Clinical and vital sign changes associated with late-onset sepsis in very low birth weight infants at 3 NICUs

Abstract

Background: In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO2) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO).

Methods: At three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO2 data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO.

Results: We analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP(p < 0.05). HR-SpO2 data were available in 266 events. Cross-correlation HR-SpO2 before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO2 variables had AUC 0.821.

Conclusion: In VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO2 variables associated with LOS versus SRO.

Keywords: Neonatal sepsis; bacteremia; infection; predictive modeling; prematurity; vital sign analytics.

Fig. 1.

A. Frequency of clinical signs prompting sepsis work-ups that were ultimately diagnosed as late-onset sepsis (LOS, black bars) due to any organism compared to sepsis ruled-out (SRO, gray bars). Signs listed in order of decreasing frequency in LOS events. Asterisks indicate signs cited more often in LOS or SRO by Fisher’s test (*p < 0.05). B. Clinical signs prompting sepsis work-ups diagnosed as LOS, excluding cases due to CONS, compared to SRO. Statistical comparisons are not shown but differ by one clinical sign; abdominal distention was no longer significant.

Fig. 2.

HR and SpO₂ features plotted as the 12hr moving average from five days before to two days after the time of blood culture, grouped by diagnosis (LOS, solid line; SRO, dashed line). Gray shaded areas represent the 95% confidence intervals and a horizontal dotted line is drawn on each panel at the mean for all UVA VLBW infants at all available times for that feature.