Commercial preterm formulas with glucose polymers and reduced lactose show higher necrotizing enterocolitis rates than breast milk

After more than 70 years of research, necrotizing enterocolitis (NEC) remains the most serious gastrointestinal disease among preterm infants and a leading cause of mortality, morbidity, and disability. Although causes of NEC are multifactorial, this contribution reviews the causal relationship between commercial preterm formulas (PTF) and NEC. The responses of the immature preterm intestine to PTF and the relationship to NEC have been extensively investigated using animal models and in human studies, but the mechanisms by which PTF increases the risk of NEC have not been fully elucidated. Two categories of risk factors may contribute to the higher rates of NEC with PTF compared to breast milk: (1) protective elements in breast milk are missing from PTF and (2) specific ingredients of PTF increase NEC risk. Our comprehensive review of animal studies and clinical trials highlights at least one substance in each category. The principle carbohydrate in breast milk is non-nocive lactose; in PTF, 50%–60% of the lactose is replaced by glucose polymers, which are not present in breast milk, and represent a pathogenic agent. We advocate a complementary research agenda to identify additional protective elements of breast milk (besides lactose) that could be added to PTF and additional nocive elements of PTF (besides glucose polymers) that could be removed to reduce the risk of NEC.