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

Abstract

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.

Keywords::

• Biomarker
• neonatal sepsis
• preterm birth
• soluble RAGE

Acknowledgment

Abstract (#O-139) entitled “sRAGE: A biomarker of prematurity and neonatal sepsis,” was an oral presentation at The Society for Gynecologic Investigation Annual Meeting in Miami, Florida, March 16–19, 2011. This work was also presented at the Philadelphia Perinatal Society Annual Neonatal-Perinatal Research Symposium and was awarded the Thomas R. Boggs, Jr, 2011 Young Investigator Award (May 18, 2011).

Declaration of Interest: The authors report no conflicts of interest. This work was funded by a March of Dimes grant [21-FY08-539, PI: Elovitz].