Background:Critically ill children are susceptible to nosocomial infections, which contribute to adverse outcome. Deficiencies within the innate immunity lectin pathway of complement activation are implicated in a child's vulnerability to infections in conditions such as cancer, but the role during critical illness remains unclear. We hypothesized that low upon-admission levels of the pathway proteins are in part genetically determined and associated with susceptibility to infectious complications and adverse outcome.Methods:We studied protein levels of mannose-binding lectin (MBL), H-ficolin and M-ficolin, three MBL-associated-serine proteases (MASPs) and MBL-associated protein (MAp44), and relation with functional genetic polymorphisms, in 130 healthy children and upon-ICU-admission in 700 critically ill children of a randomized study on glycemic control.Results:Levels of MASP-1, MASP-2, MASP-3 and MAp44 were lower and those of M-ficolin higher in ICU patients upon-admission than in matched healthy controls. Only a low upon-admission MASP-3 level was independently associated with risk of new ICU infections and prolonged ICU stay, after correction for other risk factors. Upon-admission MASP-3 varied with age, illness severity and genetic variation.Conclusion:Low upon-admission MASP-3 levels in critically ill children were independently associated with subsequent acquisition of infection and prolonged ICU stay. The biological explanation needs further investigation.Pediatric Research (2013); doi:10.1038/pr.2013.180.