Pregnancy and Perinatology -
Sunil Jain, MD (PI) Gayle Olson, MD, and George Saade, MD
The proposed project will focus on the important topic of preterm birth. The long-term goal of our research is to elucidate the role of bacterial vaginosis (BV) in preterm birth and to develop safe and effective preventive strategy for preterm birth using orally administered probiotics to reduce BV. BV is characterized by a shift in vaginal bacterial flora from lactobacilli to pathogenic bacteria like Gardnerella and Mycoplasma. BV is associated with up to 25 - 35% of premature birth.
Attempts at eradicating BV with conventional antibiotic treatment have been disappointing. During pregnancy, carrier status persists or recurs despite treatments, and may require repeated exposure to antibiotics which can lead to emergence of drug-resistance bacterial strains, and exposure of the developing fetus to various antibiotics. This dilemma presents a need for alternative therapeutic measures for BV during pregnancy.
Local vaginal production of H2O2 is toxic to the pathogenic organisms causing BV. Probiotics like L rhamnosus GR-1 and L fermentum RC-14 are H2O2 producing bacteria that prevent the growth and adhesion of pathologic bacteria to the vaginal epithelium. Dr. Reid (one of the co-investigator) is a nationally and internationally known authority on the management of BV using specific strains of probiotics in non-pregnant women. He has shown that probiotics are safe, and reduce BV by restoring the normal vaginal bacterial flora. For pregnant women, restoration of normal vaginal bacterial flora and reducing BV would be a very important step in preventing preterm birth.
The complexity of the proposed project requires the assembly of a multidisciplinary research team with scientific expertise, as well as basic and translational research experience. As a step toward our long term goal, we propose a randomized, placebo controlled pilot trial. The general approach of this project will be to test various factors and generate preliminary data that would provide us with strong rationale and background on which to build a grant application for a large clinical trial. We plan to evaluate and pilot the effect of early pregnancy oral administration of probiotics on the prevalence of BV. Within the same pilot trial, we plan to evaluate the performance of bedside clinical diagnosis of BV, the feasibility of measurement of cytokines in the vaginal secretions, and our ability to perform metagenomics of vaginal fluid to fingerprint the oral probiotics in the vaginal secretions. While we realize that the limited sample size in this pilot study may not be sufficient to provide enough power to detect an effect on preterm birth, we will also evaluate this outcome and use the data to plan the larger trial, given the short duration (12 months) of the pilot project.