Evaluation of the neonatal sequential organ failure assessment and mortality risk in preterm infants with late-onset infection
Open accessAbstract
Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants. Exposures: Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.
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The nSOFA has strong utility to predict disease-specific mortality across sepsis and necrotizing enterocolitis.
“as well as disease-specific mortality across sepsis and necrotizing enterocolitis (13–15).”
From Association of the neonatal sequential organ failure assessment score with neurological outcomes in infants diagnosed with hypoxic-ischemic encephalopathy (2026) · cites this paper as [13]
The Results (nSOFA Comparisons; page unavailable) report strong discrimination of mortality risk in preterm infants with late-onset infection, including infants with a perforated bowel. The paper does not report a separate analysis of necrotizing enterocolitis or establish predictive utility across sepsis and necrotizing enterocolitis as distinct diseases. (LLM, conf=0.86)
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Cites
The third international consensus definitions for sepsis and septic shock (Sepsis-3).
Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G. R., Chiche, J.-D., Coopersmith, C. M., et al. (2016) · JAMA · doi:10.1001/jama.2016.0287 · Cited by 28,250 · see citing works
Serial Evaluation of the SOFA Score to Predict Outcome in Critically Ill Patients
Ferreira, F. L. (2001) · JAMA · doi:10.1001/jama.286.14.1754 · Cited by 2,862 · see citing works
Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012
Stoll, B. J., Hansen, N. I., Bell, E. F., Walsh, M. C., Carlo, W. A., Shankaran, S., Laptook, A. R., Sánchez, P. J., Van Meurs, K. P., Wyckoff, M., et al. (2015) · JAMA · doi:10.1001/jama.2015.10244 · Cited by 2,791 · see citing works
Stoll, B. J., Hansen, N. I., Fanaroff, A. A., Wright, L. L., Carlo, W. A., Ehrenkranz, R. A., Lemons, J. A., Donovan, E. F., Stark, A. R., Tyson, J. E., et al. (2002) · PEDIATRICS · doi:10.1542/peds.110.2.285 · Cited by 2,349 · see citing works
Zimmerman, J. E., Kramer, A. A., McNair, D. S., & Malila, F. M. (2006) · Critical Care Medicine · doi:10.1097/01.ccm.0000215112.84523.f0 · Cited by 1,764 · see citing works
Stoll, B. J. (2004) · JAMA · doi:10.1001/jama.292.19.2357 · Cited by 1,535 · see citing works
Raith, E. P., Udy, A. A., Bailey, M., McGloughlin, S., MacIsaac, C., Bellomo, R., Pilcher, D. V., & for the Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcomes and Resource Evaluation (CORE) (2017) · JAMA · doi:10.1001/jama.2016.20328 · Cited by 1,279 · see citing works
Leteurtre, S., Duhamel, A., Salleron, J., Grandbastien, B., Lacroix, J., & Leclerc, F. (2013) · Critical Care Medicine · doi:10.1097/ccm.0b013e31828a2bbd · Cited by 683 · see citing works
Matics, T. J., & Sanchez-Pinto, L. N. (2017) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2017.2352 · Cited by 676 · see citing works
Fanaroff, A. A., Korones, S. B., Wright, L. L., Verter, J. I., Poland, R. L., Bauer, C. R., Tyson, J. E., Philips, J. B., EDWARDS, W., Lucey, J. F., et al. (1998) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-199807000-00004 · Cited by 427 · see citing works
Treatment of Neonatal Sepsis with Intravenous Immune Globulin
The INIS Collaborative Group (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1100441 · Cited by 321 · see citing works
Delayed versus Immediate Cord Clamping in Preterm Infants
Tarnow‐Mordi, W., Morris, J. M., Kirby, A. C., Robledo, K. P., Askie, L. M., Brown, R., Evans, N. J., Finlayson, S., Fogarty, M., Gebski, V., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1711281 · Cited by 307 · see citing works
