Paracetamol in pregnancy 'link to autism and ADHD' n...

"Women who take paracetamol during pregnancy 'risk having a child with autism or ADHD'," the Mail Online reports. But the Spanish study it reports on provides no evidence of a direct link to either condition.

Researchers assessed paracetamol use in more than 2,000 pregnant women, and then performed various developmental and behavioural tests on the children at the ages of one and five.

They found paracetamol use during pregnancy was linked with hyperactivity and impulse symptoms at age five, and autism symptoms in boys.

However, there was no link with full diagnostic criteria for attention deficit hyperactivity disorder (ADHD) or autism symptoms in all children. Nor was there any link with development or intellect.

Importantly, the study cannot prove using paracetamol in pregnancy caused these symptoms.

The causes of both conditions are poorly understood and may involve many hereditary, health and environmental influences, which this study has not been able to account for.

For example, the study did not assess whether the women smoked in pregnancy, and also did not take the child's secondhand smoke exposure into account.

Smoking has been linked to both conditions – though, as with this study, the link is unproven – so this seems an odd oversight.

The current viewpoint is occasionally using paracetamol as needed, and at recommended doses, is safe during pregnancy. This study alone is unlikely to have provided sufficient evidence to the contrary to change this.

Where did the story come from?

The study was carried out by researchers from various institutions in Spain, including Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra.

It received funding from multiple sources, including the Instituto de Salud Carlos III and the Spanish Ministry of Health. The authors declared that they had no conflicts of interest.

The study was published in the peer-reviewed International Journal of Epidemiology. It is available on an open-access basis and is free to read online.

The Mail, The Times and The Daily Telegraph are all guilty of publishing headlines that could cause women undue alarm. This study did not prove there is a link between women using paracetamol in pregnancy and autism or ADHD.

What kind of research was this?

This population-based Spanish cohort study aimed to see whether using paracetamol during pregnancy is associated with any neurodevelopmental or behavioural outcomes in the child up to the age of five.

As the researchers say, paracetamol is widely used during pregnancy, but some studies have linked it with adverse outcomes in the child.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) have increased in prevalence over the years.

No cause has been definitively established for these conditions, but it has been speculated various environmental factors may play a role.

The researchers wanted to see if there could be a link between maternal paracetamol use and ADHD or ASD in their children.

The main limitation of cohort studies is they can demonstrate an association between an exposure and an outcome, but can't prove cause and effect.

What did the research involve?

This study used the INfancia y Medio Ambiente (INMA) birth cohort, which recruited 2,644 expectant mothers from four different regions in Spain between 2004 and 2008.

The mothers were interviewed at 12 and 32 weeks of pregnancy, when they were asked whether they had taken any medication (sporadically or continuously) since a month before becoming pregnant or during the pregnancy.

If they answered yes, they were then asked about the specific medication, dose and frequency of use.

Women were classed as paracetamol users if they'd used any paracetamol from one month before pregnancy to up to 32 weeks.

More than 80% of children were available for assessment between the ages of one and five years.

At one year of age they were assessed using the Bayley Scales of Infant Development (BSID). They were tested again at the age of five.

The tests included:

McCarthy Scales of Children's Abilities (MCSA) – to assess cognitive and psychomotor development
California Preschool Social Competence Scale (CPSCS) – to assess social competence
Childhood Autism Spectrum Test (CAST)
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for ADHD symptoms
Conner's Kiddie Continuous Performance Test (K-CPT) – a computerised test to look at attention, reaction time, accuracy and impulse control

The researchers took various confounders into account in their analyses, such as:

child gender
prematurity
mother's health
social class
educational level

The researchers did not look at maternal smoking habits.

What were the basic results?

Overall, around 42% of children had been exposed to paracetamol during pregnancy, with pain relief being the mothers' main reason for use.

Children exposed to paracetamol were more likely to have hyperactivity and impulse symptoms on ADHD criteria than non-exposed children – a link that only just reached statistical significance (rate ratio 1.41, 95% confidence interval 1.01 to 1.98).

Paracetamol use was also associated with more of certain types of errors on the Kiddie Continuous Performance Test. Higher paracetamol use was linked with more symptoms.

There was, however, no significant link with meeting ADHD criteria overall, or with inattention symptoms specifically.

Nor was there any link with Childhood Autism Spectrum Test results overall for all children, though the researchers did find paracetamol use was significantly linked with ASD symptoms in boys specifically. There was also no clear link with ASD symptoms for girls.

There was no link with neurodevelopmental outcomes on the Bayley Scales of Infant Development (BSID) at age one, or the McCarthy Scales of Children's Abilities (MCSA) at age five.

How did the researchers interpret the results?

The researchers say being exposed to paracetamol during pregnancy was associated with a greater number of autism symptoms in boys, and more ADHD-related symptoms in both genders.

They also say how these associations seem to be dependent on the frequency of exposure.

Conclusion

This birth cohort study found some significant links between using paracetamol in pregnancy and hyperactivity or impulse symptoms at the age of five and ASD symptoms in boys.

However, this research cannot prove paracetamol use is directly responsible for these findings.

Not all links were statistically significant – for example, paracetamol was not linked with ADHD when looking at full diagnostic criteria, or with ASD when looking at the full sample of children.

It is possible the significant links identified may not be true causative links and would not be replicated if another birth cohort was used.

The researchers have tried to take account of various confounders, but given that the causes of ADHD and ASD are not clearly established, it is difficult to take account of all the hereditary, health and environmental factors that could have an influence.

And some notable factors are missing – for example, the mother's alcohol consumption, or whether or not she or anyone else in the home smoked during pregnancy or in the child's younger years – and do not appear to have been assessed.

Although the researchers have tried to look at frequency of use, they couldn't assess the effects of different paracetamol doses due to mothers' difficulties recalling the exact dose taken. This would have been useful to assess, especially with regards to potential future guidance.

Assessments of frequency of use highlight the need for caution when taking these statistical links at face value.

Despite the large initial sample size, the smaller sample sizes decrease the reliability of these links when further broken down into frequency of use – for example, less than 50 women reported persistent use of paracetamol.

And the smaller the sample size, the greater the possibility that the results have been affected by chance.

There were also only two assessments carried out at one and five years of age. Longer term and more regular follow-up of the children may have given a better indication of whether these assessments truly indicated more persistent behavioural and social difficulties.

Importantly, no link was found with developmental or intellectual outcomes in the child.

Overall, the link is worthy of further investigation, but does not prove that paracetamol use during pregnancy could cause ADHD or autism symptoms.

The current viewpoint is that occasionally using paracetamol as needed, and at recommended doses, is safe during pregnancy. This study has not provided sufficient evidence to the contrary to change this advice.

If you are experiencing chronic pain and feel the need to take painkillers frequently during your pregnancy, you should speak to your GP or midwife about alternative treatment options.