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Article |

A Systematic Review of the Role of Hydrolyzed Infant Formulas in Allergy Prevention FREE

Tiffani Hays, MS, RD, LN; Robert A. Wood, MD
[+] Author Affiliations

Author Affiliations: Division of Pediatric Gastroenterology and Nutrition, Children’s Nutrition Center (Ms Hays), and Division of Pediatric Allergy and Immunology, Department of Pediatrics (Dr Wood), The Johns Hopkins University School of Medicine, Baltimore, Md.


Arch Pediatr Adolesc Med. 2005;159(9):810-816. doi:10.1001/archpedi.159.9.810.
Text Size: A A A
Published online

Objective  To critically examine the published literature to determine whether feeding hydrolyzed infant formulas from birth has a role in allergy prevention.

Data Sources  We identified data through a MEDLINE search using allergy prevention and infant formulas as indexing terms. The search was restricted to 1985 through the present, English-language articles, and human subjects.

Study Selection  Criteria for inclusion in the review were prospective controlled trials published in peer-reviewed journals.

Data Extraction  Symptoms of allergy were defined and observed by health care providers (physicians and nurses).

Data Synthesis  Nine published trials evaluated the use of extensively hydrolyzed formulas, 12 evaluated the use of partially hydrolyzed formulas in high-risk infants, and 1 evaluated the use of partially hydrolyzed formulas in an unselected infant population. The reports compared hydrolyzed formulas with breastfeeding, cow’s milk formulas, soy formulas, and combinations thereof. The cohort of studies consistently showed reductions in the cumulative incidence of atopic disease from 12 to 60 months of age among high-risk infants fed extensively hydrolyzed casein formulas or partially hydrolyzed whey formulas vs cow’s milk formulas. No studies showed an increase in allergy risk with any hydrolyzed formulas.

Conclusions  Extensively hydrolyzed casein formulas and partially hydrolyzed whey formulas are appropriate alternatives to breast milk for allergy prevention in infants at risk. Because atopic disease in children cannot be predicted, the use of these formulas in the general population should be considered, and one must weigh cost, compliance, and long-term benefits.

The prevalence of food allergy among infants and young children is estimated to be 5% to 6% and seems to be increasing, particularly in developed countries.15 Food allergy causes significant morbidity, including severe and even life-threatening allergic reactions, and is a huge burden for patients and families. Given these facts, there has been a great deal of interest in measures that might help to prevent the development of food allergy, especially in high-risk children.

Historically, prevention efforts have relied on the early identification of high-risk infants and the avoidance of potential allergens through the first 1 to 2 years of life. The expectation is that sensitization may be reduced or eliminated through avoidance, although an equally appealing approach would be to develop strategies to enhance the development of immunologic tolerance to major food allergens. Given the difficulty in implementing these avoidance diets, it makes sense to target those infants deemed to be at highest risk. However, it is also clear that children without obvious risk factors for atopic disease may develop food allergy,6 which suggests that a simpler strategy implemented in the general population would be preferred.

PREDICTING ATOPIC DISEASE IN CHILDREN

Several laboratory approaches for the identification of high-risk children have been studied, including cord blood IgE levels, cytokine levels, eosinophil counts, and specific genetic markers.6,7 However, none of these have proven to be sufficiently superior to the family history and as a result are not recommended for use in clinical practice. The family history, therefore, remains the most useful and practical method to identify the allergy-prone infant.8,9 Allergic disease in one parent increases the likelihood of allergy in a child, and allergic disease in both parents or in a parent and a sibling further increases those odds to between 40% and 70%.10,11 Despite the predictive value of parental history, it is not always available. Most infants at risk, with or without a family history of atopic disease, go unidentified.6

ORAL TOLERANCE

While sensitization is the process by which one develops an immunologic hypersensitivity after allergen exposure, oral tolerance describes the induction of immunologic hyporesponsiveness after ingestion of a food antigen. Oral tolerance therefore permits exposure to foreign proteins, such as cow’s milk proteins, without developing hypersensitivity.12 In the normal situation, lower-molecular-weight proteins processed by the gut-associated lymphoid tissue induce oral tolerance without sensitization. The induction of oral tolerance depends on the form and dose of antigen exposure and the age at exposure.1215 Although breast milk can contain food proteins that lead to allergic sensitization,16,17 it is presumed to be the best means of inducing oral tolerance.

