The Maternal Pediatric Precision In Therapeutics (MPRINT) Hub hosted its 2nd Annual Meeting and Scientific Symposium at the Ida and Cecil Green Faculty Club on the campus of UCSD from Wednesday, April 19 through Friday, April 21, 2023.

This meeting featured presentations from the IU-OSU DMKRCC, VICE-MPRINT, and UCSD MPRINT Center of Excellence in Therapeutics and welcomed representatives from prominent research networks and groups within the Maternal and Pediatric communities.

Highlights from the MPRINT Annual Meeting 2023

The 2023 MPRINT Hub Annual Meeting & Scientific Symposium featured new research from dozens of presenters across multiple research teams and fostered important conversations about the future of maternal and pediatric research. A key emphasis throughout the conference was the importance of enhancing collaborations, setting standards for conducting and reporting pharmacokinetic studies, and exploring future directions for research. By bringing together experts from various fields, the conference fostered valuable interdisciplinary dialogue and promoted the exchange of ideas to advance the field of maternal and pediatric research.

The UC San Diego Center of Excellence in Therapeuticsinvestigates the connection between nursing, the microbiome, and the transfer of medications from mother to infant through breast milk. This research encompasses three overlapping projects—a clinical project, a data science project, and a basic science project—with support from the Pharmacometric and Analytical Chemistry Core.

• The clinical project, presented by Dr. Christina Chambers, explores commonly used antibiotics in human milk samples. The study investigates the potential impact of maternal antibiotic use on milk composition, the microbiome profile of the mother and infant, and how these factors relate to infant growth and development.
• As part of the data science project, Dr. Sydney Thomas presented her work on the relationship between human milk oligosaccharides (HMOs), the milk microbiome, and child health outcomes. The study found that not only were certain HMOs associated with specific bacteria in the milk microbiome but also with breastfeeding rates and frequency and long-term child-development outcomes.
• Dr. George Liu’s presentation on the basic science project focused on the effects of ampicillin exposure on mother and infant mice. The research examined how ampicillin affects the metabolome and how the drug’s impact on pups changes based on the route of exposure, whether transplacental, through breast milk, or via direct administration. The research identified significant changes in the young mice from exposure to ampicillin, including weight changes and anti-inflammatory responses.

The team at Vanderbilt Integrated Center of Excellence in Maternal and Pediatric Precision Therapeutics focuses on two projects. The first is a pharmacogenomic project, seeking both to understand patient knowledge and attitudes about pharmacogenomics as well as to validate gene-drug interactions in pregnant and pediatric populations. The second project works to create predictive tools to identify and aid opioid-exposed infants.

• Dr. Prince Kannankeril presented research led by Dr. Digna Velez Edwards as part of the pharmacogenomic project at Vanderbilt. In their clinical trials, they use a baseline survey to assess participant knowledge and attitudes about pharmacogenetic testing, in addition to completing pharmacogenetic testing. Participants are then randomized to either receive an educational video or not, and a follow-up survey is conducted to assess the impact of the video on their knowledge and attitudes.
• Dr. Sudeep Sunthankar presented his work as part of the second aim of Vanderbilt’s pharmacogenomic project, specifically seeking to understand the relationship between adverse events for patients using the anti-arrhythmic drug propofenone and CYP2D6 activity scores. The study found an association between lower activity scores and systemic adverse events and drug discontinuation and was ultimately able to make recommendations for closer monitoring for key patients.
• Dr. Leena Choi presented the development of a system to generate data sets from electronic health records to be used in PKPD studies. Since dosing information is often noted in an unstructured form like clinical notes, the team has developed a system to use natural language processing to pair the unstructured data with the structured data. They are also working to create a therapeutic drug monitoring tool using vancomycin for a prototype that will make drug monitoring more accessible.
• Drs. Stephen Patrick and Andrew Wiese presented their research as part of the Vanderbilt team’s second project, aimed at identifying opioid-exposed infants using electronic health records. Their research has developed and validated phenotypes and prediction tools to improve the identification of opioid exposure and to better understand the outcomes and factors that influence withdrawal symptoms.

The IU-OSU MPRINT Hub Data, Model, Knowledge, and Research Coordination Centerhas provided extensive support to various research projects, especially in physiologically-based pharmacokinetic (PBPK) modeling.

• As part of the Pharmacometric and Clinical Trial Design Core, Drs. Sara Quinney and Rob Bies both highlighted some of the collaborative research that their teams have been working on, including work with the IMPAACT network, pharmacokinetic modeling of gabapentin in lactating individuals, and PBPK modeling of monoclonal antibodies in pediatric patients.
• Dr. Tomoyuki Mizuno presented his Opportunity Pool funded project, a maternal-fetal PBPK model aimed at improving prenatal treatment for neonatal opioid withdrawal syndrome. The model focused on predicting buprenorphine exposure to the mother and fetus throughout pregnancy and was validated using literature data. The success of the preliminary model suggests the feasibility of using a model to create a precision dosing strategy for buprenorphine.
• Dr. Lang Li demonstrated the ongoing development of the Knowledgebase and Portal – a comprehensive database of information on drugs used during pregnancy and childhood. The database includes information on PK, PD, and CT studies, as well as drug outcomes, risk factors, sample types, study design, and statistical models. The database is designed to be user-friendly and accessible, with a silver version for basic queries and a golden version for more detailed information. Overall, the database provides a valuable resource for researchers, clinicians, and drug developers to understand the safety and efficacy of drugs in vulnerable populations.

This overview offers just a glimpse into research presented at the 2023 MPRINT Hub Annual Meeting & Scientific Symposium. Stay tuned for future updates that will delve deeper into this research.