Timing of Cow’s Milk or Cow ’s Milk Formula Introduction to the Infant Diet and Atopic Risk in Children: a Systematic Review and Meta-analysis

Infant feeding is an important early-life exposure that may influence the development of atopic disease. The optimal timing of introduction of food allergens, including cow’s milk (CM), is not known. This study aims to systematically review the evidence describingtheeffectsoftimingofCMorcow’smilkformula(CMF)introductiontotheinfantdietonthedevelopmentofatopic diseasesduringchildhood.Pubmed,Embase,CINAHL,CochraneCENTRAL,andCNKIweresearchedthroughMay30,2019. Study screening and data extraction by two reviewers followed the PRISMA statement. Data were extracted independently in duplicate,and meta-analyses wereperformedbypoolingunadjustedandadjustedoddsratio(OR)separately.Heterogeneitywas exploredusingI2andpublicationbiasbyfunnelplotsandBegg’stests.Intotal,45studiesfrom20countrieswereincluded.MetaanalysesusingadjusteddatashowedthatnoassociationswereobservedbetweenearlyintroductionofCMorCMFandtheriskof asthma (<4 vs. ≥4 months: OR 1.16, 95% confidence interval (CI) 0.89, 1.51), wheeze (<6 vs. ≥6 months: OR 1.15, 95% CI 0.85, 1.56), and eczema or atopic dermatitis (<6 vs. ≥6 months: OR 0.96, 95% CI 0.65, 1.41). Overall, quite little high-quality evidencewasidentifiedtoallowfordefinitiveconclusionsontheassociationbetweenearlyCMorCMFintroductionandriskof allergic diseases. Our meta-analysis on this topic highlights the specific gaps in information for public recommendations regarding CM or CMF feeding practice in an early stage of life, particularly before 3 months of age. Keywords Timingofintroduction .Cow’smilk.Infantformula .Allergy .Systematicreview .Meta-analysis