Correlation of Syndecan-1 levels with adjunct hematological markers of sepsis in preterm newborns with and without exposure to maternal chorioamnionitis

Objectives To investigate the association between Syndecan-1 (S1) serum levels with admission complete blood count (CBC) and differential, in preterm newborns (PN) exposed to chorioamnionitis (CA), with and without funisitis. Methods A cohort of PN born (< 33 weeks gestational age) admitted to the Loyola University Medical Center NICU (2015–2020) was recruited. Within 48 hours of birth, placentas were sent for pathologic analysis, and blood was drawn and stored. Serum S1 levels were quantified by ELISA. The CBC with differential, including neutrophil indices (immature-to-total neutrophil ratio and left shift) and neutropenia (absolute neutrophil count < 1.5 × 10⁹/L), was obtained within 12 hours of admission. Placentas were classified as having (1) no CA, (2) CA without umbilical cord involvement, or (3) CA with extension to the umbilical cord, known as funisitis. S1 levels, left shift, and neutropenia were compared between PN with exposure to CA vs. PN exposure to CA with funisitis vs. without exposure to CA. Results Among 56 PN, 27 (48%) had exposure to CA. Mean S1 was significantly higher in CA-exposed vs. unexposed PN (255.9 ± 129.2 ng/mL vs. 164.8 ± 77.7; p = 0.003). S1 levels rose stepwise from CA only (221.0 ± 86.0) to CA + funisitis (288.3 ± 155.6 ng/mL). A left shift was present in 12/27 CA-exposed preterm neonates (44%) and in 0/29 unexposed neonates (Fisher’s exact p  < 0.001; approximate OR for CA-exposed vs unexposed 48, 95% CI 2.6–859, using a continuity correction). Neutropenia occurred in 12/29 unexposed (41%) versus 5/27 CA-exposed (19%) neonates (OR 0.32, 95% CI 0.10–1.09, p  = 0.084). Among CA-exposed infants, left shift was more frequent in those with funisitis (9/14, 64%) than in those with CA only (3/13, 23%; OR 6.0, 95% CI 1.11–32.6, Fisher’s exact p  = 0.054), indicating a strong trend toward an augmented hematologic response in the presence of a fetal inflammatory component. Conclusions S1 is elevated in PN exposed to CA, especially when funisitis is present, and correlates with left shift on admission. Combined assessment of endothelial (S1) and hematologic immature-to-total neutrophil (I/T ratio) markers may enhance diagnostic precision for fetal inflammatory response syndrome (FIRS) and early-onset neonatal sepsis (EONS), supporting more targeted neonatal management. These findings indicate that endothelial glycocalyx degradation parallels hematopoietic activation during the fetal inflammatory response. Elevated S1 in CA-exposed PN, particularly those with funisitis, may reflect endothelial injury secondary to systemic inflammation. The strong association between left shift and increased S1 levels suggests that concurrent evaluation of admission CBC indices and S1 could improve early identification of intraamniotic infection and guide antibiotic stewardship. Accordingly, the presence of a left shift on admission in a PN could potentially guide both the maternal and neonatal diagnosis and management of intraamniotic infections and EONS.