Allergen Data Collection - Update: Cow's Milk (Bos domesticus)
Internet Symposium on Food Allergens 4(1): 19-106 (2002) [http://www.food-allergens.de]
13 Infant Formulas

[Application of Infant Formulas in CMA] [Allergenicity / Safety] [Prophylaxis of Atopic Disease]

13.1 Application of Infant Formulas in CMA
 
Parameters / Subjects Outcome References
Nutritional Status
18 children with CMA (age of 1-3.5 years)
Diets based on soy or CAS hydrolysate formula (taken by 72%) supplemented with calcium and in 11 children with vitamins A and D resulted in adequate mean intakes of nutrients Tiainen  et al. 1995
Infant Formulas
60 children with infantile colic
Improvement in 18% of children after receiving a soy formula, while symptoms were unchanged or worse in 53% (cow's milk formula and soy formula fed children), improvement with extensively hydrolyzed CAS formula (Nutramigen) Lothe et al. 1982
Infant Formulas
36 children with CMA (age of 1 month to 3 years)
Application of a) soybean and b) partially hydrolyzed milk formula:
No improvement in a) 10% (Prosobee), b) 12% (Humana SL)
Partial or total relief of symptoms in a) 69% (Prosobee), b) 76% (Humana SL)
Iwanczak et al. 1995
Infant Formulas
100 children with CMA (age of 5 months to 9 years)
Application of a) soybean and b) extensively hydrolyzed CAS formula:
Partial or total relief of symptoms in a) 37% (Prosobee), b) 42% (Nutramigen)
Korol et al. 1995
Casein Hydrolyzed Formula
a 4-day-old female with cow's milk induced eosinophilic colitis
Rectal bleeding resolved upon an extensively hydrolyzed CAS formula, and endoscopy one week later showed improvement, with only scattered areas of erythema, and no friability Wilson et al. 1990
Whey Hydrolyzed Formulas
79 infants with CMA / CMI (age of <3 months)
Application of 2 extensively whey hydrolyzed formulas (1 lactose free): during application / follow-up of 10 weeks improvement of symptoms in about 80% of children and normal growth with both formulas Verwimp et al. 1995
Whey Hydrolyzed / Amino Acid Formulas
22 infants with CMA (mean age of 6 months)
Atopic eczema improved significantly and progressively in extensively hydrolyzed whey and amino acid formula- fed groups; downward trend of serum total and milk- specific IgE levels proving the efficacy of both formulas (follow-up study of 9 months) Isolauri et al. 1995
Probiotics / Whey Hydrolyzed Formula
31 infants with atopic eczema and CMA
1-month study period: infants fed with extensively hydrolyzed whey formula a) fortified with Lactobacillus GG or b) not fortified formula
clinical score of atopic dermatitis improved significantly in a); decreased concentrations of alpha 1-antitrypsin and fecal TNF-alpha in a); concentration of fecal eosinophil cationic protein unaltered in a) and b)
Majamaa & Isolauri 1997
Amino Acid Formula
12 infants with adverse reactions to soy formula, whey hydrolysate, or CAS hydrolysate
Infant formula composed of individual amino acids: no symptoms Hill et al. 1995
Amino Acid Formula
22 infants allergic to cow's milk proteins who did not tolerate extensively hydrolyzed protein formulas
Follow-up after successful use of an amino acid-based diet 11.8 +/- 8.7 months (3-30 months):
Cow's milk protein tolerance occurred earlier in 9 patients whose allergy was limited to cow's milk proteins and to extensively hydrolyzed protein formulas (age of 11.8 +/- 3.9 months) as compared to 13 patients with associated allergies to other foods (age of 25.8 +/- 6.9 months)
de Boissieu & Dupont 2000
Amino Acid Formula
31 consecutive children with proven CMA (median age 23.3 months; 6 months to 17.5 years):
29 with multiple food allergies, 17 with acute reactions and cow's milk-specific IgE, and 14 with allergic eosinophilic gastroenteritis;
13 did not tolerate extensively hydrolyzed formulas
Amino Acid-based formula (EleCare) tested performing blinded oral food challenges in nonrandomized feeding study (each child serving as own control):
18 subjects with allergic eosinophilic gastroenteritis and/or multiple food allergies followed up while receiving formula for a median of 21 months (range, 7 to 40 months): formula was hypoallergenic and effective in maintaining normal growth
Sicherer et al. 2001
Amino Acid Formula / Extensively Hydrolyzed Formula
73 infants (median age 5.7 months) with CMA/CMI and atopic dermatitis (DBPCFC positive):
a) Amino acid formula fed group
b) Extensively hydrolyzed formula fed group
Prospective, controlled, multi-center trial:
  • SCORAD index significantly improved in both groups after 6 months
  • length standard deviation score significant increase in group a), no difference in group b)
  • weight-for-length values stable in both groups
  • energy intake similar in both groups
  • significant clinical improvement in infants with early onset of symptoms CMA/CMI in both groups
  • improved growth in group a) as compared to group b)
  • Niggemann et al.  2001a
    Chestnut Formula
    >50 infants with CMA or lactose intolerance
    Supplemented chestnut formula: normal infant's development, 2 cases of intolerance Osvaath et al. 1976
    Soy Protein Formula
    20 children with CMA and atopic dermatitis
    Cow's milk- free diet using as a soy protein formula improved the skin lesions, in addition to insuring a regular growth in all infants; possible secondary sensitization to soy 1 infant Cantani et al. 1990
    Soy Milk Formula
    17 children with CMA / CMI (age of 6 months to 3 years)
    Clinical tolerance to follow-up soybean formula in 16 children, one patient developed a severe diarrhoea within 72 hours after introduction of the soybean formula Buts et al. 1993
    Soy Milk
    20 infants with CMA
    Incidence of allergic symptoms in 17% of infants fed a 2S protein fraction depleted soy milk Marano et al. 1989
    Soy / Beef Hydrolyzed Formula
    (a) 12 infants with protracted enteritis 
    (b) 10 infants with atopic eczema
    Fed with lactose-free soy and beef hydrolysate based formula: 
    improvement of symptoms in both groups, allergic symptoms in 1 (a) and 3  (b) infants who were previously fed with intact soy protein
    Donzelli et al. 1990
    Hypoallergenic Rice, Amino Acid Formula
    1child with cow's milk and soybean allergy (age of 11 months)
    Biotin deficiency in an Japanese infant fed with an amino acid formula and hypoallergenic rice processed by protease; symptoms disappeared after oral supplementation with biotin Higuchi et al. 1996
    Lamp-Meat Based Formula
    10 infants with adverse reactions to CAS hydrolyzed formulas (age of 6 months to 3 years)
    Application of a modular lamb- meat- based formula, prompt resolution of symptoms (follow-up for 3 months to 5 years) Weisselberg et al. 1996
    Ass' Milk
    9 unweaned infants with multiple food hypersensitivity presenting severe symptoms of CMA
    Ass' milk plus medium chain triglycerides well tolerated by all patients Iacono et al. 1992
    Ass' Milk / Casein Hydrolyzed Formula

