Influence of Biological Sex and Congenital Iron Deficiency on Neonatal Cytokine Responses.

BACKGROUND/OBJECTIVES: Stimulated cord blood mononuclear cell (CBMC) cytokine responses were previously shown to predict the risk of childhood atopic disease. Iron deficiency (ID) at birth may also program atopic disease. Males are at a higher risk of pediatric atopic disease, but it is not known whether congenital ID impacts CBMC immune responses differentially by sex. METHODS: Cord blood (CB) samples were collected from healthy term or near-term neonates after elective cesarean deliveries. A transferrin saturation ≤ 25% defined congenital ID. CBMCs were stimulated with either phytohemagglutinin (PHA) or PHA plus an iron chelator. RESULTS: Of the 85 neonates, the 26 neonates with congenital ID exhibited lower plasma tumor necrosis factor-α (TNF-α), as well as higher CBMC TNF-α and IL-8 responses than iron-sufficient neonates (p = 0.017, p = 0.013, and p = 0.007, respectively). Higher CBMC TNF-α responses were seen in both males and females with congenital ID. However, females with congenital ID also had lower plasma IL-6, lower plasma TNF-α, and higher CBMC interleukin (IL)-8 responses. Additionally, iron chelation during culture influenced stimulated CBMC IFN-γ and CBMC TNF-α responses. DISCUSSION: Congenital ID may influence stimulated CBMC cytokine responses, but results point to a sex-specific regulation of immune balance at birth. Because males are more prone to infantile ID and more likely to develop early childhood asthma, future studies should further investigate how fetal sex and congenital iron status impacts childhood immune responsiveness to infections and antigenic stimulation from the rearing environment.