The burden of early onset sepsis in neonates with neonatal encephalopathy
Objective: Early-onset sepsis (EOS) is a risk factor for neonatal encephalopathy, a leading cause of neonatal deaths. We evaluated the association of EOS among newborns with neonatal encephalopathy in a low-middle income setting in South Africa; and evaluated for predictors of death in newborns with EOS and neonatal encephalopathy. Methods: We undertook a retrospective study in newbornsborn from 1st January 2016 to 30th June 2018 with gestational age ≥35 weeks and/or birth weight ≥2,500 grams, who were diagnosed with neonatal encephalopathy by the attending physician. Overall, EOS (confirmed+probable) was defined as either culture-confirmed sepsis on blood and/or cerebrospinal fluid within 72 hours of birth; or in the absence of culture confirmation, a CRP >32mg/L or an immature to total neutrophil ratio (I:T) ≥ 0.3 (i.e. probable sepsis). Results: Of 10,182 hospitalized newborns, 1,027 (10.1%) were diagnosed with neonatal encephalopathy. One-hundred and eighty-one (17.6%) neonatal encephalopathy cases had EOS (confirmed+probable), including 52 (5.1%) that were culture-confirmed sepsis and 129 (12.5%) with probable sepsis. The incidence (per 1,000 live births) of EOS (confirmed+probable) in newborns with neonatal encephalopathy was 2.3 (95% CI: 2.0-2.7); including 0.22, 0.13 and 0.06 for culture-confirmed, Group B streptococcus, Klebsiella pneumoniae and Escherichia coli, respectively. The case fatality risk (CFR) of EOS (confirmed+probable) in newborns with neonatal encephalopathy was 19.3% (95% CI: 13.9-25.9). Predictors of fatal outcome in newborns with EOS(confirmed+probable) and neonatal encephalopathy included moderate or severeneonatal encephalopathy(aOR 6.79), seizures (aOR 3.46) and in-utero HIV-exposure (aOR 3.72; p<0.05 for all predictors). Conclusion: In this low-middle income African setting, EOS (confirmed+probable) was prevalent in 17.6% of neonatal encephalopathy cases. Our study highlights the need for preventative strategies against EOS as a strategy to reduce the burden of neonatal encephalopathy.
A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Masters of Medicine in Paediatrics