What is the role of neonatal organ dysfunction and illness severity scores in therapeutic studies in sepsis?

The goal of therapeutic studies in neonatal sepsis is to increase disability-free survival. Mortality may not be an adequate measure of outcome if it is reduced at the cost of increased disability. No neonatal organ dysfunction score has yet been validated as a reliable surrogate for disability-free survival. To validate a score as a surrogate would require randomized trials showing 1) a causal connection between change in the score and change in disability-free survival and 2) that the score fully captured all the effects of treatment on disability-free survival. Neonatal illness severity scores provide a convenient, but imperfect, tool to adjust for risk of sepsis in observational studies. They can help to stratify infants by risk of sepsis at entry to trials, allowing analyses of outcome in predefined subgroups. However, they cannot circumvent the need for randomized trials of adequate size in neonatal sepsis, which address disability-free survival as the primary outcome.