Background: Neonatal sepsis complicated with neutropenia increases risk of mortality by 50%. The immature neutrophil production of neonates is often overwhelmed by severe infection. Granulocyte colony stimulating factor (G-CSF), a naturally occurring cytokine used to support neutrophil recovery during chemotherapy, is a possible treatment that can improve outcomes of neonatal sepsis. Objectives: To determine the efficacy of G-CSF in decreasing mortality and morbidity in septic neonates. Methodology: Electronic searches were conducted on online journal databases. Unpublished or ongoing studies were sought in training institutions accredited by the Philippine Pediatric Society. The investigators included randomized control trials using G-CSF on neonates with proven or suspected sepsis. Results: Twenty-two trials were identified and thirteen were assessed to be eligible for review. The studies had a total of 530 participants, with the largest having 78 subjects. Relative risks (RR), mean differences (MD) and standard mean differences (SMD) with 95% confidence intervals (CI) using the random effects model and the fixed effect model were reported in the results. There was a significant decrease in mortality (RR 0.69, 95% CI 0.48 to 0.99) with a greater reduction of mortality rates for preterm neonates (RR 0.60, 95% CI 0.39 to 0.94), neonates with low birthweight (RR 0.29, 95% CI 0.15 to 0.57) and neonates who had baseline neutropenia (RR 0.63, 95% CI 0.41 to 0.97). There was no significant reduction of morbidities caused by neonatal sepsis: Bronchopulmonary Dysplasia (RR 1.30, 95% CI 0.76 to 2.23), Necrotizing Enterocolitis (RR 0.88, 95% CI 0.12 to 6.24), Intraventricular Hemorrhage (RR 1.34, 95% CI 0.39 to 4.58), Pulmonary Hemorrhage (RR 0.29, 95% CI 0.05 to 1.64). Conclusions: There is moderate quality evidence which suggests that G-CSF as an adjunct treatment for neonatal sepsis significantly decreases mortality with greater benefit to preterm neonates, those with low birthweight and those with baseline neutropenia. The studies did not show any benefit in reducing sepsis-related morbidity. There was no toxicity from G-CSF reported in any of the studies analyzed.

To check for publication bias, the studies were analyzed using a funnel plot wherein the estimated treatment effect for each study was plotted against its standard error. The symmetric distribution of the studies, as shown in this figure, indicates that there is low risk for publication bias.

To check for publication bias, the studies were analyzed using a funnel plot wherein the estimated treatment effect for each study was plotted against its standard error. The symmetric distribution of the studies, as shown in this figure, indicates that there is low risk for publication bias.

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Figure II

Overall Mortality Rate Forest Plot

All thirteen included studies reported data on all-cause mortality. Five hundred thirty participants were included in the analysis. There were 41 deaths from the 282 participants in the treatment group while there were 54 deaths from the 248 participants in the control group. There was a significant decrease in mortality in the treatment group (RR 0.69, 95% CI 0.48 to 0.99, Fixed, P = 0.32, I2 = 13%).

Figure II

Overall Mortality Rate Forest Plot

All thirteen included studies reported data on all-cause mortality. Five hundred thirty participants were included in the analysis. There were 41 deaths from the 282 participants in the treatment group while there were 54 deaths from the 248 participants in the control group. There was a significant decrease in mortality in the treatment group (RR 0.69, 95% CI 0.48 to 0.99, Fixed, P = 0.32, I2 = 13%).

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