Research project to investigate potential link between headache pills and early-stage spontaneous abortion

It is hoped that trials with fertilised eggs from mice and humans will help us understand whether headache medication plays a role when pregnancies terminate spontaneously in the early stages.

‘We know that around 40% of all human pregnancies end shortly after fertilisation, and the true number is probably even higher. Scientists have been trying to explain why this may be for over 30 years. The most popular explanation is that it’s all down to genetics – that there are genetic abnormalities which put a definitive end to the pregnancy shortly after fertilisation. But genetics don’t explain everything,’ says David Møbjerg Kristensen, molecular cell biologist and research team leader at the Danish Headache Centre, Rigshospitalet, University of Copenhagen.

‘Within the past ten years or so we’ve identified many different links between the mother’s consumption of headache pills during pregnancy and adverse impacts on the foetus, such as genital malformations in boys. So, it’s both logical and necessary to investigate whether the active agents in painkillers could be the cause of early-stage spontaneous abortions. And that’s what we’ll start working on now.’

David Møbjerg Kristensen has received a research grant worth DKK 2 million from the Lundbeck Foundation for this scientific study. It is to run over two years, and he will be working with researchers from the fertility clinics in Region Zealand and at Rigshospitalet, University of Copenhagen, Herlev Hospital, Hvidovre Hospital and the Department of Biology at the University of Copenhagen.
These fertility clinics play a key role because they have access to some of the biological test material that should provide the answer: fertilised human eggs.

Genital malformations
For a number of years, David Møbjerg Kristensen has engaged in international research partnerships studying the unwanted effects of painkillers containing active agents such as paracetamol, ibuprofen or acetyl-salicylic acid. He has conducted some of these studies together with colleagues from the USA and Australia and others with scientists from the French Institute of Health and Medical Research (INSERM), where he also works.

The active agents in painkillers are interesting to health researchers because chemically and biologically they share certain mechanisms with endocrine disruptors such as phthalates, parabens and benzophenones, which have absolutely nothing to do with combating headaches. On the contrary, they are used as plasticisers, preservatives in cosmetics and UV protection in sun creams.

But how much does current science know about the potential damage to a foetus if the mother is exposed to substances that interfere with hormones?

David Møbjerg Kristensen says that the research partnerships in which he has participated have managed to demonstrate a direct link between a pregnant woman’s consumption of painkillers and mechanisms resulting in congenital malformations of the genitals of newborn boys.

He has also helped prove – in animal trials – that the active agents in painkillers can result in changes in sexual behaviour. The animal trials also showed incidence of malformation of ovaries and early infertility in adulthood among the females which were exposed to painkillers. He explains: ‘The animal studies have been confirmed by three other independent research groups, so we’re extremely concerned about the impact of these active agents on female fertility.’

The human eggs
David Møbjerg Kristensen says that headache medication – primarily products containing either aspirin, paracetamol or ibuprofen – is almost considered a consumer good:

‘In 2017, a single daily dose was sold to over 10% of the Danish population every day. We also know that around 2% of Danes, around 120,000 people, are caught in a vicious cycle of addiction: they take painkillers constantly, and this gives them chronic headaches. This is a health problem that researchers at the Danish Headache Center have tried to draw attention to for years.

‘Research shows that over 50% of all pregnant women in Denmark take these substances when they have a headache. If we look at countries such as France and the USA, the numbers are even higher – closer to 70–80%. And the question is whether, in some cases, this leads to spontaneous termination of the pregnancy,’ says David Møbjerg Kristensen.

In his opinion, if this causal link is proven, the explanation will probably be one of the following:

Either that the active agents in the painkillers simply kill the fertilised egg.

Or that the substances prevent the fertilised egg from implanting in the uterus.

Or that the foetus is rejected in the early stages of the pregnancy because the chemical impact of the painkillers prevents some cells from developing as they should.

In order to investigate these three hypotheses, David Møbjerg Kristensen will conduct a number of trials in which the fertilised eggs of both mice and humans are exposed to the active agents in painkillers.

He will gain access to the fertilised human eggs through the fertility clinics taking part in the project – where they have surplus eggs in their freezers. David Møbjerg Kristensen explains that these are fertilised eggs – embryos – which couples had frozen while they were undergoing IVF treatment:

‘These couples have fortunately received the help they were hoping for – they are now parents and don’t want more children. The fertilised eggs that they no longer need are in the freezer. The law says that these eggs must, at some point, be destroyed. But, instead of doing that, we would like to be allowed to use them to improve our understanding of why many pregnancies come to nothing. I’m therefore about to apply to the Danish Research Ethics Committee for permission to use these eggs in our study – in each case, with the permission of the woman and man who’ve supplied the egg and sperm.’

The study will begin during the first half of 2020. ‘And if the study shows that the active agents in headache pills are able to destroy an early-stage pregnancy, it will hopefully have an impact on advice given to pregnant women,’ says David Møbjerg Kristensen.

He adds that, in some cases, painkillers containing paracetamol, ibuprofen or acetyl-salicylic acid may be the only option for pain relief during a pregnancy:

‘But this means it’s even more important to inform these women thoroughly of the potential consequences of taking these painkillers while pregnant – so that they understand that they should use them with great caution. Today, unfortunately, a lot of pregnant women take painkillers with these active agents in the belief that they’re completely harmless to themselves and their unborn child,’ says David Møbjerg Kristensen.