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Background: Iron is crucial for growth and development, but excess iron is harmful. Neonatal mice have elevated concentrations of circulating iron, but the source of this iron is unclear. This lack of understanding makes it difficult to optimize early life iron balance., Objectives: Identify the origins of neonatal tissue-specific iron pools using dietary manipulation and cross-fostering murine models., Methods: To determine whether tissue-specific neonatal iron was primarily acquired during gestation or after birth, pups born to iron-sufficient or iron-deficient dams were cross-fostered, and tissues were harvested at postnatal days 3-5 to measure iron content. A separate set of female mice were fed a diet enriched with the stable iron isotope 57 ( 57 Fe) for 4 generations to replace naturally abundant liver iron isotope 56 ( 56 Fe) stores with 57 Fe. To quantify the proportions of neonatal iron acquired during gestation, pups born to dams with 56 Fe or 57 Fe stores were cross-fostered, and tissues were harvested at postnatal day 3-5 to determine 56 Fe: 57 Fe ratios by inductively coupled plasma mass spectrometry. Finally, to quantify the proportion of neonatal iron acquired from the maternal diet, female mice with 56 Fe or 57 Fe stores switched diets upon mating, and pup tissues were harvested on P0 to determine 56 Fe: 57 Fe ratios by inductively coupled plasma mass spectrometry., Results: Perinatal iron deficiency resulted in smaller pups, and gestational iron deficiency resulted in lower neonatal serum and liver iron. Cross-fostering between dams with 56 Fe and 57 Fe stores demonstrated that ≤70% of neonatal serum, liver, and brain iron were acquired during gestation. Dietary manipulation experiments using dams with 56 Fe and 57 Fe stores showed that over half of neonatal serum, liver, and brain iron were from the dam's gestational diet rather than preconception iron stores., Conclusions: This study provides quantitative values for the sources of neonatal iron, which may inform approaches to optimize neonatal iron status., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Necrotizing enterocolitis (NEC) is a leading cause of preterm infant morbidity and mortality. Treatment for NEC is limited and non-targeted, which makes new treatment and prevention strategies critical. Host defense peptides (HDPs) are essential components of the innate immune system and have multifactorial mechanisms in host defense. LL-37 and hBD2 are two HDPs that have been shown in prior literature to protect from neonatal sepsis-induced mortality or adult inflammatory bowel disease, respectively. Therefore, this article sought to understand if these two HDPs could influence NEC severity in murine preclinical models. NEC was induced in P14-16 C57Bl/6 mice and HDPs were provided as a pretreatment or treatment. Both LL-37 and hBD2 resulted in decreased NEC injury scores as a treatment and hBD2 as a pretreatment. Our data suggest LL-37 functions through antimicrobial properties, while hBD2 functions through decreases in inflammation and improvement of intestinal barrier integrity., Competing Interests: P.N. and J.W. (co-authors) are shareholders of Defensin Therapeutics ApS (DTA), Denmark. P.N. is CEO of DTA and B.J. (co-author) is next to his fulltime position as Ass. Prof., Head of Nutritional Immunology, University of Copenhagen, CSO of DTA. D.T. owns a patent to pursue the therapeutic use of hBD2 in graft versus host disease and the ethical pharmaceutical rights to pursue prophylactic or therapeutic use of hBD2 in NEC. DTA has supported this work by providing relevant amounts of hBD2. The company had no share in the data analysis, integration, and presentation. The company solely delivered the defensins used in the current study. The views expressed in this manuscript are those of the authors and not necessarily those of DTA or other funding bodies that could be construed as a potential conflict of interest., (© 2024 The Authors.)