By: 14 June 2019
European mega-venture for safe medication during pregnancy

You are pregnant and in need of an important medication, but nobody knows if the medication is safe for the fetus. Should you stop taking the drug? Or close your eyes and hope for the best? A new research venture is going to crack enormous amounts of data from all over Europe to find the answers that women need in these situations.

“On average, it takes an estimated 27 years to determine if a novel medication can be used by pregnant women without risking adverse effects on the fetus or child. This just can’t continue any longer”, says Professor Hedvig Nordeng at the University of Oslo’s Department of Pharmacy.

More than 5 million women become pregnant in the EU every year, and a majority takes at least one medication during pregnancy. But only as few as 5 per cent of available medications have been adequately monitored, tested and labelled for use in pregnant and breastfeeding women, Professor Nordeng explains. She is one of the researchers involved in the new and massive European research project ConcePTION, where the aim is to generate the knowledge that pregnant women want – and need – about the safety of medications.

Why is there so little knowledge about safe medications for pregnant women? The reason is that they are, as a rule, kept out of the clinical trials conducted by pharmaceutical companies before a new drug comes on sale. The reason is obvious: The companies do not want to perform experiments on pregnant women and their children, she states to

Representatives from no less than 17 academic institutions (“public partners”) and 15 pharmaceutical companies have joined forces in ConcePTION, together with several stakeholders including patient representative organizations. Most of the participating institutions have access to a lot of information about pregnant women and their children, from a variety of data sources including national health registers.

“But no solitary source of data, and not even the total number of biobanks and health registers in, for instance, Norway or the Nordic countries put together, contain enough data to discover rare effects of medications. But if we could combine data from all over Europe, we can make much better use of the enormous amount of data that has already been collected”, Nordeng explains.

“At the same time, a new biobank for breast milk is going to be established. Information and training of health personnel and pregnant patients is also a central part of the project”.

The aptly named ConcePTION project is historically inspired by the international Thalidomide scandal in the 1950s and 1960s. More than 10,000 children were born with serious malformations, following their mother’s use of a drug that was supposed to combat nausea during pregnancy.

The scandal led to the establishment of birth registers across Europe, in order to monitor the incidence of birth defects due to drug use during pregnancy. Thalidomide was widely used and caused very visible malformations, so it was relatively easy to spot the connection. But if a rarely used drug only causes a slight increase in the risk of rare and diffuse birth defects, it is much harder to discover a connection.

The risk for serious birth defects because of medications is still a concern for women, doctors and health care authorities. As recently as in 2018, the European Medicines Agency warned that the drug valproate should be used by fertile women only in combination with safe contraception. The reason is that valproate, used against epilepsy and bipolar disorder, increases the risk for malformations and brain impairment (lower IQ) in the child.

“We need to make sure that both healthcare professionals and the pregnant women themselves have access to solid information about which drugs are teratogenic, so that they can be avoided during pregnancy. But this European project is not only about identifying risky medicines, because it is equally important to acquit the safe medicines. Today, it is a big problem that some women refrain from using drugs they really need because they are afraid of possible harmful effects to the fetus”, emphasises Professor Nordeng.

She explains why researchers need to gain access to large sets of data if they shall be able to prove otherwise elusive connections between drugs and harmful side effects.

“Let’s say that we want to identify the safest way to treat diseases like lupus or multiple sclerosis (MS) in pregnant women. Both are relatively rare diseases, and the doctors can combat them by prescribing a choice of several alternative drugs, which have not been tested on pregnant women. The only way to discover rare side effects from rarely used medications is to coordinate data from many European sources,” explains Nordeng.

“But this is easier said than done. The multitude of European health registries don’t have a standardised way of entering data, nor are they in agreement about which data that should be gathered and stored. Therefore, we must initially focus a lot of effort into the standardisation of protocols and quality controls”, explains Nordeng.

Professor Hedvig Nordeng is the leader of PharmaTox, a major life science research project at theUniversity of Oslo. PharmaTox aims to generate novel insight on effects of pharmaceuticals on human neurotoxicity and neurodevelopment. In the ConcePTION project, researchers from PharmaTox will participate in the development of methods and the mapping of long-term effects of a number of drugs on the brains of children.

PharmaTox researchers are already busy trying to compensate the lack of knowledge about safe medications for pregnant women.

“Biobanks and health registries contain a lot of information about the health of children, and the sources also contain data about which medications the mothers were using. OK, so the medications have not been tested on pregnant women prior to marketing. But we have been working with methods and material to study the long term safety of medications used in real pregnancies. This is an expertise that can be very useful in the ConcePTION project”, says Nordeng.

Pregnancy is not the only area where fertile women have too little information about the drugs they are using.

“We have even less knowledge about the effects of drug use in the subsequent breastfeeding period. We don’t even know if most medications are transferred from mother to child via breastfeeding, and this is something that can’t be tested in animal models. The contents of the milk is very different between animals and humans”, adds Nordeng.

Under the auspices of ConcePTION, the participants are going to develop European standards for the study of the transfer of medicines through breastfeeding.

“There are a lot of different steps in this kind of research, and each step must be performed in a defined manner. How are we going to obtain samples of milk? How to store them? How to analyse them? And so on. Today, most researchers have their own way of doing things, and the result is that it becomes very difficult to compile the results and draw conclusions”, Nordeng emphasises.

Professor Hedvig Nordeng is enthusiastic about the ConcePTION project because it demonstrates the ability of the EU research and innovation program,Horizon 2020, to bring out the “big guns” when important societal problems need to be solved.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) represents the pharmaceutical industry operating in Europe. EFPIA members spent almost two years discussing their way to a thought-through research programme, before the call for projects and applications became public in 2017. The project is funded with 13 million euros from the EU program innovative medicines initiative (IMI) and an equivalent amount from the EFPIA members.

The University of Oslo (UiO) is currently investing heavily in life sciences; so heavily that UiO: Life Sciences is the university’s largest initiative ever. Professor Hedvig Nordeng emphasises that the ConcePTION program and the entire IMI initiative fits very well with UiO’s commitment to life science and innovation.

“This EU initiative offers many exciting opportunities for life science researchers at UiO. In the years to come, we are going to work really hard in order to give pregnant women the information and the safety that they deserve”, Nordeng concludes.