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To determine the impact of implementing the NICE Early Onset Sepsis Guidelines (CG149) in the East of England Perinatal Network.This prospective, multicentre quality improvement project involved evaluating differences between current practice and NICE recommendations in the management of term infants <72 h old with concerns of early onset sepsis.Data was collected on maternal risk factors for sepsis, neonatal symptoms, inflammatory markers and microbiology. Using NICE criteria for sepsis screening as a model, the impact of implementing the guideline against current practice was determined. Primary outcomes included frequency of sepsis screens, treatment duration, length of stay and frequency of lumbar punctures (LPs).172 term infants were recruited across 9 neonatal units, of which 130 (76%) underwent sepsis screening. If evaluated using the NICE guidelines, 117 (68%) infants would have been treated. Infants screened for sepsis received a mean of 3.7 days (SD 2.0) antibiotics. Those observed were admitted for 1.4 days (SD 0.6). Using the NICE guidelines to model treatment decisions, the estimated mean treatment length was 3.0 days (SD 2.4).Indications for LPs varied between centres and were performed in 36 infants. If a threshold C-reactive protein (CRP) of 10 were applied, 50 patients required the procedure. No cases of meningitis were identified on microscopy or culture.Applying the NICE Guidelines suggest a reduction in sepsis screens and treatment duration, however CRP thresholds > 10 increase the number of infants undergoing lumbar punctures.