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Erschienen in: European Journal of Pediatrics 8/2019

22.06.2019 | Review

Probiotics for cow’s milk protein allergy: a systematic review of randomized controlled trials

verfasst von: Sheeba Qamer, Mangesh Deshmukh, Sanjay Patole

Erschienen in: European Journal of Pediatrics | Ausgabe 8/2019

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Abstract

Cow’s milk protein allergy (CMPA) is the commonest food allergy in infancy and is associated with significant health burden. Given their immune modulatory properties, probiotics have been proposed as a strategy for management of CMPA. We aimed to systematically review efficacy and safety of probiotics in the management of CMPA. Databases PubMed, EMBASE, CINAHL, Cochrane Central Library, and Google scholar were searched in August 2018 for randomized controlled trials (RCT) of probiotic supplementation as an adjunct in the management of infants with suspected/proven CMPA. Primary outcomes were resolution of hematochezia and acquisition of tolerance to CMP at 6, 12, 24, and 36 months. Secondary outcomes included effect on allergic symptoms (SCORAD index), growth, gut microbiota, and adverse effects. A total of 10 RCTs (n = 845; probiotics, 422; control, 423) with low to unclear risk of bias were included. Meta-analysis showed probiotic supplementation was not associated with earlier resolution of hematochezia (n = 87; RR: 1.45 (95% CI: 0.96–2.18), p = 0.08; level of evidence (LOE), very low), in presumed CMPA. In confirmed CMPA, probiotics were associated with higher rate of acquisition of tolerance to CMP at the end of 3 years compared with placebo (N = 493; RR, 1.47; 95% CI, (1.17–1.84); p = 0.0009; LOE, low]. Meta-analysis was not possible for other outcomes. There were no probiotic related adverse effects.
Conclusion: Limited low-quality evidence indicates that probiotic supplementation may be associated with earlier acquisition of tolerance to CMP in children with CMPA. Large well-designed trials are essential to confirm these findings.
What is Known:
Cow’s milk protein allergy (CMPA) is one of the commonest food allergies in children. CMPA is associated with significant socioeconomic burden.
Elimination diet and extensively hydrolyzed formula is the mainstay of the management of CMPA.
What is New:
This first systematic review of randomized controlled trials shows that probiotics as an adjuvant can lead to earlier acquisition of tolerance to CMP in children at 36 months of age. However, the evidence is low quality and influenced by data from one large study.
Probiotic supplementation was not associated with earlier resolution of hematochezia.
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Literatur
1.
Zurück zum Zitat Fiocchi A, Brozek J, Schunemann H, Bahna SL, von Berg A, Beyer K, Bozzola M, Bradsher J, Compalati E, Ebisawa M, Guzman MA, Li H, Heine RG, Keith P, Lack G, Landi M, Martelli A, Rance F, Sampson H, Stein A, Terracciano L, Vieths S (2010) World Allergy Organization (WAO) diagnosis and rationale for action against cow’s milk allergy (DRACMA) guidelines. World Allergy Organ J 3(4):57–161. https://doi.org/10.1097/WOX.0b013e3181defeb9 Fiocchi A, Brozek J, Schunemann H, Bahna SL, von Berg A, Beyer K, Bozzola M, Bradsher J, Compalati E, Ebisawa M, Guzman MA, Li H, Heine RG, Keith P, Lack G, Landi M, Martelli A, Rance F, Sampson H, Stein A, Terracciano L, Vieths S (2010) World Allergy Organization (WAO) diagnosis and rationale for action against cow’s milk allergy (DRACMA) guidelines. World Allergy Organ J 3(4):57–161. https://​doi.​org/​10.​1097/​WOX.​0b013e3181defeb9​
5.
Zurück zum Zitat Walsh J, Meyer R, Shah N, Quekett J, Fox AT (2016) Differentiating milk allergy (IgE and non-IgE mediated) from lactose intolerance: understanding the underlying mechanisms and presentations. Br J Gen Pract 66(649):e609-611. https://doi.org/10.3399/bjgp16X686521 Walsh J, Meyer R, Shah N, Quekett J, Fox AT (2016) Differentiating milk allergy (IgE and non-IgE mediated) from lactose intolerance: understanding the underlying mechanisms and presentations. Br J Gen Pract 66(649):e609-611. https://​doi.​org/​10.​3399/​bjgp16X686521
