Detection of Volatile Organic Compounds as Potential Novel Biomarkers for Chorioamnionitis – Proof of Experimental Models

Abstract

Background: Histologic chorioamnionitis is only diagnosed postnatally which prevents interventions. We hypothesized that volatile organic compounds (VOCs) in the amniotic fluid might be useful biomarkers for chorioamnionitis and that VOC profiles differ between amnionitis of different origins.Methods: Time-mated ewes received intra-amniotic injections of media or saline (controls), or live Ureaplasma parvum serovar 3 (Up) 14, 7 or 3d prior to c-section at day 124 gestational age (GA). 100 μg recombinant ovine IL-1α was instilled at 7, 3 or 1d prior to delivery. Headspace VOC profiles were measured from amniotic fluids at birth using ion mobility spectrometer coupled with multi-capillary columns.Results: 127 VOC peaks were identified. 27 VOCs differed between samples from controls and Up- or IL-1α induced amnionitis. The best discrimination between amnionitis by Up vs. IL-1α was reached by 2-methylpentane, with a sensitivity/specificity of 96/95% and a positive predictive value/negative predictive values of 96 and 95%. The concentration of 2-methylpentane in VOCs peaked 7d after intra-amniotic instillation of Up.Discussion: We established a novel method to study headspace VOC profiles of amniotic fluids. VOC profiles may be a useful tool to detect and to assess the duration of amnionitis induced by Up. 2-methylpentane was previously described in the exhalate of women with pre-eclampsia and might be a volatile biomarker for amnionitis. Amniotic fluids analyzed by ion mobility spectrometry coupled with multi-capillary columns may provide bedside diagnosis of amnionitis and understanding inflammatory mechanisms during pregnancy.

Patterns of volatile organic compounds in excrements of preterm neonates

“…We could previously demonstrate that VOC profiles can be detected in the incubator atmosphere of neonates, and we were able to differentiate between empty and full incubators using the MCC/IMS in a proof‐of‐principle study 11 . Moreover, we found a potential biomarker for amnion infection syndrome (AIS) using VOC analysis via MCC/IMS 12 . In this study, we aimed to proof if we can generate VOC profiles originating from stool and urine and whether these specimens can be used for diagnostics.…”

“…11 Moreover, we found a potential biomarker for amnion infection syndrome (AIS) using VOC analysis via MCC/IMS. 12 In this study, we aimed to proof if we can generate VOC profiles originating from stool and urine and whether these specimens can be used for diagnostics. Since stool and urine are obtained noninvasively as a waste product, they seem to be suitable for easy diagnostics in preterm infants but also in term infants.…”

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

“…Another recent study used VOC analyses in the exhaled breath of pregnant sheep to diagnose intra-uterine infections ( 22 ). Chorioamnionitis was further detected using VOC profiles in the amniotic fluid of time-mated ewes ( 23 ). Uncovering microbial pathways associated with specific VOCs in sPB in humans could provide more insight into the pathophysiology of PB and could hypothetically be used as predictive biomarkers ( 22 ).…”