Pediatric Annals

Feature Article 

Infant Formulas for Food Allergy Treatment and Prevention

Hetu Parekh, MD; Sami L. Bahna, MD, DrPH

Abstract

The number of infant formulas intended for food allergy treatment or prevention has been increasing. Some products fulfill the criteria for hypoallergenicity, such as extensively hydrolyzed protein (casein or whey) and synthesized amino acid formulas (elemental diet). Numerous partially hydrolyzed formulas have been derived from bovine milk, soybean, and rice. They are not hypoallergenic and are not recommended for children allergic to the parent protein, yet certain preparations have shown efficacy for allergy prevention. Soybean-derived preparations, although not hypoallergenic, have been tolerated by a majority of children allergic to bovine milk. Studies on the addition of probiotics or prebiotics to infant formulas have shown inconsistent findings. Numerous hypoallergenic formulas or milk substitutes are available for pediatricians to choose for children with food allergy. Caution is needed in prescribing formulas that are erroneously marketed as hypoallergenic. [Pediatr Ann. 2016;45(4):e150–e156.]

Abstract

The number of infant formulas intended for food allergy treatment or prevention has been increasing. Some products fulfill the criteria for hypoallergenicity, such as extensively hydrolyzed protein (casein or whey) and synthesized amino acid formulas (elemental diet). Numerous partially hydrolyzed formulas have been derived from bovine milk, soybean, and rice. They are not hypoallergenic and are not recommended for children allergic to the parent protein, yet certain preparations have shown efficacy for allergy prevention. Soybean-derived preparations, although not hypoallergenic, have been tolerated by a majority of children allergic to bovine milk. Studies on the addition of probiotics or prebiotics to infant formulas have shown inconsistent findings. Numerous hypoallergenic formulas or milk substitutes are available for pediatricians to choose for children with food allergy. Caution is needed in prescribing formulas that are erroneously marketed as hypoallergenic. [Pediatr Ann. 2016;45(4):e150–e156.]

The prevalence of food allergy has been on the rise, with cow's milk allergy (CMA) now affecting 2% to 3% of young children.1 These children have a need for a milk substitute that should be well tolerated and nutritionally adequate. Although some “hypoallergenic” formulas were developed as early as the 1940s, it was not until 1989 that a special Subcommittee on Nutrition and Allergy of the American Academy of Pediatrics was formed to define what constitutes a hypoallergenic formula.2 Their definition is that it must be tolerated by at least 90% of children who are allergic to the parent allergen (eg, cow's milk [CM] or soy).

This review provides an update on the various formulas used as substitutes for CM based on hypoallergenicity or being derived from a different protein source. It also differentiates between preparations that may be suitable for CMA prevention but not for treatment.

Types of Formulas

Several dietary preparations are commercially available, either derived from bovine milk or other sources, as a substitute for CM. Some of them are considered hypoallergenic (Table 1).


            Common Commercial Hypoallergenic Formulas and Their Manufacturersa

Table 1.

Common Commercial Hypoallergenic Formulas and Their Manufacturers

Hypoallergenic Formulas

Immunogenic protein molecules are comprised of two types of antigenic determinants (ie, epitopes): linear and conformational. Whereas heat denatures conformational epitopes, enzymatic hydrolysis is required to denature linear epitopes. Allergy to the latter tends to persist longer.3 To reduce allergenicity, manufacturers may use various combinations of procedures such as heat, enzymatic hydrolysis, ultrafiltration, high-intensity ultrasound, and gamma irradiation. Although these processes reduce allergenicity, they may cause other undesirable effects such as changes in physico-chemical properties, hyperosmolarity, nutrient imbalance, poor taste, and high cost.4

Extensively Hydrolyzed Formulas

Extensively hydrolyzed formulas (EHFs) are generally considered the first line of treatment for children with CMA. The source can be bovine milk casein (extensively hydrolyzed casein formula [EHCF]) or whey (extensively hydrolyzed whey formula [EHWF]). Many preparations are available, although the availability varies by country (Table 1). EHCFs have been available for more than 70 years and are tolerated by 95% to 97% of patients with CMA.5–8 A recent double-blind, randomized trial showed that EHCF and EHWF were equally tolerated by CMA patients.9 However, both formulas used in that study had added probiotics: Lactobacillus rhamnosus strain GG in EHCF and Bifidobacterium lactis in EHWF. Although EHFs are enzymatically hydrolyzed to a high degree, they may contain minute quantities of incompletely hydrolyzed peptides or aggregates of small peptides capable of causing an allergic reaction.10 Additionally, it is also possible that in some rare cases, nutrient and additive contaminants (eg, maize protein) may be responsible for inciting an allergic reaction.11