7.
Zurück zum Zitat Bindslev-Jensen C, Ballmer-Weber BK, Bengtsson U, Blanco C, Ebner C, Hourihane J, Knulst AC, Moneret-Vautrin DA, Nekam K, Niggemann B, Osterballe M, Ortolani C, Ring J, Schnopp C, Werfel T (2004) Standardization of food challenges in patients with immediate reactions to foods–position paper from the European Academy of Allergology and Clinical Immunology. Allergy 59(7):690–697. https://doi.org/10.1111/j.1398-9995.2004.00466.x Bindslev-Jensen C, Ballmer-Weber BK, Bengtsson U, Blanco C, Ebner C, Hourihane J, Knulst AC, Moneret-Vautrin DA, Nekam K, Niggemann B, Osterballe M, Ortolani C, Ring J, Schnopp C, Werfel T (2004) Standardization of food challenges in patients with immediate reactions to foods–position paper from the European Academy of Allergology and Clinical Immunology. Allergy 59(7):690–697. https://​doi.​org/​10.​1111/​j.​1398-9995.​2004.​00466.​x
9.
Zurück zum Zitat Liacouras CA Food protein-induced allergic proctocolitis of infan- 542 cy. In: ScottHSicherer BUL, Alison GHoppin (ed). Accessed 23 Apr 2019 Liacouras CA Food protein-induced allergic proctocolitis of infan- 542 cy. In: ScottHSicherer BUL, Alison GHoppin (ed). Accessed 23 Apr 2019
10.
Zurück zum Zitat Høst A, Halken S, Jacobsen HP, Christensen AE, Herskind AM, Plesner K (2002) Clinical course of cow’s milk protein allergy/intolerance and atopic diseases in childhood. Pediatr Allergy Immunol 13(Suppl 15):23–28 Høst A, Halken S, Jacobsen HP, Christensen AE, Herskind AM, Plesner K (2002) Clinical course of cow’s milk protein allergy/intolerance and atopic diseases in childhood. Pediatr Allergy Immunol 13(Suppl 15):23–28
15.
Zurück zum Zitat Bisgaard H, Li N, Bonnelykke K, Chawes BL, Skov T, Paludan-Muller G, Stokholm J, Smith B, Krogfelt KA (2011) Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol 128(3):646–652.e1-e5. https://doi.org/10.1016/j.jaci.2011.04.060 Bisgaard H, Li N, Bonnelykke K, Chawes BL, Skov T, Paludan-Muller G, Stokholm J, Smith B, Krogfelt KA (2011) Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol 128(3):646–652.e1-e5. https://​doi.​org/​10.​1016/​j.​jaci.​2011.​04.​060
21.
23.
Zurück zum Zitat Berni Canani R, Di Costanzo M, Bedogni G, Amoroso A, Cosenza L, Di Scala C, Granata V, Nocerino R (2017) Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow’s milk allergy: 3-year randomized controlled trial. J Allergy Clin Immunol 139 (6):1906–1913.e1904. https://doi.org/10.1016/j.jaci.2016.10.050 Berni Canani R, Di Costanzo M, Bedogni G, Amoroso A, Cosenza L, Di Scala C, Granata V, Nocerino R (2017) Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow’s milk allergy: 3-year randomized controlled trial. J Allergy Clin Immunol 139 (6):1906–1913.e1904. https://​doi.​org/​10.​1016/​j.​jaci.​2016.​10.​050
24.
Zurück zum Zitat Lefebvre C, Manheimer E, Glanville J (2011) Searching for studies. In: Higgins JPT, Green S (eds) Cochrane handbook for systematic reviews of interventions. Version 5.1.0. Wiley, New York Lefebvre C, Manheimer E, Glanville J (2011) Searching for studies. In: Higgins JPT, Green S (eds) Cochrane handbook for systematic reviews of interventions. Version 5.1.0. Wiley, New York
25.
Zurück zum Zitat Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews andmeta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151(4):W–65-W-94. https://doi.org/10.7326/0003-4819-151-4-200908180-00136 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews andmeta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151(4):W–65-W-94. https://​doi.​org/​10.​7326/​0003-4819-151-4-200908180-00136
26.
Zurück zum Zitat Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 343:d5928. https://doi.org/10.1136/bmj.d5928 Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 343:d5928. https://​doi.​org/​10.​1136/​bmj.​d5928
27.
Zurück zum Zitat Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634 Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634
28.
