Does paracetamol cause behavioural problems?

Paracetamol is the world's most popular painkiller, a crown it stole from Bayer's aspirin - the world's first trademarked drug - on safety and side effect grounds. It's also widely used - and regarded as safe - in pregnancy. But Penn State University's Kristin Sznajder has found a possible association between paracetamol use during a pregnancy and subsequent behavioural and sleep problems in children by age 3. There was a 20% increase in the risk...

Kristin - We had seen some literature coming out showing associations between using paracetamol or acetaminophen during pregnancy and problems with neuro behavioural child development.

Chris - And you wanted to find out whether it was a causal thing; does using this agent cause this to happen or might there be other factors that actually account for it?

Kristin - Absolutely. That's exactly what we were looking for. So one of the great things about our study is that it followed women from starting during their pregnancy through three years postpartum. So we were able to see what came first and we know that they're taking acetaminophen or paracetamol during pregnancy and to follow them to see how their children were at three years.

Chris - How many women did you follow up?

Kristin - We followed up over 2000 women.

Chris - And what were you asking them? Did you or did you not take paracetamol presumably, but how fine grained was the information?

Kristin - In their last trimester of pregnancy we asked everyone in the study what medications they were taking during their pregnancy, including vitamins. Also why they were taking the medication. So we were able to then look through the medications that they listed for each woman and see which medications had paracetamol in them or if they were just taking paracetamol alone.

Chris - Did you get some insights into how much they were using? So would someone tick the same box if they had one headache once and took one paracetamol versus someone who had really bad joint pain all through pregnancy and used it every week?

Kristin - We tried to get at that, but the data weren't very reliable. We actually have a new study underway that we're hoping to get better at the dosage and frequency of acetaminophen.

Chris - And when you crunched all the numbers, what was the relationship that emerged?

Kristin - We found an association between paracetamol use during pregnancy and attention problems and problems with sleep among children at three years old.

Chris - Was the effect strong or are we talking about it being just above chance.

Kristin - It's 1.2 times more likely. So I wouldn't say it's an extremely strong association, but the association was statistically significant.

Chris - And any clues as to who's vulnerable? Was this across the board or if you then begin to ask, are there certain groups in there for whom Mum takes a lot of paracetamol perhaps because she's got some other underlying condition and it's the other underlying condition that's causing this? Or were there other factors that could be discounted and you could say, no, look, this is purely because of exposure to paracetamol.

Kristin - I think one of the strengths of the study is that we were able to take into account those factors you mentioned. So because we asked why they took paracetamol or acetaminophen during pregnancy, we could then take that into account and we found this effect of acetaminophen as an independent effect. So it wasn't a fever or infection.

Chris - The other thing that is an important component of proving that something causes something else is it's got to be biologically plausible whereby you can say, well, we know how this thing affects the body, and if that happens, we can explain how that might translate into this outcome. So can you link a pregnant woman taking paracetamol and a child with neuro behavioural problems?

Kristin - Yeah, there has been research that shows paracetamol may disrupt cell development. So we think paracetamol could disrupt cell development and also results in placental damage.

Chris - When did paracetamol first begin to be used and when were we told it's quite safe to use this in pregnancy? Because it seems to me that we've got very good at diagnosing things like developmental disorders and behavioural problems in the modern era. There seems to be a lot more of it around now. Is that because we are better at diagnosing it? We're picking it up more, but it was always there. Or is there some kind of coincident onset of we're seeing more of these cases because there were more mums using paracetamol when they were pregnant?

Kristin - That's a fabulous question. I think we're really trying to disentangle that. I'm really not sure if we know the answer to that. I think we are getting better at diagnosing developmental delays, but I do think that we're still trying to figure it out. There could be several factors related to behavioural problems in childhood genetics and environmental exposures, possibly in utero. So we're really working to figure that out.

Chris - It's, as you say, critical though that we do, isn't it? Because this is one of the world's most popular painkillers regarded as one of the safest and very broadly used during pregnancy.

Kristin - Absolutely. This is something that really needs more focused research. Literature is emerging. There has been a call to action to reduce paracetamol use during pregnancy that came out last year and I think we're really showing these trends that people should be a little more cautious as they consider using paracetamol during pregnancy.

Chris - I do feel for pregnant women though, because they're frightened to do anything these days, aren't they? What should then a pregnant woman listening to this do if she has a headache?

Kristin - I think she should talk to her doctor to weigh the options and what she could do. Or maybe talk about what medications are safe with her clinician and maybe bring up some of these findings that we're talking about to see what her clinician thinks.

Chris - I think a lot of general practitioners are going to be confronted by patients walking in there with your paper and they can say, 'what do we do?'

Kristin - Well, maybe. It's the risks and benefits that people need to take into account.