BACKGROUND: Preterm prelabor rupture of the membranes (PPROM) is frequently complicated by intraamniotic inflammatory processes such as intraamniotic infection and sterile intraamniotic inflammation. Antibiotic therapy is recommended to patients with PPROM to prolong the interval between this complication and delivery (latency period), reduce the risk of clinical chorioamnionitis, and improve neonatal outcome. However, there is a lack of information regarding whether the administration of antibiotics can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with PPROM. OBJECTIVE: The first aim of the study was to determine whether antimicrobial agents can reduce the magnitude of the intraamniotic inflammatory response in patients with PPROM by assessing the concentrations of interleukin-6 in amniotic fluid before and after antibiotic treatment. The second aim was to determine whether treatment with intravenous clarithromycin changes the microbial load of Ureaplasma spp DNA in amniotic fluid. STUDY DESIGN: A retrospective cohort study included patients who had (1) a singleton gestation, (2) PPROM between 24+0 and 33+6 weeks, (3) a transabdominal amniocentesis at the time of admission, and (4) intravenous antibiotic treatment (clarithromycin for patients with intraamniotic inflammation and benzylpenicillin/clindamycin in the cases of allergy in patients without intraamniotic inflammation) for 7 days. Follow-up amniocenteses (7th day after admission) were performed in the subset of patients with a latency period lasting longer than 7 days. Concentrations of interleukin-6 were measured in the samples of amniotic fluid with a bedside test, and the presence of microbial invasion of the amniotic cavity was assessed with culture and molecular microbiological methods. Intraamniotic inflammation was defined as a bedside interleukin-6 concentration ≥745 pg/mL in the samples of amniotic fluid. Intraamniotic infection was defined as the presence of both microbial invasion of the amniotic cavity and intraamniotic inflammation; sterile intraamniotic inflammation was defined as the presence of intraamniotic inflammation without microbial invasion of the amniotic cavity. RESULTS: A total of 270 patients with PPROM were included in this study: 207 patients delivered within 7 days and 63 patients delivered after 7 days of admission. Of the 63 patients who delivered after 7 days following the initial amniocentesis, 40 underwent a follow-up amniocentesis. Patients with intraamniotic infection (n = 7) and sterile intraamniotic inflammation (n = 7) were treated with intravenous clarithromycin. Patients without either microbial invasion of the amniotic cavity or intraamniotic inflammation (n = 26) were treated with benzylpenicillin or clindamycin. Treatment with clarithromycin decreased the interleukin-6 concentration in amniotic fluid at the follow-up amniocentesis compared to the initial amniocentesis in patients with intraamniotic infection (follow-up: median, 295 pg/mL, interquartile range [IQR], 72-673 vs initial: median, 2973 pg/mL, IQR, 1750-6296; P = .02) and in those with sterile intraamniotic inflammation (follow-up: median, 221 pg/mL, IQR 118-366 pg/mL vs initial: median, 1446 pg/mL, IQR, 1300-2941; P = .02). Samples of amniotic fluid with Ureaplasma spp DNA had a lower microbial load at the time of follow-up amniocentesis compared to the initial amniocentesis (follow-up: median, 1.8 × 104 copies DNA/mL, 2.9 × 104 to 6.7 × 108 vs initial: median, 4.7 × 107 copies DNA/mL, interquartile range, 2.9 × 103 to 3.6 × 107; P = .03). CONCLUSION: Intravenous therapy with clarithromycin was associated with a reduction in the intensity of the intraamniotic inflammatory response in patients with PPROM with either intraamniotic infection or sterile intraamniotic inflammation. Moreover, treatment with clarithromycin was related to a reduction in the load of Ureaplasma spp DNA in the amniotic fluid of patients with PPROM <34 weeks of gestation.

• Keywords
• 16S ribosomal RNA, Ureaplasma, amniocentesis, amniotic fluid, bacteria, benzylpenicillin, biomarker, chorioamnionitis, clarithromycin, funisitis, genital mycoplasmas, great obstetrical syndromes, inflammation, interleukin-6, intraamniotic infection, microbial invasion of the amniotic cavity, neonatal outcome, neonatal sepsis, nucleic acid, polymerase chain reaction, pregnancy, prematurity, preterm birth, rapid point of care test, sterile intraamniotic inflammation,
• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Bacterial Infections etiology   prevention & control   MeSH
• Chorioamnionitis etiology   prevention & control   MeSH
• DNA, Bacterial analysis   MeSH
• Adult MeSH
• Interleukin-6 analysis   MeSH
• Clarithromycin therapeutic use   MeSH
• Clindamycin therapeutic use   MeSH
• Cohort Studies MeSH
• Humans MeSH
• Penicillin G therapeutic use   MeSH
• Amniotic Fluid chemistry   MeSH
• Fetal Membranes, Premature Rupture * MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Ureaplasma genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• DNA, Bacterial MeSH
• IL6 protein, human MeSH Browser
• Interleukin-6 MeSH
• Clarithromycin MeSH
• Clindamycin MeSH
• Penicillin G MeSH

OBJECTIVE: To 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). METHODS: Two 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. RESULT: Women 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. CONCLUSION: The 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.

• MeSH
• Biomarkers MeSH
• C-Reactive Protein * MeSH
• Chorioamnionitis blood   diagnosis   microbiology   MeSH
• Adult MeSH
• Gestational Age MeSH
• Interleukin-6 metabolism   MeSH
• Pregnancy Complications MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Amniotic Fluid metabolism   microbiology   MeSH
• Fetal Membranes, Premature Rupture blood   diagnosis   etiology   MeSH
• ROC Curve MeSH
• Pregnancy MeSH
• Delivery, Obstetric methods   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• C-Reactive Protein * MeSH
• Interleukin-6 MeSH