When a baby passes through its mother’s birth canal, it is bathed in a soup of microbes. Those born by caesarean section (C-section) miss out on this bacterial baptism, and researchers are sharply split on whether that increases the risk of chronic health problems such as obesity and asthma.
A wave of clinical trials now under way could help to settle the question — and feed into the debate over whether seeding babies born by C-section with their mother’s vaginal bacteria is beneficial or potentially harmful. At least four groups of researchers — in the United States, Sweden and China — have begun separate experiments, in which they are swabbing hundreds of C-section babies with their mother’s microbes, while comparing them to a control group.
Each team plans to monitor its study participants over several years in the hope of learning more about how the collection of microbes in their bodies might influence weight, allergy risk and other factors.
But some scientists say that the trials could expose C-section babies to infection, or encourage mothers to try do-it-yourself swabbing, without much evidence that there is a benefit. “It’s not clear to me exactly what disease we’re trying to prevent or treat,” says Adam Ratner, a microbiologist at New York University.
In the worst-case scenario, he says, “you’ve taken a kid with low risk of infection and you’ve rubbed herpes all over their face”.
The idea that birth mode might affect health gained traction in 2010, when microbial ecologist Maria Gloria Dominguez Bello of Rutgers University in New Brunswick, New Jersey, found that babies delivered surgically harboured different collections of bacteria than did those born vaginally1. C-section babies, which comprise more than 30% of births in the United States, are also more prone to obesity and immune diseases such as diabetes2.
Dominguez Bello and her colleagues suspect that bacteria could be the long-sought link between birth method and long-term health. Experiments show that mice born by C-section are more prone to obesity and have impaired immune systems3. There are fewer factors that could account for these differences in the rodents, which can be studied in controlled conditions, than in people.
But many scientists say there is no evidence that differing exposure to vaginal microbes at birth can help explain variation in people’s health over time. “Right now, that whole concept is in very much a state of uncertainty,” says David Aronoff, an infectious-disease researcher at Vanderbilt University in Nashville, Tennessee. “It’s easy to make a logical argument that sounds great, but underneath it might not be solid data.”
Aronoff says that differences in microbe exposure at birth and later health could be caused by other factors, such as whether a mother takes antibiotics during her surgery, and whether a baby is breastfed or has a genetic predisposition to obesity. He argues that the only way to isolate any effect from method of birth is through the sort of large, randomized, controlled clinical trials that are now under way.
Dominguez Bello’s team began recruiting 50 pregnant women last August for a study that will swab caesarean-born babies with their mothers’ microbes. The scientists hope to expand this to more than 600 infants. A second US trial, run out of the Icahn School of Medicine at Mount Sinai in New York City, is recruiting 120 pregnant women with a family history of allergies. Researchers will compare swabbed C-section babies with a placebo group and with infants delivered vaginally.
Researchers in Sweden began a similar experiment in March, with the goal of swabbing 100 cesarean-born infants with their mothers’ vaginal and anal bacteria. Gastroenterologist Lars Engstrand of the Karolinska Institute in Stockholm, who directs the trial, says that his team will monitor the babies over two years for signs of asthma and dermatitis. And a fourth trial, in China, began recruiting roughly 100 mothers last November. Scientists will seed these women’s babies with vaginal bacteria and monitor their body mass index and allergy risk.
The researchers behind these trials say that their protocols do not increase the risk of infection for C-section babies. Nevertheless, the scientists are rigorously screening mothers participating in these trials for microbes such as HIV and group B streptococcus — a common vaginal bacterium that causes respiratory problems in newborns. “We are aware that this is something we have to be very careful about,” says Engstrand, noting that his trial design underwent an ethical review.
Still, some researchers say the experiments should not be done, given the lack of evidence that swabbing infants with their mothers’ bacteria produces any benefit. “You’d have to be sure that you understand the mechanism and the trial is based on good science, and what you know is likely to work,” says Jeffrey Keelan, a gynaecologist at the University of Western Australia in Perth.
Some scientists also worry that physicians and mothers will swab babies with vaginal microbes without proper screening or oversight, because of hype surrounding the technique. Scattered reports in media and medical journals suggest that some women are trying the technique on their own. In 2017, the American College of Obstetrics and Gynecology issued guidelines stating that vaginal seeding shouldn’t be performed except in the context of a clinical trial.
And gynaecologist Kjersti Aagaard of Baylor College of Medicine in Houston says that the focus on vaginal seeding could be too narrow. She thinks that microbes’ influence on long-term health can begin before birth, due to factors such as a mother’s diet that influence the bacteria babies pick up. By focusing on vaginal seeding, researchers are “missing actual opportunities to improve offspring health”, she said in June talk at the American Society for Microbiology meeting in San Francisco, California.
The scientists behind the current wave of seeding trials are pushing ahead. “We’re trying to repair and partially restore something that is normally in the environment of babies being born,” Dominguez Bello says, adding that the only way to determine microbes’ role in health is to do the controlled trial. “As with everything, history will tell.”
Nature 572, 423-424 (2019)