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Abstract

To the Editor:We agree with Koletzko et al1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar that our study,2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar like all studies, has some limitations. However, these limitations are by no means as severe as they suggest.1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar We address their criticisms of the scientific merit of the study here, while dealing with this group's other statements, including the delay in publication, within this article's Online Repository at www.jacionline.org.In our study 92.7% of children completed follow-up until 2 years of age compared with 79.8% for the German Infant Nutritional Intervention (GINI) study.3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar The Cochrane review on this topic4Osborn D.A. Sinn J. Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.Cochrane Database Syst Rev. 2006; : CD003664PubMed Google Scholar excluded studies with less than 80% follow-up.The slight delay in the introduction of the final formula did not materially influence the study results because the baseline risk factors remained balanced between the groups. Exclusion of the 97 children recruited before the third formula became available did not substantially alter the study outcome (odds ratio of 1.23 [95% CI, 0.80-1.89] when comparing partially hydrolyzed whey formula [pHWF] with cow's milk formula for the primary end point).It was intended that the research staff and participants be blinded in this study, but because of events beyond our control (late supply of pHWF), blinding of research staff could potentially have been broken. For this reason, we have limited the description of this study as being single (participant) blind. Despite the claims of Koletzko et al,1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar there was no evidence that participants were unblinded. We asked parents to breast-feed or only use the allocated formula up to the child's first birthday.2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Although we encouraged parents to adhere to these recommendations, parents could choose to break with this feeding protocol. As we clearly stated, most (69.1% to 76.4% across the 3 study arms) were fully compliant with these guidelines. At the conclusion of the 12-month dietary guidelines, children in our soy arm were slightly more likely to receive nonallocated soy formula.5Koplin J. Dharmage S.C. Gurrin L. Osborne N. Tang M.L. Lowe A.J. et al.Soy consumption is not a risk factor for peanut sensitization.J Allergy Clin Immunol. 2008; 121: 1455-1459Abstract Full Text Full Text PDF PubMed Scopus (10) Google ScholarSince 2006, we have published 8 articles from this study related to eczema, and all have defined eczema in the same manner as reported in the current article.5Koplin J. Dharmage S.C. Gurrin L. Osborne N. Tang M.L. Lowe A.J. et al.Soy consumption is not a risk factor for peanut sensitization.J Allergy Clin Immunol. 2008; 121: 1455-1459Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, E11Lowe A.J. Carlin J.B. Bennett C.M. Hosking C.S. Allen K.J. Robertson C.F. et al.Paracetamol use in early life and asthma: prospective birth cohort study.BMJ. 2010; 341: c4616Crossref PubMed Scopus (91) Google Scholar, E12Lowe A.J. Thien F.C. Stoney R.M. Bennett C.M. Hosking C.S. Hill D.J. et al.Associations between fatty acids in colostrum and breast milk and risk of allergic disease.Clin Exp Allergy. 2008; 38: 1745-1751PubMed Google Scholar, E13Lowe A.J. Carlin J.B. Bennett C.M. Hosking C.S. Abramson M.J. Hill D.J. et al.Do boys do the atopic march while girls dawdle?.J Allergy Clin Immunol. 2008; 121: 1190-1195Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, E14Lowe A.J. Hosking C.S. Bennett C.M. Carlin J.B. Abramson M.J. Hill D.J. et al.Skin prick test can identify eczematous infants at risk of asthma and allergic rhinitis.Clin Exp Allergy. 2007; 37: 1624-1631Crossref PubMed Scopus (82) Google Scholar, E15Lowe A.J. Abramson M.J. Hosking C.S. Carlin J.B. Bennett C.M. Dharmage S.C. et al.The temporal sequence of allergic sensitization and onset of infantile eczema.Clin Exp Allergy. 2007; 37: 536-542Crossref PubMed Scopus (82) Google Scholar, E16Lowe A.J. Carlin J.B. Bennett C.M. Abramson M.J. Hosking C.S. Hill D.J. et al.Atopic disease and breastfeeding—cause or consequence?.J Allergy Clin Immunol. 2006; 117: 682-687Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar, E17Koplin J. Dharmage S.C. Gurrin L. Osborne N. Tang M.L. Lowe A.J. et al.Soy consumption is not a risk factor for peanut sensitization.J Allergy Clin Immunol. 2008; 121: 1455-1459Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, E18Lodge C.J. Lowe A.J. Gurrin L.C. Hill D.J. Hosking C.S. Khalafzai R.U. et al.House dust mite sensitization in toddlers predicts current wheeze at 12 years.J Allergy Clin Immunol. 