Elemental or Free Amino Acids Formulas

Elemental formulas consist of synthesized free amino acids (Table 1) and are designed to meet the nutritional needs of children's growth and development. The few preparations that have been studied were reported to be well tolerated,12,13 even in children who reacted to EHFs.14–17 Free amino acids formulas (FAAFs) are often preferred over EHFs in children with acute food-induced eosinophilic gastrointestinal disorders18–20 or severe food protein-induced enterocolitis.21,22 EHFs and FAAFs have advantages as well as limitations (Table 2).


            Advantages and Limitations of Extensively Hydrolyzed Formulas and Free Amino Acids Formulas

Table 2.

Advantages and Limitations of Extensively Hydrolyzed Formulas and Free Amino Acids Formulas

Hydrolyzed Rice Protein Formulas

Several studies looked at a rice-based formula as a substitute for CM. In a multicenter study, an extensively hydrolyzed rice formula was tested in 100 children with CMA.23 Skin prick test was positive for rice extract in 4% of the participants, and for the rice formula in 3%. Specific immunoglobulin E (IgE) was positive for rice in 23% of the participants, and for the formula in 4%, but none reacted to challenge with the formula. Another extensively hydrolyzed rice formula was tolerated by all 40 infants with CMA who were tested, and all had normal growth during the 6-month study period.24 The European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guideline on CMA states that extensively hydrolyzed rice-based formulas may be considered for infants in vegan families or in those who are intolerant to EHFs.21

It is worth noting that not all commercial “rice milk” preparations are extensively hydrolyzed. A partially hydrolyzed rice preparation was tested in 41 infants with CMA compared to an EHF of bovine casein plus whey in 40 infants with CMA who were observed over a 2-year period.25 None of the infants developed a reaction to the rice formula, and only one reacted to the extensively hydrolyzed bovine milk formula; both groups had normal growth during the study.

Soybean Formulas

Soy-based formulas (Table 3) have been available for almost a century and have been proven to be adequate for growth and development of children.26 In a study of 93 children (age 3 months to 3.5 years) with IgE-mediated CMA, soy formula caused no reactions in 86%.27 However, it was not tolerated by up to 60% of children with non–IgE-mediated CM protein enterocolitis.28


            Common Commercial Preparations of Soy-Based Formulas and Their Manufacturersa

Table 3.

Common Commercial Preparations of Soy-Based Formulas and Their Manufacturers

In a study of 80 infants with CMA (age 2–11 months) who were fed soy formula, by age 2 years definite reactions had occurred in 10% and doubtful reactions in 18%.29 Reactions to soy formulas in infants with CMA younger than age 6 months were 5 times more common than in older infants. According to a recent meta-analysis, the prevalence of sensitization to soy-based formula for infants was estimated at 8.7%, and there was not enough evidence of an increased risk in infants younger than age 6 months.30 Soybean formulas are easily available, have acceptable taste, and a reasonable price. However, like any other food, it is possible for soy-based formula to induce sensitization over time.

Partially Hydrolyzed Formulas

Partially hydrolyzed formulas (PHFs) derived from various protein sources are available in various countries (Table 4). Compared to conventional CM infant formulas, PHFs have the advantages of easier digestibility, a much lower cost, and a better taste than EHFs or FAAFs. However, their large content of immunogenic peptides has caused allergic reactions in 36% to 45% of patients who are allergic to the parent protein.31,32 PHFs are not considered hypoallergenic and are not recommended for CMA treatment.


            Common Commercial Preparations of Partially Hydrolyzed Formulas and Their Manufacturersa

Table 4.

Common Commercial Preparations of Partially Hydrolyzed Formulas and Their Manufacturers

Role of Infant Formulas in Allergy Prevention

The efficacy of a certain formula for allergy prevention should be distinguished from its efficacy for treatment. Prevention studies usually involve newborns at high genetic risk of atopy. In those studies, the test formula is usually given exclusively from birth until age 4 to 6 months.

