Preterm Birth and the Vaginal Microbiome

Women's health

Preterm Birth and the Vaginal Microbiome

The vaginal microbiome has a profound impact on pregnancy health - here we dig into the science with an expert

illustration-of-woman-holding-baby

You might already be familiar with how the microbes that live in your vagina affect your health, especially when it comes to conditions like yeast infections or bacterial vaginosis (BV). But it’s not just about you - your vaginal microbiome (VMB) can also impact the outcome of your pregnancy and the health of your baby.

When it comes to the VMB’s impact on pregnancy, research has so far told us a few key things:

  1. Increased levels of some kinds of bacteria + decreased levels of other kinds of bacteria = increased risk of preterm birth
  2. Vaginal microbiomes with higher species diversity (i.e. more kinds of bacteria) are associated with a higher risk of preterm birth
  3. These risks may be related to inflammation

What is preterm birth?

Preterm birth (also known as PTB) is the birth of an infant before 37 weeks fetal development—a full-term pregnancy is usually around 40 weeks—and PTB is one of the world’s leading causes of death in children under the age of five. Being born too early can not only immediately result in an infant’s death, but can also lead to all kinds of long- and short-term health complications: increased infection risk, underdeveloped organs and immune system, neurodevelopmental delays, and more. These problems don't end with infancy, but often extend into adolescence and adulthood. Unfortunately, more than one in every 10 pregnancies end in PTB, and this incidence has not decreased despite all the advances of modern medicine.

What are the risk factors?

Researchers and clinicians have explored many potential contributing maternal factors, such as age, obesity, stress, smoking habits, and more. One particularly well-studied factor is the composition of the microbes colonizing the urogenital tract, especially those associated with conditions like urinary tract infection (UTI), vaginitis, and bacterial vaginosis (BV). Many studies have shown that these issues are caused by (and result in) imbalances of vaginal flora, and this imbalance is linked to an increased risk of preterm birth. 

In vaginal microbiome science we talk about dominance: which bacteria have the biggest share of real estate in the VMB. In VMBs with decreased  ‘good’ bacteria (particularly Lactobacillus crispatus) and increased ‘bad’ bacteria (species like Gardnerella vaginalis, Lactobacillus iners, and many more), the risk of giving birth before 37 weeks is higher than in VMBs that are Lactobacillus spp. (particularly L. crispatus) dominant. 

Gregory Buck, a professor in the department of Microbiology and Immunology at Virginia Commonwealth University and a leader of the Vaginal Microbiome Consortium, says,

“We don't know everything about why L. crispatus is optimal for women's health, but we do know that it tends to exclude less optimal bacteria by making the vaginal environment more acidic, which the less optimal bacteria don't like, and making other compounds that prevent these non-optimal bacteria from growing.”

What’s the connection?

As with many things in science, these trends are just that—trends. They are correlations, meaning that when we see a change in one variable, we see a change in the result. But causation, or how that variable may be causing the change in the result…that’s a different story altogether.

When it comes to the relationship between the vaginal microbiome and the risk of preterm birth, we still have a relatively poor understanding of the causative mechanisms at play (if indeed there are any). But the leading edge of research in this area is starting to get an idea. 

It could be a direct influence: Certain species of the ‘bad’ bacteria are producing compounds that increase inflammation in the reproductive tract, potentially altering the tissue in the vagina and cervix to be less stable, making it more likely that a baby would be born preterm. Or it could be an indirect effect: Some specific species (and/or an increase in overall species diversity) are making the VMB more susceptible to infections that we know are associated with preterm labor, such as Group B Streptococcus (GBS). In this case, the VMB community composition is ‘opening the door’ to the real problem organism, so to speak.

What can we do?

As of now, we don’t have a lot of concrete answers. Says Buck, 

Although some activities—including sexual activity with multiple partners, douching, etc.,—have been associated with less optimal vaginal microbiomes, we don't have all the information yet. Antibiotics [to treat a condition such as BV] seem to provide only short-term benefits. Some scientists and clinicians are looking at probiotics or even transplants of bacteria from women with optimal vaginal microbiomes that are dominated by L. crispatus to promote gynecological and reproductive health in women with less optimal vaginal microbiomes. There have been some reports of success using these experimental approaches, but there is still significant risk of doing harm, and much has yet to be learned.”

But as we explore these relationships further, many teams around the world are looking into how we can use microbiome community makeup (and the chemicals these organisms produce) to help us predict PTB risk. For example, “High throughput ‘next generation’ DNA sequencing has made it possible to rapidly and comprehensively identify the bacteria in a woman's vagina.” says Buck. A pregnant person may get a vaginal swab taken as a sample, which can then be sequenced for microbial genetic material and also measured for the presence of certain compounds produced by specific bacteria. 

“Rapid tests in early pregnancy (or prior to pregnancy) that identify vaginal microbiomes composed of so-called 'non-optimal bacteria' would permit clinicians to more closely monitor women for signs of possible premature delivery,” says Buck. “These women can be carefully followed in 'high risk' clinics to help to prevent preterm births.“

Ideally, tests like this will eventually allow us to provide intervention to high-risk patients—maybe that’s more targeted antibiotic treatment, maybe it’s probiotic supplementation, we’re not sure yet. But for now, finding out more about VMB community dynamics, especially using genetic sequencing, will point the research community in the direction we need to go. 

Getting to know your VMB—its composition and contributions to your health and wellbeing—can be a great place for you to start when taking control of your fertility journey, even before you’re ready to start having children. 

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Attributions
Maren Hunsberger, Msc
Maren Hunsberger, Msc

Maren Hunsberger is a microbiologist and science communicator who holds a master's in medical microbiology, with a particular research focus on the vaginal microbiome. She is passionate about breaking down the stigmas that surround female-bodied health, and shedding light on all the ways the lives of people with vaginas can be improved with more equitable research. Maren is a Californian living in London, and you can find her @marenhunsberger on Instagram, Twitter, and YouTube, and @marenmicrobe on TikTok.

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Leighton Turner, PhD
Leighton Turner, PhD

Leighton Turner is a PhD in Molecular Genetics and is Juno Bio's Chief Technology Officer.

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