    a) 21 infants (median age at diagnosis 2 months) intolerant to extensively hydrolysed proteins treated with an ass' milk-based diet

    b) 70 cow's milk intolerant infants (median age at diagnosis 3 months) treated with casein hydrolysate milk-based diet.

    Follow-up for a median period of 4 years (DBPCFC):
    Multiple food intolerance in 21/21of group a) (ass' milk group): more frequently to soybean, oranges, tomatoes and fish; goat's milk intolerance in 5/6, and sheep's milk intolerance in 4/7 receiving the respective food; these patients tolerated ass' milk; 3/21 patients in group a) became ass' milk intolerant;
    Multiple food intolerance in 20/70 infants of group b) (casein hydrolysate group);
    52% of group a) and 78% of group b) became cow's milk-tolerant; age of children at tolerance was higher in group a) than in b)
    Higher frequency of cases with elevated serum total IgE and cow's milk specific IgE in group a)
    Carroccio et al. 2000a
    Mare's Milk
    25 children with IgE-mediated CMA (age of 19 to 72 months, median 34 months)
      Mare's Milk Cow's Milk
    SPT 8% (all 2+) 100% (all 4+)
    DBPCFC 4% 100%
    IgE-binding* lower percentage higher percentage
    * SDS-PAGE immunoblotting
    Businco et al. 2000