Compared to conventional CM formula, a PHF was found to significantly reduce allergy development in one study33 but not in another.34 In a Cochrane review in 2006,35 data on a total of 411 infants showed that PHFs and EHFs were similar in significantly reducing allergy development compared to conventional CM formula. In the large German Infant Nutritional Intervention study,36 689 infants at high risk of atopy were randomized to receive for 4 months 1 of 3 formulas: an EHCF, an EHWF, or a partially hydrolized whey formula (PHWF). They were then compared with a control group receiving conventional formula. The incidence of atopic dermatitis by age 12 months was significantly lower in infants being fed EHCF or PHWF, but, surprisingly, not the EHWF. At age 6 years, children fed EHCF and PHWF still showed significant advantage over children fed conventional CM formula in reducing physician-diagnosed allergy, particularly atopic dermatitis.37 By age 10 years, the preventive effect of those two formulas on the development of allergic diseases was still present, particularly regarding atopic dermatitis (although at a lower level).38 According to the Food Allergy and Anaphylaxis Guidelines Group of the European Academy of Allergy and Clinical Immunology (EAACI) published in 2014,39,40 feeding infants PHWF, EHCF, or EHWF during the first 4 months of life had a preventive effect on allergy development.

The observation in the German study36 of a lower preventive effect of EHWF than of the PHWF may suggest that the peptides in PHFs may have a tolerance-inducing effect. This concept might be supported by the findings of a recent large study on peanuts (Learn Early about Peanut Allergy study)41 that demonstrated the early introduction of peanuts to high-risk infants between ages 4 and 11 months significantly decreased the development of peanut allergy by age 5 years. According to the Food Allergy and Anaphylaxis Guidelines Group of the EAACI,42,43 there is insufficient evidence to recommend for pregnant or lactating women to modify their diet to prevent allergies in the infant. Perhaps an advantage of breastfeeding that might be relevant to food allergy prevention is that breast-milk contains proteins from the maternal diet that induce tolerance.

To the best of our knowledge, FAAFs have not been studied for allergy prevention. With regard to soy formulas, a Cochrane systemic review found that soy-based formula does not significantly differ from conventional CM formula in allergy prevention.42

Incorporation of Probiotics or Prebiotics

Supplementation of probiotics and/or prebiotics showed a preventive effect in some studies43–45 but not others.46–49 Similarly, for treatment, some studies have shown benefit,50–53 whereas others have not.54,55 Possible causes for such inconsistent findings include the species and specific strain of probiotic, dose used, use of a combination versus a single type, method of administration, age at administration for prevention, time after disease onset for treatment, duration of administration, multiple food allergies, dietary elimination, and concomitant feeding to a hypoallergenic formula.56

Some meta-analyses have concluded that probiotic supplementation may reduce the risk of developing eczema, and thus they may be considered in a young patient with a family history of eczema.57–59 A recent meta-analysis concluded that probiotic supplementation during pregnancy and early infancy has a preventive effect with regard to atopic dermatitis but not allergic rhinitis or asthma.60 However, a 2010 report by the American Academy of Pediatrics61 and a 2010 World Allergy Organization publication22 do not categorically recommend probiotic supplementation and acknowledge that although there may be some evidence to suggest a beneficial role for probiotics in eczema prevention and treatment, further studies are necessary. Similarly, a 2012 World Allergy Organization position paper62 concluded that probiotic supplementation has not been sufficiently proven to influence allergy prevention or treatment.

A 2013 Cochrane review63 concluded that although there is insufficient evidence to recommend use of prebiotics for allergy prevention in general, there is some evidence for some beneficial effect for eczema prevention. According to a recent EAACI position paper,42 there is no evidence at present for a role for prebiotics or probiotics in allergy prevention. Similarly, the 2014 Food Allergy Practice Parameter Update64 does not recommend supplementing the maternal or infant diet with prebiotics or probiotics due to insufficient evidence of benefit.

A study of 55 infants with CMA (about half of whom were non–IgE-mediated) looked at the rate of acquiring tolerance to CM over a 12-month period while on EHCF alone or on EHCF plus Lactobacillus rhamnosus strain GG (LGG).65 At 6 months, the addition of LGG was associated with a higher rate of CM tolerance (59% vs 21%). At the end of 12 months, CM-tolerant children increased to 81% in the EHCF-plus-LGG group versus 54% in the EHCF group. In a multicenter study, 260 infants with CMA were fed 1 of 5 milk substitutes: EHCF, EHCF plus LGG, hydrolyzed rice formula, soy formula, or amino acid-based formula. At the end of 12 months, tolerance to CM was highest in those who received EHCF plus LGG.66

Conclusion

Patients with CMA, particularly young children, can be provided with a safe substitute in the form of EHF or FAAF. EHFs may not be tolerated by up to 5% of children with CMA. FAAF might be preferred, at least initially, in children with exquisite CMA, those who have severe acute symptoms, or those with multiple food allergens. The main limitations of both types of formulas are high cost and poor taste.

