The IMI ConcePTION project has developed a Core Data Elements methodology for studying drug safety during pregnancy, by exploring how data can be standardised and analysed. A recent paper in the Journal of Clinical and Experimental Reproductive Medicine demonstrates the usefulness of this approach. However, the study also highlights the challenges in pregnancy pharmacovigilance and emphasises the need for overall, worldwide accepted standards – for safer medication use during pregnancy.

Pregnancy pharmacovigilance is challenging. The number of pregnancies where the fetus has been exposed to a certain medicine are often small. Consequently, the information about those medicine exposures is scattered across several countries and data collection systems. Moreover, individual data collection systems often struggle to provide fast and reliable analysis of medication safety in pregnancy.

According to the authors, the current data collection systems lack standardisation, which reflects the absence of universal definitions across regulatory, industry, academic and clinical settings. Together with other efforts on developing Core Data Elements in the ConcePTION project, this study contributes to solving the problem by providing a standardised list of Core Data Elements and statistical outputs.

“Our efforts will contribute to harmonising the analysis of pregnancy safety data across different organisations involved in a study, including public institutions and pharmaceutical companies”, says Ursula Winterfeld, Swiss Teratology Information Service (STIS), Lausanne University Hospital and University of Lausanne.

Despite efforts to develop Core Data Element tables, the required information is not always available in existing sources. The approach that the research team applied resulted in a high level of completion for summary data tables that detail pregnancy safety study results, especially for case attrition and disposition, maternal demographics, timing of exposure, pregnancy outcomes, malformation type, and malformation prevalence.

“Despite encountering methodological challenges due to variation in data collection methodologies and study populations across data access providers, the study demonstrated the feasibility of mapping existing diverse datasets to standardised definitions and content”, says Ursula Winterfeld.

ConcePTION has provided a Core Data Elements framework and guidance for the statistical analysis. The results of this study will help promote widespread adoption and collaboration among diverse stakeholders in primary source pregnancy pharmacovigilance studies. These resources are designed to facilitate harmonisation across various steps of such studies, from selecting definitions and variables to considerations for data analysis and presentation.

According to the authors, the ConcePTION data harmonisation efforts aim to overcome current limitations in collecting pregnancy drug safety data. Providing a standardised approach that can be implemented from the start of new data collections.

“The method has significant potential to enhance the ability to compare results and facilitate meta-analyses, ultimately strengthening the evidence-base for safer medication use during pregnancy”, says Ursula Winterfeld.

Do you want to know more? Read the article: Winterfeld U, Favre G, Richardson JL, Moore A, Geissbühler Y, Jehl V, et al. Improving data harmonization in pregnancy safety studies: Demonstrating the feasibility of standardized data analysis of pregnancy reports–A contribution from the conception project. J Clin Exp Reprod Med. 2025;2(1):6-12. DOI: 10.46439/reproductivemed.2.007

By Josepine Fernow & Fanny Klingvall

Physiologically based pharmacokinetic (PBPK) models are used to predict the transfer of medications from mother to baby through breast milk. For clinical practice and research, accurate assessment of infant feeding is relevant. The ConcePTION project has developed a mathematical function that improves the estimation of the infant’s intake of breast milk, which is key for estimations of infant exposure to maternal medicines.

Measuring the infant’s breast milk intake volume is challenging. The authors reviewed literature using a dose-to-mother method called deuterium oxide dilution at different postnatal stages. According to the authors, this method is especially effective for infants up to six months of age, as it does not disturb normal feeding behavior.

By analyzing data from clinical studies, the authors developed a new mathematical function to better estimate the milk intake volume over time. According to the authors, the results of this study question earlier approaches that may have underestimated the actual breast milk intake, especially after two months of age.

The systematic review is published in the journal Nutrients. This research is providing insights for future PBPK modelling to enhance informed healthcare decisions, and improve outcomes for mothers and their infants.

“The findings have important implications for future PBPK modelling, which are critical for evaluating drug safety during breastfeeding, as this function is based on the more accurate deuterium oxide dilution method only,” says Martje Van Neste, MD & PhD student at KU Leuven and co-author of the study.

Do you want to know more? Read the article: Cloostermans L, Allegaert K, Smits A, Van Neste M. The Deuterium Oxide Dilution Method to Quantify Human Milk Intake Volume of Infants: A Systematic Review—A Contribution from the ConcePTION Project. Nutrients. 2024; 16(23):4205. DOI: 10.3390/nu16234205

By Fanny Klingvall

On 11 December, we hosted the last ConcePTION webinar on using real-world data sources for pregnancy pharmacoepidemiology. Rosa Gini presented the ConcePTION pregnancy algorithm and Judit Riera Arnau presented an algorithm to prioritize teratogenic drug safety research. A recording of the presentations is now live on YouTube!

The webinar starts with an introducton to the ConcePTION project by project coordinator Miriam Sturkenboom. Then, Rosa Gini presents the pregnancy algorithm, with methods to create lists of pregnancies and recommendations for use. The presentation also includes a segment on validation of PPV to estimate sensitivity of study outcomes and adjust study results. Lastly, Judit Riera Arnau presents an algorithm to prioritize teratogenic drug safety research. The algorithm is based on data obtained from animal studies and real-world evidence, and aims to assess the potential risk for individuals and society. Prioritisation scores are based on the prevalence of use, time trends, and repeated exposure.

Did you miss the live webinar? Watch “Using real-world data sources for pregnancy pharmacoepidemiology – The ConcePTION pregnancy & reprotox algorithm” on YouTube →

The speakers

• Prof. Dr. Miriam Sturkenboom, UMC Utrecht.
• Dr. Rosa Gini, ARS Toscana.
• Dr. Judit Riera Arnau, UMC Utrecht.