Sepsis and Mortality Prediction in Very Low Birth Weight Infants: Analysis of HeRO and nSOFA

Abstract

Objective: Scores to predict sepsis or define sepsis severity could improve care for very low birth weight (VLBW) infants. The heart rate characteristics (HRC) index (HeRO score) was developed as an early warning system for late-onset sepsis (LOS), and also rises before necrotizing enterocolitis (NEC). The neonatal sequential organ failure assessment (nSOFA) was developed to predict sepsis-associated mortality using respiratory, hemodynamic, and hematologic data. The aim of this study was to analyze the HRC index and nSOFA near blood cultures in VLBW infants relative to diagnosis and sepsis-associated mortality.

Study design: Retrospective, single-center study of VLBW infants from 2011 to 2019. We analyzed HRC index and nSOFA around blood cultures diagnosed as LOS/NEC. In a subgroup of the cohort, we analyzed HRC and nSOFA near the first sepsis-like illness (SLI) or sepsis ruled-out (SRO) compared with LOS/NEC. We compared scores by diagnosis and mortality during treatment.

Results: We analyzed 179 LOS/NEC, 93 SLI, and 96 SRO blood culture events. In LOS/NEC, the HRC index increased before the blood culture, while nSOFA increased at the time of culture. Both scores were higher in nonsurvivors compared with survivors and in LOS/NEC compared with SRO. The nSOFA 12 hours after the time of blood culture predicted mortality during treatment better than any other time point analyzed (area under the curve 0.91).

Conclusion: The HRC index provides earlier warning of imminent sepsis, whereas nSOFA after blood culture provides better prediction of mortality.

Key points: · The HRC index and nSOFA provide complementary information on sepsis risk and sepsis-related mortality risk.. · This study adds to existing literature evaluating these risk scores independently by analyzing them together and in cases of not only proven but also suspected infections.. · The impact of combining risk models could be improved outcomes for premature infants..

Fig. 1

Heart rate characteristics (HRC) index and neonatal sequential organ failure assessment (nSOFA) scores at nine time points surrounding the time of blood culture (time 0) in events diagnosed as late-onset sepsis (LOS) or necrotizing enterocolitis (NEC) for patients who died during the episode compared with those who survived. (A) The HRC index was higher for infants who died during LOS or NEC from the time of blood culture to 24 hours after (*p < 0.05). (B) nSOFA was higher for infants who died during LOS or NEC at all time points analyzed (*p < 0.01).

Fig. 2

The heart rate characteristics (HRC) index and neonatal sequential organ failure assessment (nSOFA) scores for cases diagnosed as late-onset sepsis with bacteremia or necrotizing enterocolitis (NEC), sepsis-like illnesses, and sepsis ruled out. (A) Mean HRC index was higher from 48 hours before to 24 hours after blood culture for cases of late-onset sepsis (LOS) or NEC compared with events diagnosed as sepsis-like illness or sepsis ruled-out (*p < 0.05). (B) nSOFA scores were higher for events diagnosed as LOS or NEC than those where sepsis was ruled out (*p < 0.05 at all-time points), but were not different from sepsis-like illnesses.

Fig. 3

The heart rate characteristics (HRC) index was higher at the time of blood culture and every time point after for events with neonatal sequential organ failure assessment (nSOFA) >4 compared with events with nSOFA 0–4.

Fig. 4

Receiver operator characteristic curves for the total neonatal sequential organ failure assessment (nSOFA) and component scores at the time of positive blood culture and 12 hours after culture. Points given for respiratory dysfunction (mechanical ventilation and oxygen saturation/fraction of inspired oxygen ratio) were the most predictive component at all time points analyzed. The cardiovascular component area under the curve (AUC) increased from time points before culture to after, while the hematologic component remained a poor individual predictor by AUC at every time point. By 12 hours after blood culture, performance of the total nSOFA score to predict mortality during the episode reached an AUC of 0.91.

Fig. 5

In cases of late-onset sepsis or necrotizing enterocolitis, the heart rate characteristics (HRC) index increased from baseline (48 hours before culture) by 6 hours before blood culture, while neonatal sequential organ failure assessment (nSOFA) increased compared with baseline at the time of culture.