Prognostic Value of Ionized Calcium Levels in Neonatal Sepsis

Background: Despite recent advances in the treatment of neonatal infection, mortality rates and comorbidities associated with neonatal sepsis remain high. Hypocalcemia has been reported in critically ill patients, especially in as-sociation with sepsis. However, the importance of hypo-calcemia in neonatal sepsis has not been explored in detail.

Objectives: The purpose of this study was to evaluate the prognostic value of hypocalcemia in neonatal sepsis patients and to identify the risk factors associated with sepsis-related mortality.

Methods: This retrospective study examined perinatal data from patients in a level IV neonatal in-tensive care unit between January 2010 and June 2016. Univariate analysis was performed to understand the differences in clinical and laboratory characteristics between patients with and without neonatal sepsis. Neonates with sepsis were further stratified as having ionized hypocalcemia (if serum ionized calcium [iCa] <1.0 mmol/L) or not. Uni- and multivariate logistic regression analyses were utilized to evaluate the predictive potential of iCa for identifying sepsis-related mortality.

Results: A total of 472 neonates were enrolled in this study, including 169 neonates diagnosed with culture-proven sepsis and 303 neonates without infection (control group). The comparison of neonates with and without sepsis highlighted significant differences in levels of iCa (0.97 ± 0.26 vs. 1.12 ± 0.25 mmol/L), magnesium (0.75 ± 0.22 vs. 0.89 ± 0.12 mmol/L), and phosphate (2.26 ± 1.08 vs. 1.65 ± 0.85 mmol/L; all p < 0.001). When neonates with sepsis were stratified into 2 subgroups based on serum iCa, neonates with hypocalcemia showed higher rates of organ dysfunction than those with normal iCa, as well as higher rates of cardiovascular system dysfunction (37.35 vs. 17.44%), renal dysfunction (34.94 vs. 30.95%), disseminated intravascular coagulation (26.51 vs. 11.63%), and seizure (16.04 vs. 5.8%; all p < 0.05). Among all neonates who had sepsis, the mortality rate was 13.61%, and this rate was higher among neonates with hypocalcemia than among those with normal iCa (20.48 vs. 6.98%, p < 0.05). Uni- and multivariate analyses showed that acidosis, hypoalbuminemia, hypocalcemia, and hyperphosphatemia were independent prognostic markers of sepsis-related mortality. In receiver-operating characteristic curve analysis, the areas under the curve were 0.70 (95% CI 0.624-0.768; p = 0.0004), 0.74 (95% CI 0.671-0.808; p < 0.0001), 0.73 (95% CI 0.653-0.792; p = 0.0002), and 0.67 (95% CI 0.59-0.737; p = 0.0154) for serum albumin, iCa, phosphate, and acidosis, respectively. Based on these findings, we developed a nomogram to predict sepsis-related mortality.

Conclusions: Hypocalcemia is common in neonates with sepsis and is significantly associated with organ dysfunction and sepsis-related mortality.

Keywords: Hypocalcemia; Mortality; Neonatal sepsis.