A Large Proportion of The Neonatal Iron Pool is Acquired from the Gestational Diet in a Murine Model

Background Iron is crucial for growth and development, but excess iron is harmful. Neonatal mice have elevated levels of circulating iron, but the source of this iron is unclear. This lack of understanding makes it difficult to optimize early life iron balance. Objective 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 day 3-5 (P3-5) to measure iron content. A separate set of female mice were fed a diet enriched with the stable iron isotope iron57 (57Fe) for four generations to replace naturally abundant liver iron56 (56Fe) stores with 57Fe. To quantify the proportions of neonatal iron acquired during gestation, pups born to dams with 56Fe or 57Fe stores were cross-fostered and tissues were harvested at P3-5 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry (ICP-MS). Finally, to quantify the proportion of neonatal iron acquired from the maternal diet, female mice with 56Fe or 57Fe stores switched diets upon mating and pup tissues were harvested on P0 to determine 56Fe:57Fe ratios by ICP-MS. 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 56Fe and 57Fe stores demonstrated that up to 70% of neonatal serum, liver and brain iron were acquired during gestation. Dietary manipulation experiments using dams with 56Fe and 57Fe stores showed that over half of neonatal serum, liver and brain iron were from the dam’s gestational diet rather than pre-conception iron stores. Conclusions This study provides quantitative values for the sources of neonatal iron, which may inform approaches to optimize neonatal iron status.