Full Circle Midwifery

A few years ago, a microbiologist named Gregor Reid danced before an audience of students, post-docs, and scientists at a conference held by the American Society of Microbiology.

The song he grooved to was “Sub-Culture,” a synthesizer-infused meditation on loneliness by the 1980s British band New Order. But the talk he delivered—after he finished dancing—was, in a sense, about companionship.

His presentation had the monumental title, “The Vaginal Microbiome’s Role in Humanity.” And his argument was this: Our native microbes are passed from generation to generation much like human culture; the microbes of the human vagina are paramount to our survival; and in this era of burgeoning research on the human microbiome generally, we need to pay more attention to them.

“To not place a huge focus on the vaginal microbiome is like putting human survival at risk,” he said.

The human microbiome consists of the microbes living on and within the human body. Most of these bugs inhabit the large intestine. There, a few pounds’ worth of bacteria, yeasts, archaea, and even viruses help digest food, calibrate our metabolic and immune function, and hold off would-be invaders.

A special subset—the vaginal microbiome—inhabits the vagina. And successful human reproduction, it turns out, owes an immense debt to this microbial community.

A healthy vaginal microbiome produces lactic acid and hydrogen peroxide, which maintain a level of acidity that keeps troublemaking microbes at bay. When the vaginal community becomes unbalanced, on the other hand, acidity decreases. The wrong microbes may then invade or, if they’re already present, bloom.

This disturbance can cause bacterial vaginosis—not really an infection, but an out-of-whack ecosystem. It sounds like a trifling problem, and half of women with vaginosis may display no obvious symptoms. But this minor-seeming imbalance can have major consequences.

Vaginosis increases the risk of contracting secondary infections, from herpes to HIV. But even on its own, the microbial shift may prompt low-grade inflammation that can derail reproduction. It can prevent fertilization in would-be mothers, prompt spontaneous abortion in pregnant women, and increase the risk of preterm birth later in pregnancy.

If the vaginal microbiome were suddenly to shift across the entire human population, it’s not unreasonable to predict that humanity would go extinct.

The prevalence of bacterial vaginosis is startlingly high, although it’s not clear whether the rate has always been high or has been changing. The Centers for Disease Control and Prevention estimates that nearly 30 percent of American women suffer from the condition, many unawares. Among African-American women in some studies, prevalence surpasses 60 percent.

Many factors affect the vaginal ecosystem—smoking, stress, diet, the number of sexual partners, and obesity. One of the most direct ways to upset the vaginal microbiome may be douching (more on this later). Recent studies show that the healthy state varies by ethnicity, complicating easy characterizations of “normalcy.”

Yet the consequences of vaginosis can be devastating. In a study of 1,950 urban women in Philadelphia, for example, vaginosis in the first trimester more than doubled the risk of spontaneous pregnancy loss in the second. In Belgium, vaginosis more than quintupled the risk of early preterm birth.

This relationship with preterm birth, defined as labor before 37 weeks in a 40-week pregnancy, is troubling. One in eight American children is born prematurely. These numbers began rising in the 1980s and, recent signs of a decline notwithstanding, they’ve remained stubbornly high ever since. Preterm birth is the leading cause of infant mortality in the nation. By one estimate, the costs to society surpass $26 billion yearly.

Vaginosis-related microbes have been implicated in roughly one-quarter of all preterm births. For the most vulnerable group of children, those born extremely preterm, or before 25 weeks,the number perhaps doubles.

Vaginosis “doesn’t get the attention it deserves, because it’s not a sexy STD,” says Deborah Nelson at Temple University in Philadelphia, who led the Philadelphia study.

Among the urban, mostly minority women Nelson works with, more than 60 percent suffer from the imbalance. This same population has an elevated risk of preterm birth. “It’s worrisome that young women in North Philly that have high levels of BV just don’t understand how hazardous it is,” Nelson says.

How do microscopic microbes provoke such major disasters? The immune system, scientists now realize, assists in labor. Essentially, the inflammatory response that repels invading germs also helps expel the infant. So any stimulus that prompts inflammation during pregnancy—be it from acute infection, microbial imbalance, or even gum disease, some studies show—can trigger labor prematurely.

How to treat vaginosis during pregnancy remains controversial, not least because antimicrobials may further perturb an already disturbed ecosystem. Yet according to one recent metanalysis of five studies involving 2,346 women, antibiotic treatment can lower the risk of preterm birth.

Inflammation during fetal development can have lifelong consequences for the child. That lesson has recently come to light in studies of asthma. In a condition called “chorioamnionitis,” bacteria sneak past the cervix into the uterus, inflaming the placenta. Vaginosis seems to increase the risk of chorioamnionitis, which is not quite a classic infection—like measles or the flu, say—but rather native microbes in the wrong part of the body. A pregnant mother may not notice, in fact. But the effects can be insidious.

In 2008, scientists following a cohort of nearly 1,100 Boston mothers and their children announced that premature birth increased the risk of wheezing at 6 years of age by 70 percent. The real kicker emerged when they separated children of mothers who had suffered from chorioamnionitis during pregnancy. For those children, the risk of asthma was more than four times as high.

A Finnish group has since replicated the finding among 15-to-17-year-olds, implying that the consequences of prenatal inflammation persist into adolescence and probably adulthood.

And as evidence mounts that immune activation during pregnancy contributes to developmental disorders, others have examined chorioamnionitis in autism. One study of 91 preterm toddlers, also in Boston, showed a positive association. These results are highly preliminary—the study was small and used a diagnostic tool that’s only 10 percent accurate in predicting autism.

