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.

Department of Obstetrics and Gynecology Institute of Clinical Science Sahlgrenska Academy Gothenburg University Gothenburg Sweden; Department of Obstetrics and Gynecology Region Västra Götaland Sahlgrenska University Hospital Gothenburg Sweden; Department of Genetics and Bioinformatics Domain of Health Data and Digitalisation Institute of Public Health Oslo Norway

Department of Obstetrics and Gynecology University Hospital Hradec Kralove Charles University Faculty of Medicine Hradec Kralove Czech Republic

Department of Pediatrics University Hospital Hradec Kralove Charles University Faculty of Medicine in Hradec Kralove Hradec Kralove Czech Republic

Fingerland's Department of Pathology University Hospital Hradec Kralove Charles University Faculty of Medicine in Hradec Kralove Hradec Kralove Czech Republic

Institute of Clinical Biochemistry and Diagnosis University Hospital Hradec Kralove Charles University Faculty of Medicine in Hradec Kralove Hradec Kralove Czech Republic

Institute of Clinical Microbiology University Hospital Hradec Kralove Charles University Faculty of Medicine in Hradec Kralove Hradec Kralove Czech Republic

Perinatology Research Branch Division of Obstetrics and Maternal Fetal Medicine Division of Intramural Research Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health US Department of Health and Human Services Bethesda MD and Detroit MI; Department of Obstetrics and Gynecology University of Michigan Ann Arbor MI; Department of Epidemiology and Biostatistics Michigan State University East Lansing MI; Center for Molecular Medicine and Genetics Wayne State University Detroit Michigan; Detroit Medical Center Detroit MI; Department of Obstetrics and Gynecology Florida International University Miami FL

Perinatology Research Branch Division of Obstetrics and Maternal Fetal Medicine Division of Intramural Research Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health US Department of Health and Human Services Bethesda MD and Detroit MI; Department of Obstetrics and Gynecology Wayne State University School of Medicine Detroit MI

Perinatology Research Branch Division of Obstetrics and Maternal Fetal Medicine Division of Intramural Research Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health US Department of Health and Human Services Bethesda MD and Detroit MI; Department of Obstetrics and Gynecology Wayne State University School of Medicine Detroit MI; Biomedical Research Center University Hospital Hradec Kralove Hradec Kralove Czech Republic; Department of Obstetrics and Gynecology University Hospital Hradec Kralove Charles University Faculty of Medicine Hradec Kralove Czech Republic

Perinatology Research Branch Division of Obstetrics and Maternal Fetal Medicine Division of Intramural Research Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health US Department of Health and Human Services Bethesda MD and Detroit MI; Department of Obstetrics and Gynecology Wayne State University School of Medicine Detroit MI; Department of Obstetrics and Gynecology University Hospital Hradec Kralove Charles University Faculty of Medicine Hradec Kralove Czech Republic

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Angiogenic imbalance in pregnancies with preterm prelabor rupture of membranes between 34 and 37 weeks of gestation

Development of a Rat Model of Intra-Amniotic Inflammation via Ultrasound-Guided Administration of a Triggering Agent in the Gestational Sac to Enable Analysis of Individual Amniotic Fluid Samples

Prevalence and Load of Cervical Ureaplasma Species With Respect to Intra-amniotic Complications in Women With Preterm Prelabor Rupture of Membranes Before 34 weeks

Clinical characteristics of colonization of the amniotic cavity in women with preterm prelabor rupture of membranes, a retrospective study