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

Sybelle Goedicke-Fritz,Owen Brad Spiller,Tobias Rogosch,Michelle Bous,Regine Stutz,Boris W Kramer,Thomas Werner,Rolf Felix Maier,Matthew W Kemp,Tim G A M Wolfs,Jörg Ingo Baumbach,Sascha Meyer,Hendrik J Niemarkt,Michael Zemlin,Elisabeth Kaiser,Andreas Rembert Koczulla,Alan H Jobe

doi:10.3389/fped.2021.698489

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.

Highlights

Chorioamnionitis (CA) is defined as an acute inflammation of the fetal membranes and amniotic fluids [1,2,3] and is one of the main causes of preterm delivery and prematurity-associated morbidities worldwide [4,5,6]
This study aimed at identifying Volatile organic compound (VOC) or patterns of VOCs in amniotic fluids that can be used as potential diagnostic markers for amnionitis, e.g., after the discharge of amniotic fluids after premature rupture of membranes
A total of 127 signals were identified, as characterized by drift and retention time of ions formed from amniotic fluids of sheep after intra-amniotic instillation of Ureaplasma parvum, Interleukin-1α samples and controls (Figure 2A, Supplementary Table 1)

Summary

Introduction

Chorioamnionitis (CA) is defined as an acute inflammation of the fetal membranes and amniotic fluids [1,2,3] and is one of the main causes of preterm delivery and prematurity-associated morbidities worldwide [4,5,6]. As a confirmation after delivery, the histologic detection of inflammation and/or microbes in the placenta, amnion, chorion or amniotic fluid are considered the gold standard for diagnosis [21,22,23,24]. Volatile organic compounds (VOCs) analysis might be a promising new technique for early detection and monitoring of various diseases, including CA [23]. 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

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Conclusion