Studying medicine safety in breastfeeding requires both clinical and non-clinical approaches. Our efforts include analysing how common medicines like antibiotics transfer to milk in in vivo models. A ConcePTION project publication in Journal of Pharmacological and Toxicological Methods reports on a sensitive and rapid method for estimating the concentration of amoxicillin – a commonly used antibiotic – in plasma and milk.

In addition to the clinical studies conducted using the ConcePTION European Breast Milk Collection, we use in vivo, in vitro and in silico models to understand and predict how medicines transfer from mother to infant. To accurately measure this transfer, reliable bioanalytical methods are needed. We have developed a high-throughput, robust and reliable liquid chromatography tandem mass spectrometry method to determine concentrations of amoxicillin in a large number of minipig plasma and milk samples. The method, published recently in Journal of Pharmacological and Toxicological Methods, was developed and validated according to FDA and EMA guidelines.

Pieter Annaert, Professor and chair of the Department of Pharmaceutical and Pharmacological Sciences at KU Leuven is one of the authors. According to him, the method can be used for quantitation (meaning the estimation of how much of the medicine is present) of amoxicillin in both plasma and milk. The method is high-throughput, meaning the run time and speed of sample processing is low, which makes the method efficient because it is simple and easy to use. With this method, quantitation of Amoxicillin using liquid chromatography-mass spectrometry takes only 5 minutes. It also provides a one-method approach to extract the chemicals of interest (analytes) from both plasma and milk. In addition, the validated method allows us to accurately measure concentrations in a 1000-fold range (10 ng/mL – 10 μg/mL).

Want to know more? Read the paper:

Armoudjian, Y., Lin, A., Lammens, B., Van Daele, J., Annaert, P. (2023) Sensitive and rapid method for the quantitation of amoxicillin in minipig plasma and milk by LC-MS/MS: A contribution from the IMI ConcePTION project, Journal of Pharmacological and Toxicological Methods,107264, https://doi.org/10.1016/j.vascn.2023.107264.

There is still a lot of uncertainty about the effects of most medicines on the unborn child. A paper published in BMC Medical Ethics calls for a paradigm shift in the way we generate knowledge on the effects of medicines in pregnancy, paving the way for a learning health care system.

Pregnancy is a time of close monitoring, when large amounts of health data is collected. This data can help identify problems with maternal health, but also point to problems for the unborn child. Within the framework of the ConcePTION project, researchers from UMC Utrecht have explored whether this data could support a transition to a Learning Healthcare System, using health data both to study and develop new insights about the effects of medical treatments for both mother and child, and to guide treatment decisions for women at the point of care.

However, this shift to a learning health care system requires collaboration between a wide range of stakeholders. Drawing from experiences in the field of rare diseases, where patients have played an important part in changing the way genetic conditions are both studied and treated, the authors suggest that pregnant women themselves have an important part to play in the shift to a new paradigm.

According to Marieke Hollestelle, PhD student at UMC Utrecht, the literature suggests that solidarity has played an important role for rare disease patients in changing the approaches to treatment and research. This speaks for solidarity as an entry-point to exploring the role that the pregnant woman can play. However, for solidarity to become a successful vehicle for change, individuals might need to be encouraged to rely on solidarity to achieve progress. Where solidarity means enacted commitments on the part of an individual to assist someone who they feel are similar in some aspect that feels relevant to them. In the paper, the authors explain that this kind of solidarity is not something that can be imposed upon pregnant women. However, they argue that it is possible to use empowerment as a tool to stimulate women who are pregnant to engage in the paradigm shift on the basis of solidarity.

“Empowerment means creating awareness about the situation anyone who is pregnant finds themselves in, explaining how scientific research can help close the current knowledge gap, and how someone who is pregnant can contribute, to for example the ConcePTION ecosystem” says Marieke Hollestelle.

However, the authors make it clear that to raise awareness and empower pregnant women, requires the help from other stakeholders, such as healthcare professionals, data scientists, funding agencies, registries and other professionals.

Read the paper: Hollestelle, M.J., van der Graaf, R., Sturkenboom, M.C. & van Delden J.JM. (2023) Stimulating solidarity to improve knowledge on medications used during pregnancy, BMC Med Ethics 24(44), DOI 10.1186/s12910-023-00924-x

By Josepine Fernow

Building evidence for medicine safety in pregnancy requires large sets of high quality data, but until now there were no tools available for grading pregnancy pharmacovigilance data. One of the challenges lies in the fact that a lot of pregnancy pharmacovigilance information is collected in individual case reports, not designed for drug use during pregnancy. The ConcePTION project has developed a four-step process to assess the quality of the information in case reports, listing the  elements that are essential for assessing the quality of information used to evaluate the risks associated with medicinal products used during pregnancy.

Evaluating the risk of exposure to a medicinal product during pregnancy builds on access to information that is comprehensive and clearly explained. A paper just published in Frontiers in Drug Safety and Regulation reports on a ConcePTION project process to assess case report information. The work builds on an expert focus group discussion to identify the different kinds of information that could form the basis for a quality assessment, followed by two surveys and focus group discussions to do a final selection. The work resulted in a list of twenty-one information elements. The authors categorised these elements into into seven groups: information pertaining to the association itself, the event, exposure to the medicinal product, maternal factors, pregnancy, labour, and the child.

According to Eugène van Puijenbroek, clinical pharmacologist at the Netherlands Pharmacovigilance Centre Lareb and Professor of Pharmacovigilance at the University of Groningen, this study is a first step in the development of a validated method for evaluating the clinical quality of case reports and other information sources on pregnancy pharmacovigilance data. The study aimed to identify the elements that are needed if we are to assess the quality of information. In turn allowing us to use them for risk assessment.

The study is published Open Access in Frontiers in Drug Safety and Regulation

van Rijt-Weetink, Y.R.J., Chamani, K., Egberts, A.C.G., van Hunsel, F.P.A.M., Lewis D.J., Yates, L.M., Winterfeld, U., van Puijenbroek, E.P. (2023) Elements to assess the quality of information of case reports in pregnancy pharmacovigilance data—a ConcePTION project, Frontiers in Drug Safety and Regulation 3, DOI: 10.3389/fdsfr.2023.1187888