Breastfeeding is the recommended primary source of nutrition for infants and has been associated with cognitive and other health benefits for the developing child. An estimated 50-80% of women take prescription medications while breastfeeding, yet only 2% of medications have adequate data for evaluating their safety when used in lactation. This represents a critical gap in knowledge resulting in many women either avoiding necessary medications or discontinuing breastfeeding. The primary barrier to determining the extent of drug passage into breast milk is collecting enough breast milk and blood samples to both quantify drug concentrations and account for inter-individual variability in drug exposure. For numerous reasons, it is often difficult for new mothers to come to study visits. In order to generate much-needed data on drug passage into breast milk, additional methods of sample collection are needed that will enable more lactating women to participate and to generate a sufficient critical mass of data to make strong recommendations on the safety of a given drug while breastfeeding. This proposal will rigorously test the central hypothesis that home collection of human milk and blood samples will be successfully validated against more traditional clinic-based collection methods for pharmacokinetic (PK) studies. Building on the infrastructure of the existing UC San Diego Human Milk Research Biorepository study and a highly qualified, multidisciplinary research team at UC San Diego and the University of Utah, we will enroll 20 breastfeeding women already prescribed either prednisone, oxycodone, sertraline, or methylphenidate, for a total of 80 women. In each medication group, 10 women will be randomly assigned to one of two cohorts. Women in Cohort 1 will present to clinic and provide a breast milk and blood sample that will be split into two aliquots. Aliquot 1 will be processed and stored under rigorous study collection conditions. Aliquot 2 will be processed and stored under mimicked home collection conditions. Storing the same sample under different conditions will allow comparison of home collection to the gold standard of clinic collection. The data collected from Cohort 1 will be combined with existing PK data from a collaborating network to build population PK models. These PK models will be used to generate model-predicted concentrations that will be compared with home-collected concentrations from Cohort 2. Women in Cohort 2 will be provided instructions and supplies for home collection of breast milk and dried blood spot samples that will be shipped to UC San Diego. Concentrations from home- collected samples will be compared to model-predicted concentrations from the PK models generated above. By successfully validating methods for home collections, the proposed research will transform the study of drug passage into breast milk by dramatically expanding the number of women who can participate, ultimately leading to an exponential increase in the number of medications for which there is adequate lactation safety data. The methods developed in this R21 proposal will be used to inform a large prospective, opportunistic trial of multiple drugs across numerous therapeutic areas and will involve collaboration with large US and European networks.
It is expected that there will be widespread use of vaccines to prevent SARS-CoV-2 infection among lactating women over the coming year. Due to the lack of lactation safety data for these vaccines, it is essential to understand whether COVID-19 vaccination status impacts the milk collection conditions or concentrations as outlined in the existing Aims of the parent R21. The purpose of this administrative supplement is to determine the extent to which COVID-19 vaccines affect milk composition, infant adverse events, or milk supply, which will allow for better interpretation of the differences in clinic- vs. home-collected milk samples for the four target medications.
