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Painkiller link to childhood asthma unlikely to be causal, researchers say

Previous associations made between analgesic use and pregnancy were likely not causal, researchers have said after finding an increased risk for different analgesics with different modes of action.

Pregnant woman taking a tablet


Researchers have said that the link between analgesic use in pregnancy and risk of childhood asthma was more likely to be confounded by maternal factors linked to use of these drugs, such as chronic pain

A previously reported association between analgesic use in pregnancy and childhood asthma is likely to result from confounding factors, researchers have concluded (17 March 2019)[1].

The research, published in the European Respiratory Journal, used data from a Swedish health registry on 492,999 children born between July 2005 and December 2010. Data on maternal prescribed analgesic use were obtained from the national drug register.

After adjustment for confounding factors, the risk of childhood asthma/wheeze at four years of age was elevated by 39% for offspring whose mothers were prescribed opioids, 19% for antimigraine drugs and 47% for paracetamol.

The team said that, given that there was an increased risk for different analgesics with different modes of action, it was unlikely that the observed associations were causal. They suggested that the findings were more likely to be confounded by maternal factors linked to use of these drugs, such as chronic pain or anxiety.

“There have been previous calls for placebo-controlled trials to definitively test the paracetamol-asthma hypothesis,” the team wrote.

“We would argue, on the basis of our latest findings, that the case for a trial in pregnancy, which would present considerable practical and ethical challenges, is now less strong.”

Citation: Clinical Pharmacist DOI: 10.1211/CP.2019.20206429

Readers' comments (1)

  • In this study, the authors took into account only prescribed painkillers. Whilst the possibility that patients also self-medicated with painkillers obtained over-the-counter [OTC] was acknowledged – a possibly significant source of additional exposure to paracetamol but not to codeine, dihydrocodeine, tramadol, or anti-migraine medication – this was considered by the authors to be an unlikely confounder because such additional exposure to paracetamol was, or so they believed, likely to be "sporadic" rather than "long term". This was, I believe, a dangerous assumption to make in a study that purports to examine the relationship between paracetamol exposure in utero and childhood asthma/wheeze.

    Firstly, there is no evidence of which I am aware that exposure to paracetamol during pregnancy is necessarily safe if the exposure is only sporadic. In the case of at least one known teratogen studied in experimental animals, damage occurs only during a very short window during the pregnancy. If the same pertains in the case of paracetamol, even one-off "sporadic" in utero exposure could be the cause of the asthma/wheeze later observed in children. No information appears to have been captured in this study as to when exactly during the pregnancy the painkillers were prescribed. So, on the basis that mothers-to-be [in the UK] are led to believe that paracetamol is the only safe painkiller to take during pregnancy, and paracetamol can be bought in supermarkets with the weekly shop without reference to a pharmacist, midwife, or doctor before the mother-to-be even decides to approach her GP for a prescription, it is my belief that paracetamol exposure during pregnancy is seriously under-estimated. And I am yet to be convinced that paracetamol use during [late] pregnancy is not the cause of asthma/wheeze/eczema in the child (although I would acknowledge that antibiotic exposure in early life may also be contributory, a possible confounder that was not contemplated in this study). The only way to resolve this matter would be for the regulatory authorities to change the product license to make all paracetamol products pharmacy-only medicines and not licensed for use during pregnancy so that advice to not take paracetamol during pregnancy except on a doctor's prescription / responsibility could be provided in pharmacies as part of a country-wide "clinical trial".

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