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The incidence of bacterial sepsis during the neonatal period is high. Mannan-binding lectin (MBL), L-ficolin, and H-ficolin recognize microorganisms and activate the complement system viaMBL-associated serine proteases (MASPs). This study investigated whether cord blood concentrations of the lectin pathway proteins are associated with neonatal sepsis.This was a case-control study including 47 infants with culture-proven sepsis during the first month of life and 94 matched controls. MBL, L-ficolin, H-ficolin, MASP-2, and MASP-3 levels were measured in cord blood with use of enzyme-linked immunosorbent assay and time-resolved immunofluorometric assay. Multivariate logistic regression was performed.Infants with gram-positive sepsis had significantly lower H-ficolin cord blood concentrations than controls (multivariate odds ratio [OR], 4.00; 95% confidence interval [CI], 1.51-10.56; P=.005), whereas infants with gram-negative sepsis had lower MBL cord blood concentrations (OR, 2.99; 95% CI, 0.86-10.33; P=.084). When excluding patients with postoperative sepsis, multivariate analysis confirmed that low H-ficolin was associated with a significantly higher risk of gram-positive sepsis (OR, 3.71; 95% CI, 1.26-10.92; P=.017) and late-onset sepsis (OR, 3.14; 95% CI, 1.07-9.21; P=.037). In contrast, low MBL was associated with a significantly higher risk of gram-negative sepsis (OR, 4.39; 95% CI, 1.10-17.45; P=.036) and early-onset sepsis (OR, 3.87; 95% CI, 1.05-14.29; P=.042). The concentrations of all the lectin pathway proteins increased with gestational age (P<.01).These preliminary results indicate that low MBL concentrations are a susceptibility factor for gram-negative sepsis, and low H-ficolin concentrations indicate susceptibility to gram-positive sepsis. The decreased expression of lectin pathway proteins in neonates must be considered to be an additional form of neonatal immunodeficiency.