JCI Insight. 2021 Jul 13:149257. doi: 10.1172/jci.insight.149257. Online ahead of print.
ABSTRACT
The syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and management. Individual associations between sPTB, ethnicity, vaginal microbiota, metabolome and innate immune response are known, but not fully understood and knowledge has yet to impact clinical practice. Here we use multi-data type integration and composite statistical models to gain insight into sPTB risk by exploring the cervicovaginal environment of an ethnically heterogenous pregnant population (n=346 women; n=60 sPTB <37 weeks’ gestation, including n=27 sPTB <34 weeks). Analysis of cervicovaginal samples (10-15+6 weeks) identified novel interactions between risk of sPTB and microbiota, metabolite, and maternal host defense molecules. Statistical modelling identified a composite of metabolites (leucine, tyrosine, aspartate, lactate, betaine, acetate and Ca2+) associated with risk of sPTB <37 weeks (Area Under the Curve – AUC 0.752). A combination of glucose, aspartate, Ca2+ and Lactobacillus crispatus and L. acidophilus relative abundance, identified risk of early sPTB <34 weeks, (AUC 0.758); improved by ethnicity stratification (AUC 0.835). Increased relative abundance of L. acidophilus appeared protective against sPTB <34 weeks. By using cervicovaginal fluid samples, we demonstrate the potential of multi-datatype integration for developing composite models towards understanding the contribution of the vaginal environment to risk of sPTB.
PMID:34255744 | DOI:10.1172/jci.insight.149257