Although most children tolerate infant formulas that include intact milk or soy proteins without developing sensitivity, these formulas pose an increased risk compared with breast milk. Partially hydrolyzed formulas (pHFs) have lower-molecular-weight proteins than cow’s milk formulas (CMFs) and were developed with this goal in mind. Research to support this theory is limited to animal data and preliminary human data. Experiments in rats, conducted by Fritsche,14 showed that feeding a pHF significantly suppressed β-lactoglobulin–specific IgE and IgG antibody production and mast cell response compared with extensively hydrolyzed formulas (eHFs).14 Among infants, Vaarala et al13 showed that CMFs resulted in sensitization and tolerance, whereas eHFs did not induce sensitization or tolerance; furthermore, sensitization depended on the infant’s age at exposure. These limited studies suggest that, while eHFs are an excellent alternative for children who are already sensitized to cow’s milk proteins, they may not induce tolerance to the same degree as pHFs.

HYDROLYSATE FORMULAS IN ALLERGY PREVENTION

Hydrolysate formulas have been traditionally used for the treatment of food allergies and intolerances and more recently for preventing atopic disease in high-risk infants. The extensively hydrolyzed casein formulas available in the United States include Nutramigen (Mead Johnson & Co, Evansville, Ind), Alimentum (Ross Products Division/Abbott Laboratories, Columbus, Ohio), and Pregestimil (Mead Johnson & Co). The only partially hydrolyzed whey formula available in the United States is Nestlé Good Start Supreme (Nestlé USA, Glendale, Calif). Cow’s milk proteins are subjected to chemical and enzymatic hydrolysis to reduce the molecular weight, the peptide size, and, consequently, the allergenicity of the proteins. The hydrolysate formulas are generally categorized into eHFs and pHFs based on the degree of hydrolysis and length of the remaining peptides.

PROFESSIONAL GUIDELINES

Guidelines summarizing the approach to allergy prevention in high-risk infants have been presented by the American Academy of Pediatrics (AAP)8 and the European Society for Paediatric Allergology and Clinical Immunology9 and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition.26 These recommendations are summarized in Table 1. This review focuses on what role hydrolysate formulas may play in allergy prevention and whether there is a difference between eHFs and pHFs in this role.

Table Graphic Jump LocationTable 1. Summary of Recommendations for Primary Prevention of Food Allergy by the American Academy of Pediatrics (AAP) and the European Society for Paediatric Allergology and Clinical Immunology and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPACI/ESPGHAN)
SEARCH STRATEGY

We identified studies that evaluated the role of hydrolysate formulas in allergy prevention through a MEDLINE search using allergy prevention and infant formulas as indexing terms. We restricted the search to English-language articles and human subjects. Additional studies were identified from cross-referencing.

REVIEW CRITERIA

We reviewed all published reports of prospective controlled trials evaluating hydrolysate formulas in allergy prevention that were published in peer-reviewed journals from 1985 to the present. We critically evaluated methods of randomization, blinding, duration of the dietary intervention, identification and verification of allergic symptoms, analysis of results, and support for conclusions made. We looked at the quality of the studies and the results obtained to determine whether each body of published research supports a role for hydrolysate formulas in allergy prevention.

EXTENSIVELY HYDROLYZED FORMULAS

Extensively hydrolyzed formulas contain peptides with molecular weights less than 3000 Da. They meet the American Academy of Allergy and Immunology’s definition of hypoallergenicity. Extensively hydrolyzed formulas effectively relieve symptoms in more than 90% of patients with cow’s milk allergy (CMA), with only occasional reports of hypersensitivity reactions. The AAP8 and the European Society for Paediatric Allergology and Clinical Immunology and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition9 recommend eHFs for allergy prevention.