Numerous animal experiments show that inflammation during pregnancy can cause myriad problems in offspring. Simulated chorioamnionitis in pregnant sheep, for example, interferes with lung, brain, and gut development in lambs, even when the lambs are born at term. Chorioamnionitis is, in the words of a Dutch group studying it, “a multiorgan disease of the fetus.”

These are admittedly worst-case scenarios. And it’s important to remember that while vaginosis may facilitate the migration of bacteria to the uterus, the imbalance doesn’t necessarily guarantee it. More to the point, the “normal” uterus may not be sterile anyway. A healthy vaginal microbiome may not prevent microbial migration so much as promote colonization by friendly microbes.

In 2009, Finnish scientists showed that placentas from healthy children born at term were coated in DNA from lactobacilli and bifidobacteria. Somehow indigenous microbes—or at least their DNA—found their way to this inner sanctum without causing obvious problems.

In 2011, a group at Harvard found that 40 percent of placentas from more than 500 preterm children born by C-section contained culturable microbes. In this case, those placentas colonized by vaginosis-associated species were slightly inflamed. But the placentas coated with lactobacilli were not.

Australian fertility specialists have observed that fluid extracted from ovaries wasn’t sterile, either; it also contained bacteria. The study group consisted of women seeking help with conception. Women who harbored lactobacilli, the researchers found, more often had successful outcomes than those who carried other species.

The microbes may have been introduced during the egg retrieval process, the scientists acknowledged. But they also asked, “Do we really believe that the female upper genital tract is sterile?”

“I think that there’s organisms up there all the time, in healthy people,” Reid says. Some of these microbes likely ascend from the vagina. So the best approach to reproductive health will likely be proactive and preventive, not reactive and corrective. Health is not just a question of keeping the wrong bugs out, in other words, but also ensuring the right ones are present.

“The issue is, how do we promote high lactobacilli coming into pregnancy?” says Nelson. “It starts before women are thinking of conception.” In her Philadelphia cohort, for example, women who early on harbored high counts of lactobacilli were more likely to have a healthy, full-term pregnancy than those who didn’t. Similar observations have been made at the University of Washington, Seattle, among women undergoing in-vitro fertilization. The more vaginal lactobacilli at the outset, the better the outcome.

The vaginal ecosystem may contain keystone species that are especially protective. Several studies, including one by Nelson, suggest that the presence of a single lactobacillus called L. crispatus lowers the risk of both vaginosis and preterm birth. Among HIV-positive women in the United States and Kenya, meanwhile, L. crispatus seems to lessen vaginal shedding of the virus.

Which brings us to treatments. Scientists aren’t very good at treating vaginosis, it turns out. Antibiotics can beat it back in the short term, but “the norm is for it to recur,” says Craig Cohen of the University of California, San Francisco. “That’s the problem: Our tools, our treatments, are just not sufficient.”

Enter Gregor Reid, who’s at the University of Western Ontario. He has conducted two randomized trials comparing probiotics to antibiotics. In one, which was blinded and placebo-controlled, he supplemented antibiotics with probiotic lactobacilli (L. reuteri and L. rhamnosis) taken orally. This group had an 88 percent cure rate at the one-month mark, more than twice that of the group treated with antibiotics alone.

In a second, smaller study, he compared just probiotics with an antibiotic gel, both administered vaginally. With a 90 percent cure rate, probiotics alone were 40 percent more effective than antibiotics.

Then there’s “maintenance therapy”— keeping friendly microbes around once they’re established. In Italy, women who treated vaginosis with antibiotics gradually relapsed during the subsequent year. By contrast, women who also applied probiotics vaginally for six months resisted sliding back into vaginosis.

“We’re going to see more probiotics used with antibiotics,” says Barbara Cottrell of Florida State University. In the meantime, she says, “It would be nice if the CDC had a campaign: Start talking about ecosystems—that the vagina has an ecosystem—in grade school.”

Such education might help women resist marketing. I thought of Reid’s dance and presentation on the vaginal microbiome when Summer’s Eve unleashed its “Hail to the V” campaign for douching products. In one ad, a stentorian voice intoned, “It’s the cradle of life … the center of civilization …  men have fought for it … even died for it.” When I described the ad to Reid, including the final exhortation to “show it a little love”—that is, to douche—he said, “I agree with everything, except for the last part.”

When I asked Cottrell about douching, she told me a story. About a decade ago, flummoxed by the high infant mortality rates in some African-American communities in the Florida panhandle—which were more than twice the rate for Caucasian infants—she began looking for explanations.

“I kept seeing bacterial vaginosis present in mothers whose babies died,” she recalls. “That’s when I started reading about vaginosis.”

She happened on statistics suggesting that one in three American women douche and that some African-American cohorts douched nearly twice as often. Showing that douching directly causes infant mortality remains difficult, yet her resulting paper, published in 2010, reads like an anti-douching manifesto.

Douching has been linked to preterm birth, an elevated risk of acquiring HIV, ectopic pregnancies, cervical cancer, and endometriosis, she points out. It may perpetuate the very condition it’s often intended to address: vaginosis. Scientists at Johns Hopkins have found that, after stopping the practice, bacterial imbalances resolved on their own.

“We recommend not doing it, that’s the bottom line,” says Cottrell. If something seems amiss—a strange odor or discharge—go to the doctor. Otherwise, as womenshealth.gov says, “let your vagina clean itself.”