The Risk Factors for Late Onset Sepsis on Very Preterm Neonates and the Impact on Neuroimaging At Term Equivalent Age

Background: Neonatal sepsis remains significant reason of increased mortality among extremely preterm neonates, and has been associated with white matter injury.

Objective: To examine the risk factors for late-onset sepsis (LOS) and the outcomes in extremely preterm neonates. Also, to evaluate any association between LOS and the brain MRI findings at term equivalent age.

Methods: The medical records of neonates ≤28 weeks’ gestation, admitted to the Neonatal Unit of University Hospital of Ioannina during 2006-2017 were reviewed. Neonates with LOS, confirmed with blood culture, were compared with neonates without sepsis. Neonates with early onset sepsis were excluded.

Results: Totally 155 neonates were enrolled; 55 (35%) with LOS and 100 (65%) controls.

Multiple LOS episodes were recorded in 17 neonates; among 79 sepsis episodes, Gram(+) pathogen detected in 61%, fungi in 22% and Gram(-) in 11%.

Neonates with sepsis were predominantly males (71 versus 46%, p=0.002), had a longer duration of mechanical ventilation (37 versus 16 days, p=0.001), developed bronchopulmonary dysplasia in higher proportion (64% versus 34%, p=0.001), required prolonged parenteral nutrition (35 versus 15 days, p<0.001), received more blood transfusions (8 versus 5 times, p<0.001), and had longer length of stay (95 versus 82 days, p=0.002). Survival rates were similar (71% versus 73%). Male gender (2.992, p=0.026, 95%CI 1.142-7.842) and blood transfusion (0.765, p=0.030, 95%CI 0.601-0.974) were predominant risk factors for LOS.

The 68% of neonates with LOS had a normal MRI, versus 90% controls (p=0.030). The commonest abnormal finding was diffuse periventricular leukomalacia (dPVL), in 18% of neonates with LOS versus 4% of controls (p=0.021).

In multivariate analysis, sepsis was a strong predictor for developing dPVL (3.958, p=0.048, 95%CI 1.011-15.491).

Conclusions: In extremely preterm neonates, multiple factors predispose for the development of LOS. Nonetheless, in this cohort, sepsis remains an independent risk factor for the development of dPVL.