A woman’s blood type may be associated with an increased risk of spontaneous preterm birth, the most common—and puzzling—type of early labor that occurs without warning or obvious cause.
In a consequential paper, scientists at the March of Dimes Prematurity Research Center at Imperial College London have published findings linking a woman’s blood type and her risk of spontaneous preterm birth depending on her gynecological and obstetrical history.
The paper, published recently in npj Biofilms and Microbiomes, in the Nature family of journals, details blood type and risk linkages in three different types of pregnant women: those in the general population; those considered high risk because of surgical removal of pre-cancerous tissue from the cervix as a result of Human Papilloma Virus (HPV) infection; and those considered high risk due to a previous spontaneous preterm birth.
The findings were striking, with blood type B appearing to be associated with an increased risk of preterm birth, blood type A appearing to be associated with a lower risk, and blood type O appearing to go either way depending on the composition of the woman’s vaginal microbiome, which is the collection of bacteria, or flora, in her vaginal canal. (While the vaginal microbiome also includes fungi and viruses, those were not analyzed in this study, and the vast majority of vaginal microbiome references are specific to the bacteria in the vaginal canal, since its links to reproductive outcomes are strongest.)
First, the study found that pregnant women in the general population with blood type B were at higher risk of spontaneous preterm birth before 37 weeks than women with blood types A or O.
Second, it found that pregnant women with blood type B and previous treatment to the cervix for precancerous changes were at higher risk of spontaneous preterm birth before 34 weeks than women who had blood types A or O.
And third, it found that women with a previous spontaneous preterm birth with blood type O, the most common blood type globally, were at higher risk of spontaneous preterm birth than similar women with blood types A or B. Women with a previous spontaneous preterm birth with blood type A were least at risk of having another early labor before 34 weeks.
In addition, blood type O women with a previous spontaneous preterm birth were at highest risk out of all three groups of women; their preterm birth risk was 13.6% before 34 weeks. (The 2024 spontaneous preterm birth rate before 34 weeks at Imperial College London was 1.7%.)
Ironically, there may be a silver lining for this cohort, said Dr. Lynne Sykes, one of the three directors of the Imperial PRC and the senior author of the landmark blood type study.
“Because blood type O showed the strongest direct association between bad bacteria, inflammation and preterm birth, it’s likely that their preterm birth is caused by bad bacteria in the vaginal microbiome, and that they stand to benefit from a vaginal probiotic treatment that could flip their flora from bad to good,” Dr. Sykes said.
The study also illuminated the relationship between microbiome composition and blood type. It found that blood type A women are more likely to have a good microbiome containing the protective L. crispatus bacteria; blood type B women are more likely to have a bad microbiome and local inflammation; and in blood type O women, having bad bacteria is directly related to inflammation and preterm birth. In the study, blood type O women with healthy microbiomes containing good bacteria and low inflammation were more likely to maintain a normal length cervix and deliver at term, while those with adverse microbiomes containing bad bacteria and inflammation were more likely to have a short cervix and early labor.
“This is where the microbiome really pulls out as a cause that could be modified with treatment,” said Dr. Sykes. “It looks like in blood type O, the microbiome is playing a bigger role in preterm birth than in other blood types.”
Dr. Sykes said the study findings, which she called complex yet meticulously researched, represent some of the first links between genetics and preterm birth risk. She said the findings were strengthened by the fact that the team saw the same results from analyzing medical records containing blood type and analyzing blood type sugars found in vaginal fluid.
It’s the first time a study has explored vaginal blood type sugars in the context of preterm birth risk prediction, she said. Previously, blood type B in women has been linked to gonorrhea, Group B strep, and E. coli infection.
“This work highlights how blood type can make a difference in preterm birth risk depending on the mechanism of preterm birth,” said Dr. Sykes, who credited study first author Dr. Katie Mountain and additional study funder The Parasol Foundation in supporting the research.
“It also makes clear how important it is to phenotype women” into different risk profiles, she added.
Dr. Sykes cautioned against making broad generalizations about blood type and preterm birth risk, stressing that a woman’s blood type was not the sole driving force behind risk, but that her risk status—and the reason behind that risk status—were also factors.
“It’s not just about blood type,” she said. “It’s also about your past pregnancies and your gynecological history, as well as your overall health. Risk depends not just on blood type, but on the woman, too.”
