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Published on: June 1, 2022
Screening of Chorioamnionitis Using Volatile Organic Compound Detection in Exhaled Breath: A Pre-clinical Proof of
Daan R M G Ophelders1,2, Agnes W Boots3,4, Matthias C Hütten1
1Department of Pediatrics, Maastricht University Medical Center+, Maastricht, Netherlands.
Insights
Diagnosing intra-amniotic infections in pregnant sheep using volatile organic compound (VOC) profiles in exhaled breath shows promise. This non-invasive method could enable early detection and timely intervention for high-risk pregnancies.
Area of Science:
- Reproductive Medicine
- Biochemistry
- Diagnostic Medicine
Background:
- Chorioamnionitis is a significant risk factor for preterm birth and neonatal morbidity, with limited therapeutic options.
- Early detection of intra-amniotic infections is crucial for effective management but lacks adequate diagnostic tools.
- Understanding the temporal dynamics of infection and injury is key to developing new therapeutic strategies.
Purpose of the Study:
- To investigate if volatile organic compound (VOC) profiles in exhaled breath can accurately diagnose intra-amniotic infections.
- To identify specific VOC biomarkers associated with chorioamnionitis in a pregnant sheep model.
Main Methods:
- Pregnant Texel ewes were inoculated intra-amniotically with Ureaplasma parvum.
- Exhaled breath samples were collected serially over 6 days post-inoculation.
- Volatile organic compound (VOC) profiles were analyzed to detect infection-specific signatures.
Main Results:
- Ureaplasma parvum infection induced a distinct VOC signature in exhaled breath.
- A profile of 15 VOCs correctly classified infected versus non-infected animals with 83% sensitivity and 71% specificity (AUC 0.93).
- Identified VOCs included nonanal (lipid peroxidation marker) and hydrocarbons like undecane and dodecane, linked to oxidative stress and preterm birth.
Conclusions:
- Exhaled breath VOC analysis can detect intra-amniotic infections, offering a potential non-invasive diagnostic method.
- The identified VOCs may provide insights into infection dynamics and associated oxidative stress pathways.
- This approach could facilitate early surveillance and intervention for high-risk pregnancies, potentially preventing preterm birth complications.
Abstract:
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.
