Two years ago, a Stanford team discovered that women who deliver their babies prematurely have a different community of vaginal bacteria during pregnancy than women whose pregnancies go to term.

The finding offered hope that a simple early-warning system could be developed for preterm births. Right now, premature birth is the leading cause of newborn death in the United States and has surpassed infection as the main cause of deaths in kids under 5 worldwide, but doctors lack a reliable way to predict which babies will be born three or more weeks early.

This week, the Stanford researchers, led by microbiome expert David Relman, MD, published a new study in Proceedings of the National Academy of Sciences that refines their 2015 discovery. The study replicated important aspects of the original findings in two groups of women who were not investigated before, greatly increasing the scientists’ confidence in what they’ve found.

“There is a dire need for serious efforts in microbiome research to demonstrate that initial findings can be validated,” Relman told me, adding that so far, such studies are unusual.

The 2015 study tested only a small group of women, most of whom were white and lacked known risk factors for preterm birth. In the new study, the researchers expanded the population of pregnant women they included; this time, they analyzed a new group of white, low-risk women and also a large group of African-American women who were at higher risk because they had a history of premature birth. They found some overlap, but not complete agreement, in the profiles of vaginal bacteria that predicted prematurity in the two groups.

The scientists also used new methods that allowed them to zero in more precisely on exactly which bacteria are linked to risk. For instance, according to the 2015 study, a species of bacteria called Gardnerella vaginalis increased prematurity risk. The new findings show it’s not so simple.

“We saw that Gardnerella v. is not one thing – there are nine different strains at least, and only one of them seems to account for the risk we associate with the species, while the other eight clearly don’t,” Relman said.

Lactobacillus, a group of bacterial species previously linked to lower risk for preterm birth, also plays a more complex role than the researchers initially thought. Of four species of Lactobacilli, three can exclude the risky Gardnerella from the community of vaginal bacteria, while one cannot, the new findings showed.

“This makes the whole story of the ecology of the vaginal community more interesting and complex,” Relman said.

The value of the refined signature for preterm birth is that it may let doctors risk-profile pregnant women early in their pregnancies and predict who is at heightened risk, he added. “And it more strongly suggests we should be considering an intervention of a new and different sort: to restore the vaginal microbiome to the picture we associate with low risk.”

Previously: Stanford microbiome research offers new clues to the mystery of preterm birth, Unknown bugs dominate the human microbiome and Stanford researchers are getting closer to understanding prematurity predictors

Image of lactobacillus by AJC1