“When we look at all these factors together, that’s when we start to see a clearer picture of risk, and that’s when we get closer to personalized, precision medicine in this space.”
The paper’s findings came from data gathered at Imperial College London spanning two decades. That data consisted of two cohorts. The first cohort was drawn from the Electronic Medical Records (EMR) of 74,000 completed pregnancies at Imperial NHS Healthcare Trust in collaboration with the iCARE NIHR Imperial Biomedical Research Centre. The second cohort consisted of data belonging to 2,000 high risk pregnant women who were seen at Imperial’s preterm birth prevention clinic. Those 2,000 women were further separated into two subgroups: women at risk of delivering early due to a previous cervical treatment and those at risk of delivering early due to a previous early delivery.
In the first general population group, women with blood type B were at highest risk of preterm birth before 37 weeks (5.8%), while women with blood type A were at lowest risk (4.9%). That means blood type B women were at 18% higher relative risk than blood type A women.
In the “at risk” group of women with previous treatment to the cervix, women with blood type B had more than a 150% higher relative risk of preterm birth before 34 weeks compared to blood type A or O women. In this group, blood type B women had a 7.4% risk while blood type A women had a 2.6% risk, and blood type O women had a 2.8% risk.
Finally, in the last group of women with a previous spontaneous preterm birth, blood type O women had a 49% higher relative risk of early preterm birth compared to blood type A women and a 58% higher relative risk compared to blood type B women. (The preterm birth risk was 13.6% for O, 9.1% for A and 8.6% for B.)
Dr. Sykes said the findings opened up a floodgate of new scientific paths to pursue, including trying to explain the relationship between blood type and preterm birth risk in different types of women.
It remains unclear, for example, why blood type B represents the highest risk for women in the general population, but blood type O represents the highest risk for women with a previous spontaneous preterm birth. It’s also unknown, she said, why blood type B represents the highest risk for women with previous cervical treatment for pre-cancerous cells, but speculated two inflammatory factors that could be driving the risk: persistent HPV infection, which is related to bad bacteria in the vaginal microbiome, and/or residual injury from the procedure to remove the pre-cancerous cells from the cervix.
Dr. Sykes said other imminent avenues of inquiry include attempting to alter the sugar receptors found on vaginal cells belonging to women with blood type B who were at heightened risk of preterm birth. Altering the sugars, Dr. Sykes said, may make the vaginal cells more attractive attachment sites for good bacteria, which researchers hope colonize the vagina and protect against preterm birth. She credited Imperial PRC sugar experts Ten Feizi, Yan Liu, Anne Dell and Stuart Haslam, part of the glycoscience and glycobiology group, with the team’s understanding of sugars in the female reproductive tract.
“We have a lot of questions, a lot of hypotheses and a lot of interest in this work, and we are extremely energized to peel back the layers even further,” she said, adding that in the future, this research could result in personalized treatment targets, personalized explanations for preterm birth, and even personalized risk scores through a consumer app.
She added that the team ruled out two confounding factors that could have obscured the findings: ethnicity and indicated preterm birth. This means that the associations between blood type and preterm birth held true regardless of ethnicity and did not extend to indicated preterm birth, where doctors induce labor early for the health of mother and child. This gave the team trust that the associations were strictly related to spontaneous, and not indicated, preterm birth, a preterm birth phenotype that has historically eluded associations and explanation.
“This really gave us confidence in the vigor of these findings,” she said.
The March of Dimes Prematurity Research Center at Imperial College London is a global leader in translational science around preterm birth and the vaginal microbiome. Imperial PRC scientists are spearheading some of the biggest discoveries in the field.
They include identifying the inflammatory pathway of bad bacteria in the vaginal microbiome that leads to preterm birth; creating a preterm birth risk test based on vaginal bacteria and its inflammatory status; pinpointing the best strain of good vaginal bacteria to protect against preterm birth; and conducting the first clinical trial of a vaginal probiotic to reduce preterm birth risk.
Now, with the addition of blood type sugars found in the microbiome as another driver of preterm birth, the team is poised to make even further revelatory breakthroughs in the fight against this elusive condition.
“We’re on the cusp of something really meaningful,” Dr. Sykes said. “It’s all coming together.”