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      Prevention of Allergic Sensitization and Treatment of Cow’s Milk Protein Allergy in Early Life: The Middle-East Step-Down Consensus

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          Abstract

          Allergy risk has become a significant public health issue with increasing prevalence. Exclusive breastfeeding is recommended for the first six months of life, but this recommendation is poorly adhered to in many parts of the world, including the Middle-East region, putting infants at risk of developing allergic sensitization and disorders. When breastfeeding is not possible or not adequate, a partially hydrolyzed whey formula (pHF-W) has shown proven benefits of preventing allergy, mainly atopic eczema, in children with a genetic risk. Therefore, besides stimulating breastfeeding, early identification of infants at risk for developing atopic disease and replacing commonly used formula based on intact cow milk protein (CMP) with a clinically proven pHF-W formula is of paramount importance for allergy prevention. If the child is affected by cow’s milk protein allergy (CMPA), expert guidelines recommend extensively hydrolyzed formula (eHF), or an amino acid formula (AAF) in case of severe symptoms. The Middle-East region has a unique practice of utilizing pHF-W as a step-down between eHF or AAF and intact CMP, which could be of benefit. The region is very heterogeneous with different levels of clinical practice, and as allergic disorders may be seen by healthcare professionals of different specialties with different levels of expertise, there is a great variability in preventive and treatment approaches within the region itself. During a consensus meeting, a new approach was discussed and unanimously approved by all participants, introducing the use of pHF-W in the therapeutic management of CMPA. This novel approach could be of worldwide benefit.

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          Most cited references36

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          Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis

          Objective To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease. Design Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool. Data sources Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015. Eligibility criteria for selecting studies Prospective intervention trials of hydrolysed cows’ milk formula compared with another hydrolysed formula, human breast milk, or a standard cows’ milk formula, which reported on allergic or autoimmune disease or allergic sensitisation. Results 37 eligible intervention trials of hydrolysed formula were identified, including over 19 000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows’ milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I2=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I2=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I2=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could prevent allergy to cows’ milk. Conclusion These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants. Review registration PROSPERO CRD42013004252.
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            Effect of lactose on gut microbiota and metabolome of infants with cow's milk allergy.

            Allergic infants have an unusual gastrointestinal microbiota with low numbers of Bifidobacterium/Lactobacilli and high levels of Clostridium, staphylococci and Escherichia coli. Hydrolyzed formula used to treat these infants is deprived of lactose that instead may influence the gut microbial composition. The aim of the present study is to investigate the influence of lactose on the composition of the gut microbiota and metabolome of infants with cow's milk allergy. Infants prospectively enrolled received an extensively hydrolyzed formula with no lactose for 2 months followed by an identical lactose-containing formula for an additional 2 months. Healthy, age-gender-matched infants were used as controls. The following determinations were performed before and after the introduction of lactose in the diet: enumeration of cells present in the feces using FISH, counts of viable bacterial cells and gas-chromatography mass spectrometry/solid-phase microextraction analysis. The addition of lactose to the diet significantly increases the counts of Bifidobacteria and lactic acid bacteria (p < 0.01), decreases that of Bacteroides/clostridia (p < 0.05) reaching counts found in healthy controls; lactose significantly increases the concentration of total short-chain fatty acids (p < 0.05). The addition of lactose to an extensively hydrolyzed formula is able to positively modulate the composition of gut microbiota by increasing the total fecal counts of Lactobacillus/Bifidobacteria and decreasing that of Bacteroides/Clostridia. The positive effect is completed by the increase of median concentration of short chain fatty acids, especially for acetic and butyric acids demonstrated by the metabolomic analysis. © 2012 John Wiley & Sons A/S.
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              Allergies in high-risk schoolchildren after early intervention with cow's milk protein hydrolysates: 10-year results from the German Infant Nutritional Intervention (GINI) study.

              The long-term effect of nutritional intervention with hydrolysate infant formulas on allergic manifestations in high-risk children is uncertain. We sought to investigate the effect of hydrolysate infant formulas on allergic phenotypes in children with family history of allergies at school age. We analyzed data from participants of the prospective German Infant Nutritional Intervention study after 10 years of follow-up. At birth, children were randomly assigned to receive, for the first 4 months, one of 4 blinded formulas as breast milk substitute, if necessary: partially hydrolyzed whey formula (pHF-W), extensively hydrolyzed whey formula (eHF-W), extensively hydrolyzed casein formula (eHF-C), or standard cow's milk formula. Outcomes were parent-reported, physician-diagnosed allergic diseases. Log-binomial regression models were used for statistical analysis. The relative risk for the cumulative incidence of any allergic disease in the intention-to-treat analysis (n = 2252) was 0.87 (95% CI, 0.77-0.99) for pHF-W, 0.94 (95% CI, 0.83-1.07) for eHF-W, and 0.83 (95% CI, 0.72-0.95) for eHF-C compared with standard cow's milk formula. The corresponding figures for atopic eczema/dermatits (AD) were 0.82 (95% CI, 0.68-1.00), 0.91 (95% CI, 0.76-1.10), and 0.72 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis (n = 988) effects were stronger. The period prevalence of AD at 7 to 10 years was significantly reduced with eHF-C in this analysis, but there was no preventive effect on asthma or allergic rhinitis. The significant preventive effect on the cumulative incidence of allergic diseases, particularly AD, with pHF-W and eHF-C persisted until 10 years without rebound, whereas eHF-W showed no significant risk reduction. There is insufficient evidence of ongoing preventive activity at 7 to 10 years of age. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                26 June 2019
                July 2019
                : 11
                : 7
                : 1444
                Affiliations
                [1 ]KidZ Health Castle, UZ Brussel, Vrijne Unversiteit Brussel, 1090 Brussels, Belgium
                [2 ]Department of Paediatrics, King Abdulaziz University Hospital, Jeddah 22252, Saudi Arabia
                [3 ]Department of Paediatrics, Al Salam International Hospital, Dasma 35151, Kuwait
                [4 ]Department of Paediatric Gastroenterology, King Abdullah Specialized Children’s Hospital, Ministry of National Guard Health Affairs, Riyadh 11426, Saudi Arabia
                [5 ]Clinical Nutrition Department, Dubai Health Authority, P.O. Box, Dubai 4545, UAE
                [6 ]Department of Paediatrics, National Guard Hospital, Dammam 31412, Saudi Arabia
                [7 ]Department of Paediatrics, Mediclinic Welcare Hospital, P.O. Box, Dubai 31500, UAE
                [8 ]Department of Paediatrics, Saint George Hospital University Medical Center, Balamand University, P.O. Box, Beirut 166378, Lebanon
                [9 ]Department of Clinical Nutrition Services, King Abdulaziz Medical City-Jeddah, Ministry of National Guard Health Affairs, Jeddah 21423, Saudi Arabia
                [10 ]Department of Paediatrics, Alhakeem Furat Clinic, Amman 11942, Jordan
                [11 ]Department of Paediatrics, Sheikh Khalifa Medical City, P.O. Box, Abu Dhabi 51900, UAE
                Author notes
                [* ]Correspondence: yvan.vandenplas@ 123456uzbrussel.be ; Tel.: +3224775794
                Author information
                https://orcid.org/0000-0002-1862-8651
                Article
                nutrients-11-01444
                10.3390/nu11071444
                6683055
                31248015
                dacd6383-dabd-4ca8-b5e1-971eaf9b800b
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 May 2019
                : 20 June 2019
                Categories
                Concept Paper

                Nutrition & Dietetics
                partial hydrolysate,cow’s milk protein allergy,hydrolysate,infant feeding,middle-east,step-down,infant allergy

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