The fetal inflammatory response (FIR) increases the risk of preterm neonates to adverse neonatal outcomes, such as perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, < 28 weeks of gestation). One of the mechanisms contributing to such adverse neonatal outcomes is a postnatal intermittent or sustained systemic inflammation (ISSI) following FIR. This link between fetal and neonatal systemic inflammation is supported by the presence of well-established inflammatory biomarkers in umbilical cord (UC) and peripheral blood. However, the extent of molecular changes contributing to this association is unknown. Using RNA sequencing and mass spectrometry proteomics, we have profiled the transcriptome and proteome of archived dried blood spots (DBS) from 21 ELGANs. Comparing ELGANs who were exposed to FIR (n=10) against those that were not (n=11), we identified, respectively, 783 and 27 gene and protein expression changes, with a minimum 50%-fold change and an experiment-wide significance level below 5% false discovery rate. These expression changes confirm the persistent and robust activation of the innate immune system in FIR-affected ELGANs and provide new insights into the molecular mechanisms underlying sustained systemic inflammation and perinatal brain injury. Interestingly, 21 out of the 27 differentially expressed proteins did not match transcriptomic changes, thereby concealing clues on the link between FIR and ISSI that could not be uncovered by either transcriptomics or known biomarkers alone. These findings contribute to the understanding of the association between FIR and ISSI, provide DBS biomarkers of these two systemic inflammatory conditions and may help to identify future therapeutic targets for the associated perinatal disorders.