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Neurodevelopmental outcomes after red cell transfusion exposure in male versus female extremely preterm infants

Kendell German1, Thomas R Wood2, Semsa Gogcu3

  • 1University of Washington, Department of Pediatrics, Seattle, WA, USA. germank@uw.edu.

Pediatric Research
|June 2, 2025
PubMed

Insights

Sex may influence short-term cytokine responses to packed red blood cell (pRBC) transfusions in premature infants, but does not affect long-term neurodevelopmental outcomes. Transfusion volume is negatively associated with neurodevelopmental scores.

Area of Science:

  • Neonatal Medicine
  • Pediatric Neurology
  • Hematology

Background:

  • Packed red blood cell (pRBC) transfusions are critical for extremely premature infants.
  • pRBC transfusions are linked to increased pro-inflammatory cytokines and adverse neurodevelopment.
  • Potential sex differences in these transfusion-related effects are not well understood.

Purpose of the Study:

  • To investigate the association between pRBC transfusion volume and inflammatory cytokines, MRI-defined brain injury, and neurodevelopmental outcomes in extremely preterm infants.
  • To examine potential sex-specific differences in these associations.

Main Methods:

  • Post-hoc analysis of the Preterm Erythropoietin Neuroprotection (PENUT) Trial data.
  • Evaluation of associations between pRBC transfusion volume, cytokines (0-7 and 7-14 days), MRI injury, and Bayley Scales of Infant Development (BSID-III) scores at 24 months corrected age.
  • Use of graphical network and generalized estimating equation models to assess sex interactions and hematocrit influence.

Main Results:

  • Infant sex modified the association between pRBC transfusion volume and IL-6 levels at 7-14 days.
  • Sex did not impact the association between transfusion volume/hematocrit and BSID-III scores.
  • Total pRBC transfusion volume was significantly negatively associated with all BSID-III subscales, independent of anemia and illness severity.

Conclusions:

  • Infant sex may influence short-term cytokine responses to pRBC transfusions.
  • Sex does not appear to alter the relationship between transfusion volume and long-term neurodevelopmental outcomes.
  • Current evidence suggests transfusion practices should not be altered based on infant sex.
Abstract

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