Time for a Neonatal-Specific Consensus Definition for Sepsis
Wynn, J. L., Wong, H. R., Shanley, T. P., Bizzarro, M. J., Saiman, L. M., & Polin, R. A. (2014) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000000157 · Cited by 302 · see citing works
Self-citationde Grooth, H., Geenen, I. L., Girbes, A. R. J., Vincent, J., Parienti, J., & Straaten, H. M. O. (2017) · Critical Care · doi:10.1186/s13054-017-1609-1 · Cited by 282 · see citing works
The Pediatric Risk of Mortality Score
Pollack, M. M., Holubkov, R., Funai, T., et al. (2015) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000000558 · Cited by 274 · see citing works
Giannoni, É., Agyeman, P., Stocker, M., Posfay-Barbe, K. M., Heininger, U., Spycher, B. D., Bernhard‐Stirnemann, S., Niederer-Loher, A., Kahlert, C. R., Donas, A., et al. (2018) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2018.05.048 · Cited by 267 · see citing works
Neurodevelopmental Impairment Among Extremely Preterm Infants in the Neonatal Research Network
Adams-Chapman, I. S., Heyne, R. J., DeMauro, S. B., Duncan, A. F., Hintz, S. R., Pappas, A., Vohr, B. R., McDonald, S. A., Das, A., Newman, J. E., et al. (2018) · PEDIATRICS · doi:10.1542/peds.2017-3091 · Cited by 232 · see citing works
Late-onset Sepsis in Extremely Premature Infants
Greenberg, R. G., Kandefer, S. C., Do, B. T., Smith, P. B., Stoll, B. J., Bell, E. F., Carlo, W. A., Laptook, A. R., Sánchez, P. J., Shankaran, S., et al. (2017) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000001570 · Cited by 188 · see citing works
Controlled Trial of Two Incremental Milk-Feeding Rates in Preterm Infants
Dorling, J., Abbott, J., Berrington, J. E., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1816654 · Cited by 181 · see citing works
Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial
Griffiths, J., Jenkins, P. A., Vargova, M., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32221-9 · Cited by 171 · see citing works
Wynn, J. L., & Polin, R. A. (2020) · Pediatric Research · doi:10.1038/s41390-019-0517-2 · Cited by 169 · see citing works
Self-citationNeonatal Infection and Later Neurodevelopmental Risk in the Very Preterm Infant
Rand, K., Austin, N. C., Inder, T. E., Bora, S., & Woodward, L. J. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.11.017 · Cited by 103 · see citing works
Timing of Multiorgan Dysfunction among Hospitalized Infants with Fatal Fulminant Sepsis
Wynn, J. L., Kelly, M. S., Benjamin, D. K., Clark, R. H., Greenberg, R. G., Benjamin, D. K., & Smith, P. B. (2016) · American Journal of Perinatology · doi:10.1055/s-0036-1597130 · Cited by 43 · see citing works
Self-citationBolia, R. K., Srivastava, A., Yachha, S. K., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.10.001 · Cited by 40 · see citing works
Ha, E., Kim, S., Jin, H. S., et al. (2010) · Journal of Pediatric Hematology/Oncology · doi:10.1097/mph.0b013e3181e51338 · Cited by 27 · see citing works
Zipursky, A. R., Yoon, E. W., Emberley, J., et al. (2019) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2018.12.011 · Cited by 26 · see citing works
Jhang, W. K., Kim, Y. A., Ha, E., et al. (2014) · Pediatric Nephrology · doi:10.1007/s00467-013-2741-z · Cited by 22 · see citing works
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Wynn, J. L., Mayampurath, A., Carey, K., Slattery, S., Andrews, B., & Sanchez-Pinto, L. N. (2021) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2021.05.037 · Cited by 37 · see citing works
Self-citationLewis, A. N., de la Cruz, D., Wynn, J. L., Frazer, L. C., Yakah, W., Martin, C. R., Yang, H., Itriago, E., Unger, J., Hair, A. B., et al. (2022) · Neonatology · doi:10.1159/000522560 · Cited by 36 · see citing works
