Predictive Potential of Plasma Acute Phase‐ and Adhesion‐Related Proteins and Progranulin for Intra‐Amniotic Infection/Inflammation and Spontaneous Preterm Birth in Women With Preterm Labor

OBJECTIVE: To determine whether plasma acute phase-, adhesion-related, and multifunctional proteins, alone or in combination with ultrasound and traditional blood tests, can predict the microbial invasion of the amniotic cavity and/or intra-amniotic inflammation (MIAC/IAI) and spontaneous preterm birth (SPTB) in women with preterm labor (PTL). STUDY DESIGN: A retrospective cohort study was performed on 249 singleton pregnant women with PTL (at 23+0 to 34+0 weeks) who underwent transabdominal amniocentesis. Plasma samples were obtained at amniocentesis. MIAC/IAI was characterized by a positive amniotic fluid (AF) culture and/or an elevated interleukin (IL)-6 level (≥2.6 ng/mL) in the AF. Plasma levels of hepcidin, mannose-binding lectin (MBL), retinol-binding protein 4 (RBP4), serum amyloid A1 (SAA1), E-selectin, P-selectin, progranulin, transforming growth factor β1, and vitamin d-binding protein levels were measured using enzyme-linked immunosorbent assay. C-reactive protein levels, white blood cell (WBC) counts, neutrophil-to-lymphocyte ratio, and sonographic cervical lengths (CLs) were measured. RESULTS: After adjusting for baseline covariates, multivariable logistic regression analyses showed significant associations between (i) decreased RBP4 and E-selectin levels and elevated SAA1 levels in the plasma and MIAC/IAI; and (ii) decreased RBP4 and progranulin levels and elevated SAA1 levels in the plasma and SPTB ≤7 days of sampling. Using stepwise regression analyses, noninvasive prediction models for MIAC/IAI and SPTB ≤7 days were developed, comprising plasma RBP4, SAA1, MBL, and E-selectin levels; CL; and WBC counts, with area under the curve values of 0.86 and 0.89, respectively. CONCLUSIONS: SAA1, RBP4, E-selectin, and progranulin may represent valuable plasma biomarkers for predicting MIAC/IAI and imminent SPTB in women with PTL. Particularly, the combination of these plasma biomarkers with ultrasound and traditional inflammatory blood markers can significantly support the diagnosis of MIAC/IAI and imminent SPTB.