Human milk (HM) contains critical nutrients and possibly other neurotrophic factors that could benefit the less\ndeveloped brain of preterm infants, particularly those with very low birth weight (VLBW). This study aims to\nsystematically review the original studies to determine whether there is a reproducible independent effect of HM\nfeeding on neurodevelopment outcome in preterm VLBW infants. Search of seven databases (PubMed, Cochrane,\nCINAHL, Embase, Proquest Research Library, Google Scholar, and Web of Science) identified 24 original studies. Each\nstudy was evaluated by two authors independently for 8 non-nutritive (study design, target population, a priori\npower calculation, adjustment for baseline growth status, postnatal complication, other confounders, observer\nblinding to feeding status, effect size) and 5 nutritive (definition and duration of HM intake, use of HM fortifier,\nsource of HM data, infant formula used) methodology parameters, and consistency and directness of outcome\nmeasures. Thirteen reports of preterm infants with wide ranges of birth weights were excluded as none provided\nsufficient data to delineate the effects of HM feeding on developmental outcome of subjects with VLBW. Eleven\nreports included only VLBW children and 7 studies were reviewed after elimination of preliminary data from same\ncohort or lack of appropriate standardized testing or control group. These 7 studies (n = 18 to 704, median 219)\nwere performed at <3 years (3 studies) and at 5 to 11 years (4 studies). Six studies were secondary analysis of data\nfrom other studies. Each study met or only partially met 4 to 10 methodological parameters. VLBW children with no\nneurological impairment fed HM achieved normal or low normal range of test scores. Formula feeding using older\nformulations was associated with a lower subtest score in 4 studies. There is no randomized clinical trial comparing\nthe neurodevelopment outcome of HM versus formula or minimal HM feeding that included only children with\nVLBW. The role of HM in the neurodevelopment and cognitive function of VLBW children needs reassessment with\nhigh quality studies in the context of current formulations of HM fortifier and preterm formula.
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