Volatile organic compound analysis, a new tool in the quest for preterm birth prediction\u2014an observational cohort study

Lauren Lacey,James A Covington,Emma Daulton,Alfian Wicaksono,Siobhan Quenby

doi:10.1038/s41598-020-69142-4

Abstract

Preterm birth is the leading cause of death worldwide in children under five years. Due to its complex multifactorial nature, prediction is a challenge. Current research is aiming to develop accurate predictive models using patient history, ultrasound and biochemical markers. Volatile organic compound (VOC) analysis is an approach, which has good diagnostic potential to predict many disease states. Analysis of VOCs can reflect both the microbiome and host response to a condition. We aimed to ascertain if VOC analysis of vaginal swabs, taken throughout pregnancy, could predict which women go on to deliver preterm. Our prospective observational cohort study demonstrates that VOC analysis of vaginal swabs, taken in the midtrimester, is a fair test (AUC 0.79) for preterm prediction, with a sensitivity of 0.66 (95%CI 0.56–0.75) and specificity 0.89 (95%CI 0.82–0.94). Using vaginal swabs taken closest to delivery, VOC analysis is a good test (AUC 0.84) for the prediction of preterm birth with a sensitivity of 0.73 (95%CI 0.64–0.81) and specificity of 0.90 (95%CI 0.82–0.95). Consequently, VOC analysis of vaginal swabs has potential to be used as a predictive tool. With further work it could be considered as an additional component in models for predicting preterm birth.

Highlights

Preterm birth is the leading cause of death worldwide in children under five years
Treatment of bacterial vaginosis (BV) with antibiotics has not been demonstrated to prevent preterm birth as demonstrated by a recent randomised controlled trial (RCT) and a preceding systematic review and meta-analysis[12,13]. This trial focused on the low risk population for spontaneous preterm birth,[12] and the meta-analysis had substantial heterogeneity (I2 = 48%)[13], treatment of the high risk population for BV with antibiotics to reduce the risk of preterm birth could warrant further investigation due to numerous factors contributing to the onset of preterm labour in a susceptible individual
We aimed to identify if specific patterns of Volatile organic compound (VOC) from vaginal swabs taken in pregnancy, were associated with preterm delivery in a population of pregnant women attending a preterm prevention clinic due to pre-existing risk factors for preterm birth using VOC detection and analysis technology involving machine learning, which with development has the potential to be translated into clinical practice and overcome the previously discussed concerns

Summary

Introduction

Preterm birth is the leading cause of death worldwide in children under five years. Due to its complex multifactorial nature, prediction is a challenge. Research is being carried out to try to improve the predictive value of various tests for preterm birth, including the development of prognostic models that account for both the maternal susceptibility and the insult, using patient history, ultrasound findings and biomarkers[4,5,6,7,8]. This aims to enable earlier interventions to facilitate targeted prevention strategies. The mutualistic association between the vagina and the microbiota is a fine balance under the influence of many factors, including sex steroid h ormones[19,20,21,22,23], sexual activity[24,25] and hygiene p ractices[25,26]

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