Predictors of Mortality in Late-Onset Sepsis in Very Low Birth Weight Newborns

Abstract

Objective Late-onset sepsis (LOS) is a major public health burden globally. Newborns with very low birth weight (VLBW) are at high risk of mortality related to LOS. The protective effect of breast milk feeding against many infections has been studied but data on the effect of breast milk feeding on LOS mortality are limited. In this study, we aimed to evaluate the risk factors for LOS-related mortality.

Methods This single-center, case–control study was conducted retrospectively from August 2013 to July 2018. VLBW newborns with ≤32 weeks of gestational age who had culture-proven LOS were included in the study. Demographics, clinical and laboratory data, and parenteral and enteral feeding details within 72 hours before LOS episodes were extracted from electronic and paper medical records.

Results A total of 190 LOS episodes were identified in 168 VLBW newborns with a median birth weight of 888 (695–1,143) g. Lower birth weight (adjusted odds ratio [aOR] 0.81, 95% confidence interval [CI] [0.69–0.96], p = 0.01), C-section delivery (aOR 0.38, 95% CI [0.17–0.84], p = 0.02), gram-negative (aOR 4.97, 95% CI [2.01–12.28], p = 0.001) and polymicrobial sepsis (aOR 6.29, 95% CI [1.34–29.47], p = 0.03), and lower breast milk feeding 72 hours before LOS episodes (aOR 0.89, 95% CI [0.80–0.99], p = 0.03) were independently associated with higher odds of LOS related death.

Conclusion Gram-negative sepsis was associated with higher odds of LOS mortality and C-section delivery was associated with lower odds of LOS mortality. Additionally, every 10 mL/kg/day increase in breast milk feeding was associated with 11% lower odds of LOS mortality although this finding should be interpreted cautiously as there may be unadjusted confounders due to the study design.

Keywords

very low birth weight - late-onset sepsis - mortality - breast milk

Ethical Approval

This retrospective study was approved by the Ethics Committee (August 4, 2017, approval number: 124). Informed consent was waived because of the retrospective design of the study.

Publikationsverlauf

Eingereicht: 26. April 2024

Angenommen: 09. Juli 2024

Artikel online veröffentlicht:
22. Juli 2024

• References

• 1 World Health Organization. Newborn infections. Accessed October 6, 2023 at: https://www.who.int/teams/maternal-newborn-child-adolescent-health-and-ageing/newborn-health/newborn-infections
• 2 Gan MY, Lee WL, Yap BJ. et al. Contemporary trends in global mortality of sepsis among young infants less than 90 days: a systematic review and meta-analysis. Front Pediatr 2022; 10: 890767
• 3 Kochanowicz JF, Nowicka A, Al-Saad SR, Karbowski LM, Gadzinowski J, Szpecht D. Catheter-related bloodstream infections in infants hospitalized in neonatal intensive care units: a single center study. Sci Rep 2022; 12 (01) 13679
• 4 Gerios L, Rodrigues VHB, Corrente JE, Lyra JC, Rugolo L, Bentlin MR. Late-onset sepsis in very low birth weight premature infants: a 10-year review of a Brazilian Tertiary University Hospital-the challenge remains. Am J Perinatol 2023
• 5 Parker MG, Stellwagen LM, Noble L, Kim JH, Poindexter BB, Puopolo KM. Section on Breastfeeding, Committee on Nutrition, Committee on Fetus and Newborn. Promoting human milk and breastfeeding for the very low birth weight infant. Pediatrics 2021; 148 (05) e2021054272
• 6 Kleist SA, Knoop KA. Understanding the elements of maternal protection from systemic bacterial infections during early life. Nutrients 2020; 12 (04) 1045
• 7 Noel G, In JG, Lemme-Dumit JM. et al. Human breast milk enhances intestinal mucosal barrier function and innate immunity in a healthy pediatric human enteroid model. Front Cell Dev Biol 2021; 9: 685171
• 8 Koc E, Demirel N, Bas AY. et al. Early neonatal outcomes of very-low-birth-weight infants in Turkey: a prospective multicenter study of the Turkish Neonatal Society. PLoS ONE 2019; 14 (12) e0226679
• 9 Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36 (05) 309-332
• 10 Koç E, Baş AY, Özdek Ş, Ovalı F, Başmak H. Turkish Neonatal and Turkish Ophthalmology Societies consensus guideline on the retinopathy of prematurity. Turk Pediatri Ars 2018; 53 (Suppl. 01) S151-S160
• 11 Fleischmann C, Reichert F, Cassini A. et al. Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Arch Dis Child 2021; 106 (08) 745-752
• 12 Belachew A, Tewabe T. Neonatal sepsis and its association with birth weight and gestational age among admitted neonates in Ethiopia: systematic review and meta-analysis. BMC Pediatr 2020; 20 (01) 55
• 13 Frank NM, Lynch KF, Uusitalo U. et al; TEDDY Study Group. The relationship between breastfeeding and reported respiratory and gastrointestinal infection rates in young children. BMC Pediatr 2019; 19 (01) 339
• 14 Lyons KE, Ryan CA, Dempsey EM, Ross RP, Stanton C. Breast milk, a source of beneficial microbes and associated benefits for infant health. Nutrients 2020; 12 (04) 1039
• 15 Lu J, Francis JD, Guevara MA. et al. Antibacterial and anti-biofilm activity of the human breast milk glycoprotein lactoferrin against Group B Streptococcus . ChemBioChem 2021; 22 (12) 2124-2133
• 16 Miller J, Tonkin E, Damarell RA. et al. A systematic review and meta-analysis of human milk feeding and morbidity in very low birth weight infants. Nutrients 2018; 10 (06) 707
• 17 Knoop KA, Coughlin PE, Floyd AN. et al. Maternal activation of the EGFR prevents translocation of gut-residing pathogenic Escherichia coli in a model of late-onset neonatal sepsis. Proc Natl Acad Sci U S A 2020; 117 (14) 7941-7949
• 18 Goh GL, Lim CSE, Sultana R, De La Puerta R, Rajadurai VS, Yeo KT. Risk factors for mortality from late-onset sepsis among preterm very-low-birthweight infants: a single-center cohort study from Singapore. Front Pediatr 2022; 9: 801955
• 19 Bandyopadhyay T, Kumar A, Saili A, Randhawa VS. Distribution, antimicrobial resistance and predictors of mortality in neonatal sepsis. J Neonatal Perinatal Med 2018; 11 (02) 145-153
• 20 Miselli F, Crestani S, Maugeri M. et al. Late-onset sepsis mortality among preterm infants: beyond time to first antibiotics. Microorganisms 2023; 11 (02) 396
• 21 Olivier F, Bertelle V, Shah PS, Drolet C, Piedboeuf B. Association between birth route and late-onset sepsis in very preterm neonates. J Perinatol 2016; 36 (12) 1083-1087
• 22 Racusin DA, Antony KM, Haase J, Bondy M, Aagaard KM. Mode of delivery in premature neonates: does it matter?. AJP Rep 2016; 6 (03) e251-e259
• 23 Jiang S, Yang C, Yang C. et al; REIN-EPIQ Study Group. Epidemiology and microbiology of late-onset sepsis among preterm infants in China, 2015-2018: a cohort study. Int J Infect Dis 2020; 96: 1-9
• 24 Wold AE, Adlerberth I. Breast feeding and the intestinal microflora of the infant–implications for protection against infectious diseases. Adv Exp Med Biol 2000; 478: 77-93