Zurück zum Zitat Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, Brozek J, Norris S, Meerpohl J, Djulbegovic B (2013) GRADE guidelines: 12. Preparing summary of findings tables—binary outcomes. J Clin Epidemiol 66(2):158–172CrossRefPubMed Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, Brozek J, Norris S, Meerpohl J, Djulbegovic B (2013) GRADE guidelines: 12. Preparing summary of findings tables—binary outcomes. J Clin Epidemiol 66(2):158–172CrossRefPubMed
30.
Zurück zum Zitat Ahanchian H, Nouri Z, Jafari SA, Moghiman T, Amirian MH, Ezzati A, Kianifar HR (2014) Synbiotics in children with cow’s milk allergy: a randomized controlled trial. Iran J Pediatr 24(1):29–34PubMedPubMedCentral Ahanchian H, Nouri Z, Jafari SA, Moghiman T, Amirian MH, Ezzati A, Kianifar HR (2014) Synbiotics in children with cow’s milk allergy: a randomized controlled trial. Iran J Pediatr 24(1):29–34PubMedPubMedCentral
31.
32.
Zurück zum Zitat Berni Canani R, Nocerino R, Terrin G, Frediani T, Lucarelli S, Cosenza L, Passariello A, Leone L, Granata V, Di Costanzo M, Pezzella V, Troncone R (2013) Formula selection for management of children with cow’smilk allergy influences the rate of acquisition of tolerance: a prospectivemulticenter study. J Pediatr 163(3):771–777.e1. https://doi.org/10.1016/j.jpeds.2013.03.008 Berni Canani R, Nocerino R, Terrin G, Frediani T, Lucarelli S, Cosenza L, Passariello A, Leone L, Granata V, Di Costanzo M, Pezzella V, Troncone R (2013) Formula selection for management of children with cow’smilk allergy influences the rate of acquisition of tolerance: a prospectivemulticenter study. J Pediatr 163(3):771–777.e1. https://​doi.​org/​10.​1016/​j.​jpeds.​2013.​03.​008
33.
Zurück zum Zitat Hol J, van Leer EH, Elink Schuurman BE, de Ruiter LF, Samsom JN, Hop W, Neijens HJ, de Jongste JC, Nieuwenhuis EE (2008) The acquisition of tolerance toward cow’s milk through probiotic supplementation: a randomized, controlled trial. J Allergy Clin Immunol 121(6):1448-1454. https://doi.org/10.1016/j.jaci.2008.03.018 Hol J, van Leer EH, Elink Schuurman BE, de Ruiter LF, Samsom JN, Hop W, Neijens HJ, de Jongste JC, Nieuwenhuis EE (2008) The acquisition of tolerance toward cow’s milk through probiotic supplementation: a randomized, controlled trial. J Allergy Clin Immunol 121(6):1448-1454. https://​doi.​org/​10.​1016/​j.​jaci.​2008.​03.​018
34.
Zurück zum Zitat Kirjavainen PV, Salminen SJ, Isolauri E (2003) Probiotic bacteria in the management of atopic disease: underscoring the importance of viability. J Pediatr Gastroenterol Nutr 36(2):223–227CrossRefPubMed Kirjavainen PV, Salminen SJ, Isolauri E (2003) Probiotic bacteria in the management of atopic disease: underscoring the importance of viability. J Pediatr Gastroenterol Nutr 36(2):223–227CrossRefPubMed
35.
Zurück zum Zitat Burks AW, Harthoorn LF, Van Ampting MT, Oude Nijhuis MM, Langford JE, Wopereis H, Goldberg SB, Ong PY, Essink BJ, Scott RB, Harvey BM (2015) Synbiotics-supplemented amino acid-based formula supports adequate growth in cow’s milk allergic infants. Pediatr Allergy Immunol 26(4):316-322. https://doi.org/10.1111/pai.12390 Burks AW, Harthoorn LF, Van Ampting MT, Oude Nijhuis MM, Langford JE, Wopereis H, Goldberg SB, Ong PY, Essink BJ, Scott RB, Harvey BM (2015) Synbiotics-supplemented amino acid-based formula supports adequate growth in cow’s milk allergic infants. Pediatr Allergy Immunol 26(4):316-322. https://​doi.​org/​10.​1111/​pai.​12390
36.
Zurück zum Zitat Candy DCA, Van Ampting MTJ, Oude Nijhuis MM, Wopereis H, Butt AM, Peroni DG, Vandenplas Y, Fox AT, Shah N, West CE, Garssen J, Harthoorn LF, Knol J, Michaelis LJ (2018) A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants. Pediatr Res 83(3):677–686. https://doi.org/10.1038/pr.2017.270 CrossRefPubMed Candy DCA, Van Ampting MTJ, Oude Nijhuis MM, Wopereis H, Butt AM, Peroni DG, Vandenplas Y, Fox AT, Shah N, West CE, Garssen J, Harthoorn LF, Knol J, Michaelis LJ (2018) A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants. Pediatr Res 83(3):677–686. https://​doi.​org/​10.​1038/​pr.​2017.​270 CrossRefPubMed
38.
