Contribution of Concurrent Comorbidities to Sepsis-Related Mortality in Preterm Infants ≤32 Weeks of Gestation at an Academic Neonatal Intensive Care Network

Abstract

Objective This study sought to identify concurrent major comorbidities in preterm infants ≤32 weeks of gestation that may have contributed to sepsis-related mortality following a diagnosis of bacteremia or blood culture-negative sepsis within the neonatal period (≤28 days of life).

Study Design This is a retrospective chart review of infants ≤32 weeks of gestation who were admitted to a single academic network of multiple neonatal intensive care units between January 1, 2012, and December 31, 2015, to determine the primary cause(s) and timing of death in those diagnosed with bacteremia or blood culture-negative sepsis. Direct comparisons between early-onset sepsis (EOS; ≤72 hours) and late-onset sepsis (LOS; >72 hours) were made.

Results In our study cohort, of 939 total patients with ≤32 weeks of gestation, 182 infants were diagnosed with 198 episodes of sepsis and 7.7% (14/182) died. Mortality rates did not significantly differ between neonates with bacteremia or blood culture-negative sepsis (7/14 each group), and those diagnosed with EOS compared with LOS (6/14 vs. 8/14). Nearly 80% (11/14) of infants were transitioned to comfort care prior to their death secondary to a coinciding diagnosis of severe grade-3 or -4 intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and/or intestinal perforation.

Conclusion Preexisting comorbidities commonly associated with extreme preterm birth contributed to sepsis-related mortality in our patient cohort.

Key Points

• Concurrent comorbidities contribute to, and may artificially inflate, sepsis-related mortality.

• Absence of a consensus definition for neonatal sepsis complicates the investigation of infection.

• Accurate assessment of the incidence of sepsis in very low birth weight infants is vital for future investigations.

Keywords

neonatal sepsis - sepsis-related mortality - prematurity - bacteremia - blood culture-negative sepsis - comorbidities - comfort care

Author' Contribution

The study's conceptualization and design were spearheaded by B.W.B., J.L.W., and S.M.L. The data acquisition involved efforts from B.W.B., S.L., and A.R. B.W.B., B.T.S., R.F.A., and S.M.L. played pivotal roles in the analysis and interpretation of the gathered data. The initial draft of the manuscript was collaboratively crafted by B.W.B. and S.M.L. All authors contributed significantly to the critical revision of the manuscript.

Publikationsverlauf

Eingereicht: 27. April 2021

Angenommen: 22. September 2021

Accepted Manuscript online:
21. Oktober 2021

Artikel online veröffentlicht:
31. Dezember 2021

• References

• 1 Anand KJ, Aranda JV, Berde CB. et al. Summary proceedings from the neonatal pain-control group. Pediatrics 2006; 117 (3, pt. 2): S9-S22
• 2 Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet 2017; 390 (10104): 1770-1780
• 3 Puopolo KM, Benitz WE, Zaoutis TE. Management of neonates born at </=34 6/7 weeks' gestation with suspected or proven early-onset bacterial sepsis. Pediatrics 2018;142(06):
• 4 Zea-Vera A, Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr 2015; 61 (01) 1-13
• 5 Khan AM, Morris SK, Bhutta ZA. Neonatal and perinatal infections. Pediatr Clin North Am 2017; 64 (04) 785-798
• 6 Ely DM, Driscoll AK. Infant mortality in the United States, 2017: data from the period linked birth/infant death file. Natl Vital Stat Rep 2019; 68 (10) 1-20
• 7 Stoll BJ, Hansen N, Fanaroff AA. et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110 (2, pt. 1): 285-291
• 8 Greenwood C, Morrow AL, Lagomarcino AJ. et al. Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J Pediatr 2014; 165 (01) 23-29
• 9 Kiser C, Nawab U, McKenna K, Aghai ZH. Role of guidelines on length of therapy in chorioamnionitis and neonatal sepsis. Pediatrics 2014; 133 (06) 992-998
• 10 Ramasethu J. Prevention and treatment of neonatal nosocomial infections. Matern Health Neonatol Perinatol 2017; 3: 5
• 11 Stoll BJ, Hansen NI, Higgins RD. et al; National Institute of Child Health and Human Development. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J 2005; 24 (07) 635-639
• 12 Schrag SJ, Cutland CL, Zell ER. et al; PoPS Trial Team. Risk factors for neonatal sepsis and perinatal death among infants enrolled in the prevention of perinatal sepsis trial, Soweto, South Africa. Pediatr Infect Dis J 2012; 31 (08) 821-826
• 13 Stoll BJ, Puopolo KM, Hansen NI. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early-Onset neonatal sepsis 2015 to 2017, the rise of Escherichia coli, and the need for novel prevention strategies. JAMA Pediatr 2020; 174 (07) e200593
• 14 Wynn JL, Wong HR, Shanley TP, Bizzarro MJ, Saiman L, Polin RA. Time for a neonatal-specific consensus definition for sepsis. Pediatr Crit Care Med 2014; 15 (06) 523-528
• 15 Wynn JL. Defining neonatal sepsis. Curr Opin Pediatr 2016; 28 (02) 135-140
• 16 McGovern M, Giannoni E, Kuester H. et al; Infection, Inflammation, Immunology and Immunisation (I4) section of the ESPR. Challenges in developing a consensus definition of neonatal sepsis. Pediatr Res 2020; 88 (01) 14-26
• 17 Molloy EJ, Wynn JL, Bliss J. et al; on behalf of the Infection, Inflammation, Immunology and Immunisation (I4) section of the ESPR. Neonatal sepsis: need for consensus definition, collaboration and core outcomes. Pediatr Res 2020; 88 (01) 2-4
• 18 Wynn JL, Polin RA. A neonatal sequential organ failure assessment score predicts mortality to late-onset sepsis in preterm very low birth weight infants. Pediatr Res 2020; 88 (01) 85-90
• 19 Fleiss N, Coggins SA, Lewis AN. et al. Evaluation of the neonatal sequential organ failure assessment and mortality risk in preterm infants with late-onset infection. JAMA Netw Open 2021; 4 (02) e2036518
• 20 Stoll BJ, Hansen NI, Adams-Chapman I. et al; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004; 292 (19) 2357-2365
• 21 Spasojević I, Obradović B, Spasić S. Bench-to-bedside review: neonatal sepsis-redox processes in pathogenesis. Crit Care 2012; 16 (03) 221
• 22 Stoll BJ, Hansen N. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin Perinatol 2003; 27 (04) 293-301
• 23 Bizzarro MJ, Dembry LM, Baltimore RS, Gallagher PG. Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics 2008; 121 (04) 689-696
• 24 Stoll BJ, Hansen NI, Sánchez PJ. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 2011; 127 (05) 817-826
• 25 Jacob J, Kamitsuka M, Clark RH, Kelleher AS, Spitzer AR. Etiologies of NICU deaths. Pediatrics 2015; 135 (01) e59-e65
• 26 Stoll BJ, Hansen NI, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (03) 443-456
• 27 Sung TJ, Sohn JA, Oh S, Lee JA. The influence of the variation in sepsis rate between neonatal intensive care units on neonatal outcomes in very-low-birth-weight infants. Sci Rep 2020; 10 (01) 6687