Paracetamol in pregnancy linked to asthma
“Pregnant women who take paracetamol could be increasing the risk of their child developing asthma,” the Daily Express has reported.
The news is based on a review that systematically combined the findings from six previous studies examining whether paracetamol use in pregnancy is associated with asthma in early childhood. It should be noted that the review looked at cases of wheeze, which may not necessarily indicate asthma. Of the six studies examined, three found a significant association with paracetamol use and three did not. When pooled, the results suggested a 21% higher risk of wheeze for children whose mothers had used the painkiller.
There are important limitations to the review, particularly the fact that it looked at wheeze rather than asthma. The contradictory results of the individual studies and the lack of adjustment for factors such as parental smoking also undermine the reliability of the results. However, the findings of this initial review are important, and the topic is worthy of further research to try to clarify any possible association.
Expectant mothers should not be overly concerned. There are many causes of childhood asthma, and exposing the developing foetus or child to smoke is likely to be a more important one. Paracetamol remains safe for use at standard adult dose if required during pregnancy or breastfeeding.
Where did the story come from?
The study was carried out by researchers from the Medical Research Institute of New Zealand, the University of Otago Wellington, New Zealand, and the University of Southampton. No sources of funding were reported. The study was published in the peer-reviewed medical journal, Clinical and Experimental Epidemiology.
The Daily Express has accurately reflected the reporting of this review, though the review itself has several important limitations which mean that further, carefully conducted and reported research is needed to clarify these associations.
What kind of research was this?
This was a systematic review, which aimed to investigate whether paracetamol use in pregnancy may be associated with asthma in infancy and childhood. A previous systematic review had noted an association between paracetamol use in a child or an adult and the risk of them developing wheeze or asthma.
A systematic review of cohort studies is the best way of gathering together the global evidence regarding a particular exposure (paracetamol) and subsequent development of a disease outcome (asthma). All reviews involve a degree of limitation due to the variation in study methods, the populations included, follow-up periods and methods of outcome assessment used in the individual studies.
What did the research involve?
The authors searched medical databases and reference lists for relevant randomised controlled trials or observational studies published up to 2010. Eligible studies were either RCTs of women randomised to paracetamol or a placebo drug during pregnancy, or cohort studies that had compared a group of women who had used paracetamol during pregnancy against a control group who had not used paracetamol. All studies had investigated how this affected the likelihood of wheeze or asthma in the child.
The gathered studies were assessed in detail for their quality and the methods used. The main outcome of interest to the reviewers was ‘current wheeze’, which was defined as wheeze in the 12 months prior to the assessment. The reviewers pooled the odds of asthma or wheeze in those who took paracetamol and those who did not, and used them to calculate a ratio of risk. During this process they applied statistical processes that took into account the differences in methods and results of the various studies.
What were the basic results?
Six studies met the inclusion criteria: five cohort studies and one cross-sectional survey. No RCTs were identified. Studies assessed children between the ages of 2.5 and 7 years, and all looked at how paracetamol use during pregnancy related to the outcome of current wheeze. Only one of the five cohorts reported the specific period of pregnancy during which paracetamol was used (20-32 weeks). The review classified women as either users or non-users of paracetamol, but did not look at dosage or length of paracetamol use.
The six studies gave very variable results. Three of them found a significant association between paracetamol use and current wheeze. Three of them found no association. All of these risk associations were reported to be unadjusted for any confounders. When the authors of the current review pooled these six results, they found that there was a 21% increased chance of current wheeze in the child if the mother had used paracetamol during pregnancy (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.02 to 1.44).
How did the researchers interpret the results?
The researchers conclude that “the use of paracetamol during pregnancy is associated with an increased risk of childhood asthma”. They say that further research is now required “to determine the impact of paracetamol during pregnancy on the risk of wheezing in offspring so that appropriate public health recommendations can be made”.
Conclusion
The findings of this study should be interpreted carefully, particularly as the six observational studies included in the review had variable results: three had found a significant association between pregnant paracetamol use and wheeze, and three did not. While the odds ratio when pooling these six results found a statistically significant association, this finding should also be considered in light of some important limitations:
- The review categorised paracetamol use in each study as either ‘yes’ or ‘no’. Only one of the pooled studies specifically looked at paracetamol use during the latter half of pregnancy (20-32 weeks). This, along with wide differences in the categorisation of paracetamol doses in the individual studies, means that when pooling the results, only the broad considerations of whether women had used paracetamol or not could be used. Therefore this cannot inform us about, for example, dosage or duration of use.
- The review reported a considerable variation across the included studies in the adjustments they made for confounders. The review did not explicitly report these. It presented its summary odds ratio of 1.21 as an unadjusted summary calculated without considering any confounders. This means that there are other factors, both measured or unmeasured, that could vary between paracetamol users and non-users, which could also account for the difference seen. The authors mention maternal smoking, respiratory disease, length of pregnancy, pet ownership and social class as possible confounders.
- The main outcome of the review was ‘current wheeze’, defined as wheeze in the 12 months prior to the assessment. Asthma is notoriously difficult to diagnose during infancy and childhood; sometimes a nocturnal cough can be the only symptom. Likewise, a wheeze can commonly occur with respiratory tract infections in a child who does not have asthma. Therefore it is not possible to know for certain whether the children categorised as having ‘current wheeze’ actually had asthma.
The findings of this review, as the authors conclude, are clearly worthy of further study to see whether an association could exist between paracetamol use in pregnancy and asthma or wheeze in the child. However, given the uncertainty surrounding these initial findings, pregnant women should not be overly concerned by this possible association until this further research is complete.
Asthma is a relatively common condition in children and can be increased by several risk factors or triggers. A family history of asthma and other allergic conditions, combined with environmental irritants, are the most established triggers. Key among these is exposure to smoke in infancy and childhood. Other research has linked smoking while pregnant to risk of asthma in the child.
Paracetamol use in pregnancy, or while breastfeeding, is not known to be associated with any harms to the developing foetus or infant. Current advice is that it remains safe for use during pregnancy at the recommended adult dose (up to 1g every 4-6 hours, with a maximum of 4g in any 24-hour period).
