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

Lacey, Lauren; Daulton, Emma; Wicaksono, Alfian; Covington, James A.; Quenby, Siobhán

doi:10.1038/s41598-020-69142-4

Cited by 7 publications

(6 citation statements)

References 47 publications

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“…Lacey et al ( 46 ) showed that VOC analysis of vaginal swabs obtained in the mid trimester, has potential in the prediction of preterm delivery, with a sensitivity of 0.66 (95%CI 0.56–0.75) and specificity 0.89 (95%CI 0.82–0.94). However, in order to validate the e-nose as a diagnostic tool, studies using elaborate techniques such as liquid chromatography and mass spectrometry, allowing for detection of individual VOC molecules rather than the pattern-recognition based are needed.…”

Section: Discussionmentioning

confidence: 99%

The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review

Ronde

Reiss²,

Hankemeier

et al. 2021

Front. Endocrinol.

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Scopeas the leading cause of perinatal mortality and morbidity worldwide, the impact of premature delivery is undisputable. Thus far, non-invasive, cost-efficient and accurate biochemical markers to predict preterm delivery are scarce. The aim of this systematic review is to investigate the potential of non-invasive metabolomic biomarkers for the prediction of preterm delivery.Methods and ResultsDatabases were systematically searched from March 2019 up to May 2020 resulting in 4062 articles, of which 45 were retrieved for full-text assessment. The resulting metabolites used for further analyses, such as ferritin, prostaglandin and different vitamins were obtained from different human anatomical compartments or sources (vaginal fluid, serum, urine and umbilical cord) and compared between groups of women with preterm and term delivery. None of the reported metabolites showed uniform results, however, a combination of metabolomics biomarkers may have potential to predict preterm delivery and need to be evaluated in future studies.

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Section: Discussionmentioning

confidence: 99%

The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review

Ronde

Reiss²,

Hankemeier

et al. 2021

Front. Endocrinol.

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“…Those findings indicate that the UP infection can be detectable with good accuracy using exhaled breath profile from 96 h onwards post-infection. The discovery of a distinct VOC profile to determine and monitor an intraamniotic UP infection extends recent clinical studies by Lacey et al in which they demonstrated that VOC testing of vaginal swabs can be used to predict group B streptococcus infection during pregnancy (45) and detect bacterial vaginosis which was linked to preterm labor (46).…”

Section: Discussion/conclusionmentioning

confidence: 71%

Screening of Chorioamnionitis Using Volatile Organic Compound Detection in Exhaled Breath: A Pre-clinical Proof of Concept Study

et al. 2021

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Chorioamnionitis is a major risk factor for preterm birth and an independent risk factor for postnatal morbidity for which currently successful therapies are lacking. Emerging evidence indicates that the timing and duration of intra-amniotic infections are crucial determinants for the stage of developmental injury at birth. Insight into the dynamical changes of organ injury after the onset of chorioamnionitis revealed novel therapeutic windows of opportunity. Importantly, successful development and implementation of therapies in clinical care is currently impeded by a lack of diagnostic tools for early (prenatal) detection and surveillance of intra-amniotic infections. In the current study we questioned whether an intra-amniotic infection could be accurately diagnosed by a specific volatile organic compound (VOC) profile in exhaled breath of pregnant sheep. For this purpose pregnant Texel ewes were inoculated intra-amniotically with Ureaplasma parvum and serial collections of exhaled breath were performed for 6 days. Ureaplasma parvum infection induced a distinct VOC-signature in expired breath of pregnant sheep that was significantly different between day 0 and 1 vs. day 5 and 6. Based on a profile of only 15 discriminatory volatiles, animals could correctly be classified as either infected (day 5 and 6) or not (day 0 and 1) with a sensitivity of 83% and a specificity of 71% and an area under the curve of 0.93. Chemical identification of these distinct VOCs revealed the presence of a lipid peroxidation marker nonanal and various hydrocarbons including n-undecane and n-dodecane. These data indicate that intra-amniotic infections can be detected by VOC analyses of exhaled breath and might provide insight into temporal dynamics of intra-amniotic infection and its underlying pathways. In particular, several of these volatiles are associated with enhanced oxidative stress and undecane and dodecane have been reported as predictive biomarker of spontaneous preterm birth in humans. Applying VOC analysis for the early detection of intra-amniotic infections will lead to appropriate surveillance of these high-risk pregnancies, thereby facilitating appropriate clinical course of action including early treatment of preventative measures for pre-maturity-associated morbidities.

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“…However, another recent study into prediction of PB ( 26 ), showed that VOCs from vaginal swabs obtained closest to delivery analyzed by GC-IMS were most predictive for PB with a positive predictive value of up to 86%. These results indicate that VOCs from vaginal swabs change longitudinally during pregnancy, which could also be in line with our findings of differences in VOC profiles between the different gestational categories.…”

Section: Discussionmentioning

confidence: 99%

“…Within each fold, a Wilcoxon rank sum test was used for calculating p -values in the training set to identify the important features. The 100 features with the smallest p -values were used to train different classifiers, specifically Sparse Logistic Regression, Support Vector Machine and Gaussian Process, which have been previously used in such clinical studies ( 26 ). These classifiers were applied to the test set, and this was repeated until every sample has been classified.…”

Section: Methodsmentioning

confidence: 99%

Detection of spontaneous preterm birth by maternal urinary volatile organic compound analysis: A prospective cohort study

Ronde

Frerichs²,

Brantenaar

et al. 2022

Front. Pediatr.

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Accurate prediction of preterm birth is currently challenging, resulting in unnecessary maternal hospital admittance and fetal overexposure to antenatal corticosteroids. Novel biomarkers like volatile organic compounds (VOCs) hold potential for predictive, bed-side clinical applicability. In a proof of principle study, we aimed to assess the predictive potential of urinary volatile organic compounds in the identification of pregnant women at risk for preterm birth. Urine samples of women with a high risk for preterm birth (≧24 + 0 until 36 + 6 weeks) were collected prospectively and analyzed for VOCs using gas chromatography coupled with an ion mobility spectrometer (GS-IMS). Urinary VOCs of women delivering preterm were compared with urine samples of women with suspicion of preterm birth collected at the same gestation period but delivering at term. Additionally, the results were also interpreted in combination with patient characteristics, such as physical examination at admission, microbial cultures, and placental pathology. In our cohort, we found that urinary VOCs of women admitted for imminent preterm birth were not significantly different in the overall group of women delivering preterm vs. term. However, urinary VOCs of women admitted for imminent preterm birth and delivering between 28 + 0 until 36 + 6 weeks compared to women with a high risk for preterm birth during the same gestation period and eventually delivering at term (>37 + 0 weeks) differed significantly (area under the curve: 0.70). In addition, based on the same urinary VOCs, we could identify women with a confirmed chorioamnionitis (area under the curve: 0.72) and urinary tract infection (area under the curve: 0.97). In conclusion, urinary VOCs hold potential for non-invasive, bedside prediction of preterm birth and on the spot identification of intra-uterine infection and urinary tract infections. We suggest these observations are further explored in larger populations.

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

Cited by 7 publications

References 47 publications

The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review

The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review

Screening of Chorioamnionitis Using Volatile Organic Compound Detection in Exhaled Breath: A Pre-clinical Proof of Concept Study

Detection of spontaneous preterm birth by maternal urinary volatile organic compound analysis: A prospective cohort study

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