparing siblings does not prove Tylenol is safe — it only hides risk that may exist under certain biological conditions.

References

Ahlqvist, V. H., Magnusson, P. K. E., Lundholm, C., Viktorin, A., Larsson, H., Almqvist, C., & Magnusson, C. (2024). Acetaminophen use during pregnancy and risks of neurodevelopmental disorders in offspring: Population-based cohort and sibling-controlled cohort study. JAMA, 331(1), 52–62. https://doi.org/10.1001/jama.2023.28291

James, S. J., Cutler, P., Melnyk, S., Jernigan, S., Janak, L., Gaylor, D. W., & Neubrander, J. A. (2004). Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. American Journal of Clinical Nutrition, 80(6), 1611–1617. https://doi.org/10.1093/ajcn/80.6.1611

Kaplowitz, N. (2004). Acetaminophen hepatotoxicity: What do we know, what don’t we know, and what do we do next? Hepatology, 40(1), 23–26. https://doi.org/10.1002/hep.20300

Molloy, A. M., Kirke, P. N., Troendle, J. F., Burke, H., Sutton, M., Brody, L. C., Scott, J. M., & Mills, J. L. (2009). Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics, 123(3), 917–923. https://doi.org/10.1542/peds.2008-1173