A majority of children with CMA can tolerate soybean-derived formula and extensively hydrolyzed rice preparation. PHFs are not hypoallergenic and are not recommended for children with CMA. PHFs did, however, show a preventive effect, primarily of eczema, and may be used for prevention in high-risk infants. Supplementation with pre- or probiotics seems to be of help in reducing the development of eczema and possibly in treatment; however, more well-designed studies are needed to delineate their role.

References

  1. Host A. Frequency of cow's milk allergy in childhood. Ann Allergy Asthma Immunol. 2002;89(Suppl 1):33–37. doi:10.1016/S1081-1206(10)62120-5 [CrossRef]
  2. Kleinman RE, Bahna SL, Powell GF, Sampson HA. Use of infant formulas in infants with cow milk allergy: a review and recommendations. Pediatr Allergy Immunol. 1991;4:146–155. doi:10.1111/j.1399-3038.1991.tb00200.x [CrossRef]
  3. Järvinen KM, Chatchatee P, Bardina L, Beyer K, Sampson HA. IgE and IgG binding epitopes on alpha-lactalbumin and beta-lactoglobulin in cow's milk allergy. Int Arch Allergy Immunol. 2001;126:111–118. doi:10.1159/000049501 [CrossRef]
  4. Bahna SL. Hypoallergenic formulas: optimal choices for treatment versus prevention. Ann Allergy Asthma Immunol. 2008;101:453–459. doi:10.1016/S1081-1206(10)60281-5 [CrossRef]
  5. Niggemann B, von Berg A, Bollrath C, et al. Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy. Pediatr Allergy Immunol. 2008;19:348–354. doi:10.1111/j.1399-3038.2007.00653.x [CrossRef]
  6. Isolauri E, Sütas Y, Mäkinen-Kiljunen S, Oja SS, Isosomppi R, Turjanmaa K. Efficacy and safety of hydrolyzed cow milk and amino acid-derived formulas in infants with cow milk allergy. J Pediatr. 1995;127:550–557. doi:10.1016/S0022-3476(95)70111-7 [CrossRef]
  7. Vandenplas Y, Plaskie K. Safety and adequacy of an optimized formula for pediatric patients with cow's milk-sensitive enteropathy. Minerva Pediatr. 2010;62:339–345.
  8. Martín-Esteban M, García-Ara MC, Banqué-Molas M, Boyano-Martínez MT, Martín-Muñoz F, Díaz-Pena JM. Evaluation of an extensively hydrolyzed casein-whey protein formula in immediate cow's milk protein hypersensitivity. J Pediatr Gastroenterol Nutr. 1998;26:398–401. doi:10.1097/00005176-199804000-00007 [CrossRef]
  9. Vandenplas Y, Steenhout P, Planoudis Y, Grathwohl DAlthera Study Group. Treating cow's milk protein allergy: a double-blind randomized trial comparing two extensively hydrolysed formulas with probiotics. Acta Paediatr. 2013;102:990–998. doi:10.1111/apa.12349 [CrossRef]
  10. Wal JM. Cow's milk proteins/allergens. Ann Allergy Asthma Immunol. 2002;89(Suppl 1):3–10. doi:10.1016/S1081-1206(10)62115-1 [CrossRef]
  11. Frisner H, Rosendal A, Barkholt V. Identification of immunogenic maize proteins in a casein hydrolysate formula. Pediatr Allergy Immunol. 2000;11:106–110. doi:10.1034/j.1399-3038.2000.00041.x [CrossRef]
  12. Niggemann B, Binder C, Dupont C, Hadji S, Arvola T, Isolauri E. Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow's milk allergy/intolerance and atopic dermatitis. Pediatr Allergy Immunol. 2001;12:78–82. doi:10.1034/j.1399-3038.2001.012002078.x [CrossRef]
  13. Sampson HA, James JM, Bernhisel-Broadbent J. Safety of an amino acid-derived infant formula in children allergic to cow milk. Pediatrics. 1992;90:463–465.
  14. Kelso JM, Sampson HA. Food protein-induced enterocolitis to casein hydrolysate formulas. J Allergy Clin Immunol. 1993;92(6):909–910. doi:10.1016/0091-6749(93)90069-R [CrossRef]
