Sex-Specific Cytokine Responses and Neurocognitive Outcome after Blood Transfusions in Preterm Infants

BACKGROUND: The objective of this study was to determine sex-specific differences in inflammatory cytokine responses to RBC transfusion in preterm infants in the neonatal period and their relationship to later neurocognitive status. METHODS: Infants with a birth weight <1000 grams and gestational age 22–29 weeks were enrolled in the Transfusion of Prematures (TOP) trial. The total number of transfusions was used as a marker of transfusion status. 19 cytokines and biomarkers were analyzed from 71 infants longitudinally during neonatal period. 26 infants completed the Bayley Scales of Infant & Toddler Development, 3rd Edition (Bayley-III) at 12 months’ corrected age. RESULTS: Nine cytokine levels were significantly elevated in proportion to the number of transfusions received. Of those, one cytokine showed a sex-specific finding (p=0.004): monocyte chemoattractant protein, MCP-1, rose substantially in females (8.9% change per additional transfusion), but not males (−0.8% change). Higher concentrations of MCP-1 exclusively were associated with worse Bayley-III scores: decreased cognitive raw scores (p=0.0005) and motor scaled scores (p<0.0001). CONCLUSION: This study provides evidence of a sex-specific difference in the inflammatory response to RBC transfusions during neonatal life, with MCP-1 levels rising only in females and inversely correlating with neurocognitive status at 12 months old.