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

Article type: Research Article

Authors: Sullivan, B.A.^{a; i; *} | Nagraj, V.P.^{g; h} | Berry, K.L.^{c; d} | Fleiss, N.^e | Rambhia, A.^f | Kumar, R.^a | Wallman-Stokes, A.^e | Vesoulis, Z.A.^f | Sahni, R.^e | Ratcliffe, S.^{d; i} | Lake, D.E.^{b; i} | Moorman, J.R.^{b; i} | Fairchild, K.D.^{a; i}

Affiliations: [a] Department of Pediatrics, Division of Neonatology, University of Virginia School of Medicine, Charlottesville, VA, USA | [b] Department of Medicine, Division of Cardiology, University of Virginia School of Medicine, Charlottesville, VA, USA | [c] University of Virginia School of Medicine, Charlottesville, VA, USA | [d] University of Virginia School of Public Health Sciences, Charlottesville, VA, USA | [e] Department of Pediatrics, Division of Neonatology, Columbia University, New York, NY, USA | [f] Department of Pediatrics, Division of Newborn Medicine, Washington University School of Medicine, St. Louis, MO, USA | [g] Department of Research Computing, University of Virginia School of Medicine, Charlottesville, VA, USA | [h] Signature Science, LLC, Charlottesville, Virginia, USA | [i] University of Virginia Center for Advanced Medical Analytics, Charlottesville, VA, USA

Correspondence: [*] Address for correspondence: Brynne A. Sullivan, MD, University of Virginia, Pediatrics, PO Box 800386, Charlottesville, VA, 22908 0386, USA. Tel.: +1 434 924 5428; Fax: +1 434 924 2816; E-mail: [email protected].

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, infection, bacteremia, prematurity, vital sign analytics, predictive modeling

DOI: 10.3233/NPM-200578

Journal: Journal of Neonatal-Perinatal Medicine, vol. 14, no. 4, pp. 553-561, 2021