Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants with Necrotizing Enterocolitis

Abstract

Introduction: The neonatal sequential organ failure assessment (nSOFA) score is a tool for calculating mortality risk of infants in the neonatal intensive care unit. The utility of the nSOFA in determining the risk of mortality or the association with surgical intervention among infants with necrotizing enterocolitis (NEC) has not been investigated.

Methods: We performed a retrospective, cohort study of preterm (<37 weeks) infants with NEC Bell's stage ≥ IIA at six hospitals from 2008 to 2020. An nSOFA score (range 0-15) was assigned to each patient at nine time points from 48 h before or after clinical illness was suspected.

Results: Of the 259 infants, nSOFA scores for infants who died (n = 39) or had the composite outcome of surgery or death (n = 114) were significantly higher (p < 0.05) early in the NEC course compared to nSOFA scores for infants who survived medical NEC. Twelve hours after evaluation, the area under the receiver operating characteristic curve was 0.87 (95% confidence interval [CI], 0.80-0.93) to discriminate for mortality and 0.84 (95% CI, 0.79-0.90) for surgery or death (p < 0.001). A maximum nSOFA score of ≥4 at -6, 0, 6, or 12 h following evaluation was associated with a 20-fold increase in mortality and 19-fold increase in surgery or death compared with a score of <4 (p < 0.001).

Conclusion: In this multicenter cohort, the nSOFA score was able to discriminate well for death as well as surgery or death among infants with NEC. The nSOFA is a clinical research tool that may be used in infants with NEC to improve classification by objective quantification of organ dysfunction.

Keywords: Illness severity; Necrotizing enterocolitis; Neonate; Organ dysfunction.

Figure 1.. nSOFA scores among preterm NEC survivors compared to non-survivors.

(A) Median, quartiles, and probability density of nSOFA scores for survivors (n=220, white) and non-survivors (n=39, blue) are shown. Comparisons by Kruskal-Wallis with Dunn’s multiple comparisons test. ***P<0.001 (B) Receiver operating curve (ROC) for mortality based on nSOFA scores at 0, +6, and +12 hours relative to evaluation (Evaluation: Black circles; +6 hours: blue squares; +12 hours: orange triangles). All ROCs with P<0.001. (C) Heat map of nSOFA scores for individual survivors and non-survivors. The nSOFA score is displayed at each of the nine time points relative to sepsis evaluation. Data organized by nSOFA score compared to the time from NEC evaluation (T−48 to T+48). Blue indicates a higher nSOFA score. Black indicates a time point after death.

Figure 2.. Change in nSOFA scores during a NEC episode for survivors and non-survivors.

The change in nSOFA scores between the specified time intervals are shown for survivors (n=220, white) compared to non-survivors (n=39, blue). Median, quartiles, and probability density of are shown for the (A) pre-evaluation, (B) post-evaluation, and (C) peri-evaluation intervals. Comparisons by Kruskal-Wallis with Dunn’s multiple comparisons test. ***P<0.001, ****P<0.0001.

Figure 3.. nSOFA component scores among NEC survivors and non-survivors.

(A) Respiratory, (B) Cardiovascular, and (C) Hematologic components of the nSOFA score compared to the time from NEC evaluation (T−48 to T+48). Median, quartiles, and probability density of component nSOFA for survivors (n=220, white) and non-survivors (n=39, blue) are shown. Comparisons by Kruskal-Wallis with Dunn’s multiple comparisons test. *P< 0.05, ***P<0.001, ****P<0.0001.

Figure 4.. nSOFA scores among preterm survivors compared to non-survivors with NEC with or without a positive blood culture.

Median, quartiles, and probability density of nSOFA scores for survivors (white) and non-survivors (blue) with (A) positive blood culture (n=44, 16) and (C) negative blood cultures (n=177, 22). Comparisons by Kruskal-Wallis with Dunn’s multiple comparisons test. **P<0.01, ***P<0.001, ****P<0.0001. ROC for mortality based on nSOFA scores at 0, +6, and +12 hours relative to evaluation with (B) positive blood culture and (D) negative blood cultures. All ROCs with P<0.05.

Figure 5.. nSOFA scores among preterm medical NEC survivors compared to infants that died or had surgical intervention.

(A) Median, quartiles, and probability density of nSOFA scores for medical NEC survivors (n=145, white) and infants with non-survivors and surgical NEC survivors (n=114, blue) are shown. Comparisons by Kruskal-Wallis with Dunn’s multiple comparisons test. *P<0.05, **P<0.01, ****P<0.0001. (B) ROC for the combined need for surgery and mortality based on nSOFA score at 0, +6, and +12 hours relative to sepsis evaluation. All ROCs with P<0.001.