2011; ([Epub ahead of print])Google Scholar The prior definitions mentioned1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar were used in 2 articles published before 2004.In contrast, the definitions used by GINI have changed between publications from clinically diagnosed disease6von Berg A. Koletzko S. Grubl A. Filipiak-Pittroff B. Wichmann H.E. Bauer C.P. et al.The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.J Allergy Clin Immunol. 2003; 111: 533-540Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar, 7von Berg A. Koletzko S. Filipiak-Pittroff B. Laubereau B. Grubl A. Wichmann H.E. et al.Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study.J Allergy Clin Immunol. 2007; 119: 718-725Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar to parent-reported outcomes.3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar The reason provided by the GINI group to justify this change was that the “[p]reventive effects for AD and AM were more often significant when the diagnosis was based on parent-reported physician's diagnosis,”3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar suggesting the possibility of selective outcome reporting from this study.To allow direct comparison of the results of both the GINI study3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 6von Berg A. Koletzko S. Grubl A. Filipiak-Pittroff B. Wichmann H.E. Bauer C.P. et al.The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.J Allergy Clin Immunol. 2003; 111: 533-540Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar, 7von Berg A. Koletzko S. Filipiak-Pittroff B. Laubereau B. Grubl A. Wichmann H.E. et al.Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study.J Allergy Clin Immunol. 2007; 119: 718-725Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar and the Melbourne Allergy Cohort Study,2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar the 2 largest studies on this topic, we have provided a table with the reported results (see Table E1 in this article's Online Repository at www.jacionline.org). Both studies failed to demonstrate a beneficial effect of pHWF for allergic manifestations, eczema, asthma or allergic rhinitis with intention-to-treat analysis. The only area in which the results of these studies diverge is on the per-protocol analysis within the first year of life. Per-protocol analyses are not protected (from bias) by the randomization process. Furthermore, a per-protocol analysis of our data2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar does not confirm the findings of the GINI analysis.3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 6von Berg A. Koletzko S. Grubl A. Filipiak-Pittroff B. Wichmann H.E. Bauer C.P. et al.The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.J Allergy Clin Immunol. 2003; 111: 533-540Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar, 7von Berg A. Koletzko S. Filipiak-Pittroff B. Laubereau B. Grubl A. Wichmann H.E. et al.Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study.J Allergy Clin Immunol. 2007; 119: 718-725Abstract Full Text Full Text PDF PubMed Scopus (97) Google ScholarIt is necessary to integrate data across studies to obtain an overview of the effectiveness of a treatment. To this end, we have informed the authors of the Cochrane review on this topic,4Osborn D.A. Sinn J. Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.Cochrane Database Syst Rev. 2006; : CD003664PubMed Google Scholar the most reliable and independent meta-analysis on this subject to date, that the results of our study have now been published. We have requested that these review authors consider this study when they next update their review. We look forward to the proper integration of the current study2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar into the literature before any decisions are made to change (or retain) the current infant-feeding guidelines. To the Editor: We agree with Koletzko et al1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar that our study,2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar like all studies, has some limitations. However, these limitations are by no means as severe as they suggest.1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar We address their criticisms of the scientific merit of the study here, while dealing with this group's other statements, including the delay in publication, within this article's Online Repository at www.jacionline.org. In our study 92.7% of children completed follow-up until 2 years of age compared with 79.8% for the German Infant Nutritional Intervention (GINI) study.3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar The Cochrane review on this topic4Osborn D.A. Sinn J. Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.Cochrane Database Syst Rev. 2006; : CD003664PubMed Google Scholar excluded studies with less than 80% follow-up. The slight delay in the introduction of the final formula did not materially influence the study results because the baseline risk factors remained balanced between the groups. Exclusion of the 97 children recruited before the third formula became available did not substantially alter the study outcome (odds ratio of 1.23 [95% CI, 0.80-1.89] when comparing partially hydrolyzed whey formula [pHWF] with cow's milk formula for the primary end point). It was intended that the research staff and participants be blinded in this study, but because of events beyond our control (late supply of pHWF), blinding of research staff could potentially have been broken. For this reason, we have limited the description of this study as being single (participant) blind. Despite the claims of Koletzko et al,1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar there was no evidence that participants were unblinded. We asked parents to breast-feed or only use the allocated formula up to the child's first birthday.2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Although we encouraged parents to adhere to these recommendations, parents could choose to break with this feeding protocol. As we clearly stated, most (69.1% to 76.4% across the 3 study arms) were fully compliant with these guidelines. At the conclusion of the 12-month dietary guidelines, children in our soy arm were slightly more likely to receive nonallocated soy formula.5Koplin J. Dharmage S.C. Gurrin L. Osborne N. Tang M.L. Lowe A.J. et al.Soy consumption is not a risk factor for peanut sensitization.J Allergy Clin Immunol. 2008; 121: 1455-1459Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Since 2006, we have published 8 articles from this study related to eczema, and all have defined eczema in the same manner as reported in the current article.5Koplin J. Dharmage S.C. Gurrin L. Osborne N. Tang M.L. Lowe A.J. et al.Soy consumption is not a risk factor for peanut sensitization.J Allergy Clin Immunol. 2008; 121: 1455-1459Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, E11Lowe A.J. Carlin J.B. Bennett C.M. Hosking C.S. Allen K.J. Robertson C.F. et al.Paracetamol use in early life and asthma: prospective birth cohort study.BMJ. 2010; 341: c4616Crossref PubMed Scopus (91) Google Scholar, E12Lowe A.J. Thien F.C. Stoney R.M. Bennett C.M. Hosking C.S. Hill D.J. et al.Associations between fatty acids in colostrum and breast milk and risk of allergic disease.Clin Exp Allergy. 2008; 38: 1745-1751PubMed Google Scholar, E13Lowe A.J. Carlin J.B. Bennett C.M. Hosking C.S. Abramson M.J. Hill D.J. et al.Do boys do the atopic march while girls dawdle?.J Allergy Clin Immunol. 2008; 121: 1190-1195Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, E14Lowe A.J. Hosking C.S. Bennett C.M. Carlin J.B. Abramson M.J. Hill D.J. et al.Skin prick test can identify eczematous infants at risk of asthma and allergic rhinitis.Clin Exp Allergy. 2007; 37: 1624-1631Crossref PubMed Scopus (82) Google Scholar, E15Lowe A.J. Abramson M.J. Hosking C.S. Carlin J.B. Bennett C.M. Dharmage S.C. et al.The temporal sequence of allergic sensitization and onset of infantile eczema.Clin Exp Allergy. 2007; 37: 536-542Crossref PubMed Scopus (82) Google Scholar, E16Lowe A.J. Carlin J.B. Bennett C.M. Abramson M.J. Hosking C.S. Hill D.J. et al.Atopic disease and breastfeeding—cause or consequence?.J Allergy Clin Immunol. 2006; 117: 682-687Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar, E17Koplin J. Dharmage S.C. Gurrin L. Osborne N. Tang M.L. Lowe A.J. et al.Soy consumption is not a risk factor for peanut sensitization.J Allergy Clin Immunol. 2008; 121: 1455-1459Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, E18Lodge C.J. Lowe A.J. Gurrin L.C. Hill D.J. Hosking C.S. Khalafzai R.U. et al.House dust mite sensitization in toddlers predicts current wheeze at 12 years.J Allergy Clin Immunol. 2011; ([Epub ahead of print])Google Scholar The prior definitions mentioned1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar were used in 2 articles published before 2004. In contrast, the definitions used by GINI have changed between publications from clinically diagnosed disease6von Berg A. Koletzko S. Grubl A. Filipiak-Pittroff B. Wichmann H.E. Bauer C.P. et al.The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.J Allergy Clin Immunol. 2003; 111: 533-540Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar, 7von Berg A. Koletzko S. Filipiak-Pittroff B. Laubereau B. Grubl A. Wichmann H.E. et al.Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study.J Allergy Clin Immunol. 2007; 119: 718-725Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar to parent-reported outcomes.3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar The reason provided by the GINI group to justify this change was that the “[p]reventive effects for AD and AM were more often significant when the diagnosis was based on parent-reported physician's diagnosis,”3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar suggesting the possibility of selective outcome reporting from this study. To allow direct comparison of the results of both the GINI study3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 6von Berg A. Koletzko S. Grubl A. Filipiak-Pittroff B. Wichmann H.E. Bauer C.P. et al.The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.J Allergy Clin Immunol. 