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BACKGROUND: Despite the implementation of preventive guidelines and advances in neonatal care, group B streptococcal (GBS) disease remains an important cause of neonatal morbidity and mortality. OBJECTIVE: To estimate the incidence and case fatality rates of neonatal GBS disease, maternal and infant risk factors for GBS disease, and identify limitations and gaps in the implementation of prevention and treatment guidelines in British Columbia. METHODS: A retrospective cohort study using population-based data from the Perinatal Data Registry from 2004 to 2014 was conducted. Poisson regression analysis was used to determine regional and yearly trends in the incidence of neonatal GBS disease. A multiple logistic regression was conducted to examine the association between risk factors and neonatal GBS disease outcome. Unadjusted proportions of maternal GBS screening and antibiotic administration, and the presence of risk factors were computed. A descriptive analysis of retrospective case series data obtained from a chart review at the BC Women’s and Children’s Hospital was conducted to identify guideline failures and lack of adherence. RESULTS: The annual average incidence rate of neonatal GBS disease in BC was 0.54 per 1000 live births, ranging from 0.62 to 0.57 per 1000 live births over a 10-year period. An overall case fatality of 3.4% was observed. Risk factors found to be significantly associated with neonatal GBS disease included positive GBS culture result, prolonged rupture of membranes, younger gestational age at delivery, prematurity, spontaneous labour, emergency caesarean delivery and decreased maternal age. From 2004 through 2014, maternal screening for GBS increased by approximately 10% and antibiotic administration during labour for at-risk women increased by 11.7%. GBS colonization during pregnancy remained relatively stable, ranging from 22.5%-25.3% over the time period. An estimated 48% of neonatal GBS cases may be irreducible due to failures of the screening and prophylaxis components of the guidelines; the remaining 52% of neonatal GBS cases were associated with lack of adherence to the GBS guidelines.CONCLUSION: The burden of neonatal GBS disease could be further reduced with additional prevention measures, including increased levels of antepartum and intrapartum screening, and use of intrapartum antibiotics for screen positive and at-risk mothers.