Compartmentalization of acute phase reactants Interleukin-6, C-Reactive Protein and Procalcitonin as biomarkers of intra-amniotic infection and chorioamnionitis

Abstract

Background The arsenal of maternal and amniotic fluid (AF) immune response to local or systemic infection includes among others the acute-phase reactants IL-6, C-reactive protein (CRP) and procalcitonin (PCT). If these molecules can be used as non-invasive biomarkers of intra-amniotic infection (IAI) in the subclinical phase of the disease remains incompletely known. Methods We used time-matched maternal serum, urine and AF from 100 pregnant women who had an amniocentesis to rule out IAI in the setting of preterm labor, PPROM or systemic inflammatory response (SIR: pyelonephritis, appendicitis, pneumonia) to infection. Cord blood was analyzed in a subgroup of cases. We used sensitive immunoassays to quantify the levels of inflammatory markers in the maternal blood, urine and AF compartment. Microbiological testing and placental pathology was used to establish infection and histological chorioamnionits. Results PCT was not a useful biomarker of IAI in any of the studied compartments. Maternal blood IL-6 and CRP levels were elevated in women with subclinical IAI. Compared to clinically manifest chorioamnionitis group, women with SIR have higher maternal blood IL-6 levels rendering some marginal diagnostic benefit for this condition. Urine was not a useful biological sample for assessment of IAI using either of these three inflammatory biomarkers. Conclusions In women with subclincal IAI, the large overlapping confidence intervals and different cut-offs for the maternal blood levels of IL-6, CRP and PCT likely make interpretation of their absolute values difficult for clinical decision-making.

Noninvasive Sampling of the Intrauterine Environment in Women with Preterm Labor and Intact Membranes

“…There are few references exploring the maternal blood compartment in women with available information on amniotic fluid and although some authors [45,46] have reported higher levels of some acute inflammatory biomarkers, such as IL-6 and C-reactive protein, in maternal blood, the observed inflammatory response was too weak to be taken into consideration in clinical practice. …”

Limiting the Exposure of Select Fetuses to Intrauterine Infection/Inflammation Improves Short-Term Neonatal Outcomes in Preterm Premature Rupture of Membranes

“…So far, the validation of Hp&HpRP as a biomarker of antenatal exposure to IAI has only been performed in CB available at birth, a time frame which is far too late for clinical decisions by physicians. A previous study by Dulay et al [28] showed that the compartmentalization process characteristic to human pregnancy is a significant obstacle to using levels of maternal blood or urine inflammatory cytokines to infer information on the same analytes in AF or CB (fetal) compartment. Although the study by Dulay et al [28] did not include the evaluation of Hp&HpRP as a biomarker, it is known that maternal blood Hp&HpRP expression or levels are clinically irrelevant in this context, since Hp is normally expressed in the adult at high levels [14,15] .…”

Prediction and Diagnosis of Preterm Delivery: Review

“…İnflamatuar belirteçlerin preterm doğumların öngörüsünde kullanılabileceği iddia edilmiştir. 134,135 Enfeksiyonun bir akut faz reaktanı olan CRP, hızlı artan ve yarılanma süresi kısa olan, hepatositlerden sentezlenen bir proteindir. İnflamasyon ve doku hasarını yansıtan CRP, non invaziv, çabuk sonuç alınan, ucuz ve kolay ulaşılabilir bir testtir.…”

“…Preterm eylem nedeni ile izlenen gebelerde CRP artışının, amniyotik sıvı enfeksiyonunu ve ilk hafta içinde preterm doğum riskini öngördüğü bildirilmiştir. [134][135][136] Salih ÇETİNKAYA ve ark.…”

“…134,139 İn-traamniyotik enfeksiyonun araştırılmasında, amniyotik sıvıdaki glukoz değerlerine bakılmış ve enfeksiyonu olanlarda anlamlı şekilde düşük dü-zeyler saptanmıştır. 139 Preterm eylem veya EMR olgularında servikovajinal pH yüksek bulunmuştur.…”