2003; 111: 533-540Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar, 7von Berg A. Koletzko S. Filipiak-Pittroff B. Laubereau B. Grubl A. Wichmann H.E. et al.Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study.J Allergy Clin Immunol. 2007; 119: 718-725Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar and the Melbourne Allergy Cohort Study,2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar the 2 largest studies on this topic, we have provided a table with the reported results (see Table E1 in this article's Online Repository at www.jacionline.org). Both studies failed to demonstrate a beneficial effect of pHWF for allergic manifestations, eczema, asthma or allergic rhinitis with intention-to-treat analysis. The only area in which the results of these studies diverge is on the per-protocol analysis within the first year of life. Per-protocol analyses are not protected (from bias) by the randomization process. Furthermore, a per-protocol analysis of our data2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar does not confirm the findings of the GINI analysis.3von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 6von Berg A. Koletzko S. Grubl A. Filipiak-Pittroff B. Wichmann H.E. Bauer C.P. et al.The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.J Allergy Clin Immunol. 2003; 111: 533-540Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar, 7von Berg A. Koletzko S. Filipiak-Pittroff B. Laubereau B. Grubl A. Wichmann H.E. et al.Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study.J Allergy Clin Immunol. 2007; 119: 718-725Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar It is necessary to integrate data across studies to obtain an overview of the effectiveness of a treatment. To this end, we have informed the authors of the Cochrane review on this topic,4Osborn D.A. Sinn J. Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.Cochrane Database Syst Rev. 2006; : CD003664PubMed Google Scholar the most reliable and independent meta-analysis on this subject to date, that the results of our study have now been published. We have requested that these review authors consider this study when they next update their review. We look forward to the proper integration of the current study2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar into the literature before any decisions are made to change (or retain) the current infant-feeding guidelines. Additional responses to Koletzko et alKoletzko et alE1Koletzko S. Filipiak-Pittroff B. Koletzko B. von Berg A. Krämer U. Berdel D. et al.No reason to change the current guidelines on allergy prevention.J Allergy Clin Immunol. 2012; 129: 262Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar comment extensively on the high prevalence of eczema reported within this studyE2Lowe A.J. Hosking C.S. Bennett C.M. Allen K.J. Axelrad C. Carlin J.B. et al.Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: a randomized controlled trial.J Allergy Clin Immunol. 2011; 128: 360-365Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar when compared with results of their own.E3von Berg A. Koletzko S. Grubl A. Filipiak-Pittroff B. Wichmann H.E. Bauer C.P. et al.The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.J Allergy Clin Immunol. 2003; 111: 533-540Abstract Full Text Full Text PDF PubMed Scopus (377) Google Scholar, E4von Berg A. Koletzko S. Filipiak-Pittroff B. Laubereau B. Grubl A. Wichmann H.E. et al.Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: three-year results of the German Infant Nutritional Intervention Study.J Allergy Clin Immunol. 2007; 119: 718-725Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar, E5von Berg A. Filipiak-Pittroff B. Kramer U. Link E. Bollrath C. Brockow I. et al.Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).J Allergy Clin Immunol. 2008; 121: 1442-1447Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar First, the difference in the rate of eczema observed between these studies is related to differences in baseline prevalence. Australia leads the world in rates of eczema and other allergic diseases. For example, from the International Study of Asthma and Allergies in Childhood Phase Three study, the estimated prevalence of eczema in 6-year-old Melbourne children was 17.1% compared with 7.9% in Germany,E6Asher M.I. Montefort S. Bjorksten B. Lai C.K. Strachan D.P. Weiland S.K. et al.Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys.Lancet. 2006; 368: 733-743Abstract Full Text Full Text PDF PubMed Scopus (3077) Google Scholar where the GINI study was conducted.E3von Berg A. Koletzko S. Grubl A. Filipiak-Pittroff B. Wichmann H.E. Bauer C.P. et al.The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.J Allergy Clin Immunol. 2003; 111: 533-540Abstract Full Text Full Text PDF PubMed Scopus (377) Google Scholar, E4von Berg A. Koletzko S. Filipiak-Pittroff B. Laubereau B. Grubl A. 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