From 1985 to the present, 9 published reports on 8 patient cohorts prospectively evaluated eHF for allergy prevention in high-risk infants.11,1825Table 2 summarizes the details of the methods and results of some of these published reports. The reports compared eHFs with breastfeeding (BF), CMFs, soy formulas, pHFs, and combinations thereof. Eight of the 9 studies evaluated casein hydrolysate formulas, whereas 1 study20 assessed casein hydrolysate and whey hydrolysate formulas. For the purpose of this review, when we refer to eHFs, we are referring to extensively hydrolyzed casein formulas. Seven reports11,1821,23,24 evaluated eHF as a supplement to BF, while 2 studies22,25 evaluated eHF as an exclusive diet in infants at high risk of atopy. In total, all of the trials reported a lower cumulative incidence of atopy, or a lower prevalence of atopy, among infants supplemented with eHFs compared with infants supplemented with CMFs, and these results were comparable to those of BF alone.

Table Graphic Jump LocationTable 2. Prospective Trials Evaluating Extensively Hydrolyzed Formulas (eHFs) for Allergy Prevention in Infants at High Atopic Risk

Variations in methods make it difficult to directly compare the results of these studies. All of these studies recruited infants at high risk of atopy, but the definition of high risk varied. The studies attempted to randomize and blind the formula assignments when or if BF was insufficient, but complete randomization was impossible because of ethical concerns about interfering with BF. The studies differed in the duration of the dietary intervention, with only 1 study22 meeting the AAP’s8 recommendation for exclusive formula feeding until 6 months of age. The studies also differed greatly in maternal and infant dietary restrictions, from no restrictions to specific allergen avoidance through 36 months of age. The studies differed significantly in the allergy symptoms recorded and the diagnostic measures that were used, ranging from an assessment of eczema alone22 to the use of skin prick tests, serum antigen-specific IgE levels, open food challenges, and double-blind placebo-controlled food challenges (DBPCFCs). Two studies24,25 prospectively compared eHFs with pHFs and BF in infants at high risk of atopy. These studies are discussed in more detail with the pHF studies in the next subsection titled “Partially Hydrolyzed Formulas.” Halken et al24 found a significantly lower incidence of CMA in infants receiving eHFs compared with those receiving pHFs, although the cumulative incidence of allergic symptoms was similar among groups.

A 2003 study20 prospectively compared eHFs with pHFs and CMFs among high-risk infants in Germany. The infants were randomized to receive eHFs, extensively hydrolyzed whey formulas, pHFs, or CMFs as a supplement to breast milk during the first 4 months of life. This was the only study that evaluated extensively hydrolyzed whey formulas. Among children 12 months of age, the authors reported significantly diminished atopic manifestations in the group fed eHFs compared with CMFs. The groups fed eHFs and pHFs had significantly less atopic dermatitis compared with CMFs, and results from the extensively hydrolyzed whey formula group were not different from those of the group fed CMFs. The differences found in this study suggest that factors such as the protein type and method of hydrolysis may play important roles in determining the protective effect. This study used well-defined definitions of atopy, including open food challenges and DBPCFCs; however, the study formulas were not fed exclusively for 6 months.

In summary, the data support a protective effect for eHFs, but the research falls short of meeting the AAP’s8 criteria for evidence of allergy prevention because the eHF were usually used as a supplement to BF and allergy symptoms were not sufficiently evaluated with DBPCFCs. Extensively hydrolyzed formulas are significantly more expensive and less palatable than standard CMFs, which makes compliance with exclusive feeding of eHFs difficult for many families.

PARTIALLY HYDROLYZED FORMULAS

Partially hydrolyzed formulas were first developed in 1985 for use in infants with formula intolerance. The initial formula was a whey protein hydrolysate in which the peptides have molecular weights in the range of 3000 to 10 000 Da. The pHFs do not meet the AAP’s8 definition of hypoallergenicity because they have not been shown to relieve symptoms in most patients with established CMA and are not recommended for treatment of CMA. Recently, the AAP,8 the European Society for Paediatric Allergology and Clinical Immunology,9 and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition26 acknowledged a potential role for pHFs in the primary prevention of atopic disease. Like eHFs, pHFs have not met the AAP’s8 criteria for allergy prevention because of differences in allergy symptom scoring and a lack of studies with sufficient DBPCFCs. However, studies27,28 have been completed with pHFs as the exclusive diet for 6 months that demonstrated a significantly lower cumulative incidence of atopy over time compared with CMFs. In addition, although no human data are available, in animal models pHFs have been shown to induce oral tolerance without sensitization.14,15

