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Preterm birth is associated with immune dysregulation which persists in infants exposed to histologic chorioamnionitis

By Gemma Sullivan, Paola Galdi, Nis Borbye-Lorenzen, David Q. Stoye, Gillian J Lamb, Margaret J Evans, Kristin Skogstrand, Siddharthan Chandran, James P. Boardman

Posted 30 Apr 2021
medRxiv DOI: 10.1101/2021.04.29.21256310

Abstract Objective. To characterise the umbilical cord blood immune profile in preterm infants compared to term-born controls and the postnatal immune response following exposure to histologic chorioamnionitis (HCA) in preterm infants. Design. Descriptive, observational cohort study. Setting. Edinburgh, UK. Population. 118 preterm infants (mean gestational age 29+0 weeks, range 23+2 to 32+0) and 59 term-born controls. Methods. Placental histopathology was used to identify reaction patterns indicative of HCA, and a customised immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group. Results. The umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 5 immune proteins on postnatal day 5 (BDNF, C3, IL-8, MIP-1{beta} and MMP-9) when compared to preterm infants who were not exposed. Conclusion. Preterm birth is associated with a distinct immune profile in umbilical cord blood and infants exposed to HCA experience specific alterations in immune function that persist to day 5 of postnatal life.

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