  15. de Boissieu D, Dupont C. Time course of allergy to extensively hydrolyzed cow's milk proteins in infants. J Pediatr. 2000;136:119–120. doi:10.1016/S0022-3476(00)90063-5 [CrossRef]
  16. Hill DJ, Cameron DJ, Francis DE, Gonzalez-Andaya AM, Hosking CS. Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas in infants with multiple food protein intolerance. J Allergy Clin Immunol. 1995;96:386–394. doi:10.1016/S0091-6749(95)70058-7 [CrossRef]
  17. Sicherer SH, Noone SA, Koerner CB, Christie L, Burks AW, Sampson HA. Hypoallergenicity and efficacy of an amino acid-based formula in children with cow's milk and multiple food hypersensitivities. J Pediatr. 2001;138:688–693. doi:10.1067/mpd.2001.113007 [CrossRef]
  18. Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology. 1995;109:1503–1512. doi:10.1016/0016-5085(95)90637-1 [CrossRef]
  19. Vanderhoof JA, Murray ND, Kaufman SS, et al. Intolerance to protein hydrolysate infant formulas: an underrecognized cause of gastrointestinal symptoms in infants. J Pediatr. 1997;131:741–744. doi:10.1016/S0022-3476(97)70103-3 [CrossRef]
  20. Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA. Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents. Am J Gastroenterol. 2003;98:777–782. doi:10.1111/j.1572-0241.2003.07390.x [CrossRef]
  21. Koletzko S, Niggemann B, Arato A, et al. European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines. J Pediatr Gastroenterol Nutr. 2012;55:221–229. doi:10.1097/MPG.0b013e31825c9482 [CrossRef]
  22. Fiocchi A, Brozek J, Schünemann H, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines. World Allergy Organ J. 2010;3:57–161. doi:10.1097/WOX.0b013e3181defeb9 [CrossRef]
  23. Fiocchi A, Restani P, Bernardini R, et al. A hydrolysed rice-based formula is tolerated by children with cow's milk allergy: a multi-centre study. Clin Exp Allergy. 2006;36:311–316. doi:10.1111/j.1365-2222.2006.02428.x [CrossRef]
  24. Vandenplas Y, De Greef E, Hauser BParadice Study Group. Safety and tolerance of a new extensively hydrolyzed rice protein-based formula in the management of infants with cow's milk protein allergy. Eur J Pediatr. 2014;173:1209–1216. doi:10.1007/s00431-014-2308-4 [CrossRef]
  25. Reche M, Pascual C, Fiandor A, et al. The effect of a partially hydrolysed formula based on rice protein in the treatment of infants with cow's milk protein allergy. Pediatr Allergy Immunol. 2010;21:577–585. doi:10.1111/j.1399-3038.2010.00991.x [CrossRef]
  26. Vandenplas Y, Castrellon PG, Rivas R, et al. Safety of soya-based infant formulas in children. Br J Nutr. 2014;111:1340–1360. doi:10.1017/S0007114513003942 [CrossRef]
  27. Zeiger RS, Sampson HA, Bock SA, et al. Soy allergy in infants and children with IgE-associated cow's milk allergy. J Pediatr. 1999;134:614–622. doi:10.1016/S0022-3476(99)70249-0 [CrossRef]
  28. Burks AW, Casteel HB, Fiedorek SC, Williams LW, Pumphrey CL. Prospective oral food challenge study of two soybean protein isolates in patients with possible milk or soy protein enterocolitis. Pediatr Allergy Immunol. 1994;5:40–45. doi:10.1111/j.1399-3038.1994.tb00217.x [CrossRef]
  29. Klemola T, Vanto T, Juntunen-Backman K, Kalimo K, Korpela R, Varjonen E. Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow's milk allergy: a prospective, randomized study with a follow-up to the age of 2 years. J Pediatr. 2002;140:219–224. doi:10.1067/mpd.2002.121935 [CrossRef]
  30. Katz Y, Gutierrez-Castrellon P, González MG, Rivas R, Lee BW, Alarcon P. A comprehensive review of sensitization and allergy to soy-based products. Clin Rev Allergy Immunol. 2014;46:272–281. doi:10.1007/s12016-013-8404-9 [CrossRef]
