Scientists Say Mom’s Cervical Bacterial May be Key to Preventing Premature Birth Essay

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LAS VEGAS, JAN. 23, 2017 – A team of researchers that has confirmed the presence of bacteria in a woman’s vagina and cervix may either increase the risk of premature birth or have a protective effect against it, has won the March of Dimes Award for Best Abstract on Prematurity at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting™. The findings will be presented Thursday, January 26, at 1:15 p.m. PST at Caesars Palace Augustus Ballroom in Las Vegas.

Michal Elovitz, M.D., and colleagues at the Perelman School of Medicine at the University of Pennsylvania and the University of Maryland studied 2,000 pregnant women, taking vaginal swabs at three distinct time points in pregnancy, and performed analyses on the specimens to determine the microbial colonies that were present. They found that the presence of many bacteria actually conferred a lower risk of spontaneous preterm birth while other bacteria were associated with a significant increased risk. The bacteria associated with spontaneous preterm birth, in conferring either protection or risk, were different between African-American and non-African-American women.

Premature birth (before 37 weeks of pregnancy) is the #1 killer of babies in the United States and the leading cause of death in children under age 5 around the world. Babies who survive an early birth often face serious and lifelong health problems, including breathing problems, jaundice, vision loss, cerebral palsy and intellectual delays. In addition to the human toll, preterm birth accounts for more than $26 billion annually in avoidable medical and societal costs, according to the National Academy of Medicine.

Dr. Elovitz, who is professor of Obstetrics and Gynecology at the University of Pennsylvania, vice chair of Translational Research and Director of the Maternal and Child Health Research Center at PENN, says doctors have been frustrated by the lack of treatments that reliably prevent premature birth. Furthermore, she says, clinicians currently have no good screening test to determine which women are at highest risk for preterm birth. In the quest for a new approach to the problem of prematurity, she began to engage with leading researchers in other fields such as bioengineering, immunology, pharmacology and microbiology.

“Although conventional wisdom says premature birth begins in the uterus, we decided to take an entirely new look at the problem,” she says.

Dr. Elovitz and her colleagues decided to investigate whether the initiation of preterm birth might begin in the cervicovaginal space, specifically leading to early changes in the cervix. “We started with the hypothesis that there is some difference in the molecular, biological, biochemical and/or microbial events in cervicovaginal space in women who ultimately have a premature birth compared to women who ultimately have a full term baby,” she says. Dr. Elovitz has been able to pursue this line of research as a co-investigator for the March of Dimes Prematurity Research Center at the University of Pennsylvania as well as through her National Institutes of Health funded studies.

In a study titled “Motherhood and the Microbiome,” funded by the National Institute of Nursing Research, Dr. Elovitz and her team were able to target one part of this hypothesis by studying the cervicovaginal microbial communities in a large prospective cohort of pregnant women.  “We are very excited to report that we did find significant differences in the microbial communities early in pregnancy in women who ultimately have a preterm birth compared to a term birth,” she says. “Different bacterial species were associated with quite a dramatic increased risk of premature birth. If our study is confirmed, it could mean that targeting CV bacteria may be a new therapy to prevent premature birth in the immediate future, not decades from now.”

Edward R.B. McCabe, MD, PhD, senior vice president and chief medical officer of the March of Dimes, agreed. “From these data, we may learn how to prevent preterm birth either by eliminating the CV bacteria that are associated with an increased risk and/or by enhancing the presence of protective bacteria. This is a promising new area that should become a research priority,” he says.

The team receiving the March of Dimes award includes Michal Elovitz, Pawel Gajer, Katheryne Downes and Jacques Ravel.

Abstract 10  Distinct microbiota in the cervicovaginal space are associated with spontaneous preterm birth: findings from a large cohort and validation study

Michal Elovitz¹ , Pawel Gajer² , Katheryne Downes¹ , Jacques Ravel²   ¹University of Pennsylvania, Philadelphia, PA,   ²University of Maryland, Baltimore, MD

OBJECTIVE: Changes in microbial communities have been implicated in both health and disease. Investigations into the association between the cervicovaginal (CV) microbiota and spontaneous preterm birth (SPTB) have been limited in scope and number. This study sought to assess if longitudinal cohort of pregnant women and then to perform validation in a 2nd prospective cohort.

STUDY DESIGN: A prospective cohort of singleton pregnancies were enrolled (“M&M”, n=1500). Biospecimens were collected at 3 time points in pregnancy (16-20 (V1), 20-24 (V2), 24-28 (V3) weeks). All cases of PTB were adjudicated by the PI. From the larger cohort, a nested case-control was performed with 80 SPTB cases and 320 term controls that were frequency matched by race to the cases. 16S rRNA gene analyses were performed to characterize the composition and structure of the CV microbiota. The effect of bacteria was quantified as the log ratio between the mean relative abundance at SPTB samples vs. TERM delivery samples. The log ratios were estimated using zero-inflated negative binomial models. A second cohort of woman (“STOP”) with specimens collected between 22-32 weeks was used as validation (N=616).

RESULTS: When performing phylotype analyses, 127 phylotypes were detected in all samples from both cohorts. Significant associations were demonstrated between specific bacteria, in both a positive and negative manner, with SPTB. 37 bacteria were significantly associated with a decreased risk of SPTB while 13 were associated with an increased risk in the primary cohort. Racial differences in these associations were evident (figure 1). The validation cohort confirmed the highly significant associations between specific microbes and SPTB. Bifidobacterium species were noted to be significantly protective against SPTB at all gestational time points while BVAB2, BVAB3 and Mobiluncus were associated with a dramatic increase risk of SPTB (all q-values <0.0001).

CONCLUSION: CV microbiota are significantly associated with SPTB. Targeting the bacteria that are associated with an increased risk of SPTB and/or enhancing the presence of the protective bacteria may serve as new therapies to reduce the rate of PTB. With this new evidence, these types of studies should become a research priority.

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