Supplementary Material for: Long Term Neurodevelopmental Impairment among Very Preterm Infants with Sepsis, Meningitis and Intraventricular Hemorrhage

Introduction: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long term neurodevelopmental outcomes in very preterm infants (VPI), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine long-term neurodevelopmental outcomes of VPI with late onset sepsis and meningitis, with and without IVH, in Canada. Methods: We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units (NICU) in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-up Network (CNFUN) databases, from January 1, 2010 to December 31, 2016. Results: Of the 6322 infants in the cohort, 4575 had no infection, 1590 had late onset culture positive blood-stream infection (CPBSI) only and 157 had late onset meningitis. There was a significant (p<0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment (NDI), cerebral palsy, and individual Bayley-III scores<85 for cognitive, language and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. Discussion/Conclusion: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect.