Multiple Sclerosis, often referred to as MS, is an unpredictable disease that affects the central nervous system. The disease can debut at any age, but most often manifests between the ages of 20 and 40 and women are more at risk. Certain forms of MS respond well to a drug called dimethyl fumarate. Because we don’t know enough about how this drug transfers to breastmilk, new mothers who are on this medication often face difficult decisions about breastfeeding. A recent case report published in Frontiers in Public Health shares findings that help fill this knowledge gap – towards a future where women can make informed decisions.

MS disrupts the communication within the brain, and between the brain and body. Dimethyl fumarate can help protect the nerves and prevent the disease from progressing. And although breastfeeding has benefits for both mother and child, to prevent the infant from unnecessary risk, dimethyl fumarate is often advised against during breastfeeding by healthcare professionals when there is not enough evidence that confirms a drug is safe for them too.

“With this case report, we are completing part of the puzzle. From what we can tell, so far, a small amount of the drug transfers from the mother’s blood into her breastmilk. This indicates that the infant exposure is also low. But to complete the puzzle, we need more evidence. This is the goal of ConcePTION, taking a comprehensive approach that integrates data from multiple sources and employs robust methodologies to assess the safety of medicines for pregnant and breastfeeding women,” says Martje Van Neste, MD & PhD student at KU Leuven and one of the authors of the recent Frontiers in Public Health publication.

One previous case series has reported low infant exposure of dimethyl fumarate in breastfeeding. Both case reports provide estimations, as none of the infants ingested the breastmilk. The current case report covers a patient who took dimethyl fumarate (120 mg, twice per day) and expressed milk, when the baby was already weaned. Based on the amount of the drug that was in the mother’s milk, it was possible for the researchers to calculate an estimation of how much of the drug in the mother’s milk would have transferred into the blood stream of the baby.

Compared with the other available cases, three women in total, there is a high variability of medication levels in breastmilk. This means how much of the drug is transferred into the breastmilk differs between individuals, and even between samples from the same mother. According to the authors, it is important to note that because no infants actually ingested the breastmilk, it is not possible to say for certain how much of the drug is absorbed and what the effects of exposure would be.

“Studying medicine safety in breastfeeding is complicated. Researchers need more data but at the same time we want to encourage caution to protect these children. Making sure it is possible to collect and analyse breastmilk samples and data from real-world cases is key to close this knowledge gap. It is a slow process, and I’m sure it’s frustrating to many women who face these decisions between continuing treatment and breastfeeding that we cannot yet offer a straight answer. But at least we can tell them that there are networks of researchers working to fill these knowledge gaps,” Martje Van Neste concludes.

Want to read the paper? Van Neste, M., Nauwelaerts, N., Ceulemans, M., Cuppers B., Annaert, P., Smits, A. & Allegaert, K., Very low monomethyl fumarate exposure via human milk: a case report—a contribution from the ConcePTION project, Front. Public Health, Volume 12, 02 July 2024, DOI: 10.3389/fpubh.2024.1393752

Want to take a look at the study protocol? Van Neste, M., Nauwelaerts, N., Ceulemans, M., Van Calsteren, K., Eerdekens, A., Annaert, P., Allegaert, K., & Smits, A. Determining the exposure of maternal medicines through breastfeeding: the UmbrelLACT study protocol—a contribution from the ConcePTION project, BMJ Paediatrics Open 2024;8:e002385. DOI: 10.1136/bmjpo-2023-002385

By Anna Holm Bodin

Since the launch in 2019, 80 partners representing key stakeholders in the field have worked together to build an ecosystem that can empower pregnant and breastfeeding women to make informed decisions about medicines. On June 13-14, The IMI ConcePTION consortium convened one last time at the historic De Bazel building in Amsterdam to reflect on the advancements and make plans for the last six months of the project.

Over the course of two days, the participants discussed what needs to happen before the end of the year, and how our efforts can be sustained. The outcome of the ConcePTION project is a set of systems that can generate evidence on medicine safety in pregnancy and breastfeeding. Since the beginning in 2019, we have developed data-driven approaches to study medicines in, along with a longitudinal system to study exposure to medicines in utero. This “Lifetime” framework system is already used in four European pilot centres, and has recruited 1,200 mother-child pairs. We have also developed in vitro, in vivo and in silico tools to study how maternal medicines transfer to the infant via breastfeeding, and infrastructures for clinical lactation studies.

