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Longitudinal inflammatory biomarker profiling in intrauterine growth restricted preterm infants
Laura E Lorenger1, Timothy J Boly2, Rachael M Hyland3
1Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA; Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Insights
Intrauterine growth restriction (IUGR) in premature infants leads to a sustained pro-inflammatory state, indicated by elevated IL-8 and MCP-1. This inflammation, along with increased immune cells, may worsen outcomes for these vulnerable newborns.
Area of Science:
- Neonatal immunology
- Inflammatory biomarkers
- Premature infant health
Background:
- Intrauterine growth restriction (IUGR) is linked to increased neonatal morbidities.
- Previous studies show elevated pro-inflammatory biomarkers in IUGR infants post-birth.
- The longitudinal inflammatory profile in IUGR infants requires further investigation.
Purpose of the Study:
- To assess the longitudinal inflammatory profile of premature infants with IUGR.
- To compare inflammatory markers and immune cell populations between IUGR and appropriate for gestational age (AGA) infants.
- To understand the inflammatory state from birth to neonatal intensive care unit discharge.
Main Methods:
- A case-control study involving 24 IUGR and 24 AGA premature infants (≤32 6/7 weeks gestational age).
- Serum samples analyzed for cytokines (IL-1β, sIL2Rα, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1α, TNF-α) using multiplex assay.
- Peripheral blood mononuclear cells analyzed by flow cytometry to assess immune cell populations.
Main Results:
- Significant differences in birth weight and percentile between IUGR and AGA groups.
- Elevated IL-8, IL-10, and MCP-1 observed in IUGR infants during admission.
- Increased activated classical monocytes and cytotoxic T cells in IUGR infants one month post-delivery, despite no overall population differences.
Conclusions:
- IUGR contributes to a persistent fetal and neonatal pro-inflammatory state, evidenced by elevated IL-8 and MCP-1.
- Increased activated monocytes and cytotoxic T cells in IUGR infants suggest a role in tissue-specific inflammation.
- This pro-inflammatory state may exacerbate neonatal outcomes in premature IUGR 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.
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