Genome-wide postnatal changes in immunity following fetal inflammatory response

Area of Science:

• Neonatal immunology
• Perinatal medicine
• Molecular biology

Background:

• Fetal inflammatory response (FIR) elevates the risk of perinatal brain injury in extremely low gestational age newborns (ELGANs).
• Postnatal intermittent or sustained systemic inflammation (ISSI) following FIR is a key mechanism contributing to this risk.
• While inflammatory biomarkers link prenatal and postnatal inflammation, the underlying molecular changes are not fully understood.

Purpose of the Study:

• To investigate the molecular alterations associated with fetal inflammatory response (FIR) in extremely low gestational age newborns (ELGANs).
• To identify gene and protein expression changes linking FIR to postnatal inflammation and brain injury.

Main Methods:

• RNA sequencing and mass spectrometry proteomics were used to profile transcriptome and proteome.
• Archived neonatal dried blood spot (DBS) specimens from 21 ELGANs were analyzed.
• Comparison between FIR-affected and unaffected ELGANs was performed.

Main Results:

• 782 gene and 27 protein expression changes (≥50% magnitude, <5% FDR) were identified between FIR-affected and unaffected ELGANs.
• Confirmed robust postnatal innate immune system activation in FIR-affected ELGANs.
• Revealed, for the first time, an impairment of adaptive immunity in FIR-affected ELGANs.

Conclusions:

• Identified molecular pathways provide insights into mechanisms triggering ISSI after FIR.
• Findings offer clues to the molecular basis of perinatal brain injury onset in ELGANs.
• The study highlights significant immune dysregulation following fetal inflammation in vulnerable newborns.