Molecular and metabolic mechanisms of secretory activation and pumped milk volume in mothers with infants in the NICU

/Abstract Increasing the number of infants in the neonatal intensive care unit (NICU) who can be fed using mothers’ own milk (MOM) is crucial for reducing expensive co-morbidities experienced by premature and ill infants. Mothers on NICU infants have delayed secretory activation (SA) and challenges to maintain SA, and coming to volume (≥500 mL/d by d 14 postpartum, CTV). However, the biological mechanisms that are involved in inhibiting the initiation and establishment of lactation in this at-risk population are generally poorly understood. SA involves the closing of tight junctions in the mammary gland and the transition to copious milk production. Following this transition, the mammary gland transitions from endocrine to paracrine/autocrine regulation of lactation, leading to an increase in milk volume. Both SA and CTV are critical for initiation and maintenance of lactation, and prior data suggest that both may be impacted by maternal health factors. In our prior work, we found that both transcriptomic gene expression and lipid metabolism are associated with milk production in mothers of term infants later in lactation. However, similar work has not been done during early lactation or in the NICU population. In this project, we will use samples from a highly-controlled parent trial to investigate the molecular and metabolic pathways that are associated with the achievement of SA and CTV in the first 2 weeks postpartum (pp). We will use transcriptomics, as well as biochemical analysis of inflammatory and lipid metabolism pathways to elucidate the biological mechanisms associated with 1) the achievement of SA by week 1 pp and 2) pumped milk volume at 2 weeks in a population of mothers with infants in the NICU. As participants in the parent clinical trial, all mothers will receive consistent, state-of-the art lactation support and care, reducing the possibility of variability in access and quality of care. The results of this study will provide evidence to support the development of future interventions that are targeted to promote sufficient milk production and prevent lactation problems in vulnerable populations. Project Number: 1R21HD120835-01 | Fiscal Year: 2026 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Rachel Walker (+1 co-PI) | Institution: PENNSYLVANIA STATE UNIVERSITY, THE, UNIVERSITY PARK, PA | Award Amount: $470,816 | Activity Code: R21 | Study Section: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER] View on NIH RePORTER: https://reporter.nih.gov/project-details/11287023