  31. Ragno V, Giampietro PG, Bruno G, Businco L. Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy. Eur J Pediatr. 1993;152(9):760–762. doi:10.1007/BF01953996 [CrossRef]
  32. Giampietro PG, Kjellman NI, Oldaeus G, Wouters-Wesseling W, Businco L. Hypoallergenicity of an extensively hydrolyzed whey formula. Pediatr Allergy Immunol. 2001;12(2):83–86. doi:10.1034/j.1399-3038.2001.012002083.x [CrossRef]
  33. Vandenplas Y, Hauser B, Blecker U, et al. The nutritional value of a whey hydrolysate formula compared with a whey predominant formula in healthy infants. J Pediatr Gastroenterol Nutr. 1993;17:92–96. doi:10.1097/00005176-199307000-00014 [CrossRef]
  34. Willems R, Duchateau J, Magrez P, Denis R, Casimir G. Influence of hypoallergenic milk formula on the incidence of early allergic manifestations in infants predisposed to atopic diseases. Ann Allergy. 1993;71:147–150.
  35. Osborn DA, Sinn J. Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants. Cochrane Database Syst Rev. 2006;4:CD003664.
  36. von Berg A, Koletzko S, Grübl A, et al. German Infant Nutritional Intervention Study Group. 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;111:533–540. doi:10.1067/mai.2003.101 [CrossRef]
  37. von Berg A, Filipiak-Pittroff B, Krämer U, et al. GINIplus study group. 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;121:1442–1447. doi:10.1016/j.jaci.2008.04.021 [CrossRef]
  38. von Berg A, Filipiak-Pittroff B, Krämer U, et al. GINIplus study group. 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. J Allergy Clin Immunol. 2013;131:1565–1573. doi:10.1016/j.jaci.2013.01.006 [CrossRef]
  39. Muraro A, Halken S, Arshad SH, et al. EAACI Food Allergy and Anaphylaxis Guidelines Group. EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy. Allergy. 2014;69:590–601. doi:10.1111/all.12398 [CrossRef]
  40. de Silva D, Geromi M, Halken S, et al. EAACI Food Allergy and Anaphylaxis Guidelines Group. Primary prevention of food allergy in children and adults: systematic review. Allergy. 2014;69:581–589. doi:10.1111/all.12334 [CrossRef]
  41. Du Toit G, Roberts G, Sayre PH, et al. LEAP Study Team. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803–813. doi:10.1056/NEJMoa1414850 [CrossRef]
  42. Osborn DA, Sinn J. Soy formula for prevention of allergy and food intolerance in infants. Cochrane Database Syst Rev. 2006;4:CD003741.
  43. Rautava S, Kalliomäki M, Isolauri E. Probiotics during pregnancy and breastfeeding might confer immunomodulatory protection against atopic disease in the infant. J Allergy Clin Immunol. 2002;109:119–121. doi:10.1067/mai.2002.120273 [CrossRef]
  44. Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001;357:1076–1079. doi:10.1016/S0140-6736(00)04259-8 [CrossRef]
  45. Moro G, Arslanoglu S, Stahl B, Jelinek J, Wahn U, Boehm G. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child. 2006;91:814–819. doi:10.1136/adc.2006.098251 [CrossRef]
  46. Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immunol. 2007;119:184–191. doi:10.1016/j.jaci.2006.08.036 [CrossRef]
  47. Kuitunen M, Kukkonen K, Juntunen-Backman K, et al. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol. 2009;123:335–341. doi:10.1016/j.jaci.2008.11.019 [CrossRef]
  48. Boyce JA, Assa'ad A, Burks AW, NIAID-Sponsored Expert Panel et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126(Suppl):S1–58. doi:10.1016/j.jaci.2010.10.008 [CrossRef]
  49. Ly NP, Litonjua A, Gold DR, Celedón JC. Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity?J Allergy Clin Immunol. 2011;127:1087–1094. doi:10.1016/j.jaci.2011.02.015 [CrossRef]
