The paper “Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood” found modest increases in conduct problems in hyperactivity in children born to mothers in the UK who consumed paracetamol at either 18 weeks or 32 weeks of their pregnancy. The association with consumption of paracetamol at 18 weeks was weak. In this particular study the findings had to be adjusted for smoking and consumption of alcohol during the same periods. While the finding is of an association between paracetamol use and behaviour issues, rather than the paracetamol caused these effects, and there still could be other factors involved, or that correction for the effect of cigarette smoking and alcohol was inadequate, a link is plausible. Animal studies and other human studies have shown that long term use of paracetamol during pregnancy can affect testis development in males, so a potential link through changes in hormonal levels is possible. However, the study did not investigate the amount of paracetamol taken or how long it was taken for. Previous association studies and experimental work show that long term consumption (one to four weeks) was a risk, and in the 1990’s the consumption of paracetamol was generally higher than it is today. Although paracetamol has not been shown to be the cause of the behavioural issues, the current recommendations for dose and length of time that paracetamol can be taken should mean that any potential behavioural risk is much lower now than in studies conducted in the 1990’s. Anyone taking paracetamol should follow the advice of their health practitioner and follow the dosage instructions for paracetamol.

While of interest, further studies are still needed before we jump to changing clinical practice recommendations. Paracetamol is useful in treating fever and different types of pain and it still remains our first choice for treating these conditions during pregnancy. Because it is so commonly used and easy to get your hands on, women may reach for paracetamol as soon as they experience any symptoms, without necessarily thinking much about it. We know, however, that many things change in pregnancy and it is important that the treatment is right for the symptoms and that there is not something else going on that requires further attention. Therefore we would encourage pregnant women to talk to their local pharmacist or go and see their doctor for some advice if they are unsure of what to use and for how long to use it. The key message from this study is only to take paracetamol when absolutely necessary and to take it for the shortest possible duration, not to avoid it completely.

The authors describe a study in which they collected and analyzed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort. They studied 7796 mothers enrolled in ALSPAC between 1991 and 1992 along with their children and partners.
 
They report that in 5% of offspring exposed to paracetamol through administration to their pregnant mothers, there were various behavioural problems such as conduct problems or hyperactivity symptoms.
 
The authors make the bold claim “Children exposed to acetaminophen [paracetamol] prenatally are at increased risk of multiple behavioral difficulties”.

However, such a causal relationship is not established by this sort of data. All that can be claimed (or should be claimed) is that an association has been uncovered, which certainly is potentially serious enough to warrant further investigation. 
 
The authors point to a number of limitations of their study, but some limitations they either did not acknowledge or do not give enough weight to. Mothers were asked at 18 and 32 weeks of pregnancy if they had used paracetamol in the previous 3 months. They were also asked if they had muscle and joint problems, infections (including cold or flu, urinary, or other infections), migraine, or headaches at the same times. Such retrospective information depending on patient recall is notoriously unreliable and might be biased by the manner in which the questions are asked. 
 
There is good clinical and animal experimental evidence that generalized infection at some periods in pregnancy, including at the times studied by the authors, may be associated with serious neurological disorders such as cerebral palsy. The authors did not analyse separately possible associations with the different reasons why the paracetamol had been taken; for example this might have revealed an association with infections such as flu or cold, which would have been an alternative explanation for the problems identified in the children.
 
The study illustrates a general problem in obstetric practice that there is no regulation of drugs used in pregnancy and there for there is no evidence base to guide clinical practice. The US Federal Drug Administration and the European Medicines Agency have recently become aware of this problem. But it is difficult to deal with because the gold standard for determining the effectiveness of a drug is a clinical trial, but there are considerable ethical difficulties in running such trials in pregnant women.