Zurück zum Zitat Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, Carpenter J, Rucker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BM J343:d4002. https://doi.org/10.1136/bmj.d4002 Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, Carpenter J, Rucker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BM J343:d4002. https://​doi.​org/​10.​1136/​bmj.​d4002
39.
Zurück zum Zitat Ataee P, Zoghali M, Nikkhoo B, Ghaderi E, Mansouri M, Nasiri R, Eftekhari K (2018) Diagnostic value of fecal calprotectin in response to mother’s diet in breast-fed infants with cow’s milk allergy colitis. Iran J Pediatr 28(4):e66172. https://doi.org/10.5812/ijp.66172 Ataee P, Zoghali M, Nikkhoo B, Ghaderi E, Mansouri M, Nasiri R, Eftekhari K (2018) Diagnostic value of fecal calprotectin in response to mother’s diet in breast-fed infants with cow’s milk allergy colitis. Iran J Pediatr 28(4):e66172. https://​doi.​org/​10.​5812/​ijp.​66172
40.
Zurück zum Zitat Merras-Salmio L, Kolho KL, Pelkonen AS, Kuitunen M, Makela MJ, Savilahti E (2014) Markers of gut mucosal inflammation and cow’s milk specific immunoglobulins in non-IgE cow’s milk allergy. Clin Transl Allergy 4(1):8. https://doi.org/10.1186/2045-7022-4-8 Merras-Salmio L, Kolho KL, Pelkonen AS, Kuitunen M, Makela MJ, Savilahti E (2014) Markers of gut mucosal inflammation and cow’s milk specific immunoglobulins in non-IgE cow’s milk allergy. Clin Transl Allergy 4(1):8. https://​doi.​org/​10.​1186/​2045-7022-4-8
41.
Zurück zum Zitat Visser JT, Lammers K, Hoogendijk A, Boer MW, Brugman S, Beijer-Liefers S, Zandvoort A, Harmsen H, Welling G, Stellaard F, Bos NA, Fasano A, Rozing J (2010) Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat. Diabetologia 53(12):2621–2628. https://doi.org/10.1007/s00125-010-1903-9 CrossRefPubMedPubMedCentral Visser JT, Lammers K, Hoogendijk A, Boer MW, Brugman S, Beijer-Liefers S, Zandvoort A, Harmsen H, Welling G, Stellaard F, Bos NA, Fasano A, Rozing J (2010) Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat. Diabetologia 53(12):2621–2628. https://​doi.​org/​10.​1007/​s00125-010-1903-9 CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat Aitoro R, Simeoli R, Amoroso A, Paparo L, Nocerino R, Pirozzi C, di Costanzo M, Meli R, De Caro C, Picariello G, Mamone G, Calignano A, Nagler CR, Berni Canani R (2017) Extensively hydrolyzed casein formula alone or with L. rhamnosus GG reduces beta-lactoglobulin sensitization in mice. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 28 (3):230–237. https://doi.org/10.1111/pai.12687 Aitoro R, Simeoli R, Amoroso A, Paparo L, Nocerino R, Pirozzi C, di Costanzo M, Meli R, De Caro C, Picariello G, Mamone G, Calignano A, Nagler CR, Berni Canani R (2017) Extensively hydrolyzed casein formula alone or with L. rhamnosus GG reduces beta-lactoglobulin sensitization in mice. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 28 (3):230–237. https://​doi.​org/​10.​1111/​pai.​12687
43.
Zurück zum Zitat Rzehak P, Sausenthaler S, Koletzko S, Reinhardt D, von Berg A, Kramer U, Berdel D, Bollrath C, Grubl A, Bauer CP, Wichmann HE, Heinrich J (2011) Long-term effects of hydrolyzed protein infant formulas on growth--extended follow-up to 10 y of age: results from the German Infant Nutritional Intervention (GINI) study. Am J Clin Nutr 94(Suppl 6):1803S–1807S. https://doi.org/10.3945/ajcn.110.000679 Rzehak P, Sausenthaler S, Koletzko S, Reinhardt D, von Berg A, Kramer U, Berdel D, Bollrath C, Grubl A, Bauer CP, Wichmann HE, Heinrich J (2011) Long-term effects of hydrolyzed protein infant formulas on growth--extended follow-up to 10 y of age: results from the German Infant Nutritional Intervention (GINI) study. Am J Clin Nutr 94(Suppl 6):1803S–1807S. https://​doi.​org/​10.​3945/​ajcn.​110.​000679
Metadaten
Titel
Probiotics for cow’s milk protein allergy: a systematic review of randomized controlled trials
verfasst von
Sheeba Qamer
Mangesh Deshmukh
Sanjay Patole
Publikationsdatum
22.06.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Pediatrics / Ausgabe 8/2019
Print ISSN: 0340-6199
Elektronische ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-019-03397-6

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