Characterization of Inflammation/Immune‐, Acute Phase‐, Extracellular Matrix‐, Adhesion‐, and Serine Protease‐Related Proteins in the Amniotic Fluid of Women With Early Preterm Prelabor Rupture of Membranes

Abstract

ProblemTo determine whether altered concentrations of various inflammation/immune‐, acute phase‐, extracellular matrix‐, adhesion‐, and serine protease‐related proteins in the amniotic fluid (AF) are independently associated with microbial invasion of the amniotic cavity and/or intra‐amniotic inflammation (MIAC/IAI), imminent spontaneous preterm delivery (SPTD; ≤7 days), and major neonatal morbidity/mortality (NMM) in women with early preterm prelabor rupture of membranes (PPROM).Method of StudyThis was a retrospective cohort study involving 111 singleton pregnant women with PPROM (24–31 weeks) undergoing amniocentesis to diagnose MIAC/IAI. The following proteins were measured in stored AF samples by enzyme‐linked immunosorbent assay (ELISA): APRIL, DKK‐3, Gal‐3BP, IGFBP‐2, IL‐8, VDBP, lumican, MMP‐2, MMP‐8, SPARC, TGFBI, TGF‐β1, E‐selectin, ICAM‐5, P‐selectin, haptoglobin, hepcidin, SAA1, kallistatin, and uPA.ResultsMultivariate logistic regression analyses revealed that (i) elevated APRIL, IL‐8, MMP‐8, and TGFBI levels in the AF, reduced lumican and SPARC levels in the AF, and high percentages of samples above the lower limit of quantification for AF TGF‐β1 and uPA were significantly associated with MIAC/IAI; (ii) elevated AF levels of IL‐8 and MMP‐8 were significantly associated with SPTD within 7 days; and (iii) elevated AF IL‐6 levels were significantly associated with increased risk for major NMM, when adjusted for baseline covariates.ConclusionECM (lumican, SPRAC, TGFBI, and TGF‐β1)‐ and serine protease (uPA)‐associated proteins in the AF are involved in the regulation of the host response to infection/inflammation in the amniotic cavity, whereas AF inflammation (IL‐8, MMP‐8, and IL‐6)‐associated mediators are implicated in the development of preterm parturition and major NMM in early PPROM.