Anna Simonsen-Meehan felt robbed. Advised by doctors to plan a cesarean delivery for her first child, she had wanted desperately to give birth naturally. But Anna and her husband were determined not to let their son’s surgical entrance into the world rob him of the profuse coating of bacteria babies normally acquire during their passage through the birth canal.
Within a minute or so of their baby’s December 2015 birth, new father Joseph Meehan took a piece of gauze that had been soaking in his wife’s vagina just before surgery and methodically swabbed it across their son’s 8-pound body — starting with his lips, nose, and hands, then working his way down to the infant’s back and genital area.
The novel technique was an opportunity the New York City couple had been envisioning from the start of Anna’s pregnancy, since earlier uterine surgery dimmed hopes for a vaginal birth. Avidly tracking several years of research indicating that babies born naturally may have an edge over those born via C-section — with lower risks of myriad chronic health conditions such as asthma, allergies, obesity, and type 1 diabetes — the pair decided that their son should be swabbed with his mother’s vaginal microbiome.
“If you are going to have an intervention that changes a natural process — in this case, a C-section — can you normalize everything else?”
Joseph appreciated the opportunity to get close to his son so quickly after birth — the blond-haired boy was still purple and coated with curd-like vernix from the womb — and the intensity of the moment was magnified by excitement over the potential benefits the quick wipe-down might offer their baby.
“We were trying to give him as fair a starting point as any other child,” says Joseph, 36. “The worst-case scenario is it does nothing, and I personally don’t believe that. It could be as simple as him just having the bacteria to digest his first meal … and everything downstream from that. We’re setting him up for success.”
“Since the window of opportunity is so short — within the first hour after birth — we didn’t want to miss out on that and find out later he had some medical issue as an adult because of it,” adds Anna, 38. “It felt really good to have something we could give back to him, to get back a sense of control.”
While every parent would like to set up his or her child for success, scientists are still trying to understand the effects of this procedure on C-section babies and if other factors are involved in predicting an infant’s future health and well-being.
The “Second Genome”
Long ignored, the human micro-biome — the collection of bacteria living all over and inside people’s bodies — is now being dubbed the “second genome” because of increasing awareness of its apparent impact on health and disease. The same next-generation DNA sequencing technologies that have evolved over the past dozen years, making genomic analysis far quicker and cheaper, have also fueled scientists’ efforts to identify and analyze the trillions of human bacteria — good and bad — lurking on the skin and in locales such as the gut, the ears, and the vagina.
These advances have offered microbiologists previously unheard-of opportunities to characterize these bacteria and tease out how they help humans digest food; metabolize drugs; interact with certain genes to contribute to, or protect from, disease; and even “seed” development of newborns’ immune systems to ward off chronic health ills.
“We now realize our microbiome is not just there by accident — it evolved with us,” says Gregory Buck, a professor of microbiology and immunology and director of the Center for the Study of Biological Complexity at Virginia Commonwealth University in Richmond. “We are truly looking at the second human genome. It relates to not only unhealthy conditions but healthy conditions as well, and it’s important to keep that in mind. In the last 10 years it’s become much more obvious to me and most other scientists in the field.”
“Given that it’s not that hard to transfer the microbes from the appropriate part of the mother to the
baby, we decided to take matters into our own hands.”
With more than 1.2 million babies in the U.S. being born by C-section each year, comprising about one-third of all births, researchers say reseeding newborns with their mother’s bacteria may produce health effects that endure across generations.
Evidence is still preliminary and not entirely consistent, but a growing body of observational studies suggests babies born via C-section face higher chances of developing an array of chronic illnesses as they get older. But scientists can’t yet tell if cesarean deliveries actually cause these lasting health issues, if other factors are involved, or how much higher the risks actually are.
A research review published in June 2015 in the British Medical Journal found 20 studies linking C-sections to type 1 diabetes, 23 studies connecting them to asthma, and nine tying them to obesity. In a study of more than 320,000 babies published in the December 2015 Journal of the American Medical Association, those born by C-section had higher risks of asthma requiring hospitalization and death from all causes by age 21, but no significant differences in obesity, inflammatory bowel disease, type 1 diabetes, or cancer.
“There could be genetic factors that predispose to all of them, but they seem to have a microbial component,” explains Maria Gloria Dominguez-Bello, an associate professor at the Human Microbiome Program at New York University School of Medicine. “It’s probably a combination of risk factors,” including a higher rate of formula feeding by C-section mothers, she says.
A Simple Technique
Dominguez-Bello’s research on the maternal microbiome is some of the most seminal in the field. She and her colleagues published a 2010 study — the first to use molecular techniques — showing that babies delivered via C-section harbor different bacteria than those born vaginally. The gut microbiome of a naturally born newborn, for instance, aligns more closely with that of his mother’s birth canal than those of C-section babies, whose microbiomes resemble their mothers’ skin.
These findings formed the basis for Dominguez-Bello’s current research, in which surgically delivered babies are swabbed with their mothers’ vaginal bacteria just after birth. The notion is still new enough that the Simonsen-Meehans’ hospital staff needed convincing they should allow the couple to do it with their son. “You want to take what from where and put it on whom?” Anna’s obstetrician asked incredulously. But Dominguez-Bello’s research lent credence to their request, and the couple is now enrolled in her study.
In a pilot study published in the February 2016 issue of the journal Nature Medicine, Dominguez-Bello and her team compared the microbiome of four C-section babies swabbed with their mothers’ bacteria with that of seven C-section infants not swabbed and seven born vaginally. More than 1,500 microbial samples were taken from the skin, anus, and mouth of all babies during their first 30 days of life.
