Building an ecosystem for better monitoring and communicating of medication safety in pregnancy and breastfeeding: validated and regulatory endorsed workflows for fast, optimised evidence generation

Project Information

ConcePTION

Grant agreement ID: 821520

DOI

10.3030/821520

Project closed

EC signature date 6 May 2019

Start date 1 April 2019

End date 31 December 2024

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 28 782 491,01

EU contribution

€ 15 299 991,00

Coordinated by

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands

Periodic Reporting for period 5 - ConcePTION (Building an ecosystem for better monitoring and communicating of medication safety in pregnancy and breastfeeding: validated and regulatory endorsed workflows for fast, optimised evidence generation)

Reporting period: 2023-04-01 to 2024-12-31

Summary of the context and overall objectives of the project

More than 5 million people get pregnant in the EU every year and more than 90% take at least one medicine during pregnancy. Yet there is almost no evidence-based information available on most medicines to guide a person’s fully informed decision. Even less information is available regarding medicine exposure through breastfeeding. As few as 5% of available medicines have been adequately monitored, tested and labelled for use in pregnant and breastfeeding people. On average, it takes an estimated 27 years to determine the teratogen status of a novel medicine. The field has suffered from a lack of systematically gathered insights that could lead to more effective data generation methodologies. Fragmentation and misinformation abounds, resulting in confusing and contradictory communication and perception of risks by both health professionals and people and their families. Obtaining reliable safety information for pregnant or breastfeeding people can take 20 or more years to collect after a medicine is on the market, if it arrives at all.

Building on (1) the rising awareness of the problem, and (2) the exponential growth and innovation in capture and use of health, surveillance and digital patient-generated data, ConcePTION created a paradigm shift in how we generate and disseminate evidence on the effects of medicine in pregnancy. We made strides toward a trusted ecosystem that can efficiently, systematically, and in an ethically responsible manner, generate and disseminate reliable evidence-based information regarding effects of medicines used during pregnancy and breastfeeding to people and their healthcare providers. This was achieved by generating, cataloguing, linking, collecting and analysing pharmacovigilance, modelling, routine healthcare, pregnant people and their children through a large network. ConcePTION validated non-clinical models that predict medicine transfer to breastmilk using a multipronged approach consisting of in vivo, in vitro and in silico models, and worked towards the set-up of the first Europe-wide research biobank to measure medicine levels in human breastmilk.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In its first two years, ConcePTION created the network, tools, and common data models needed to harmonise diverse data sources, defined core elements for pregnancy pharmacovigilance, and shared expertise with global networks. In years three and four, the project conducted demonstration studies, built models to predict drug transfer into breastmilk, established a framework for data quality, laid the foundation for a Europe-wide breastmilk biobank, and launched the knowledge bank to make evidence accessible. In its final year, ConcePTION advanced five research projects, refined analytical methods, and strengthened regulatory collaboration.

Key achievements:
- Core data elements (CDE): A structured framework of 98 CDEs to guide standardized data collection in pregnancy pharmacovigilance research.
- Data pipeline: A five-step pharmacoepidemiology pipeline for studying medicine use and safety in pregnancy and lactation, adaptable to many research questions.
- Toolkit: Guidance on push–pull strategies, value propositions, and adaptable digital/print materials for targeted communications in multiple languages.
- MUMS Knowledge Bank: A free, publicly accessible source of reliable information on medicine use during pregnancy (www.mums.eu).
- Meds4Mums2B: A UK mobile app providing trusted medicine information for parents and healthcare professionals, while collecting medicine-use data.
- E-learning: An 11-chapter interactive online course for healthcare professionals, launching in 2025.
- Breastmilk collection: Five lactation studies on transfer of amoxicillin, levocetirizine, metformin, prednisolone, and venlafaxine, creating a framework for future research.
- Bioanalytical methods: Standardized, validated methods for measuring medicine levels in breast milk and plasma, supporting model validation.
- LIFETIME: A framework for long-term follow-up of neurodevelopment in children exposed to medicines during pregnancy, through school age.
- In vivo, in vitro & PBPK models: A non-clinical framework to study and predict medicine transfer into milk, combining in vitro models, in vivo verification, and PBPK simulations.
- Ethics framework: An approach for data-intensive research involving pregnant and breastfeeding women within learning healthcare systems.
- Secondary data sources: Methods to use and expand existing databases for case-control and cohort studies.

See also: https://www.imi-conception.eu/results.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

There is a societal obligation to reduce uncertainty about the effects of medicine use during pregnancy and breastfeeding. ConcePTION is the first large European project dedicated to this population, uniting 88 organisations from 22 countries, including the European Medicines Agency, pharmaceutical companies, academia, public health organisations, and teratology networks. By combining routine health data, patient-reported information, and novel research capabilities to predict and measure drug transfer into breastmilk, the project addresses knowledge gaps and improves healthcare for this underserved group.

Substantial progress has been made. The MUMS Knowledge Bank (www.mums.eu) provides publicly accessible, evidence-based information, empowering healthcare professionals and patients. The foundation for a centralised EU breastmilk biobank was established, enabling systematic research with ethical approvals for long-term follow-up. Regulatory practice has advanced, with harmonised methodologies for assessing medicine safety in pregnancy and frameworks to prioritise drug safety studies based on preclinical and real-world data. Novel in vitro, in vivo, and in silico models predicting drug transfer into human milk have gained regulatory recognition, with EMA Qualification Advice pending.

Accepted approaches for studying medication safety were implemented across data partners, with 14+ scripts, 20+ outcome definitions, and 11 data providers submitting characterization data. Data sources for adverse effects in fetuses, newborns, and children totalled 609, with 21 listed in the catalogue and several included in demonstration studies. Pharmacovigilance was harmonised via the Meds4MumsS2B application (available in the UK), and over 1,000 pregnant and breastfeeding women contributed case reports and follow-up outcomes.

Advanced methodologies now predict milk transfer for >20 medicines, supported by standardised lactation study protocols. Human studies enrolled 122 women and 23 infants, with breastmilk kept at the Uppsala biobank accessible through BBMRI-ERIC. Open science efforts include 18 open-source tools (https://zenodo.org/record/7734196) 400 data sources in the open catalogue (https://pubmed.ncbi.nlm.nih.gov/36976447/) 59 deliverables (https://shorturl.at/s2XFJ) and 48 open-access publications (https://www.imi-conception.eu/results/papers/).

ConcePTION has set new benchmarks in research, regulatory practice, and clinical guidance, bridging critical gaps in pregnancy and breastfeeding pharmacovigilance. Its common data model, analytical tools, and sustainability framework ensure long-term impact, supporting evidence-based decision-making, strengthening Europe’s scientific and industrial leadership, and ultimately improving the health and well-being of people and their children across Europe.

ConcePTION ecosystem workflow

ConcePTION ecosystem infographic

ConcePTION project logo