Acute-Phase Proteins and Resistin in the Cervicovaginal Fluid of Women With Preterm Premature Rupture of Membranes

Problem

To determine whether altered cervicovaginal fluid (CVF) levels of acute-phase proteins (APPs) and resistin, alone or in combination with conventional clinical and blood-based markers, could predict microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) and acute histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM).

Methods of study

Women with singleton pregnancies with PPROM at 20 + 0–34 + 0 weeks (n = 82) were retrospectively evaluated. Amniotic fluid (AF) obtained via amniocentesis was cultured to diagnose MIAC, and interleukin-6 levels (≥ 2.6 ng/mL) were used to diagnose IAI. Haptoglobin, MBL, pentraxin-2, RBP4, serpin A1, and resistin levels in CVF samples, collected during amniocentesis, were determined by ELISA. Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein levels were measured.

Results

The prevalence of MIAC and/or IAI and acute HCA was 53.6% (44/82) and 49.3% (38/77), respectively. Multivariate logistic regression analyses revealed that (i) elevated CVF haptoglobin (adjusted odds ratio [aOR], 5.857; 95% confidence interval [CI], 1.263–27.173), pentraxin-2 (aOR, 1.024; 95% CI, 1.005–1.043), and resistin (aOR, 1.009; 95% CI, 1.003–1.015) levels were independently associated with MIAC/IAI, and (ii) elevated CVF resistin levels (aOR, 1.009; 95% CI, 1.003–1.015) were independently associated with acute HCA after adjusting for baseline covariates. Using stepwise regression analysis, a noninvasive prediction model comprising CVF, resistin, and pentraxin-2 levels, NLR, and gestational age at sampling was developed, which provided a good prediction of MIAC/IAI (area under the curve [AUC], 0.87; 95% CI, 0.78–0.95), with greater predictive potential than any single covariate included in the model (resistin: AUC, 0.72; 95% CI, 0.60-0.83; pentraxin-2: AUC, 0.64; 95% CI, 0.52-0.76; NLR: AUC, 0.74; 95% CI, 0.62-0.85; gestational age: AUC, 0.71; 95% CI, 0.60–0.82) (p < 0.05 for each).

Conclusions

Haptoglobin, pentraxin-2, and resistin levels in the CVF may be valuable to evaluate the risk of MIAC, IAI, and acute HCA in women with PPROM. In particular, the combination of these acute-phase and inflammatory CVF biomarkers with conventional clinical and blood-based markers can significantly support MIAC/IAI diagnosis.