Bacterial community in pregnant women linked to preterm birth, study finds

A specific pattern of high bacterial diversity in the vagina during pregnancy increases a woman’s risk of giving birth prematurely, a new study finds.

A specific pattern of high diversity in the vaginal bacteria of pregnant women raised the likelihood of premature birth, according to a new study.
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Risk for premature birth is linked to the composition of the vaginal bacterial community in the mother during pregnancy, according to a study from the Stanford University School of Medicine that tracked women's microbial communities on a week-by-week basis during pregnancy.

A high-diversity pattern in the vaginal bacteria raised the likelihood of premature birth, and the longer the bacteria followed this pattern, the higher the risk, the study found. The study may also help explain why prematurity risk is elevated in women who have closely spaced pregnancies.

A paper describing the research was published online Aug. 17 in the Proceedings of the National Academy of Sciences.

Babies born more than three weeks early are considered premature. About 450,000 premature infants are born each year in the United States. Prematurity is the leading cause of newborn deaths. About half of such births occur after spontaneous preterm labor, whose triggers are not well-understood.

“We wanted to develop a baseline understanding of what happens to the human microbiome during pregnancy, both in women who deliver healthy, term babies and in those who deliver prematurely,” said the study’s senior author, David Relman, MD, professor of medicine and of microbiology and immunology at Stanford, and chief of infectious diseases at the Veterans Affairs Palo Alto Health Care System.

Missing puzzle piece

When the research began, little was known about whether or how the body’s indigenous communities of bacteria change in pregnancy, said Relman, who is also a project leader at the March of Dimes Prematurity Research Center at Stanford. “It seemed like a big missing piece of the story.”

David Relman

Relman’s team studied 49 pregnant women, 15 of whom delivered prematurely. The women gave weekly samples during pregnancy, and monthly samples for up to a year after delivery, that allowed researchers to characterize the bacterial communities in the vagina, lower gut, saliva and tooth and gum areas.

The scientists found that vaginal microbial communities fell into five patterns, consistent with prior research. For most women, the communities in the vagina and at the three other body sites did not change much during the course of pregnancy. “It’s a bit surprising how stable the communities are, since there are lots of other body features that change dramatically in pregnancy, such as maternal hormone levels, metabolism and weight,” said Relman, who holds the Thomas C. and Joan M. Merigan Professorship.

Four patterns of vaginal bacteria were characterized by little bacterial diversity and by dominance of various kinds of lactobacillus bacteria, which have been previously associated with health in women. None of these patterns were linked in the study to preterm birth.

The remaining pattern — characterized by greater bacterial diversity, high levels of gardnerella and ureaplasma bacteria, and low levels of lactobacillus — was linked with increased risk for preterm birth, especially if the bacterial community displayed this pattern for several weeks.

“I think our data suggest that if the microbiome plays a role in premature birth, it may be something that is long in the making,” said the study’s lead author, Daniel DiGiulio, MD, a research associate and clinical instructor in medicine. “It may be that an event in the first trimester or early second trimester, or even prior to pregnancy, starts the clock ticking.”

Study co-author David Stevenson, MD, the principal investigator of the prematurity research center and director of the Johnson Center for Pregnancy and Newborn Services at Lucile Packard Children’s Hospital Stanford, said the research “is part of our larger effort to find the microbial and immunological signature for preterm birth.”

Big bacterial changes after birth

The researchers also found that, in all women, vaginal bacterial communities changed significantly after birth. This was true both of women who delivered prematurely and at term. The change was seen after both vaginal and cesarean deliveries. For up to a year after birth, women tended to have the more-diverse bacterial pattern. “This was a surprise,” Relman said, adding that his team plans to conduct further research to find out whether the shift may help explain the increased risk for preterm birth in women whose pregnancies are closely spaced.

It may be that an event in the first trimester or early second trimester, or even prior to pregnancy, starts the clock ticking.

Though the findings need to be confirmed in a larger, more diverse group of women, they may ultimately help doctors identify which women are at risk for premature delivery, the researchers said. The findings also raise the possibility that treatment with probiotics or other interventions designed to alter the body’s communities of bacteria may help ward off prematurity, a concept the researchers hope to test in future studies.

“Traditionally, we viewed microbes as pathogens — as bad actors,” said DiGiulio. “We now recognize that our bodies’ microbial communities perform many beneficial functions, yet there may be times when the communities get out of whack.”

Other Stanford-affiliated co-authors of the study are research associates Benjamin Callahan, PhD, Elizabeth Costello, PhD, and Paul McMurdie, PhD; Deirdre Lyell, MD, associate professor of obstetrics and gynecology; Anna Robaczewska, MS, research assistant; postdoctoral scholars Christine Sun, PhD, and Daniela Goltsman, PhD; Ronald Wong, PhD, senior research scientist; Gary Shaw, DrPH, professor of pediatrics; and Susan Holmes, PhD, professor of statistics. Lyell, Shaw and Stevenson are members of Stanford’s Child Health Research Institute.

The research was funded by the March of Dimes Prematurity Research Center at Stanford University, the National Institutes of Health (grants UL1TR001085 and R01GM086884), the Stanford Child Health Research Institute and the National Science Foundation.

Information about Stanford’s Department of Microbiology and Immunology, which also supported this work, is available at http://microimmuno.stanford.edu/


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