From 1990 to the present, 12 published reports15,20,24,25,2734 involving 10 separate study populations prospectively evaluated partially hydrolyzed whey formulas in allergy prevention, and 1 study18 evaluated partially hydrolyzed casein formula. Table 3 gives the details of the methods and results of these published reports. The reports compared partially hydrolyzed whey formulas with BF, CMFs, soy formulas, eHFs, and many combinations thereof. Thirteen reports15,18,20,24,25,2734 evaluated pHFs in infants at high risk of atopy, 1 of which compared pHFs as part of a prevention program in an unselected infant population.33 Each of these trials reported a reduction in the cumulative incidence of atopy in infants fed pHFs (exclusively or as a supplement to BF) compared with infants fed CMFs, and these results were comparable to those of BF alone. Seven separate investigative groups prospectively evaluated pHFs compared with CMFs in infants at high risk of atopic disease.15,18,20,27,30,32,34 Marini et al29 only compared pHFs with BF, while other studies15,18,27,28,3034 attempted to randomize and often to double-blind formula assignment when or if BF was insufficient.

Table Graphic Jump LocationTable 3. Prospective Trials Evaluating Partially Hydrolyzed Formulas (pHF) for Allergy Prevention in Infants at High Atopic Risk

As with the studies of eHFs, variations in methods make it difficult to compare the results of the studies of pHFs. Variations include provision of an adequate sample size, differences in the definition of high risk, issues with randomization, duration of the dietary intervention (range, 3-6 months), maternal and infant dietary restrictions (ranging from no restrictions to allergen avoidance recommended through 24 months of age), environmental recommendations for allergy prevention (such as no smoking, pets, or day care), symptoms that were recorded, and diagnostic methods. The outcomes are also difficult to compare because some authors reported the cumulative incidence of atopic disease,15,18,20,24,25,2729,34 while others reported the point prevalence or number of atopic patients.3033 Information regarding individual symptoms such as eczema, asthma, and CMA were presented inconsistently across studies. Despite these differences, however, the overall data demonstrate a reduction in the cumulative incidence of atopic disease in infants fed partially hydrolyzed whey formulas vs CMFs.

Two recent studies24,25 prospectively compared pHFs with eHFs and BF. In these studies, the hydrolysate formulas were not compared with CMFs because the authors considered it unethical to feed CMFs to infants at high risk of atopy. Although Halken et al24 reported a statistically significant difference in CMA incidence between infants fed pHFs vs eHFs (4.7% vs 0.6%), neither study found any overall difference in the cumulative incidence of atopy with pHFs or eHFs vs BF.

One study18 evaluated a partially hydrolyzed whey-whey formula compared with eHFs and BF. This study found less atopy in infants fed this formula compared with CMFs. The incidences of allergy were 51% for eHFs, 64% for the partially hydrolyzed casein-whey formulas, 84% for CMFs, and 67% for BF.18

The German Infant Nutritional Intervention Study20 prospectively compared pHFs, eHFs, and eHFs with whey and CMFs as supplements to BF in more than 2000 high-risk infants. The authors found a significantly lower incidence of atopic dermatitis in the groups fed pHFs and eHFs compared with CMFs at 12 months of age. The incidence of allergic manifestation was lower in the group fed pHFs compared with CMFs but only reached significance for eHFs.

Another study33 evaluated pHFs as part of a comprehensive allergy prevention program in an unselected infant population. The study recruited infants from all births in 2 towns, with infants in one town receiving the allergy prevention intervention and those in the other town receiving standard medical advice and attention. The intervention program included advice on infant feeding and environmental restrictions, namely, exclusive BF, with pHFs as needed during the first 4 months of life, and the avoidance of smoking and pets in the home. The study prospectively evaluated the infants for atopic symptoms and found a significant reduction in atopic symptoms at 6 months of age in all intervention groups and among the infants exclusively fed pHFs vs CMFs.

In summary, the data support a preventive effect for partially hydrolyzed whey formulas, but the research falls short of meeting the AAP’s8 criteria for evidence of allergy prevention because in studies15,27,28 that exclusively fed partially hydrolyzed whey formulas for 6 months, the allergy symptoms were not sufficiently evaluated with DBPCFCs. Notably, partially hydrolyzed whey formulas are comparable in price and palatability to CMFs and are available as starter formulas in the United States.

