Sharon L. Hillier

The purpose of the study was to examine intercenter variability in the interpretation of Gram-stained vaginal smears from pregnant women. The intercenter reliability of individual morphotypes identified on the vaginal smear was evaluated by comparing them with those obtained at a standard center. A new scoring system that uses the most reliable morphotypes from the vaginal smear was proposed for diagnosing bacterial vaginosis. This scoring system was compared with the Spiegel criteria for diagnosing bacterial vaginosis. The scoring system (0 to 10) was described as a weighted combination of the following morphotypes: lactobacilli, Gardnerella vaginalis or bacteroides (small gram-variable rods or gram-negative rods), and curved gram-variable rods. By using the Spearman rank correlation to determine intercenter variability, gram-positive cocci had poor agreement (0.23); lactobacilli (0.65), G. vaginalis (0.69), and bacteroides (0.57) had moderate agreement; and small (0.74) and curved (0.85) gram-variable rods had good agreement. The reliability of the 0 to 10 scoring system was maximized by not using gram-positive cocci, combining G. vaginalis and bacteroides morphotypes, and weighting more heavily curved gram-variable rods. For comparison with the Spiegel criteria, a score of 7 or higher was considered indicative of bacterial vaginosis. The standardized score had improved intercenter reliability (r = 0.82) compared with the Spiegel criteria (r = 0.61). The standardized score also facilitates future research concerning bacterial vaginosis because it provides gradations of the disturbance of vaginal flora which may be associated with different levels of risk for pregnancy complications.

BACKGROUND: Bacterial vaginosis is believed to be a risk factor for preterm delivery. We undertook a study of the association between bacterial vaginosis and the preterm delivery of infants with low birth weight after accounting for other known risk factors. METHODS: In this cohort study, we enrolled 10,397 pregnant women from seven medical centers who had no known medical risk factors for preterm delivery. At 23 to 26 weeks' gestation, bacterial vaginosis was determined to be present or absent on the basis of the vaginal pH and the results of Gram's staining. The principal outcome variable was the delivery at less than 37 weeks' gestation of an infant with a birth weight below 2500 g. RESULTS: Bacterial vaginosis was detected in 16 percent of the 10,397 women. The women with bacterial vaginosis were more likely to be unmarried, to be black, to have low incomes, and to have previously delivered low-birth-weight infants. In a multivariate analysis, the presence of bacterial vaginosis was related to preterm delivery of a low-birth-weight infant (odds ratio, 1.4; 95 percent confidence interval, 1.1 to 1.8). Other risk factors that were significantly associated with such a delivery in this population were the previous delivery of a low-birth-weight infant (odds ratio, 6.2; 95 percent confidence interval, 4.6 to 8.4), the loss of an earlier pregnancy (odds ratio, 1.7; 1.3 to 2.2), primigravidity (odds ratio, 1.6; 1.1 to 1.9), smoking (odds ratio, 1.4; 1.1 to 1.7); and black race (odds ratio, 1.4; 1.1 to 1.7). Among women with bacterial vaginosis, the highest risk of preterm delivery of a low-birth-weight infant was found among those with both vaginal bacteroides and Mycoplasma hominis (odds ratio, 2.1; 95 percent confidence interval, 1.5 to 3.0). CONCLUSIONS: Bacterial vaginosis was associated with the preterm delivery of low-birth-weight infants independently of other recognized risk factors.

BACKGROUND: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS: Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).

To study the role of infection in prematurity, we studied the demographic and obstetrical characteristics, chorioamnionic cultures, and placental histologic features of women who delivered prematurely and compared these findings with those in women who delivered at term. Microorganisms were isolated from the area between the chorion and the amnion (chorioamnion) in 23 of 38 placentas (61 percent) from women with preterm labor who delivered before 37 weeks' gestation and in 12 (21 percent) of 56 placentas from women without preterm labor who delivered at term (odds ratio, 5.6; 95 percent confidence interval, 2.1 to 15.6). The most frequent isolates from the placentas of those whose infants were delivered prematurely were Ureaplasma urealyticum (47 percent) and Gardnerella vaginalis (26 percent). The recovery of any organism from the chorioamnion was strongly associated with histologic chorioamnionitis (odds ratio, 7.2; 95 percent confidence interval, 2.7 to 19.5) and with bacterial vaginosis (odds ratio, 3.2; 95 percent confidence interval, 1.1 to 6.6). When multiple logistic regression was used to control for demographic and obstetrical variables, premature delivery was still related to the recovery of organisms from the chorioamnion (odds ratio, 3.8; 95 percent confidence interval, 1.5 to 9.9) and with chorioamnionitis (odds ratio, 5.0; 95 percent confidence interval, 1.6 to 15.3). The proportion of placentas with evidence of infection was highest among those who delivered at the lowest gestational age. We conclude that infection of the chorioamnion is strongly related to histologic chorioamnionitis and may be a cause of premature birth.