No clear evidence that paracetamol in pregnancy is '...

"Study links taking Tylenol in pregnancy to two-fold higher risks of having children with ADHD and autism – but experts say the household painkiller is an unlikely cause," reports Mail Online.

The story published by Mail Online uses the US name for paracetamol (acetaminophen) and the US brand name Tylenol.

Researchers in the US measured the levels of paracetamol or broken-down paracetamol in the umbilical cords of nearly 1,000 babies after birth. They compared this with the chances of the babies being diagnosed later in childhood with either:

attention deficit hyperactivity disorder (ADHD)
autism
other developmental disabilities

The study found that babies with higher levels of paracetamol in their umbilical cords were more likely to have been diagnosed with ADHD or autism. However, we do not know that paracetamol was the cause.

The study only measured paracetamol use around the time of childbirth, not earlier in pregnancy, and many maternal and child health and environmental factors could be influencing the link.

There are also questions about how mothers and babies were selected for inclusion in this study. About 2 in 3 of the children were diagnosed with ADHD, autism or a developmental disability, which is a far higher rate than you would expect in a random population sample.

If you're pregnant and feel you need to take painkillers, paracetamol is usually safe to take. But if you find you're needing to take paracetamol regularly, speak to your doctor or midwife.

Find out more about taking paracetamol when you're pregnant.

Where did the story come from?

The researchers who carried out the study were from Johns Hopkins University, the US Department of Health and Human Services and Boston University School of Medicine. It was funded by the US Department of Health and Human Services. The study was published in the peer-reviewed medical journal JAMA Psychiatry.

The story in Mail Online uses the US name for paracetamol (acetaminophen) and the US brand name Tylenol. The news story reports the researchers "found a higher risk of both [ADHD and autism] where the drug was present". This is not strictly true, as they found paracetamol in all samples, but some samples had higher levels than others.

In its main headline, and later in the article, Mail Online does acknowledge that experts have noted limitations to this study and say that there is no clear evidence.

What kind of research was this?

This was a cohort study, looking at whether exposure to paracetamol is linked to outcomes such as autism and ADHD.

The main limitation of cohort studies is they can demonstrate an association between an exposure and an outcome, but cannot prove cause and effect. That's because other, unmeasured factors may be the cause of both.

What did the research involve?

Researchers at the Boston Medical Center in the US recruited mothers shortly after giving birth, in 1998. Samples of plasma from their baby's umbilical cord were taken and stored. They then followed their children for 20 years, up until 2018.

For this study, researchers analysed the 996 mother and child pairs with an available umbilical cord plasma sample. They analysed the amount of paracetamol and substances formed by breakdown of paracetamol and combined them into a measure of paracetamol burden.

They divided the children into 3 equal groups, depending on how much paracetamol burden was found in their samples – high, medium or low.

The researchers then looked at the children's medical records to see whether they had been diagnosed with ADHD, autism or any other developmental disability up to 2018. They then compared the children in the 3 different paracetamol exposure groups with their chances of having been diagnosed with one of these conditions.

They adjusted their figures to take account of a range of potential confounders, including the mother's:

age
ethnic background
education
marital status
stress during pregnancy
smoking, drug and alcohol use
body mass index (BMI)
fever during pregnancy

They also looked at whether the child was male or female, had been born prematurely, and their birthweight.

What were the basic results?

The number of children diagnosed with ADHD, autism, or a form of developmental disability was surprisingly high. The researchers said:

25.8% had ADHD
6.6% had autism
4.2% had both ADHD and autism
30.5% had other developmental disability
only 32.8% had no developmental disorders

The researchers do not explain or discuss why such a high number of children in their sample had been diagnosed with one of these conditions. They also found that all babies had signs of paracetamol in their umbilical cord plasma.

They found:

those with the highest paracetamol burden were 2.8 times more likely to have ADHD than those with the lowest burden (adjusted odds ratio (OR) 2.86, 95% confidence interval (CI) 1.77 to 4.67).
those with the highest paracetamol burden were 3.6 times more likely to have autism than those with the lowest burden (OR 3.63, 95% CI 1.62 to 8.60).

There was no association between paracetamol and diagnosis of other developmental disabilities.

How did the researchers interpret the results?

The researchers said: "The findings from this study contribute knowledge to ongoing research regarding the potential adverse neurodevelopmental consequences of perinatal acetaminophen exposure."

Conclusion

This study into potential links between paracetamol, ADHD and autism raises more questions than it answers. There are a number of unexplained findings which make the results seem questionable.

Firstly, we do not know why so many of the children in this study were diagnosed with developmental disorders. In the US, the Center for Disease Control estimates around 9.4% of children have an ADHD diagnosis, whereas the percentage in this study was 25.8%. Only 1 in 3 children in the study had not been diagnosed with a developmental disorder, which seems very unusual.

All babies had paracetamol in their umbilical cord blood at some level, even though you would not usually expect all pregnant women to be taking paracetamol around the time of giving birth.

Overall, it suggests this was not a random or representative sample of mothers and children, for reasons that are not explained. We do not know whether the results of the study would apply to the general population.

The results do not tell us at what age children were diagnosed with developmental disorders, or how long after entering the study they received their diagnosis.

Based on the samples, we do not know what dose of paracetamol the mothers had taken. This is because people's bodies break down paracetamol at different rates.

We also do not know when the mothers took paracetamol. The umbilical cord samples only tell us about paracetamol use in the hours before giving birth, not during their entire pregnancy. This means that even if there is a true link, it's not possible to inform "safe" or "unsafe" levels of paracetamol use.

Ultimately, cohort studies cannot tell us whether risk factors such as paracetamol can cause outcomes such as ADHD or autism. Various health, lifestyle and environmental factors could be linked, both with the reason the mothers took paracetamol, and the reason for development problems in children. This is especially important to consider in an unusual sample such as the one used in this study.

There is currently no clear evidence that paracetamol will harm your baby, and it is understood to be safe to take during pregnancy and while breastfeeding. But as with any medicine taken during pregnancy, use paracetamol at the lowest effective dose for the shortest possible time.