TY - JOUR
T1 - Exploratory and confirmatory analysis to investigate the presence of vaginal metabolome expression of microbial invasion of the amniotic cavity in women with preterm labor using high-performance liquid chromatography
AU - Polat, Ibrahim H.
AU - Marin, Silvia
AU - Ríos, José
AU - Larroya, Marta
AU - Sánchez-García, Ana B.
AU - Murillo, Clara
AU - Rueda, Claudia
AU - Cascante, Marta
AU - Gratacós, Eduard
AU - Cobo, Teresa
N1 - Funding Information:
This project has been partially funded by the Instituto de Salud Carlos III (PI10/01308; PI15/00344 and CM09/00213) integrado en el Plan Nacional de I+D+I and co-funded by the ISCIII-Subdirecci?n General de Evaluaci?n y el Fondo Europeo de Desarrollo Regional ?Una manera de hacer Europa? and the Cellex Foundation. T.C. has received funding by the grant SLT008/18/00126 from the Departament de Salut, Generalitat de Catalunya. E.G. has received funding from the ?la Caixa? Foundation under grant agreements LCF/PR/GN14/10270005 and LCF/PR/GN18/10310003, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, United Kingdom), and Agency for Management of University and Research Grants 2017 under SGR grant number 1531.
Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Background: Although the influence of microbial invasion of the amniotic cavity on the development of spontaneous preterm delivery is unquestionable, the use of an invasive procedure to diagnose the status of an infection limits its clinical translation. Objective: This study aimed to use exploratory and confirmatory analyses to investigate the presence of vaginal metabolome expression of microbial invasion of the amniotic cavity in women diagnosed as having preterm labor using high-performance liquid chromatography. Study Design: In 140 women with singleton pregnancies and a diagnosis of preterm labor at <34 weeks’ gestation, we analyzed vaginal amino acid concentrations using high-performance liquid chromatography. Vaginal samples were collected shortly after the amniocentesis performed at admission to rule out microbial invasion of the amniotic cavity. Data were normalized for the median of all the amino acid concentrations evaluated. Microbial invasion of the amniotic cavity was defined as a positive aerobic or anaerobic amniotic fluid culture for the presence of bacteria or yeast or Ureaplasma species or Mycoplasma hominis in the mycoplasma culture or a positive polymerase chain reaction result for 16S rRNA gene sequence. Exploratory analysis was performed in half of the sample and confirmatory analysis in the other half. We compared vaginal amino acid concentrations between women with and without microbial invasion of the amniotic cavity in both cohorts. The area under the curve with 95% confidence interval values were calculated for vaginal amino acids with significant differences. Results: In the exploratory cohort (2014–2015), 17 of 76 women (22.3%) had microbial invasion of the amniotic cavity compared with 14 of 72 (19.4%) in the confirmatory cohort (2016–2017). In the exploratory cohort, we found significantly higher amino acid concentrations of vaginal taurine, lysine, and cysteine and significantly lower concentrations of vaginal glutamate, aspartate, and the aspartate to asparagine ratio. These significant differences were confirmed in the confirmatory cohort. The area under the curve of these vaginal amino acids to predict microbial invasion of the amniotic cavity ranged between 0.72 and 0.79, with cysteine being the amino acid with the best performance with an area under the curve of 0.79 (95% confidence interval, 0.71–0.88). Conclusion: We found the vaginal metabolome expression of microbial invasion of the amniotic cavity in women with preterm labor and intact membranes. These findings might open the possibility to develop noninvasive diagnostic tools of microbial invasion of the amniotic cavity with the aim of selecting women who would most likely benefit from an amniocentesis for this indication.
AB - Background: Although the influence of microbial invasion of the amniotic cavity on the development of spontaneous preterm delivery is unquestionable, the use of an invasive procedure to diagnose the status of an infection limits its clinical translation. Objective: This study aimed to use exploratory and confirmatory analyses to investigate the presence of vaginal metabolome expression of microbial invasion of the amniotic cavity in women diagnosed as having preterm labor using high-performance liquid chromatography. Study Design: In 140 women with singleton pregnancies and a diagnosis of preterm labor at <34 weeks’ gestation, we analyzed vaginal amino acid concentrations using high-performance liquid chromatography. Vaginal samples were collected shortly after the amniocentesis performed at admission to rule out microbial invasion of the amniotic cavity. Data were normalized for the median of all the amino acid concentrations evaluated. Microbial invasion of the amniotic cavity was defined as a positive aerobic or anaerobic amniotic fluid culture for the presence of bacteria or yeast or Ureaplasma species or Mycoplasma hominis in the mycoplasma culture or a positive polymerase chain reaction result for 16S rRNA gene sequence. Exploratory analysis was performed in half of the sample and confirmatory analysis in the other half. We compared vaginal amino acid concentrations between women with and without microbial invasion of the amniotic cavity in both cohorts. The area under the curve with 95% confidence interval values were calculated for vaginal amino acids with significant differences. Results: In the exploratory cohort (2014–2015), 17 of 76 women (22.3%) had microbial invasion of the amniotic cavity compared with 14 of 72 (19.4%) in the confirmatory cohort (2016–2017). In the exploratory cohort, we found significantly higher amino acid concentrations of vaginal taurine, lysine, and cysteine and significantly lower concentrations of vaginal glutamate, aspartate, and the aspartate to asparagine ratio. These significant differences were confirmed in the confirmatory cohort. The area under the curve of these vaginal amino acids to predict microbial invasion of the amniotic cavity ranged between 0.72 and 0.79, with cysteine being the amino acid with the best performance with an area under the curve of 0.79 (95% confidence interval, 0.71–0.88). Conclusion: We found the vaginal metabolome expression of microbial invasion of the amniotic cavity in women with preterm labor and intact membranes. These findings might open the possibility to develop noninvasive diagnostic tools of microbial invasion of the amniotic cavity with the aim of selecting women who would most likely benefit from an amniocentesis for this indication.
KW - high-performance liquid chromatography
KW - metabolomics
KW - microbial invasion of amniotic cavity
KW - minimally invasive diagnoses
KW - preterm labor
KW - vaginal fluid
UR - http://www.scopus.com/inward/record.url?scp=85090753161&partnerID=8YFLogxK
U2 - 10.1016/j.ajog.2020.07.040
DO - 10.1016/j.ajog.2020.07.040
M3 - Artículo
C2 - 32717258
AN - SCOPUS:85090753161
VL - 224
SP - 90.e1-90.e9
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
SN - 0002-9378
IS - 1
ER -