Objective: Prediction of preterm birth is currently not feasible, resulting in maternal and fetal overexposure to prenatal corticosteroids and unnecessary hospital admittance. Novel biomarkers seem to hold potential for predictive applicability, including non-invasive volatile organic compounds. In this study, we aimed to assess the potential of urinary volatile organic compound profiles (VOCs) in the identification of pregnant women at risk for preterm birth. Design, setting, population: We prospectively collected urine of women admitted for imminent preterm birth (≧ 24+0 weeks until 36+6 weeks), collected data on maternal characteristics, including urine cultures, time between admission and delivery and mode of delivery. Methods and main outcome measures: Urine samples were analyzed using gas chromatography coupled to an ion mobility spectrometer (GC-IMS). VOCs of women delivering preterm and term were compared. Results: Urinary VOCs differed between women delivering between 28+0 until 36+6 weeks compared to women admitted for imminent preterm birth but delivering at term (area under the curve: 0.70). We identified women with either chorioamnionitis (area under the curve: 0.72) and positive bacterial cultures (area under the curve: 0.97) based on their urinary VOCs. Conclusions: Urinary VOCs hold potential for non-invasive prediction of preterm birth. Furthermore, they may allow for detection of chorioamnionitis and urinary tract infections in the investigated population. These observations need to be validated in a larger population prior to clinical implementation. Funding: This study was funded by the Department of Obstetrics and Prenatal diagnosis. Keywords: preterm birth, premature delivery, volatile organic compounds, chorioamnionitis, urinary tract infection, infection

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.