Basic vaginal pH, bacterial vaginosis and aerobic vaginitis: prevalence in early pregnancy and risk of spontaneous preterm delivery, a prospective study in a low socioeconomic and multiethnic South American population.

BACKGROUND: Bacterial vaginosis (BV) increases the risk of spontaneous preterm deliveries (PD) in developed countries. Its prevalence varies with ethnicity, socioeconomic conditions and gestational age. Aerobic vaginitis (AV) has also been implicated with spontaneous PD. The present study aimed to estimate the prevalence of asymptomatic BV, the accuracy of vaginal pH level to predict BV and to estimate the risk of spontaneous PD <34 and <37 weeks' gestation of BV and AV. METHODS: Women attending prenatal public services in Rio de Janeiro were screened to select asymptomatic pregnant women, < 20 weeks' gestation, with no indication for elective PD and without risk factors of spontaneous PD. Vaginal smears of women with vaginal pH > = 4.5 were collected to determine the Nugent score; a sample of those smears was also classified according to a modified Donders' score. Primary outcomes were spontaneous PD < 34 and <37 weeks' gestation and abortion. RESULTS: Prevalence of asymptomatic BV was estimated in 28.1% (n = 1699); 42.4% of the smears were collected before 14 weeks' gestation. After an 8-week follow up, nearly 40% of the initially BV positive women became BV negative. The prevalence of BV among white and black women was 28.1% (95% CI: 24.6%-32.0%) and 32.5% (95% CI: 28.2%-37.2%), respectively. The sensitivity of vaginal pH= > 4.5 and = > 5.0 to predict BV status was 100% and 82%, correspondingly; the 5.0 cutoff value doubled the specificity, from 41% to 84%. The incidence of < 37 weeks' spontaneous PDs among BV pregnant women with a pH= > 4.5 was 3.8%. The RR of spontaneous PD < 34 and <37 weeks among BV women with pH > =4.5, as compared with those with intermediate state, were 1.24 and 1.86, respectively (Fisher's exact test, p value = 1; 0.52, respectively, both ns). No spontaneous case of PD or abortion was associated with severe or moderate AV. CONCLUSIONS: A high prevalence of asymptomatic BV was observed without statistically significant difference between black and white women. The RRs of spontaneous PD < 34 and <37 weeks among women with BV, as compared with those with intermediate state were not statistically significant but were consistent with those found in the literature.

A randomised controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with bacterial vaginosis: preliminary results.

BACKGROUND: Bacterial vaginosis increases the risk of spontaneous preterm delivery at less than 34 weeks of gestation. OBJECTIVE: The purpose of this study was to evaluate the efficacy of the early administration of selected lactobacilli strains (probiotics) to pregnant women with asymptomatic bacterial vaginosis/intermediate-degree infections to prevent spontaneous premature delivery and associated neonatal morbidity. METHODS/DESIGN: Asymptomatic pregnant women at less than 20 weeks of gestation, with no indication of elective preterm delivery, with a vaginal pH ≥ 4.5 and Nugent score > 3 were randomly assigned to the placebo or intervention group (oral administration of selected lactobacilli up to the 24th to 26th week of gestation). The randomisation was stratified for the history of premature delivery (HPD) and blocked. The allocation was concealed, and the participating health professionals and patients were blinded. The primary outcome was preterm delivery (<34 to <32 weeks), and the secondary outcomes were associated neonatal complications. RESULTS: In total, 4,204 pregnant women were screened; 320 and 324 individuals were respectively randomly assigned to the placebo and intervention groups, and 62% finished the trial. None of the randomised patients were lost to follow-up. For the non-HPD stratum, the intent-to-treat relative risks of spontaneous premature birth at < 34 and < 37 weeks' gestation were 0.33 (0.03, 3.16) and 0.49 (0.17, 1.44), respectively, and they were non-significant (ns) with p = 0.31 and 0.14. The corresponding actual treatment figures were zero and 0.32 (0.09, 1.19), which were ns with p = 0.12 and 0.06. The intent-to-treat relative risk of spontaneous premature birth at < 37 weeks of gestation for the trial as a whole, including HPD and non-HPD participants, was 0.69 (0.26, 1.78), p = 0.30 (ns). The neonatal complications under evaluation occurred in only one infant (< 34 weeks; placebo group) who presented with respiratory distress syndrome and suspected early neonatal sepsis. The recorded adverse events were minor and relatively non-specific. CONCLUSIONS: The efficacy of the tested probiotics to prevent preterm delivery among women without a history of preterm delivery was not determined because the study sample was insufficient to estimate statistically significant intent-to-treat effects; additional studies are needed to evaluate this intervention among these women. TRIAL REGISTRATION: Trial registration at NIH register: NCT00303082. Sources of funding: the Brazilian Health Ministry and the State of Rio de Janeiro Research Foundation.

Randomized controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with intrauterine infection: study protocol.

BACKGROUND: Spontaneous preterm deliveries that occur before the 34th week of gestation, and particularly before the 32nd week of gestation, have been strongly associated to intrauterine infection, ascending from vagina, and represent the largest portion of neonatal deaths and neurological problems. Bacterial vaginosis, characterized by a diminished or absent flora of lactobacilli and increased colonization of several anaerobic or facultative microorganisms, increases two times the risk of preterm delivery before the 34th week. Trials of antibiotics failed to show efficacy and effectiveness against spontaneous preterm birth related to bacterial vaginosis. Some studies indicate benefit from selected probiotics to treat genitourinary infections, including bacterial vaginosis. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of the early administration of selected probiotics to pregnant women with asymptomatic bacterial vaginosis/intermediate degree infection to reduce the occurrence of spontaneous preterm delivery and related neonatal mortality and morbidity. METHODS/DESIGN: Women attending public prenatal care services in Rio de Janeiro will be screened to select asymptomatic pregnant women, less than 20 weeks' gestation, with no indication of elective preterm delivery. Those with vaginal pH > = 4.5 and a Nugent score between 4 and 10 (intermediate degree infection or bacterial vaginosis) will be randomized to either the placebo or the intervention group, after written informed consent. Intervention consists in the use of probiotics, Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, 2 capsules a day, each capsule containing more than one million bacilli of each strain, for 6-12 weeks, up to the 24th-25th wk of gestation. Ancillary analyses include quantification of selected cervicovaginal cytokines and genotyping of selected polymorphisms. The randomization process is stratified for history of preterm delivery and blocked. Allocation concealment was designed as well as blinding of women, caregivers and outcome evaluators. The study will be supervised by an independent monitoring committee. Outcomes under study are preterm delivery (< 34- < 32 weeks of gestation) and associated neonatal complications: early neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, and prematurity-related retinopathy; definitions were adapted from those recommended by the 2002 version of the Vermont-Oxford Network. Trial registration at NIH register: NCT00303082.