The majority of pregnant women take some kind of medication. Whether it’s for a pregnancy-associated ailment or an existing health condition, up to 90% are exposed to a prescription drug at some point during pregnancy. What’s more, usage of certain medicines (like antidepressants) is on the rise.
Unfortunately, relatively little is known when it comes to drug safety at this time. In some cases, otherwise safe medications can affect the growing foetus, increasing the risk of abnormalities. On top of this, drug pharmacokinetics (the way the drug moves round the body) can change during pregnancy, potentially altering the dosage required.
As Dr Miriam Sturkenboom, a professor at UMC Utretcht, explains, the information gap is vast. More than five million women in the EU get pregnant every year, and they are forced to contend with many unknowns.
“Only 5% of medications have been monitored, tested and labeled for use in pregnancy,” she says. “For the remainder it usually states ‘do not use’, to be on the safe side. The evidence on the possibility of using while breastfeeding is even less.”
She adds that this uncertainty falls squarely on the shoulders of the woman and the treating physician, who are tasked with making some complicated decisions.
“If a woman is not treated because of uncertainty, an uncontrolled disease may lead to damage for the mother and the foetus,” she says. “But if the woman is treated, health care professionals and the woman need to make a risk-benefit decision without proper evidence.”
What’s more, because of the lack of information surrounding drug safety during breastfeeding, women may be advised not to breastfeed. This can have detrimental impacts on the child.
“The other way around is that, in some lower income countries, breastfeeding is the only option, and we do not know the impact of the drug on the neonate, says Sturkenboom.
A paradigm shift
Sturkenboom is project coordinator for a landmark public-private partnership called ConcePTION, which unites 88 organisations from 22 countries. It is designed to close the research gap around medicines during pregnancy.
“ConcePTION aims to create a paradigm shift in how we generate and disseminate evidence on the effects of drugs during pregnancy and breastfeeding,” she says.
The current evidence gap is not surprising, given that pregnant and breastfeeding women are usually excluded from clinical trials. Or, if they become pregnant during the course of a trial, their medication is typically stopped.
That said, we don’t necessarily need a clinical trial to determine drug safety during pregnancy. Doctors gather data during routine appointments, which, if appropriately harnessed, could rapidly reduce uncertainty. The ConcePTION team, buoyed by a sense of social responsibility, will work to do just that.
“The project aims to develop an ecosystem that can efficiently and systematically generate evidence by using available real-world evidence from existing routine care data, and data reported by pregnant and lactating women,” says Sturkenboom. “It will translate all the evidence into a knowledge databank that will be searchable online.”
This will mean developing better data collection methods, moving away from the uncoordinated approaches currently in use. By bringing together the major data sources across Europe, they will be able to turn isolated pockets of information into a networked system of Big Data. And by applying advanced analytics, they will be able to learn more about how medicines affect pregnancy outcomes.
They will also create the first Europe-wide breast milk biobank. This will be used for research purposes, allowing scientists to determine how much maternal medication is transferred into breast milk. They will develop new predictive models for this purpose too.
“Over the first year we will do the building of the system and all the development,” says Sturkenboom. “In years two-four we will test the system with all sorts of demonstration studies. And in the last year we will create guidance documents. We have already started to think about the sustainability and how we can maintain the ecosystem after the project funding ends.”
Taking the guesswork out of the equation
The project kicked off in April, when it was awarded a five-year, €28.6m grant by the Innovative Medicines Initiative (IMI2). This grant comprises €15.3m of public money from the European Commission, along with €13.3m from the European pharmaceutical industry.
The ConcePTION consortium, which features nearly 200 researchers, is jointly led by Novartis and UMC Utrecht. It is governed and managed by a 50/50 split of public and private partners. As Sturkenboom explains, collaboration will be key to the project’s success.
“We need to connect and build trust and build the ecosystem together with organisations that have a stake,” she says. “This is because they have expertise in this area, because they can provide information services, and because they have access to data or produce drugs. We want to build this together and take away the current fragmentation.”
Once the databank is complete, the benefits will be significant and wide-ranging. For many pregnant women, simply eschewing medication isn’t an option. If we know exactly what the risks are, we can take the guesswork out of the equation and will be able to determine which treatments are more suitable than others.
“In view of the current lack of proper evidence, and the availability of health data that can be used to study safety, we need to close the evidence gap and make it easier on women and health care professionals to take informed decisions,” says Sturkenboom. “In real life many women need to be treated during pregnancy because they have chronic diseases, and we have a moral duty to learn from this real life experience at least to inform other women.”