Self-citationHourly kinetics of critical organ dysfunction in extremely preterm infants
Lavilla, O. C., Aziz, K. B., Lure, A. C., Gipson, D., de la Cruz, D., & Wynn, J. L. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202106-1359oc · Cited by 22 · see citing works
Self-citationYeo, K. T., Goh, G. L., Park, W. Y., Wynn, J. L., & Aziz, K. B. (2023) · Neonatology · doi:10.1159/000533467 · Cited by 13 · see citing works
Self-citationEarly prediction of mortality after birth asphyxia with the nSOFA
Dathe, A.-K., Stein, A., Bruns, N., Craciun, E.-D., Tuda, L., Bialas, J., Brasseler, M., Felderhoff-Mueser, U., & Huening, B. M. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12134322 · Cited by 13 · see citing works
Kurul, Ş., Reijnierse, J. J., Koppens, H. J., Onland, W., Simons, S. H. P., Reiss, I. K. M., Taal, H. R., & Visser, D. H. (2024) · BMJ Paediatrics Open · doi:10.1136/bmjpo-2024-002884 · Cited by 10 · see citing works
Lagnese, K., Sheth, S., Vice, S., Rajderkar, D., Roig, J. C., Weiss, M., & Wynn, J. L. (2026) · Frontiers in Pediatrics · doi:10.3389/fped.2026.1844058
“Validated in multicenter studies, the nSOFA has strong utility to predict all-cause mortality (11) including ELBWs (12), as well as disease-specific mortality across sepsis and necrotizing enterocolitis (13 – 15).”
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- Authors
- Fleiss, N., Coggins, S. A., Lewis, A. N., Zeigler, A., Cooksey, K. E., Walker, L. A., Husain, A. N., de Jong, B. S., Wallman-Stokes, A., Alrifai, M. W., Visser, D. H., Good, M., Sullivan, B., Polin, R. A., Martin, C. R., & Wynn, J. L.
- Affiliations
- Columbia University Irving Medical Center (US)
- Children's Hospital of Philadelphia (US)
- Washington University in St. Louis (US)
- University of Virginia (US)
- Vanderbilt University (US)
- Department of Neonatology, Amsterdam UMC University of Amsterdam, Vrije Universiteit, Emma Children’s Hospital, Amsterdam, the Netherlands
- Emma Kinderziekenhuis (NL)
- Harvard University (US)
- University of Florida Health (US)
- Corresponding author
- Wynn, James L.
- ORCID
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2021-02-04
- Volume
- 4
- Issue
- 2
- Pages
- e2036518
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC7862993
- OpenAlex
- W3127344717
- Cited by
- 121
- References
- 27
- Citations by year
- 2026: 23 · 2025: 21 · 2024: 22 · 2023: 24 · 2022: 18 · 2021: 13
- FWCI
- 16.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JAMA Network Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Funders
- National Institute of General Medical Sciences (R01GM128452)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD089939)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Neonatal and Maternal Infections
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
- Keywords
- late-onset infection, preterm infants, very low birth weight infants, mortality risk, sepsis, bacteremia, fungemia, peritonitis, organ failure, mortality prediction, generalizability, neonatal intensive care, very preterm infants, sex differences
- MeSH terms
- Neonatal Sepsis, Female, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Intensive Care Units, Neonatal, Intestinal Perforation, Male, Peritonitis, Prognosis, Fungemia, Bacteremia, Gram-Negative Bacterial Infections, Gram-Positive Bacterial Infections, Hospital Mortality, Risk Assessment, Infant, Very Low Birth Weight, Infant, Extremely Low Birth Weight, Catheter-Related Infections, Infant, Extremely Premature, Organ Dysfunction Scores
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