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Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Infection/inflammation is responsible for a significant percentage of preterm birth, particularly at early gestations. A recent clinical recommendation by a guidelines group of the Danish Society of Obstetrics and Gynecology advised against the use of clindamycin for the treatment of bacterial vaginosis in pregnancy to reduce the risk of spontaneous preterm birth based on lack of evidence of efficacy. We believe that the evidence for the use of clindamycin for this indication is robust and that this recommendation was reached erroneously on the basis of flawed inclusion criteria: the inclusion of an unpublished study with poorly diagnosed bacterial vaginosis and the exclusion of an important pivotal study on the use of clindamycin in early pregnancy for the prevention of preterm birth. Had these errors been corrected, the conclusions would have been different., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Preterm birth is the major cause of perinatal mortality and morbidity in high-income countries. The etiology of preterm birth is multifactorial but there is overwhelming evidence to implicate infection as a major cause. Abnormal genital tract flora in early pregnancy is predictive of preterm birth so it is logical to consider the use of antibiotics for the prevention of preterm birth., Areas Covered: Infection and antibiotics in the etiology, prediction and prevention of preterm birth., Expert Opinion: Antibiotics for the prevention of preterm birth have addressed different risk groups, diagnostic methods, degrees of abnormal flora, antibiotic dose regimens, routes of administration, host susceptibilities, host response, gestational age at time of treatment, outcome parameters and definitions of success and outcomes. To address this confusion, a number of systematic reviews/meta-analyses have been conducted but none has simultaneously addressed the optimal choice of agent, patient and timing of intervention. We conclude that inappropriate antibiotics used in inappropriate women at inappropriately late gestations do not reduce preterm birth. Conversely, a focused systematic review/meta-analysis, which targeted the use of clindamycin before 22 weeks gestation, in women with objective evidence of abnormal genital tract flora, demonstrated that clindamycin produced a significant decrease in late miscarriage and preterm birth.

The purpose of this study was to determine whether the administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation reduces the risk of preterm birth and late miscarriage. We conducted a systematic review and metaanalysis of randomized controlled trials of the early administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation. Five trials that comprised 2346 women were included. Clindamycin that was administered at <22 weeks of gestation was associated with a significantly reduced risk of preterm birth at <37 weeks of gestation and late miscarriage. There were no overall differences in the risk of preterm birth at <33 weeks of gestation, low birthweight, very low birthweight, admission to neonatal intensive care unit, stillbirth, peripartum infection, and adverse effects. Clindamycin in early pregnancy in women with abnormal vaginal flora reduces the risk of spontaneous preterm birth at <37 weeks of gestation and late miscarriage. There is evidence to justify further randomized controlled trials of clindamycin for the prevention of preterm birth. However, a deeper understanding of the vaginal microbiome, mucosal immunity, and the biology of BV will be needed to inform the design of such trials., (Published by Mosby, Inc.)

Objective: To assess the ability of clindamycin vaginal cream to reduce the incidence of preterm birth in women with abnormal genital tract flora in the second trimester of pregnancy., Methods: This was a randomized, double-blind, placebo-controlled, tricenter study. A total of 409 women with abnormal genital tract flora on Gram stain of vaginal secretions at 13-20 weeks' gestation were randomized to receive a 3-day course of clindamycin vaginal cream or placebo. Those women who still had abnormal vaginal flora 3 weeks later received a 7-day course of the original study drug (ie, either clindamycin vaginal cream or placebo as per original randomization). The primary outcome measure was the incidence of preterm birth., Results: There was a statistically significant reduction in the incidence of preterm birth in the clindamycin vaginal cream group (4%) compared with placebo (10%) (P <.03). Significantly more babies born preterm (63%) required admission to the neonatal intensive care unit compared with term infants (4%) (P <.001)., Conclusion: A 2% clindamycin vaginal cream, when compared with placebo administered to women with abnormal genital tract flora before 20 weeks' gestation, can reduce the incidence of preterm birth by 60% and hence the need for neonatal intensive care.

Objective: To assess the efficacy of 2% clindamycin vaginal cream (CVC) to treat bacterial vaginosis (BV) in pregnancy., Methods: A prospective, randomized, double-blind, placebo-controlled, tricenter study. Four hundred and four women with BV on Gram stain at their first antenatal clinic visit were randomized to receive a 3-day course of 2% CVC or placebo. The outcome was assessed using an intention to treat analysis at 3 weeks and 6 weeks post-treatment according to three different diagnostic methods based on five criteria (Gram stain and all four elements of clinical composite criteria: vaginal discharge, abnormal vaginal pH, clue cells, amine odor), three criteria (vaginal pH, clue cells, amine odor) or two criteria (clue cells and amine odor) to reflect stringency of diagnosis, historical precedence and government agency recommendations respectively., Results: Using five diagnostic criteria, 18% of CVC patients were cured and 70.8% either cured and/or improved compared to 1.6% and 12% of placebo patients respectively (p < 0.0001). Using three diagnostic criteria, 44.8% of CVC patients were cured and 77.3% were either cured and/or improved compared to 9.3% and 28.8% of placebo patients respectively (p < 0.000 1). Using two diagnostic criteria, 75.0% of CVC patients were cured compared to 18.0% of placebo patients (p < 0.0001 ). Recurrence rates in those CVC patients successfully treated were approximately 6% at 6 weeks post baseline and 10% at 28 to 34 weeks gestation., Conclusions: A 3-day course of CVC appears to be well tolerated by the mother and statistically significantly more efficacious than placebo in the treatment of BV during the second trimester of pregnancy.

Background: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. Objectives: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time‐to‐delivery. Data Sources: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013–September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). Study Selection and Data Extraction: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one‐step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2. Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random‐donor hot‐deck" imputation, using IPD studies as donors. Results: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2 = 62%, and 0.59 (95% CI 0.42, 0.82), I2 = 0 before; and 0.95 (95% CI 0.81, 1.11), I2 = 59%, and 0.90 (95% CI: 0.72, 1.12), I2 = 0, after imputation. Time‐to‐delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. Conclusions: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation. [ABSTRACT FROM AUTHOR]

Spontaneous preterm labor leading to preterm birth is a major cause of perinatal mortality and morbidity worldwide. The etiology of spontaneous preterm labor is multifactoral but there is overwhelming evidence to implicate infection in up to 40% of cases. Historically, this infective link has focused on the associations between abnormal genital tract flora in pregnancy (diagnosed by the presence of bacterial vaginosis) and preterm birth. Recently, another condition related to abnormal flora (periodontal disease) has been linked with preterm birth. There are microbiological similarities between the oral cavity and the female genital tract giving rise to a possible common pathophysiology. This review records the interrelationship between periodontal disease, bacterial vaginosis, and preterm birth. We postulate on the mechanism linking the three conditions, particularly through microbiology and gene-environmental interactions. Periodontal disease and bacterial vaginosis may be risk factors in their own rights or may be interrelated. We speculate on whether periodontitisis a marker for an immune hyperresponse to abnormal flora which in the oral cavity results in periodontitis and in the case of bacterial vaginosis might result in preterm birth. We also postulate on the riskof preterm birth by periodontitis alone, bacterial vaginosis alone, or both. [ABSTRACT FROM AUTHOR]