Women sometimes need medicines. This is true in all stages of life, also after having a baby. Breastfeeding is often encouraged, but we don’t know enough about the amount of medicine being transferred to breastmilk. The UmbrelLACT study will collect data on how a mother’s medicines transfer from her blood to her breastmilk, to what extent the child is exposed to the drug compound in question, and the general health outcome of the child. As part of the ConcePTION project, they have developed a generic study protocol for how to collect this data.

As the name indicates, the UmbrelLACT study takes an umbrella approach to clinical lactation studies – to make sure data collection and analysis is as efficient as possible. Before, researchers had to prepare a new study for each medicine that was to be studied – a very time-consuming way of working. Now, the UmbrelLACT study offers a universal protocol adaptable to different medicines. This flexibility allows for quicker, more responsive research, crucial for studying breastfeeding, which occurs only for a limited time. The study protocol is outlined in an article recently published in BMJ Paediatrics Open.

“The data we collect can provide new insights into the medicine transfer from the mother’s bloodstream to human milk, and the nursing infant. With ethics and biobank approval, we hope to recruit 5-15 women per year through UZ Leuven, the BELpREG project, the Belgian pregnancy registry, and other healthcare facilities,” says Martje Van Neste, MD and PhD Student at KU Leuven, and one of the authors of the paper.

The UmbrelLACT study protocol allows for adaptable sample collection, with the option to add maternal and children’s blood collection in addition to human milk and medical characteristics. From these samples, researchers can then calculate the concentration of the drug compound in milk versus blood (milk-to-plasma ratio) and to which extent the child is exposed to the compound in question, the so-called daily and relative infant dose.

“Another important feature of the study is our ability to use it also to evaluate different prediction models. Our lactation and paediatric PBPK models allow us to predict the concentration that reaches the human milk and the child. But these need to be accurate. And here, we are offered an opportunity to check this accuracy,” says Nina Nauwelaerts, PhD Student at KU Leuven, shared first author of the paper.

According to the authors, their study protocol provides a generic workflow that can be utilized also by others – if adapted to local regulation. And to close the knowledge gap about medicine safety in pregnancy and breastfeeding, many contributors are needed.

By Anna Holm Bodin

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

ConcePTION’s goal is to give women the opportunity to take informed decisions about their health and treatment also during the vulnerable periods of pregnancy and breastfeeding. This is hard, because these women are often excluded from clinical trials to protect their babies. And to be able to offer sound advice, a lot of data is needed. To be able to explore the safety of medicines during breastfeeding at a scale that provides enough data to fill the knowledge gap, animal models and in vitro studies are necessary. A recent publication outlines why isolated epithelial cells from Göttingen Minipigs are a good fit to create an in vitro model to study the blood milk barrier.

Epithelial tissue covers almost all surfaces in and on the body. This tissue is made up of tightly packed epithelial cells that form a protective barrier. Heat, sensations, and gases all have to cross this barrier. The same is true for medications travelling through our bodies. To understand if a drug passes from the blood stream into breastmilk, finding out if the drug compound can cross the blood-milk barrier through the epithelial tissue is the key.

Among different animal models, pigs are more physiologically and anatomically similar to humans than other species. For this reason, they are often used in biomedical research. ConcePTION uses a Göttingen Minipig model to study the safety of medicines during breastfeeding. In fact, the Göttingen Minipigs have greater genetic stability and offer more microbiological control than other pigs commonly used for pharmacological and toxicological studies. Genetic stability ensures consistency in experimental results, while microbiological control minimises the risk of contamination, both of which are crucial for reliable research outcomes.

“The mammary epithelial cells isolated from Göttingen Minipigs have physical and functional traits that make them well-suited for studying the epithelial barrier in laboratory settings. Using the isolated epithelial cells from Göttingen Minipigs allows us to reduce animal experiments with alternative methods when possible,” says Chiara Bernardini, researcher of the Department of Veterinary Medical Science at the University of Bologna, and one of the authors of the recent Research in Veterinary Science publication.

She continues: “The morphological and phenotypic characteristics of these cells show that they are suitable for studying the structure and function of the epithelial barrier, offering insights into its role in mammary biology and potentially broader implications for human health and disease – and for women who want to breastfeed.”

By Anna Holm Bodin

Bernardini, C., Nesci, S., La Mantia, D., Salaroli, R., Nauwelaerts, N., Ventrella, D., Elmi, A., Trombetti, F., Zannoni, A. & Forni, M. Isolation and characterization of mammary epithelial cells derived from Göttingen Minipigs: A comparative study versus hybrid pig cells from the IMI-ConcePTION Project, Research in Veterinary Science, Volume 172, June 2024, DOI:10.1016/j.rvsc.2024.105244

Understanding how medicines transfer from a mother to the breastfeeding infant is crucial for women who need to take informed decisions about medical treatment. Right now, we are launching two clinical studies to collect breast milk and blood samples from mothers and infants, to study how two commonly used medicines transfer through milk. This study paves the way for evidence-based recommendations for treating diabetes, rheumatoid arthritis and other diseases during breastfeeding.

To avoid exposing a child to risks, women are often advised not to breastfeed. At the same time, we know that breastfeeding is good for both mother and child.

Metformin, prescribed for Type 2 Diabetes, and prednisolone, used to treat rheumatoid arthritis, can help manage chronic illness. However, the data in relation to breastfeeding is over 40 years old. And based on outdated methods. The Innovative Medicines Initiative-funded ConcePTION project is making an important contribution to our understanding of medicine safety in breastfeeding. The new studies follow in the footsteps of ConcePTION partners at the University of Oslo, the University Hospital of Toulouse and the University Hospital of Lausanne, that have conducted other lactation studies on different medicines.

What makes the Swedish study unique is the analysis of blood from infants, allowing researchers to determine, not just estimate, how these drugs transfer from mother to child, according to Mats Hansson, Senior Professor of Biomedical Ethics and Uppsala University. But adding this step to a lactation study also complicates things. It has turned what would normally be considered research studies into formal clinical trials. Both studies have been approved by The Swedish Medical Product Agency as low-intervention clinical trials, with informed consent obtained both for the sampling and the possibility of conducting future research on the stored samples.

Making this happen requires close collaboration with clinical centres and national biobanks. The studies are part of a large biobanking effort, with samples stored as part of the European Breast Milk Collection: a cornerstone of these efforts to advance medicine safety for breastfeeding mothers and infants.

As part of a broader initiative, the Swedish endeavour represents a coordinated effort towards establishing a comprehensive research infrastructure for collecting, storing and analysing breast milk samples. This structure will support the bridging of knowledge gaps in lactation studies.

As a self-sustaining platform, the Breast Milk Collection not only supports current research endeavours but also promises to pave the way for future advancements in evidence-based healthcare – benefiting both mothers and infants, says Mats Hansson.

By Anna Holm Bodin