Abstract
ObjectiveNecrotizing enterocolitis (NEC) or death often occur in very low birthweight (VLBW, <1500 g) infants. Intestinal maturation and normal bacterial colonization, which help prevent these outcomes, induce FUT2 ["secretor"] and dampen sialyltransferase gene expression. We tested whether a low secretor, high sialylglycan phenotype predicts risk of NEC or death.MethodsSalivary secretor and sialylglycans and FUT2 genotype, indirect measures of intestinal phenotype, were analyzed in 385 VLBW infants. Saliva samples collected on day 9 were analyzed by enzyme immunoassay using monoclonal antibodies. Risk cut‐points were identified by Classification and Regression Tree analysis. NEC was defined as Bell's stage >2.ResultsNEC or death occurred in 39 infants. Of infants with low secretor (H‐2), high sialyl (sialyl Lewis a [sLea ], n=104), 23% developed NEC and 18% died; of those with the reciprocal phenotype (high H‐2/low sLea, n=73), no NEC or death occurred; risk was intermediate when H‐2 and sLea were both high or low (p<0.0001; predictive value=0.73). FUT2 genotype was strongly associated with death (13% of non‐secretors [AA], 5% of heterozygotes [AG], 1% of secretor dominant [GG], p=0.001) but not NEC.ConclusionsSalivary glycans and FUT2 genotype are associated with risk of NEC and death in VLBW infants, and provide powerful biomarkers for clinical research and practice.
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