A Combination of Cervicovaginal Fluid Glutamate, Acetate and D-Lactate Identified Asymptomatic Low-Risk Women Destined to Deliver Preterm: a Prospective Cohort Study

Emmanuel Amabebe,Dilly O C Anumba

doi:10.1007/s43032-021-00711-2

Emmanuel Amabebe, Dilly O C Anumba

Open Access

https://doi.org/10.1007/s43032-021-00711-2

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Abstract

Due to the modest predictive capacities and limited clinical application of transvaginal ultrasonographic cervical length (CL) and quantitative fetal fibronectin (qfFN) in pregnant women at low risk of preterm birth (PTB), we sought to determine the utility of cervicovaginal fluid (CVF) metabolites (by-products of host-microbial metabolism) for prediction of spontaneous PTB in asymptomatic low-risk women at mid-gestation. This was a prospective sub-cohort study from the ECCLIPPx study cohort. CVF from asymptomatic singleton women (20–22 weeks, n = 168) without a prior history of PTB were analysed for metabolites by enzyme-based spectrophotometry. CL, vaginal pH and qfFN were also measured. Correlation and predictive analyses were performed by Spearman’s correlation, and binary logistic regression and area under receiver operating characteristic curve (AUC), respectively. Of the 168 women enrolled, only CVF samples from 135 (80.4%) women were analysed. There were 6/135 (4.4%) spontaneous PTB (sPTBs), with two of these pregnancies ending ≤ 28 weeks’ gestation. Individually (AUC, 95% CI), only glutamate (0.72, 0.64–0.80) and CL (0.69, 0.60–0.77) were predictive of PTB. However, five multivariable models that more accurately predicted sPTB were also identified, i.e. a combination of: glutamate, acetate and D-lactate (GAD, 0.82, 0.74–0.89); CL and qfFN only (0.78, 0.70–0.85); CL, qfFN, glutamate and acetate (0.88, 0.81–0.93); CL, qfFN and GAD (0.94, 0.88–0.98); and GAD and pH (0.86, 0.79–0.92). Correlations between CL, pH and qfFN and metabolites were also observed. In this cohort, a midtrimester combination of CVF glutamate, acetate and D-lactate predicted preterm birth more accurately than individual metabolites, cervical length and fetal fibronectin with a very low false-positive rate and high positive predictive value. Further testing in populations with higher preterm birth rates is required.

Highlights

Accurate prediction of deliveries before 37 completed weeks of gestation in asymptomatic pregnant women with transvaginal ultrasound cervical length (CL) > 25 mm and without a prior history of preterm birth (PTB) has been a challenge to obstetricians and other caregivers
The clinical and demographic characteristics as well as cervicovaginal fluid (CVF) metabolite concentrations of women with preterm and term delivery were subjected to Shapiro–Wilk normality test before analysis by Mann–Whitney U test or unpaired Student’s t-test depending on the result of the normality test
Of the 168 predominantly Caucasian women enrolled in the study, only CVF samples from 135 (80.4%) women were analysed for metabolites by enzyme-based spectrophotometry—a targeted metabolomics technique with great potential for clinical translation

Summary

Introduction

Accurate prediction of deliveries before 37 completed weeks of gestation (preterm birth, PTB) in asymptomatic pregnant women with transvaginal ultrasound cervical length (CL) > 25 mm and without a prior history of PTB has been a challenge to obstetricians and other caregivers. Such women are reported to have a lower risk of spontaneous PTB (sPTB) compared to women with a previous history of PTB and short cervix [1, 2]. A previous history of PTB increases a woman’s risk of subsequent premature deliveries by 4–6 times [2, 7].

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