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Previous studies show that neurodevelopmental outcomes of preterm infants are dependent in part on the degree of anemia. In a developmentally appropriately-timed neonatal mouse model, phlebotomy induced anemia (PIA) of the degree commonly seen in hospitalized preterm infants results in brain iron deficiency and hypoxia and significant short-term and long-term brain dysfunction, especially in the hippocampus. Iron and oxygen are critical for mitochondrial oxidative phosphorylation-mediated ATP production and thus energetically demanding brain developmental processes (e.g., axon\/dendrite growth, myelination, synaptogenesis).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To test the hypothesis that neonatal PIA acutely impairs mitochondrial respiratory capacity and electron transport chain (ETC) complex function in the developing hippocampus.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Neonatal mice were phlebotomized daily beginning on postnatal day 3 (P3). On P14, mitochondria were isolated from the hippocampus of male and female PIA and non-bled mice. Seahorse bioenergetic analyses were performed to determine the effects of PIA on mitochondrial oxidative phosphorylation activity and ETC complex functional capacity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PIA hippocampal mitochondria demonstrated an overall reduced oxygen consumption rate (OCR) compared to non-bled controls when ETC oxygen consumption was coupled to ATP production. PIA reduced hippocampal mitochondrial OCR that was not due to the ETC in females not males. Basal respiration, proton leak, and maximal respiratory capacity were significantly reduced in PIA hippocampal mitochondria, an effect that did not differ by sex. When mitochondrial ETC oxygen consumption was uncoupled from ATP production with the protonophore FCCP, a mild reduction in OCR was observed across all ETC complexes, with only complex I-mediated OCR being significantly lower than non-bled controls.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings suggest that impaired mitochondrial energetic capacity may mechanistically contribute to the persistent neurobehavioral deficits caused by PIA, through dysregulation of energy-demanding neurodevelopmental processes (e.g., neuron structural maturation).<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.05.692675","type":"posted-content","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:00:25Z","timestamp":1765353625000},"source":"Crossref","is-referenced-by-count":1,"title":["Neonatal phlebotomy-induced anemia compromises mitochondrial bioenergetics in the developing hippocampus"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-9471","authenticated-orcid":false,"given":"Thomas W.","family":"Bastian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana J.","family":"Wallin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda K.","family":"Barks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghavendra B","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Georgieff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025121113050994000_2025.12.05.692675v1.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2303347"},{"key":"2025121113050994000_2025.12.05.692675v1.2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-1884"},{"key":"2025121113050994000_2025.12.05.692675v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2006.05.011"},{"key":"2025121113050994000_2025.12.05.692675v1.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2020248"},{"key":"2025121113050994000_2025.12.05.692675v1.5","doi-asserted-by":"publisher","DOI":"10.1542\/neo.9-11-e520"},{"key":"2025121113050994000_2025.12.05.692675v1.6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.tmrv.2016.06.005","article-title":"Research Opportunities to Improve Neonatal Red Blood Cell Transfusion","volume":"30","year":"2016","journal-title":"Transfus Med Rev"},{"key":"2025121113050994000_2025.12.05.692675v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.4"},{"key":"2025121113050994000_2025.12.05.692675v1.8","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32834ee5cc"},{"key":"2025121113050994000_2025.12.05.692675v1.9","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.clp.2023.07.009","article-title":"Iron Supplementation, and the Brain","volume":"50","year":"2023","journal-title":"Clinics in Perinatology"},{"key":"2025121113050994000_2025.12.05.692675v1.10","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/s41390-021-01536-0","article-title":"Sex-specific cytokine responses and neurocognitive outcome after blood transfusions in preterm infants","volume":"91","year":"2022","journal-title":"Pediatr Res"},{"key":"2025121113050994000_2025.12.05.692675v1.11","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jpeds.2021.12.051","article-title":"Sex Differences in the Association of Pretransfusion Hemoglobin Levels with Brain Structure and Function in the Preterm Infant","volume":"243","year":"2022","journal-title":"J Pediatr"},{"key":"2025121113050994000_2025.12.05.692675v1.12","unstructured":"Whyte RK , Kirpalani H , Asztalos EV , Andersen C , Blajchman M , Heddle N , LaCorte M , Robertson CMT , Clarke MC , Vincer MJ , et al. 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