META-ANALYSES OF HYDROLYSATE FORMULAS IN ALLERGY PREVENTION

Two meta-analyses evaluating pHF in allergy prevention were published in the literature.35,36 In 1998, Baumgartner et al35 reported odds ratios for developing atopic disease that were significantly less than 1 when comparing pHFs with CMFs. More recently, Osborn and Sinn concluded that “there is some evidence that prolonged supplementation with hydrolyzed formula as opposed to cow’s milk formula reduces the risk of allergy”36(p12) and suggested that there was “insufficient evidence” that eHFs have any advantage over pHFs.

Prospective controlled trials examining eHFs and partially hydrolyzed whey formulas for allergy prevention among high-risk infants demonstrate significant reductions in the cumulative incidence of atopic disease through the first 1 to 5 years of life compared with feeding CMF. However, based on the studies reported to date, neither eHFs nor pHFs meet the AAP’s8 criteria for allergy prevention because the studies were not consistent in the methods used to score allergic symptoms or confirm reactions, including DBPCFCs. Despite these limitations, the AAP,8 the European Society for Paediatric Allergology and Clinical Immunology,9 and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition26 recommend feeding eHFs to infants at high risk of atopic disease when BF is insufficient. Furthermore, these groups acknowledge that pHFs have a potential role in allergy prevention.

Most of the studies addressed allergy prevention only in high-risk populations. However, in general practice, most infants manifesting atopic symptoms may not have been identified as high risk, whether or not they had a positive family history for the disease. It could be beneficial to broaden the use of eHF or partially hydrolyzed whey formulas for allergy prevention in the general population, weighing potential benefits against the issues of cost, compliance, and palatability. In that regard, although the studies in the literature do not provide overwhelming evidence, they suggest that partially hydrolyzed whey formulas may serve as a reasonable first defense against allergic disease in the general population. Partially hydrolyzed whey formulas are comparable in nutrition, price, and palatability to traditional CMFs and are available as starter formulas for newborns.

Because most studies were conducted in high-risk infants, to determine the potential allergy prevention role in the general population, we need additional prospective randomized controlled trials comparing pHFs, eHFs, and CMFs using clinical scoring systems and DBPCFCs to define atopic disease in the general infant population. In addition, it seems as if different hydrolysate formulas have different potentials for allergy prevention, which appear to depend on factors beyond the degree of protein hydrolysis. Therefore, to demonstrate benefits, specific hydrolysate formulas need to be individually evaluated in clinical trials.

Correspondence: Tiffani Hays, MS, RD, LN, Division of Pediatric Gastroenterology and Nutrition, Children’s Nutrition Center, The Johns Hopkins University School of Medicine, 18924 Graystone Rd, White Hall, Baltimore, MD 21161 (thays@jhmi.edu).

Financial Disclosure: Ms Hays is a nutrition consultant to Nestlé USA.

Accepted for Publication: March 15, 2005.

