Longitudinal inflammatory biomarker profiling in intrauterine growth restricted preterm infants

OBJECTIVES: Intrauterine growth restriction (IUGR) places premature infants at an increased risk of multiple neonatal morbidities. Previous studies have found increased concentrations of pro-inflammatory biomarkers in IUGR infants at the time of birth and through the first postnatal month. This study aims to assess the longitudinal inflammatory profile of IUGR infants from birth to discharge from the neonatal intensive care unit. MATERIALS AND METHODS: A case-control study was performed with 24 IUGR infants and 24 appropriate for gestational age (AGA) infants born prematurely at or before 32 6/7 weeks' gestational age included. Residual clinical serum samples were collected and serum concentrations of IL-1β, sIL2Rα, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1α, and TNF-α were measured by multi-plex protein assay. Residual clinical whole blood samples were collected, peripheral mononuclear blood cells were isolated, and flow cytometry was performed to assess differences in populations of peripheral immune cells. RESULTS: There were significant differences in the birth weight and birth weight percentile between the IUGR and AGA groups, but no further demographic differences. The was significant elevation of IL-8, IL-10, and MCP-1 in the IUGR population at various timepoints during admission. There were no differences in overall cell populations between the two groups, however there were significantly increased activated classical monocytes and cytotoxic T cells in the IUGR group one month post-delivery. CONCLUSION: Intrauterine growth restriction contributes to a fetal and continued neonatal pro-inflammatory state, as evidenced by elevation in IL-8 and MCP-1. Though there are increased populations of activated classical monocytes and cytotoxic T cells in these infants, this pro-inflammatory state may also contribute to tissue-specific inflammation which contributes to worsened neonatal outcomes for premature IUGR infants.