Acute-phase response- and inflammation-, but not extracellular matrix-related proteins in the amniotic fluid are associated with spontaneous preterm delivery in asymptomatic women with midtrimester short cervix

Abstract

Background: To determine whether (i) altered levels of acute-phase response (APR)-, inflammation-, and extracellular matrix (ECM)-related proteins in the amniotic fluid (AF) were associated with spontaneous preterm delivery (SPTD) in asymptomatic women with midtrimester short cervix (SCX) and (ii) if SPTD risk severity was related to the expression levels of inflammation-related proteins in the AF. Methods: This retrospective cohort study included 70 singleton pregnant women diagnosed with a SCX (<25 mm) at 17–25 weeks, who were subjected to amniocentesis to exclude intraamniotic inflammation (IAI; defined as AF interleukin [IL]-6 ≥ 2.6 ng/mL). APR (i.e., hepcidin, kallistatin, MBL, pentraxin-2, RBP4, and serpin A1), inflammatory (i.e., IL-6, IL-8, and resistin), and ECM-related (i.e., lumican, MMP-8, TGFBI, and uPA) molecules were assayed in the AF by ELISA. The primary outcome measure was SPTD at <34 weeks. The levels of each identified dysregulated inflammatory mediator were divided into quartiles to assess the correlation between their AF expression profiles and SPTD risk severity. Results: Multivariable Firth logistic regression analyses revealed that elevated AF levels of IL-6, IL-8, kallistatin, pentraxin-2, resistin, and serpin A1, and IAI presence were independently associated with SPTD at <34 weeks after adjusting for baseline covariates. The areas under the curves of the aforementioned mediators ranged from 0.67 to 0.79 for outcome prediction. The odds of SPTD at <34 weeks, even after adjusting for confounders, significantly increased with each increasing quartile of baseline AF levels of IL-6/8, pentraxin-2, and resistin. Conclusions: APR (kallistatin, pentraxin-2, and serpin A1)- and inflammation (IL-6/8 and resistin)-, but not ECM-related mediators in the AF are involved in SPTD development in asymptomatic women with a midtrimester SCX. In particular, SPTD risk (especially risk severity) is associated with the degree of the inflammatory response in the AF, as categorized by inflammatory protein expression profiles, as well as IAI presence.