Quasi Experiment of Prenatal Probiotics Against Group B Streptococcus Colonization
Condition: Pregnancy
Study type: Interventional

Summary: 
      This pilot quasi experiment was designed to determine the feasibility of a randomized
      controlled trial of the oral probiotic combination of Florajen3 (>7.5 x109 L. acidophilus,
      >6.0 x109. B. lactis, and >1.5 x109 B. longum) taken orally once daily beginning at 28 weeks
      gestation, against placebo, to reduce the colonization of group B Streptococcus at 36 weeks.
    

Detailed description: 
      Methods

      A non-blinded, open-label, quasi-experimental design was approved by the Institutional Review
      Boards of three institutions (two universities and the clinical research site). The study
      setting was a large Certified Nurse-Midwife (subsequently referred to as midwife) clinical
      practice serving a culturally and economically diverse urban population in the Midwest region
      of the USA.

      Participants Women self-selected to participate in screening and informed consent procedures
      done by the first two authors. The following inclusion criteria were used at study
      enrollment: low risk (no obstetric, fetal, medical or genetic risk factors), adult (≥18 years
      of age), pregnant at 28 ± 2 weeks gestation, able to speak and write English, and expressing
      willingness to participate in the study intervention (oral probiotic) and data collection
      (vaginal and rectal swabs, questionnaires).

      A convenience sample of 20 healthy pregnant participants was sought. Following informed
      consent, the first 10 subjects were assigned to the experimental group. Nonrandom assignment
      was used to assure that the 10 experimental group participants were enrolled while remaining
      within funding, and time constraints. After enrolling the experimental group, the next ten
      women were assigned to the control group.

      Intervention

      The study intervention consisted of one capsule of Florajen3 (previously described) orally
      each day. Florajen3 meets the internationally established probiotic criteria (FAO/WHO, 2001).
      The probiotics contained in Florajen3 are non-spore-forming, lactose- and
      hydrogen-peroxide-producing bacteria. The manufacturer recommends refrigeration to maintain
      maximum potency. As part of the preparation for this study, a sample of Florajen3 was left
      unrefrigerated for a period of 6 weeks and appropriate colony counts were sustained.
      Therefore for the purpose of the study, the participants in the experimental group were
      allowed to leave the probiotic unrefrigerated in an effort to improve daily compliance.
      Experimental group study participants were made aware of the probiotic brand used (open
      label) as the intervention.

      Further, the current state of knowledge about prenatal probiotics, including potentially rare
      side effects, were discussed at length using a 10-page informed consent document. The
      Florajen3 was placed in a study bottle equipped with an electronic cap monitoring system
      (MEMS ®AARDEX), designed to record each time the bottle was opened by the participant. Each
      opening of the cap bottle equipped with this system is recorded on a microchip. The number of
      openings are retrievable via computer software when the bottle caps are returned.
      Researchers, midwives, and participants were aware of group assignment. The control group
      participants did not receive a placebo.

      Procedures

      Midwife prenatal care providers and staff were oriented to the study data collection
      procedures. Study data were collected at three points during routine prenatal visits with
      each participant's midwife (28±2 weeks, 32±2 weeks, and 36±2 weeks gestation). The study was
      considered completed at the 36±2 weeks gestation visit. All participants received
      compensation at the completion of 2 study visits; 25 USD at 32±2 weeks and 75 USD at 36±2
      weeks gestation. Probiotic group participants were offered a supply of probiotics for the
      remainder of pregnancy.

      The midwife prenatal provider collected demographic information (birth date, race, and
      gestational age), and the vaginal and rectal swabs for GBS and wet mount, using accepted
      criteria to identify the vaginal pH and the presence of normal flora and/or pathogens. The
      wet mounts were examined microscopically by each midwife using standardized wet mount
      diagnostic procedures with normal saline and potassium hydroxide and documented in a standard
      format. Participants completed a brief questionnaire at each study visit that asked them to
      describe yogurt ingestion, sexual activity (frequency and type), and vaginal cleansing
      practices (if used) in the past week; these were considered potential confounding variables.
      The participants were also asked if these practices were typical for them, and if not, how
      they were atypical. Women in the experimental group were asked to report any side effects
      that they attributed to the probiotics by notifying their midwife immediately, if necessary,
      and then also noting the information on the study questionnaire. As part of routine prenatal
      care, the CDC-required GBS vaginal to rectal swab was collected by each participant's midwife
      and sent to the hospital laboratory between the 35 and 37 week visit. This was the only
      result that determined the need for IAP.

      Researchers oversaw data collection and sample packaging. Participants were asked to return
      their probiotic bottles at each study visit and the Florajen3 capsules were replaced with a
      fresh supply. This gave the researchers the opportunity to notify the laboratory to record
      the date for later evaluation of the electronic cap monitoring results and conduct pill
      counts as an additional means to monitor women's responses to study participation, as well as
      probiotic adherence at each study visit. The vaginal and rectal swabs were placed on ice,
      packaged according to accepted procedures for human specimen handling, and shipped overnight
      to the laboratory of the final author, located 80 miles from the study site, for processing
      and analysis.

      Laboratory Analysis Upon receipt at the laboratory, the vaginal and rectal swabs were
      processed for quantitative colony counts of GBS. Polymerase chain reaction (PCR) was
      performed to determine whether bacteria isolated were the same as those in Florajen3. If
      positive for PCR, pulsed field gel electrophoresis (PFGE) would be performed to confirm the
      strain identity.

      These results were for research purposes only and were not available to the practicing
      midwives.

      The routine CDC-recommended prenatal GBS vaginal to rectal swabs were analyzed at the
      hospital laboratory, using a culture based method in which a threshold for GBS positive
      results is considered greater than 102 colony forming units (CFU) per swab. These results
      determined the need for IAP and were available to the midwives for management during labor.

      Statistical Analysis

      Demographics, the study variables, and laboratory data were entered into and analyzed with a
      statistical software package. Descriptive statistics, Confidence Intervals, Chi-squares,
      T-tests, and correlations were used for analysis. Data were compared between subjects at each
      study visit and between groups at each data collection point. The qualitative prenatal GBS
      culture results (positive or negative) from the hospital laboratory were compared to the
      quantitative vaginal and rectal GBS study results, adherence data, and confounding variables
      (yogurt ingestion, sexual activity, and vaginal cleansing practices).
    

Intervention name(s): Probiotic dietary supplement
Intervention type(s): Dietary Supplement
Intervention description(s): Florajen3 is a commercially available probiotic supplement containing three bacteria of human origin (>7.5 x10^9 L. acidophilus, >6.0 x10^9 .B. lactis, and >1.5 x10^9 B .longum). Once capsule was administered daily by mouth from 28 through 36 weeks gestation.
Other intervention name(s): Florajen3 Probiotic
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: group B Streptococcus colonization; Probiotic; Pregnancy