HumanMilk–ComparedwithBovineMilk–Derived FortifiersinPretermInfants:ASystematicReview andMeta-Analysis

Abstract

This systematic review assessed outcomes after using human milk–derived fortifier (HMF) compared with bovine milk–derived fortifier (BMF) in preterminfants.Sixrandomizedcontrolledtrials(RCTs)wereincluded.Meta-analysisusingarandom-effectsmodelshowedthefollowingresults:1) lowerriskofnecrotizingenterocolitis(NEC;≥StageII)(RR:0.38;95%CI:0.15,0.95;P=0.04,I2 =9%;n=334,4RCTs)andsurgicalNEC(RR:0.13;95% CI:0.02,0.67;P=0.02,I2=0%;n=209,3RCTs)intheHMFgroup;2)nosignificantdifferenceinmortality(RR:0.40;95%CI:0.14,1.15;P=0.09,I2=0%; n=334,4RCTs);3)lowerweightgainintheHMFgroup[meandifference(MD)=−1.08g·kg−1·d−1;95%CI:−1.96,−0.21g·kg−1·d−1;P=0.02, I2 =0%;n=241,4RCTs],4)nodifferencesforlength(MD=−0.11cm/wk;95%CI:−0.26,0.04cm/wk;P=0.14,I2 =68%)andheadcircumference (MD=−0.02cm/wk;95%CI:−0.08,0.05cm/wk;P=0.59,I2 =23%),and5)nosignificantdifferenceinlate-onsetsepsis(RR:0.96;95%CI:0.56,1.67; P=0.90,I2 =63%;n=334, 4 RCTs). The beneficial effects ofHMF for NEC were no longer significant insensitivity analyses after excludingstudies withhighriskofbias.QualityofevidenceasperGradingofRecommendations,Assessment,DevelopmentandEvaluationanalysiswaslowtovery low,andhencetheconfidenceintheseresultsislow.Insummary,fortificationofmilkinpreterminfantswithHMFcomparedwithBMFdecreased theriskofNECbutwasassociatedwithlowerweightgain.Giventhelowqualityofevidence,adequatelypoweredandwell-designedRCTswithout theinfluenceofindustryarerequiredinthisfield