Maternal serum C-reactive protein concentration and intra-amniotic inflammation in women with preterm prelabor rupture of membranes

Abstract

ObjectiveTo evaluate maternal serum C-reactive protein (CRP) concentrations in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) in relation to the presence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).MethodsTwo hundred and eighty-seven women with singleton pregnancies complicated by PPROM between 2014 and 2016 were included in this study. Maternal blood and amniotic fluid samples were collected at the time of admission. Maternal serum CRP concentration was measured using a high-sensitivity immunoturbidimetric assay. Interleukin-6 (IL-6) concentration was measured using a point-of-care test. MIAC was diagnosed based on a positive polymerase chain reaction result for Ureaplasma species, Mycoplasma hominis, and/or Chlamydia trachomatis and for the 16S rRNA gene. IAI was characterized by an amniotic fluid IL-6 concentration of ≥ 745 pg/mL.ResultWomen with MIAC and IAI had higher maternal serum CRP concentrations than did women without (with MIAC: median 6.9 mg/L vs. without MIAC: median 4.9 mg/L; p = 0.02; with IAI: median 8.6 mg/L vs. without IAI: median 4.7 mg/L; p < 0.0001). When women were split into four subgroups based on the presence of MIAC and/or IAI, women with the presence of both MIAC and IAI had higher maternal serum CRP than did women with IAI alone, with MIAC alone, and women without MIAC and IAI (both MIAC and IAI: median: 13.1 mg/L; IAI alone: 6.0 mg/L; MIAC alone: 3.9 mg/L; and without MIAC and IAI: median 4.8 mg/L; p < 0.0001). The maternal serum CRP cutoff value of 17.5 mg/L was the best level to identify the presence of both MIAC and IAI, with sensitivity of 47%, specificity of 96%, positive predictive value of 42%, negative predictive value of 96%, and the positive likelihood ratio of 10.9.ConclusionThe presence of both MIAC and IAI was associated with the highest maternal serum CRP concentrations. Maternal serum CRP concentration in women with PPROM at the time of admission can rule out the presence of the combined condition of both MIAC and IAI, therefore, it may serve as a non-invasive screening tool to distinguish between women with PPROM who are at high or at low risk for the presence of both MIAC and IAI.

Evaluation of the role of CRP as an early predictor of chorioamnionitis in PPROM

“…Our results from this study is supported by relatively large cohort of women with PPROM that the presence of CAM is associated with higher maternal serum CRP concentrations. 5 The control group shows CRP < 6 mg/L in all cases. On comparing C-reactive protein levels with other laboratory tests and indicators of infection (e.g.…”

“…4 Since expectant management of PPROM less than 34 weeks of gestational age is broadly recommended, the placental results cannot be correlated with amniotic fluid results due to the long latency between sampling and delivery. 5 Early infection is not reliably predicted by commonly used laboratory variables such as erythrocyte sedimentation rate, white blood cell count, neutrophil count or vaginal bacterial culture. Clinical signs such as fever and fetomaternal tachycardia usually appear late.…”

Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

“…Additionally, the highest levels of cell‐free nDNA were detected in women with PPROM, where the presence of bacteria in the amniotic fluid led to the development of IAI (microbial‐associated IAI). This specific subgroup of PPROM is known to be associated with the highest maternal, intra‐amniotic, and fetal inflammatory response . We hypothesized that intra‐amniotic inflammation driven by the amniotic fluid bacteria induces necrosis and apoptosis of fetal membranes and the placenta, followed by more intense cell‐free nDNA release from these tissues .…”

“…This specific subgroup of PPROM is known to be associated with the highest maternal, intra-amniotic, and fetal inflammatory response. 4,42,43 We hypothesized that intraamniotic inflammation driven by the amniotic fluid bacteria induces An association between cell-free nDNA and IL-6 levels in systemic circulation was previously identified when serious inflammatory conditions were present. 47,48 Interestingly, such a relationship between cell-free nDNA and IL-6 levels in the blood are revealed in women with labor at the time of delivery.…”

Microbial burden and inflammasome activation in amniotic fluid of patients with preterm prelabor rupture of membranes

“…There are several microorganisms associated with intra-amniotic infection that are difficult to culture in a clinical laboratory setting, namely mycoplasmas (e.g. Ureaplasma urealyticum) [23,32,66,79,143,[182][183][184], Sneathia spp. [23,32,66,152,184], Neisseria spp.…”