Since there are no randomised, placebo-controlled studies on the benefits and risks of pain medications in pregnant women, one has no other choice than to rely on other, less informative investigations. In the case of paracetamol, several observational studies found an association between its use during pregnancy and various diseases such as ADHD, autism, asthma and cryptorchidism. In July a study from Spain made its contribution to the debate.
The study published in JAMA Paediatrics is a prospective cohort study which took in as part of the “Avon Longitudinal Study of Parents and Children” (ALSPAC) 7,796 mothers from Bristol, England. Their use of paracetamol was conveyed using one of the questionnaires completed by the women in the 18th and 32nd week of pregnancy as well as shortly after the 5th birthday of the child. When the children were 7 years old the mothers reported about behavioural problems in their children by way of a questionnaire (“Strengths and Difficulties Questionnaire”, SDQ).
When evaluating the data it was shown that taking paracetamol was common – in the 18th week of pregnancy 53% of the mothers reported that they had used paracetamol within the past three months; in the 32th week this figure was 42%. The researchers also found that the relative risks of behavioural disorders and hyperactivity with the paracetamol-user group, with figures of 31 and 42%, were higher than in the non-user group. In addition, the use of paracetamol in the 32nd week of pregnancy was generally associated with a 29% increased risk of emotional symptoms in children and a 46% increased risk of behavioural difficulties.
Yet how are we to categorise these numbers? First of all, an observational study like this never proves causality – other factors not considered in the analysis could have influenced the results. One weakness of the study in addition to this is that intake of paracetamol was not measured directly, but rather defined by the responses of the women – therefore memory plays an important role here. In addition, no information was collected on the dosage and duration of treatment with paracetamol.
Furthermore, the indicated risk ratios are relative values – in actuality the absolute values are low, because child behavioural problems occurred with only 5-6% of paracetamol users and 4-5% of non-users (determined on the basis of total SDQ score). Even putting aside the idea that the observed effect of paracetamol may therefore only be mere statistical artefacts or interfering factors, there only exists a small increase from an already low level of risk. Such is also the view of study leader Dr. Evie Stergiakouli and she warns against alarmism: “It is still considered safe to use paracetamol during pregnancy, so doctors and other health professionals ought not recommend that pregnant women restrict their use of paracetamol”.
Nevertheless, it is important to study the phenomenon in more detail, in order to make a more accurate estimate of the benefits and risks of paracetamol on the basis of better data, because as it stands now paracetamol, due to its good safety profile, is the drug of choice for relieving pain in pregnant women: the risk of malformations is not increased by paracetamol and there is no evidence of feto-neonatal toxicity.
What about the alternatives?
It’s especially during pregnancy that women are more often afflicted with pain, because in addition to the frequent causes of pain affecting non-pregnant women, such as headaches and colds, the female body during pregnancy goes through significant changes. Added body weight is a burden for example on joints and spine – roughly every second woman complains of back pain during pregnancy. Should pain persist, this can create a significant psychological burden, thereby increasing the risk of pregnancy complications. “Not treating pain or fever during pregnancy carries risks”, Dr. Stergiakouli states, “and this should be carefully weighed against potential negative effects on the child. For example, untreated fever can lead to premature labour during pregnancy”.
When pain occurs during the course of pregnancy, non-drug treatment options should of course always be tried out first, but unfortunately in many cases no adequate pain relief is achieved. Suitable alternative nonsteroidal anti-inflammatory drugs (NSAIDs) which come into the picture include ibuprofen and diclofenac, but with ongoing administration these may result in severe gastrointestinal side effects such as ulceration and bleeding. They are also contraindicated during the third trimester due to the risk of premature closure of the child’s ductus arteriosus. Furthermore, NSAIDs demonstrate a variety of drug interactions and during treatment can lead to cardiovascular complications such as myocardial infarction and stroke, and renal dysfunction.
One alternative for the treatment of moderate to severe pain where the relevant indication exists is opioid analgesics, although when they are used there exists the risk of mental and physical dependence. In addition there is also evidence that after intake through the mother ends, respiratory depression and withdrawal symptoms may occur in the newborn.
And what’s next?
Since no painkiller is free of side effects, no medication should be used during pregnancy without a valid reason. And if legitimate doubts arise with regard to the benefits or the safety of a long-standing drug, this should also be taken into consideration in therapy. Currently however, the available data seems to indicate that paracetamol is still the safest choice among the available pharmacological options. Further studies have to clarify whether maternal intake is actually associated with an increased risk of childhood behavioural problems, but the currently raging fear of possible damage should not be permitted to lead to pregnant women ending up unnecessarily enduring pain.