Swabbed babies had higher levels of two types of what some have found to be, by association at least, “good” bacteria, Lactobacillus and Bacteroides. They are normally present in smaller amounts among C-section infants, while their mouth, gut, and skin microbes more closely resembled that of naturally born infants.
“It was proof of principle that if you expose a baby to maternal vaginal fluids who has not crossed the birth canal, the baby picks up vaginal bacteria,” she says. “If you are going to have an intervention that changes a natural process — in this case, a C-section — can you normalize everything else? The way I see restoration (of bacteria) is an attempt to do that.”
One Bacterium Stands Out
Fledgling research is attempting to determine how the maternal microbiome contributes to healthy babies. But while there’s much scientists still don’t know, they have learned that the bacteria in a woman’s vagina changes dramatically during pregnancy — an altered blend that then coats their babies, if born vaginally. Topping the list for some researchers is Lactobacillus, which wards off infection. But ongoing trials are also revealing a compelling variety of microbes in women’s vaginas, depending on their race, age, and other individual factors.
“Lactobacillus becomes completely dominant; it’s amazing,” Dominguez-Bello says. “There are six different compositions of microbiome in non-pregnant women … but when they get pregnant, they all become dominant in Lactobacillus.”
Why? Scientists aren’t sure, though they’re keen on the idea that evolution has made it this way for distinct reasons. “It’s not surprising it changes, but what’s interesting is how it changes,” she says. “Nature is very clever and evolution has made mechanisms that … confer advantages to the new generation.”
Part of Lactobacillus’ purpose may have to do with keeping the baby inside its mother until it’s ready to thrive on its own. In expectant mothers, low levels of Lactobacillus have been linked to a higher risk of preterm labor, which is 1.5 times more common among African-Americans than white women. Too many or too few of certain bacteria can also heighten the risk for infertility and miscarriage, in addition to preterm birth.
Buck and his fellow researchers have also identified tiny bacteria known as Mycoplasma hominis that’s particularly prevalent among women who give birth prematurely. “Preterm birth is a huge problem — about 10 percent of kids are born preterm, and 3 percent very preterm,” he notes. “There are cases where there’s a much higher frequency in some communities … and we have some ideas about why this is so. But the goal is to establish causality, and understand what the association is between the microbiome and adverse outcomes.”
Hoping for an Enormous Impact
In hopes of solving this puzzle and shedding more light on the link between new mothers’ vaginal microbiome and their children’s future health, Buck and his colleagues launched the Multi-Omic Microbiome Study – Pregnancy Initiative (MOMS-PI) in late 2013. The research, which aims to collect samples from 2,000 women during prenatal visits, will characterize pregnancy-related microbiome changes in many body areas, including the vagina, using six leading-edge “omics” technologies.
The technologies, including metagenomic rRNA gene sequencing, immunoproteomics, and interactomics, will, among other things, help characterize previously unknown bacteria and examine how bacteria interact and impact humans and their immune systems, Buck says. Funded by the National Institutes of Health’s Human Microbiome Project, which launched in 2007, the MOMS-PI effort is enrolling expectant mothers through late 2017 at Virginia Commonwealth University’s women’s and children’s clinics as well as an assortment of hospitals in Washington state.
“We are trying to do this with relatively high numbers of pregnant women and are taking a very broad approach,” Buck says. “It’s longitudinal, it’s broad, and it’s deep. I think that distinguishes us from most groups.”
Other infant microbiome research focuses not just on how infants are born, but how they’re fed, and how this issue potentially affects future health. In a 2013 study, scientists found that babies who were strictly formula-fed exhibited significant differences in intestinal bacteria — which are known to stimulate digestion as well as the immune system — compared to babies who were partially or exclusively breastfed.
When might this emerging research affect everyday medical practice? Will there come a point where every C-section baby is swabbed with its mother’s vaginal bacteria as standard care? Until long-term studies point the way, it’s still unknown how long the benefits of swabbing last. For example, researchers have also found that while babies delivered vaginally are more highly colonized by Lactobacillus in the first three months after birth, there is no difference in colonization after this period. And other factors, such as the mother’s race, age, and whether a baby is breastfed, may be just as influential for an infant’s microbiome.
Taking Matters into our Own Hands
In the meantime, people like the Simonsen-Meehans — and even some microbiome researchers — are hedging their bets on that outcome. Computational biologist Rob Knight of the University of California, San Diego, a co-investigator of Dominguez-Bello’s, swabbed his own daughter with his partner’s vaginal bacteria after an unplanned C-section in 2011.
A hasty decision was in order for the couple when her labor stalled and their baby girl’s heart rate increased with each contraction. Just before his partner’s surgery, Knight took a handful of sterile cotton swabs and quickly gathered a sample of her vaginal bacteria. Two hours after the birth of their daughter, he used those swabs to transfer the bacteria to their newborn.
Knight acknowledges that mothers considering this technique should first know their status for sexually transmitted infections such as human papillomavirus, chlamydia, HIV, and other pathogens, along with group B Streptococcus, for which pregnant women are typically tested before term.
“Given that it’s not that hard to transfer the microbes from the appropriate part of the mother to the baby, we decided to take matters into our own hands,” Knight says, noting that his now 4-year-old daughter is completely healthy. “We’re not talking about a very technically advanced procedure, nor was it planned. But as with so many decisions you make as parents, figuring out what you should do is based on a lot of incomplete evidence.”