  50. Majamaa H, Isolauri E. Probiotics: a novel approach in the management of food allergy. J Allergy Clin Immunol. 1997;99:179–185. doi:10.1016/S0091-6749(97)70093-9 [CrossRef]
  51. Isolauri E, Arvola T, Sütas Y, Moilanen E, Salminen S. Probiotics in the management of atopic eczema. Clin Exp Allergy. 2000;30:1604–1610. doi:10.1046/j.1365-2222.2000.00943.x [CrossRef]
  52. Rosenfeldt V, Benfeldt E, Nielsen SD, et al. Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J Allergy Clin Immunol. 2003;111:389–395. doi:10.1067/mai.2003.389 [CrossRef]
  53. Viljanen M, Savilahti E, Haahtela T, et al. Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial. Allergy. 2005;60:494–500. doi:10.1111/j.1398-9995.2004.00514.x [CrossRef]
  54. Brouwer ML, Wolt-Plompen SA, Dubois AE, et al. No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial. Clin Exp Allergy. 2006;36:899–906. doi:10.1111/j.1365-2222.2006.02513.x [CrossRef]
  55. Sistek D, Kelly R, Wickens K, Stanley T, Fitzharris P, Crane J. Is the effect of probiotics on atopic dermatitis confined to food sensitized children?Clin Exp Allergy. 2006;36:629–633. doi:10.1111/j.1365-2222.2006.02485.x [CrossRef]
  56. Bahna SL. Reflections on current food allergy controversies: specific IgE test application, patch testing, eosinophilic esophagitis, and probiotics. Allergy Asthma Proc. 2008;29:447–452. doi:10.2500/aap.2008.29.3150 [CrossRef]
  57. Lee J, Seto D, Bielory L. Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. J Allergy Clin Immunol. 2008;121:116–121. doi:10.1016/j.jaci.2007.10.043 [CrossRef]
  58. Pelucchi C, Chatenoud L, Turati F, et al. Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: a meta-analysis. Epidemiology. 2012;23:402–414. doi:10.1097/EDE.0b013e31824d5da2 [CrossRef]
  59. Osborn DA, Sinn JK. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev. 2007;4:CD006475.
  60. Zuccotti G, Meneghin F, Aceti A, et al. Italian Society of Neonatology. Probiotics for prevention of atopic diseases in infants: systematic review and meta-analysis. Allergy. 2015;70(11):1356–1371. doi:10.1111/all.12700 [CrossRef]
  61. Thomas DW, Greer FRAmerican Academy of Pediatrics Committee on NutritionAmerican Academy of Pediatrics Section on Gastroenterology, Hepatology, and Nutrition. Probiotics and prebiotics in pediatrics. Pediatrics. 2010;126:1217–1231. doi:10.1542/peds.2010-2548 [CrossRef]
  62. Fiocchi A, Burks W, Bahna SL, et al. WAO Special Committee on Food Allergy and Nutrition. Clinical Use of Probiotics in Pediatric Allergy (CUPPA): a World Allergy Organization position paper. World Allergy Organ J. 2012;5:148–167. doi:10.1097/WOX.0b013e3182784ee0 [CrossRef]
  63. Osborn DA, Sinn JK. Prebiotics in infants for prevention of allergy. Cochrane Database Syst Rev. 2013;3:CD006474.
  64. Sampson HA, Aceves S, Bock SA, et al. Joint Task Force on Practice Parameters. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol. 2014;134:1016–1025. doi:10.1016/j.jaci.2014.05.013 [CrossRef]
  65. Berni Canani R, Nocerino R, Terrin G, et al. Effect of Lactobacillus GG on tolerance acquisition in infants with cow's milk allergy: a randomized trial. J Allergy Clin Immunol. 2012;129:580–582. doi:10.1016/j.jaci.2011.10.004 [CrossRef]
  66. Berni Canani R, Nocerino R, Terrin G, et al. Formula selection for management of children with cow's milk allergy influences the rate of acquisition of tolerance: a prospective multicenter study. J Pediatr. 2013;163:771–777. doi:10.1016/j.jpeds.2013.03.008 [CrossRef]