Dean  T Prevalence of allergic disorders in early childhood. Pediatr Allergy Immunol 1997;8 ((10, suppl)) 27- 31
PubMed
Tariq  SMMatthews  SMHakim  EAStevens  MArshad  SHHide  DW The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study. J Allergy Clin Immunol 1998;101587- 593
PubMed Link to Article
Bousquet  JBurney  P Evidence of an increase in atopic disease and possible causes. Clin Exp Allergy 1993;23484- 492
PubMed Link to Article
Zeiger  RS Prevention of food allergy in infants and children. Immunol Allergy Clin North Am 1999;19619- 646
Link to Article
van Odijk  JAhlstedt  SBengtsson  UHulthen  LBorres  MP Specific IgE antibodies to peanut in western Sweden? Allergy 2001;56573- 577published correction appears inAllergy 2001;561229
PubMed Link to Article
Bergmann  RLEdenharter  GBergmann  KE  et al.  Predictability of early atopy by cord blood–IgE and parental history. Clin Exp Allergy 1997;27752- 760
PubMed Link to Article
Croner  S Kjellman NI. Development of atopic disease in relation to family history and cord blood IgE levels. Pediatr Allergy Immunol 1990;114- 20
Link to Article
Committee on Nutrition; American Academy of Pediatrics, Hypoallergenic infant formulas. Pediatrics 2000;106 ((pt 1)) 346- 349
PubMed Link to Article
Host  AKoletzko  BDreborg  S  et al.  Dietary products used in infants for treatment and prevention of food allergy: joint statement of the European Society for Paediatric Allergology and Clinical Immunology (ESPACI) Committee on Hypoallergenic Formulas and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition. Arch Dis Child 1999;8180- 84
PubMed Link to Article
Kjellman  NI Atopic disease in seven-year-old children: incidence in relation to family history. Acta Paediatr Scand 1977;66465- 471
PubMed Link to Article
Zeiger  RSHeller  S The development and prediction of atopy in high-risk children. J Allergy Clin Immunol 1995;951179- 1190
PubMed Link to Article
Strobel  S Dietary manipulation and induction of tolerance. J Pediatr 1992;121 ((pt 2)) S74- S79
PubMed Link to Article
Vaarala  OSaukkonen  TSavilahti  EKlemola  TAkerblom  HK Development of immune response to cow’s milk proteins in infants receiving cow’s milk or hydrolyzed formula. J Allergy Clin Immunol 1995;96 ((pt 1)) 917- 923
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Fritsche  R Induction of oral tolerance to cow’s milk proteins in rats fed with a whey protein hydrolysate. Nutr Res 1998;181335- 1341
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Marini  AAgosti  MMotta  GMosca  F Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years’ follow-up. Acta Paediatr Suppl 1996;4141- 21
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Vadas  PWai  YBurks  WPerelman  B Detection of peanut allergens in breast milk of lactating women. JAMA 2001;2851746- 1748
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Lifschitz  CHHawkins  HKGuerra  CByrd  N Anaphylactic shock due to cow’s milk protein hypersensitivity in a breast-fed infant. J Pediatr Gastroenterol Nutr 1988;7141- 144
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Oldaeus  GAnjou  KBjorksten  BMoran  JRKjellman  NI Extensively and partially hydrolysed infant formulas for allergy prophylaxis. Arch Dis Child 1997;774- 10
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Zeiger  RSHeller  SMellon  MH  et al.  Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study. J Allergy Clin Immunol 1989;8472- 89published correction appears inJ Allergy Clin Immunol 1989;84 (pt 1) 677
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von Berg  AKoletzko  SGrubl  A  et al.  The effect of hydrolyzed cow’s milk formula for allergy prevention in the first year of life. J Allergy Clin Immunol 2003;111533- 540
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Mallet  EHenocq  A Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. J Pediatr 1992;121 ((pt 2)) S95- S100
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Chandra  RKPuri  SHamed  A Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants. BMJ 1989;299228- 230published correction appears inBMJ 1989;299896
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Halken  SHost  AHansen  LGOsterballe  O Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula: a prospective, randomized, comparative clinical study. Pediatr Allergy Immunol 1993;4173- 181
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Halken  SHansen  KSJacobsen  HP  et al.  Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective randomized study. Pediatr Allergy Immunol 2000;11149- 161
PubMed Link to Article
Porch  MCShahane  ADLeiva  LE  et al.  Influence of breast milk, soy, or two hydrolyzed formulas on the development of allergic manifestations in infants at risk. Nutr Res 1998;181413- 1424
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Aggett  PJHaschke  FHeine  W  et al. ESPGAN Committee on Nutrition, Comment on antigen-reduced infant formulae. Acta Paediatr 1993;82314- 319
PubMed Link to Article
Chandra  RK Five-year follow-up of high-risk infants with family history of allergy who were exclusively breast-fed or fed partial whey hydrolysate, soy, and conventional cow’s milk formulas. J Pediatr Gastroenterol Nutr 1997;24380- 388
PubMed Link to Article
Chandra  RKHamed  A Cumulative incidence of atopic disorders in high-risk infants fed whey hydrolysate, soy, and conventional cow’s milk formulas. Ann Allergy 1991;67129- 132
PubMed
Marini  AAgosti  MMotta  G A dietary prevention program including whey hydrolyzed formula for high-risk atopic babies: 0-24 months follow-up. Dev Physiopathol Clin 1990;1131- 141
Willems  RDuchateau  JMagrez  PDenis  RCasimir  G Influence of hypoallergenic milk formula on the incidence of early allergic manifestations in infants predisposed to atopic diseases. Ann Allergy 1993;71147- 150
PubMed
Vandenplas  YHauser  BVan den Borre  CSacre  LDab  I Effect of a whey hydrolysate: prophylaxis of atopic disease. Ann Allergy 1992;68419- 424
PubMed
Vandenplas  YHauser  BVan den Borre  C  et al.  The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease. Eur J Pediatr 1995;154488- 494
PubMed Link to Article
Exl  BMDeland  UWall  M  et al.  ZUG-Frauenfeld Nutritional Survey (ZUFF study): allergen reduced nutrition in a normal infant population and its health-related effects: results at the age of 6 months. Nutr Res 1998;181443- 1462
Link to Article
Chan  YHShek  LPAw  MQuak  SHLee  BW Use of hypoallergenic formula in the prevention of atopic disease among Asian children. J Paediatr Child Health 2002;3884- 88
PubMed Link to Article
Baumgartner  MBrown  CAExl  BM  et al.  Controlled trials investigating the use of one partially hydrolyzed whey formula for dietary prevention of atopic manifestations until 60 months of age. Nutr Res 1998;181425- 1442
Link to Article
Osborn  DASinn  J Formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Cochrane Database Syst Rev 2003;4CD003664
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1. Summary of Recommendations for Primary Prevention of Food Allergy by the American Academy of Pediatrics (AAP) and the European Society for Paediatric Allergology and Clinical Immunology and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPACI/ESPGHAN)
Table Graphic Jump LocationTable 2. Prospective Trials Evaluating Extensively Hydrolyzed Formulas (eHFs) for Allergy Prevention in Infants at High Atopic Risk
Table Graphic Jump LocationTable 3. Prospective Trials Evaluating Partially Hydrolyzed Formulas (pHF) for Allergy Prevention in Infants at High Atopic Risk