Disseminating information about medicine safety in pregnancy and breastfeeding is another important objective for the ConcePTION project. During the meeting, we launched the MUMS knowledge bank, designed to provide guidance and advice for women and healthcare professionals. Another important result of the project is a set of e-learning modules for health care professionals.

All of this and more will be made available on the ConcePTION website before the project comes to an end in December 2024.

Participants at the ConcePTION General Assembly Meeting in Amsterdam 13-14 June 2024

A recent paper published by researchers involved in the ConcePTION project explores the complexities of health information collected in electronic databases, commonly used to study the safety and effectiveness of medicines. Understanding the diverse features of these data sources is crucial for researchers to reproduce studies and validate their results. Something that can help us fill the knowledge gap on medicine safety in pregnancy and breastfeeding.

“ConcePTION has been instrumental in the expansion of research like this, providing a foundation to explore and address the challenges and opportunities presented by the diversity of real-world data sources,” says Rosa Gini, co-lead of ConcePTION WP7 and Head of the Pharmacoepidemiology Unit of ARS Toscana, Italy.

Rosa Gini and her colleagues have published the first systematic exploration of approaches to describe the diversity across data sources generating Real World Evidence. Based on 91 documents analysed in the scoping review, they identify 9 dimensions to represent diversity across data sources: organization accessing the data source, data originator, prompt, inclusion of population, content, data dictionary, time span, healthcare system and culture, and data quality. The scoping review lays the groundwork for a framework to characterise data sources used to generate Real World Evidence. The dimensions are compatible with both the ConcePTION conceptual framework that was used to create the ConcePTION Common Data Model, and the ConcePTION metadata incorporated in the ConcePTION Data Catalogue.

“The ConcePTION pipeline is ready by design to embrace and profit from data diversity”, concludes Rosa Gini.

Gini R, Pajouheshnia R, Gardarsdottir H, Bennett D, Li L, Gulea C, et al. Describing diversity of real world data sources in pharmacoepidemiologic studies: The DIVERSE scoping review. Pharmacoepidemiology and Drug Safety. 2024;33(5):e5787.

Related ConcePTION work

Thurin, N.H., Pajouheshnia, R., Roberto, G., Dodd C., Hyeraci, G., Bartolini, C., Paoletti, O., Nordeng, H., Wallach-Kildemoes, H., Ehrenstein, V., Dudukina, E., MacDonald, T., De Paoli, G., Loane, M., Damase-Michel, C., Beau, A-B., Droz-Perroteau, C., Lassalle, R., Bergman, J., … Gini, R. (2021). From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding. Clinical Pharmacology & Therapeutics, vol 2022:111(1), 321-331. DOI: 10.1002/cpt.2476

Dodd, C., Gini, R., Sturkenboom, M., Hoxhaj, V., Hollestelle, M., Thurin, N., Bartolini, C., Paoletti, O., Roberto, G., Cunnington, M., Georgiou, B., Nordeng, H., Loane, M., Leinonen, M., Ehrenstein, V., Damase-Michel, C., Beau, A.-B., van Kammen, J., Swart, K., … Pierini, A. (2020). Report on existing common data models and proposals for ConcePTION (D7.5). Zenodo. DOI: 10.5281/zenodo.5829417

Swertz, M., Hyde, E., de Andrade, F., Gini, R., Pajouheshnia, R., Sturkenboom, M., Cunnington, M., Holub, P., Dolk, H., Loane, M., Given, J., Lewis, D., Yates, L., van Puijenbroek, E., & te Winkel, B. (2021). Prototype of FAIR data catalogue – 2nd (D7.7). Zenodo. DOI: 10.5281/zenodo.5829438

Thayer, D., Menon, K. B., & Gini, R. (2021). Wiki page with description of tools and GITHUB repository (D7.11). Zenodo. DOI: 10.5281/zenodo.5829464