Does taking paracetamol during pregnancy affect children?

New US research has found an association between prenatal exposure to paracetamol and attention problems and sleep issues in offspring by age three.
 
After adjusting for confounding variables, including stress, researchers found children of women who used paracetamol during pregnancy were 23% more likely to display sleep problems and 21% more likely to display attention problems compared to those whose mothers did not use acetaminophen while pregnant.
 
Published in PLOS, the study indicated children who were exposed to paracetamol during pregnancy scored significantly higher on two of seven Child Behaviour Checklist (CBCL) syndrome scales – sleep problems and attention problems – compared to those who were not.
 
The research included 2423 mother-child pairs and used CBCL for ages 1.5–5, with the mothers rating their own children.
 
However, while the children of mothers who took paracetamol scored much higher for sleeping and attention problems, experts have expressed wariness about the way in which the findings were determined.
 
Gavin Pereira, a Professor of Epidemiology and Biostatistics at Curtin University, told newsGP in studies like this it is difficult to discount an issue called ‘confounding by indication’.
 
‘These outcomes were assessed by mothers, rather than by a relatively more independent party such as a teacher or clinician,’ he said.
 
‘The very fact that paracetamol was taken indicates an underlying issue experienced by the mother that could pass either directly or indirectly to the child. It is plausible that anxious parents are more likely to both take paracetamol and report attention and sleep problems for their children.
 
‘The researchers [also] controlled for prenatal stress, which can in some situations cause bias rather than control for it.’
 
Women reported taking paracetamol in pregnancy for a range of reasons including fever, infection, allergies, muscle pain, headaches and trouble sleeping.
 
For Dr Ian Musgrave, a senior pharmacology lecturer at the University of Adelaide, this represents a flaw in the study.
 
‘A big problem in studies like these is the issue of other conditions, the mothers who took paracetamol were taking it for issues like fever, infection and allergies, all of which can potentially affect the mental development of the child,’ he said.
 
‘For example, maternal stress was associated with the child being withdrawn, having sleep problems and attention problems.
 
‘The authors attempted to control for these confounders, but the association of paracetamol with sleep problems and attention problems after this correction is marginal and may simply be due to other factors associated with the need to use paracetamol for pain relief.’
 
Meanwhile, the study did not include dosages of paracetamol taken, another problem according to Professor Pereira.
 
‘The presence of a dose-response effect would provide greater credibility in the results,’ he said.
 
‘It would be more informative to both physicians and patients to know the dose above which harm is most likely to occur.’
 
Other limitations noted by the study authors include that the timing of paracetamol use in pregnancy was not recorded, while interviews with the pregnant women were conducted at an average of 35 weeks’ gestation, thereby missing the last few weeks of pregnancy.
 
While the study has a variety of limitations, it is not the first to raise concerns regarding pregnant women taking paracetamol.
 
Previous studies in 2018, 2019 and 2021 have also linked paracetamol use with child ADHD and autism and the medication is known to cross the placental barrier.
 
However, for women experiencing pain and fever in pregnancy, Dr Musgrave says options are limited due to the known risks of NSAIDs and opiates on a foetus.
 
‘There are few alternatives to paracetamol,’ he said. ‘NSAIDS should not be used after 30 weeks of pregnancy because of rare kidney issues in the child, pulmonary hypertension and premature closure of the ductus arteriosus, [while] chronic opioids need to be used with care to avoid withdrawal issues in the child when born, and the potential for addiction in the mother as well.’
 
Dr Musgrave says, like with any medication, the ‘rule’ is to give the smallest amount for the shortest period of time needed to achieve relief.
 
‘There have been suggestions from animal experiments, using doses much higher than would be used by humans, that paracetamol given during pregnancy could impact the mental development of the growing child,’ he said.
 
‘[But] paracetamol is one of the few relatively safe drugs for treating pain in pregnancy.
 
‘As always pregnant women should discuss any concerns with their physicians.’
 
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