Neurological sequelae of healthcare-associated sepsis in very-low-birthweight infants: Umbrella review and evidence-based outcome tree

Sepsis is a frequent cause of death in very-low-birthweight infants and often results in neurological impairment. Its attributable risk of sequelae has not been systematically assessed. To establish an outcome tree for mapping the burden of neonatal sepsis, we performed systematic literature searches to identify systematic reviews addressing sequelae of neonatal sepsis. We included cohort studies and performed meta-analyses of attributable risks. Evidence quality was assessed using GRADE. Two systematic reviews met inclusion criteria. The first included nine cohort studies with 5,620 participants and five outcomes (neurodevelopmental impairment, cerebral palsy, vision impairment, hearing impairment, death). Pooled risk differences varied between 4% (95% confidence interval (CI):2-10) and 13% (95% CI:5-20). From the second review we analysed four studies with 472 infants. Positive predictive value of neurodevelopmental impairment for later cognitive impairment ranged between 67% (95% CI:22-96) and 83% (95% CI:36-100). Neonatal sepsis increases risk of permanent neurological impairment. Effect size varies by outcome, with evidence quality being low to very low. Data were used to construct an outcome tree for neonatal sepsis. Attributable risk estimates for sequelae following neonatal sepsis are suitable for burden estimation and may serve as outcome parameters in interventional studies.