Laura Anglim

Women with preterm birth have a distinct cervicovaginal metabolome

OBJECTIVE Metabolomics has the potential to reveal novel pathways involved in the pathogenesis of preterm birth (PTB). The objective of this study was to investigate whether the cervicovaginal (CV) metabolome was different in asymptomatic women destined to have a PTB compared with term birth. STUDY DESIGN A nested case-control study was performed using CV fluid collected from a larger prospective cohort. The CV fluid was collected between 20-24 weeks (V1) and 24-28 weeks (V2). The metabolome was compared between women with a spontaneous PTB (n = 10) to women who delivered at term (n = 10). Samples were extracted and prepared for analysis using a standard extraction solvent method. Global biochemical profiles were determined using gas chromatography/mass spectrometry and ultra-performance liquid chromatography/tandem mass spectrometry. An ANOVA was used to detect differences in biochemical compounds between the groups. A false discovery rate was estimated to account for multiple comparisons. RESULTS A total of 313 biochemicals were identified in CV fluid. Eighty-two biochemicals were different in the CV fluid at V1 in those destined to have a PTB compared with term birth, whereas 48 were different at V2. Amino acid, carbohydrate, and peptide metabolites were distinct between women with and without PTB. CONCLUSION These data suggest that the CV space is metabolically active during pregnancy. Changes in the CV metabolome may be observed weeks, if not months, prior to any clinical symptoms. Understanding the CV metabolome may hold promise for unraveling the pathogenesis of PTB and may provide novel biomarkers to identify women most at risk.

The soluble receptor for advanced glycation end products can prospectively identify patients at greatest risk for preterm birth

Objective: Our primary objective was to determine whether there was an association between levels of antenatal maternal serum soluble RAGE (sRAGE), drawn at the time of presentation with preterm labor (PTL), and subsequent preterm birth (PTB). Secondary objectives were to determine whether levels of sRAGE – analyzed from both antenatal maternal serum (MS) and postpartum umbilical cord serum (CS) – were associated with neonatal sepsis. Methods: Nested case-control analyses were performed within a prospective cohort of patients at risk for PTB. MS was obtained at enrollment and CS at delivery. The sRAGE levels were analyzed. Non-parametric calculations and receiver-operator analyses were performed. Results: Overall, 39.8% of patients delivered < 37 weeks (n = 498) and 15% had neonatal sepsis (n = 193). In comparing cases and controls, sRAGE was significantly lower in those with than those without an adverse event (PTB: median MS-sRAGE 771.79 versus 948.485 pg/mL, p = 0.004; neonatal sepsis: 25-centile CS-sRAGE 1220.49 versus 2244.41 pg/mL, p = 0.0013). Adding MS-sRAGE to models of clinical variables significantly enhanced the ability of the model to predict both PTB (area under the curve [AUC] 0.71 versus 0.79, p = 0.004) and neonatal sepsis (AUC 0.65 versus 0.75, p = 0.04). The negative predictive value of CS-sRAGE for neonatal sepsis was very strong (NPV = 0.91). Conclusions: The sRAGE can be used to help predict adverse perinatal outcomes. Patients with higher levels of sRAGE – who therefore may have an enhanced capability to regulate their immune response – appear less likely to experience PTB and neonatal sepsis.