References

Dean  T Prevalence of allergic disorders in early childhood. Pediatr Allergy Immunol 1997;8 ((10, suppl)) 27- 31
PubMed
Tariq  SMMatthews  SMHakim  EAStevens  MArshad  SHHide  DW The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study. J Allergy Clin Immunol 1998;101587- 593
PubMed Link to Article
Bousquet  JBurney  P Evidence of an increase in atopic disease and possible causes. Clin Exp Allergy 1993;23484- 492
PubMed Link to Article
Zeiger  RS Prevention of food allergy in infants and children. Immunol Allergy Clin North Am 1999;19619- 646
Link to Article
van Odijk  JAhlstedt  SBengtsson  UHulthen  LBorres  MP Specific IgE antibodies to peanut in western Sweden? Allergy 2001;56573- 577published correction appears inAllergy 2001;561229
PubMed Link to Article
Bergmann  RLEdenharter  GBergmann  KE  et al.  Predictability of early atopy by cord blood–IgE and parental history. Clin Exp Allergy 1997;27752- 760
PubMed Link to Article
Croner  S Kjellman NI. Development of atopic disease in relation to family history and cord blood IgE levels. Pediatr Allergy Immunol 1990;114- 20
Link to Article
Committee on Nutrition; American Academy of Pediatrics, Hypoallergenic infant formulas. Pediatrics 2000;106 ((pt 1)) 346- 349
PubMed Link to Article
Host  AKoletzko  BDreborg  S  et al.  Dietary products used in infants for treatment and prevention of food allergy: joint statement of the European Society for Paediatric Allergology and Clinical Immunology (ESPACI) Committee on Hypoallergenic Formulas and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition. Arch Dis Child 1999;8180- 84
PubMed Link to Article
Kjellman  NI Atopic disease in seven-year-old children: incidence in relation to family history. Acta Paediatr Scand 1977;66465- 471
PubMed Link to Article
Zeiger  RSHeller  S The development and prediction of atopy in high-risk children. J Allergy Clin Immunol 1995;951179- 1190
PubMed Link to Article
Strobel  S Dietary manipulation and induction of tolerance. J Pediatr 1992;121 ((pt 2)) S74- S79
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