A new study suggests that mothers at risk of premature birth may be identified far sooner in pregnancy than current tests allow by identifying specific bacteria and metabolites in their cervico-vaginal fluid.
A study exploring cervico-vaginal samples taken at 10-15 and 16-23 weeks from 346 mothers, which included 60 spontaneous preterm births at or before 37 weeks, has identified potentially risk-reducing interactions in microbiota and maternal host defence molecules.(1) Notably, an increased relative abundance of two lactobacilli, L. crispatus, and L. acidophilus, appeared protective against spontaneous preterm birth before 34 weeks. The implications of the study, according to its part-sponsor Tommy’s Charity in the UK, means that mothers at risk of premature birth could be identified far sooner in pregnancy than current tests allow.
As background to the study the authors acknowledge that the syndrome of spontaneous preterm birth (PTB) is a major cause of neonatal death and morbidity. They note the considerable effort so far directed toward defining causal mechanisms, with inflammation and/or infection consistently emerging as important factors for mid-trimester miscarriage, early PTB (<34 weeks) and preterm pre-labour rupture of membranes. They further note that the role of vaginal microbiota/microbiome has been explored in many studies, but has yet to result in a clear understanding of the pathophysiology — or in the identification of effective biomarkers and clinical interventions to improve pregnancy outcomes. Now, this prospective longitudinal study, known as INSIGHT, shows for the first time that a specific type of bacteria can limit the risk of early premature birth.
Specifically, a combination of bacteria (L. crispatus and L. acidophilus) and certain biochemicals (glucose, aspartate and calcium) was linked to birth at or before 34 weeks, while seven different metabolites (leucine, tyrosine, aspartate, lactate, betaine, acetate and calcium) were associated with birth at or before 37 weeks. These findings proved equally significant in tests from the first and second trimester, suggesting that vulnerable mothers and babies could be accurately identified much sooner than current tests allow - and thus may benefit from medical or surgical treatments that aren’t possible in late pregnancy.
In a press statement issued by the Tommy’s Charity, one of the study authors, Professor Andrew Shennan from King’s College London, explained that his group had already developed some preterm birth prediction tools which are very accurate later in pregnancy (fetal fibronectin, for example), but at this stage, he said, ‘you can only manage the risks, not stop it from happening. The sooner we can find out who’s at risk, the more we can do to keep mothers and babies safe.’
His colleague, Professor Rachel Tribe, added: ‘With so many factors in play, it’s unlikely that testing for the same single bacteria species will predict premature birth in every mother, but we now have a panel of bacteria and metabolites that could be useful. In particular, tests during early pregnancy for Lactobacillus crispatus and L. acidophilus could provide reassurance to mothers who would otherwise be unduly worried, and help those who need it get specialist care as soon as possible.’
The authors note that disturbances of the cervico-vaginal microbiota are increasingly implicated in the cause of PTB, but without the realisation of any clinical benefit. Now, in this analytical and modelling study, we seem to have a direct association of risk with the cervico-vaginal metabolic profile, alterations to host response markers, and the presence of specific bacteria – which together present ‘a possible tool in the prevention of sPTB’. ‘These observations,’ they add, ‘strengthen our working hypothesis that an inflammatory environment evoked by the vaginal bacteria increases the risk of inadequate cervicovaginal defence and reduced cervical integrity.’
Tommy’s defines PTB as ‘extremely preterm’ as before 28 weeks, ‘very preterm’ as 28-32 weeks, and ‘moderate to late preterm’ as 32 to 37 weeks. Around 8% of all births are born before week 37, very often with little or no sign or warning. Risks have been identified in cervical insufficiency, intrauterine infection, cone biopsy and multiple pregnancy – and a previous history of PTB.
The role of vaginal microbial composition has also been studied in miscarriage, which has largely been attributed to embryonic aneuploidy. However, another UK study presented at this year’s annual meeting of ESHRE found that the vaginal microbiota, notably Lactobacillus spp, play an important aetiological role in euploid miscarriage and may represent a target to modify the risk of pregnancy loss.(2)
1. Falaviani F, Hezelgrave NL, Kanno T, et al. Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort. JCI Insight 2021; 6: e149257. doi.org/10.1172/jci.insight.149257.
2. Grewal K, Lee Y, Smith A, et al. O-129 Lactobacillus deplete vaginal microbial composition is associated with chromosomally normal miscarriage and local inflammation. Hum Reprod 2021;3 6; Supply 1. doi.org/10.1093/humrep/deab126.054