A biomarker for bacteremia in pregnant women with acute pyelonephritis: soluble suppressor of tumorigenicity 2 or sST2

Abstract

Objective

Sepsis is a leading cause of maternal death, and its diagnosis during the golden hour is critical to improve survival. Acute pyelonephritis in pregnancy is a risk factor for obstetrical and medical complications, and it is a major cause of sepsis, as bacteremia complicates 15–20% of pyelonephritis episodes in pregnancy. The diagnosis of bacteremia currently relies on blood cultures, whereas a rapid test could allow timely management and improved outcomes. Soluble suppression of tumorigenicity 2 (sST2) was previously proposed as a biomarker for sepsis in non-pregnant adults and children. This study was designed to determine whether maternal plasma concentrations of sST2 in pregnant patients with pyelonephritis can help to identify those at risk for bacteremia.

Study design

This cross-sectional study included women with normal pregnancy (n = 131) and pregnant women with acute pyelonephritis (n = 36). Acute pyelonephritis was diagnosed based on a combination of clinical findings and a positive urine culture. Patients were further classified according to the results of blood cultures into those with and without bacteremia. Plasma concentrations of sST2 were determined by a sensitive immunoassay. Non-parametric statistics were used for analysis.

Results

The maternal plasma sST2 concentration increased with gestational age in normal pregnancies. Pregnant patients with acute pyelonephritis had a higher median (interquartile range) plasma sST2 concentration than those with a normal pregnancy [85 (47–239) ng/mL vs. 31 (14–52) ng/mL, p < .001]. Among patients with pyelonephritis, those with a positive blood culture had a median plasma concentration of sST2 higher than that of patients with a negative blood culture [258 (IQR: 75–305) ng/mL vs. 83 (IQR: 46–153) ng/mL; p = .03]. An elevated plasma concentration of sST2 ≥ 215 ng/mL had a sensitivity of 73% and a specificity of 95% (area under the receiver operating characteristic curve, 0.74; p = .003) with a positive likelihood ratio of 13.8 and a negative likelihood ratio of 0.3 for the identification of patients who had a positive blood culture.

Conclusion

sST2 is a candidate biomarker to identify bacteremia in pregnant women with pyelonephritis. Rapid identification of these patients may optimize patient care.

Keywords:

• Cytokines
• IL-1
• IL-33
• pregnancy
• sepsis
• septic shock
• urinary tract infection

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, with Federal funds from NICHD/NIH/DHHS under Contract No. HHSN275201300006C. Dr. Romero has contributed to this work as part of his official duties as an employee of the United States Federal Government.