Common Commercial Hypoallergenic Formulas and Their Manufacturersa

Extensively Hydrolyzed Formulas Manufacturer
Bovine milk casein
Nutramigen (100% LCT) Nutramigen with Enflora LGG Pregestimil (55% MCT/45% LCT) Mead Johnson (Glenview, IL)
Similac Expert Care Alimentum Abbott (Lake Forest, IL)
Blemil plus 1 FH (0–6 months) Blemil plus 2 FH (>6 months) Ordesa Group (Barcelona, Spain)
Novalac Allernova AR (or Comfort) (thickened for acid reflux, lactose-free, 0–36 months) United Pharmaceuticals SAS (Paris, France)
Whey
Gerber Extensive HA (with Bifidobacteriumlactis) Althera Alfare (lactose-free) Nestle S.A. (Vevey, Switzerland)
Almiron Pepti 1, Aptamil Pepti 1, Nutrilon Pepti 1 (0–6 months) Almiron Pepti 2, Aptamil Pepti 2, Nutrilon Pepti 2 (>6 months) Pregomin Pepti (>6 months) Danone (Paris, France)
Free amino acids formulas
Neocate Infant DHA/ARA (0–12 months) Neocate Nutra (>6 months) Neocate Junior (>12 months) Neocate Junior with Prebiotics (>12 months) Neocate Splash (>12 months) E028 Splash (>12 months) Nutricia (Gaithersburg, MD)
EleCare (0–12 months) EleCare Junior (>12 months) Abbott (Lake Forest, IL)
Alfamino Infant (0–12 months) Alfamino Junior (12 months to 13 years) Nestle S.A. (Vevey, Switzerland)
PurAmino Mead Johnson (Glenview, IL)
Rice-based formulas
NovaRice United Pharmaceuticals SAS (Paris, France)
Plasmon Risolac H. J. Heinz Company (Pittsburgh, PA)

Advantages and Limitations of Extensively Hydrolyzed Formulas and Free Amino Acids Formulas

Extensively Hydrolyzed Formulas Free Amino Acids Formulas
Advantages Tolerated by >95% of patients with cow's milk allergy For prevention, can be used as a supplement or substitute to breast-feeding in infants at high risk of allergy Nutritionally adequate Tolerated by almost 100% of food-sensitive patients For prevention, can be used as a supplement or a substitute to breast-feeding in infants at high riskof allergy Nutritionally adequate
Limitations High cost Unpalatable taste Potential errors in reconstitution High osmolality potential May cause allergy in exquisitely milk allergic children (<5%) High cost Unpalatable taste Potential errors in reconstitution

Common Commercial Preparations of Soy-Based Formulas and Their Manufacturersa

Soybean-Based Manufacturer
Enfamil Prosobee (0–12 months) Enfagrow Toddler Transitions Soy (9–18 months) Mead-Johnson (Glenview, IL)
Blemil plus 2 Soja Ordesa Group (Barcelona, Spain)
Similac Soy Isomil (0–12 months) Similac Go and Grow Soy Stage 3 (12–24 months) Abbott (Lake Forest, IL)
NAN Soya Nestle S.A. (Vevey, Switzerland)
Store brand soy Perrigo (Dublin, Ireland)
Partially hydrolyzed soy
Gerber Good Start Soy (0–12 months) Gerber Graduates Soy (9–24 months) Nestle S.A. (Vevey, Switzerland)

Common Commercial Preparations of Partially Hydrolyzed Formulas and Their Manufacturersa

Bovine Whey-Based Manufacturer
Beba HA,b Nidina HAb Good Start Gentle (0–12 months) Good Start Soothe (0–12 months, with Lactobacillus reuteri) NAN H.A.b 1 (0–6 months) NAN H.A. b2 (6–12 months) Peptamen Junior (1–3 years) Nestle S.A. (Vevey, Switzerland)
Similac Total Comfort Abbott (Lake Forest, IL)
Novalac HAb United Pharmaceuticals SAS (Paris, France)
Tender (store brand) Perrigo (Dublin, Ireland)
Bovine casein plus whey-based
Enfamil Gentlease Mead Johnson (Glenview, IL)
Aptamil HAb Danone (Paris, France)
Gentle (store brand) Perrigo (Dublin, Ireland)
Soy-based
Gerber Good Start Soy (0–12 months) Gerber Graduates Soy (9–24 months) Nestle S.A. (Vevey, Switzerland)
Rice-based
Blemil 1 Riso Blemil Plus 1 Arroz Hidrolizado (0–6 months) Blemil 2 Riso Blemil Plus 2 Arroz Hidrolizado (>6 months) Ordesa Group (Barcelona, Spain)
Authors

Hetu Parekh, MD, is a Senior Fellow, Allergy and Immunology Fellowship Program, Louisiana State University Health Sciences Center. Sami L. Bahna, MD, DrPH, is a Professor of Pediatrics and the Chief, Allergy and Immunology Fellowship Program, Louisiana State University Health Sciences Center.

Address correspondence to Sami L. Bahna, MD, DrPH, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103-3932; email: sbahna@lsuhsc.edu.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00904481-20160225-01

Sign up to receive

Journal E-contents