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.