Background Standardized written guidelines and protocols in NICU are known to impact neonatal outcomes and improve survival. Objective To study and compare the morbidity and mortality outcomes of very low birth weight (VLBW) neonates before and after introduction of structured approach to standardized management guidelines on four interventions in a tertiary care hospital in North India. Methodology Structured approach to standardized management guidelines on four interventions were implemented for VLBW infants in NICU. a) Humidified and Heated High Flow Nasal Cannula (HHHFNC) as the initial mode of ventilator support in preterm VLBW babies. b) Expressed breast milk for feeding preterm VLBW babies and absolutely no formula milk. c) Hand washing and following “Bundle Care Approach” for Central lines as the cardinal cornerstones for maintaining strict asepsis. d) Development and supportive care to be regularly followed. Data was collected prospectively from July 2015 to December 2016 (Intervention Group) and compared with retrospective matched controls from the previous year (July 2014–June 2015) (Control Group). Results There was a significant decrease in culture positive sepsis in the intervention group compared to control group (3 (2.97%) CI:0.006–0.08 vs 11 (19.64%) CI:0.10–0.32; P = .0004). There was no significant difference in the mortality (5.35% vs3.96% P = .74) amongst the two groups. Conclusion Implementing structured approach to above mentioned interventions in the form of standardized management guidelines for preterm VLBW neonates was associated with significant reduction in culture proven sepsis and mechanical ventilation days without affecting mortality or other co-morbidities.

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