Necrotising enterocolitis (NEC) causes significant morbidity and mortality in premature infants. The role of innate immunity in the pathogenesis of NEC remains unclear. Mannose-binding lectin (MBL) recognizes microorganisms and activates the complement system via MBL-associated serine protease-2 (MASP2). The aim of this study was to investigate whether MBL and MASP-2 are associated with NEC. This observational case-control Study included 32 infants with radiologically confirmed NEC and 64 controls. MBL and MASP-2 were measured in cord blood using ELISA. Multivariate logistic regression was performed. Of the 32 NEC cases (median gestational age, 30.5 wk). 13 (41 %) were operated and 5 (16%) died. MASP-2 cord blood concentration ranged front undetectable (< 10 ng/mL) to 277 ng/mL. Eighteen of 32 (56%) NEC cases had higher MASP-2 levels (>= 30 ng/mL) compared with 22 of 64 (34%) controls (univariate OR 2.46: 95% CI 1.03-5.85: p = 0.043). Higher cord blood MASP-2 levels were significantly associated with all increased risk of NEC in multivariate analysis (OR 3.00: 95% CI 1.17-7.93; p = 0.027). MBL levels were not associated with NEC (p = 0.64). In conclusion. infants later developing NEC had significantly higher MASP-2 cord blood levels compared with controls. Higher MASP-2 may favor complement-mediated inflammation and Could thereby predispose to NEC. (Pediatr Res 64: 562-566, 20081)