ABO blood group antigens influence host-microbe interactions and risk of early spontaneous preterm birth

The mechanisms by which vaginal microbiota shape spontaneous preterm birth (sPTB) risk remain poorly defined. Using electronic clinical records data from 74,913 maternities in conjunction with metaxanomic (n=596) and immune profiling (n=314) data, we show that the B blood group phenotype associates with increased risk of sPTB and adverse vaginal microbiota composition. The O blood group associates with sPTB in women who have a combination of a previous history of sPTB, an adverse vaginal microbial composition and pro-inflammatory cervicovaginal milieu. In contrast, women of blood group A have a higher prevalence of vaginal Lactobacillus crispatus, a lower risk of sPTB, with sPTB cases showing no association with vaginal microbiota composition or inflammation. We found that cervicovaginal fluid contains ABH(O) glycans, and show variable binding to key vaginal bacteria. This indicates that cervicovaginal ABH(O) glycans influence microbiota-host interactions implicated in sPTB risk, suggesting a novel target for sPTB prediction and prevention.