Stress and Metabolomics for Prediction of Spontaneous Preterm Birth: A Prospective Nested Case-Control Study in a Tertiary Hospital

Dongni Huang; Zheng Liu; Xiyao Liu; Yuxiang Bai; Mengshi Wu; Xin Luo; Hongbo Qi

doi:10.3389/fped.2021.670382

Stress and Metabolomics for Prediction of Spontaneous Preterm Birth: A Prospective Nested Case-Control Study in a Tertiary Hospital

Front Pediatr. 2021 Sep 7:9:670382. doi: 10.3389/fped.2021.670382. eCollection 2021.

Authors

Dongni Huang^{1

2

3

4}, Zheng Liu^{1

2

3}, Xiyao Liu^{1

2

3}, Yuxiang Bai^{1

2

3}, Mengshi Wu^{1

2

3}, Xin Luo^{1

2

3}, Hongbo Qi^{1

2

3}

Affiliations

¹ Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² China-Canada-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China.
³ Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
⁴ Department of Obstetrics, Chongqing Health Center for Women and Children, Chongqing, China.

Abstract

Spontaneous preterm birth (sPTB) is the leading cause of infant morbidity and mortality worldwide. Deficiency of effective predict methods is an urgent problem that needs to be solved. Numbers of researchers spare no efforts to investigate differential indicators. To evaluate the value of the differential indicators, a prospective nested case-control study was carried out. Among an overall cohort of 1,050 pregnancies, 20 sPTB pregnancies, and 20 full-term pregnancies were enrolled in this study. Participants were followed-up until labor. The psychological profile was evaluated utilizing the Zung Self-Rating Depression Scale at 11-14 weeks. Stress-related biomarker-cortisol and metabolites were detected by Electrochemiluminescence Immunoassay (ECLIA) and Gas Chromatography-Mass Spectrometry (GC-MS) in serum samples during pregnancy, respectively. The expression level of cortisol was up-regulated in serum and the score of the Zung Self-Rating Depression Scale was significantly higher in the sPTB group when compared to the control group. Note that, 29 metabolomics were differentially expressed between the sPTB group and the control group. The scores of the Zung Self-Rating Depression Scale, the level of cortisol, Eicosane, methyltetradecanoate, and stearic acid in serum were selected to establish the model with lasso logistic regression. Validation of the model yielded an optimum corrected AUC value of 89.5%, 95% CI: 0.8006-0.9889 with a sensitivity of 100.0%, and specificity of 78.9%. In conclusion, this study establishes a prediction model of sPTB with five variables, which may predict sPTB more accurately and sensitively in the second trimester.

Keywords: cortisol; metabolomics; predictive model; serum; spontaneous preterm birth.