ArticlePediatric research2022
Dose- and sex-dependent effects of phlebotomy-induced anemia on the neonatal mouse hippocampal transcriptome.
Article in Pediatric research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 16 citations in OpenAlex.
- Immune landscape in liver of neonatal mice with phlebotomy-induced anemia.Pediatric research · 2026Article
- Dysfunctional connectivity within hippocampal and entorhinal networks underlies early-life iron deficiency induced social recognition deficits, a preliminary study.Scientific reports · 2026Article
- Red blood cell transfusion exacerbates phlebotomy-induced anemia-associated neuroinflammation in murine neonates.Transfusion · 2026Article
- Neonatal phlebotomy-induced anemia compromises mitochondrial bioenergetics in the developing hippocampus.bioRxiv : the preprint server for biology · 2025Article
- Anemia and retinopathy of prematurity: A narrative review.Pediatric investigation · 2025Review
- Phlebotomy-induced anemia reduces oxygen-induced retinopathy severity and dampens retinal developmental transcriptomic pathways in rats.Pediatric research · 2025Article
- Sex-specific association between maternal mild anemia and children's behavioral development: a birth cohort study.European child & adolescent psychiatry · 2024Article
- Sex differences in the association of pretransfusion haemoglobin and cognition in preterm infants.BMJ paediatrics open · 2024Observational
- Identification of Genes Responding to Iron or Choline Treatment for Early-Life Iron Deficiency in the Male Rat Hippocampal Transcriptomes.The Journal of nutrition · 2024Article
- Anemia, Iron Supplementation, and the Brain.Clinics in perinatology · 2023Review
- Survey of transfusion practices in preterm infants in Europe.Archives of disease in childhood. Fetal and neonatal edition · 2023Article
- Identification of clinical factors associated with timing and duration of spontaneous regression of retinopathy of prematurity not requiring treatment.Journal of perinatology : official journal of the California Perinatal Association · 2023Article
- Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome.Nutrients · 2023Article
- Impact of level of neonatal care on phlebotomy and blood transfusion in extremely low birthweight infants: a prospective, multicenter, observational study.Frontiers in pediatrics · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
backgroundPhlebotomy-induced anemia (PIA) is universal and variable in degree among preterm infants and may contribute to neurodevelopmental risk. In mice, PIA causes brain tissue hypoxia, iron deficiency, and long-term sex-dependent neurobehavioral abnormalities. The neuroregulatory molecular pathways disrupted by PIA underlying these effects are unknown.
methodsMale and female pups were phlebotomized daily from postnatal day (P)3-P14 via facial venipuncture to target hematocrits of 25% (moderate, mPIA) and 18% (severe, sPIA). P14 hippocampal RNA from non-bled control and PIA mice was sequenced by next-generation sequencing to identify differentially expressed genes (DEGs) that were analyzed using Ingenuity Pathway Analysis.
resultsmPIA females showed the least DEGs (0.5% of >22,000 genes) whereas sPIA females had the most (8.6%), indicating a dose-dependent effect. mPIA and sPIA males showed similar changes in gene expression (5.3% and 4.7%, respectively), indicating a threshold effect at mPIA. The pattern of altered genes induced by PIA indicates sex-specific and anemia-dose-dependent effects with increased pro-inflammation in females and decreased neurodevelopment in males.
conclusionThese gene-expression changes may underlie the reduced recognition memory function in male and abnormal social-cognitive behavior in female adult mice following neonatal PIA. These results parallel clinical studies demonstrating sex-specific behavioral outcomes as a function of neonatal anemia. IMPACT: Phlebotomy-induced anemia (PIA) in neonatal mice results in an altered hippocampal transcriptome and the severity of changes are dependent upon degree of anemia and sex of neonatal mice. The reported findings provide context to the sex-specific outcomes that have been reported in transfusion threshold clinical trials of preterm infants and therefore may inform treatment strategies that may be based on sex. These data advance the field by showing that consequences of PIA may be based in sex-specific transcriptomic alterations. Such changes may also result from other causes of neonatal anemia that also affect term infants.
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