    13.2 Allergenicity / Safety of Infant Formulas
     
    Reported Adverse Reactions References
    Human Milk see 11 Allergen Sources Reported Adverse Reactions
    Infant Formulas
    Acute allergic reactions in a 7-year old girl with CMA after challenge with 6 different partially and extensively hydrolyzed whey and CAS formulas (DBPCFC); anaphylactic reactions to a extensively hydrolysed CAS formula (Alimentum) (1, 2)
    (1) Amonette et al. 1991
    (2) Schwartz & Amonette 1991
    Infant Formulas
    20 children with CMA (age of 15 to 76 months) allergic reactions (challenge tests) to
    a) extensively hydrolyzed CAS formula in 10%,
    b) extensively hydrolyzed whey formula 13%,
    c) partially hydrolyzed whey formula in 45%
    (1) Ragno et al. 1993
    Infant Formulas
    4 children developed immediate anaphylactic symptoms after ingesting extensively hydrolyzed whey and casein formulas, respectively, and 4 children demonstrated subacute or chronic gastrointestinal symptoms. All children with anaphylactic symptoms had positive SPT and RAST to cow's milk and/or hydrolyzed proteins, while SPT and RAST were negative in 3 of 4 children with chronic symptoms (1)
    (1) Sotto et al. 1999
    Casein Hydrolyzed Formula
    Anaphylaxis  in a newborn infant after ingestion of extensively hydrolyzed CAS formula (Pregestimil) (1)
    (1) Lifschitz et al. 1988
    Casein Hydrolyzed Formula
    Systemic urticaria in 1 of 11 children with CMA after DBPCFC with extensively hydrolyzed CAS formula (Alimentum) (1)
    (1) Oldaeus et al. 1991
    Casein Hydrolyzed Formula
    Anaphylaxis in a newborn infant after ingestion of extensively hydrolyzed CAS formula (Nutramigen) (1)
    (1) Saylor & Bahna 1991
    Whey Hydrolyzed Formula
    Anaphylaxis after ingestion of extensively hydrolysed whey protein formula (Alfa-ré) in infants aged 3 to 8 months (1)
    (1) Businco et al. 1989
    Whey Hydrolyzed Formula
    Sytemic urticarial and respiratory reactions in 8 of 13 children with more severe sytemic IgE- mediated CMA (groups B and C: positive SPT to cow's milk, whey and CAS hydrolyzed formulas) when fed a partially hydrolysed whey formula (Good Start) (1)
    (1) Schwartz et al. 1991
    Whey Hydrolyzed Formula
    Anaphylaxis after ingestion of partially hydrolyzed whey formula (Good Start) (1)
    Anaphylaxis after ingestion of partially hydrolyzed whey formula in 2 infants (2)
    (1) Ellis et al. 1991
    (2) Businco et al. 1994
    Extensively Hydrolyzed Formula
    13 infants allergic to extensively hydrolyzed cow's milk protein formulas fed for treatment of chronic digestive symptoms (1)
    (1) de Boissieu et al. 1997
    Soy Hydrolyzed Formula
    43 patients with possible milk- and/or soy-protein enterocolitis:
    23% had positive challenge with cow's milk, and 33% and 30% had positive challenge to 2 hydrolyzed soy protein isolates
    (1) Burks et al. 1994

     
    Reportedly Safe Applications References
    Casein Hydrolyzed Formula
    1 extensively hydrolyzed CAS infant formula tested by DBPCFC in 5 children with IgE- mediated CMA, no symptoms occured (1)
    (1) Host & Samuelsson 1988
    Casein Hydrolyzed Formula
    1 extensivelyhydrolyzed CAS infant formula tested by SDS-PAGE immunoblot, ELISA and DBPCFC in 25 cow's milk allergic children, even in open challenge no reactions occured (1)
    (1) Sampson et al. 1991
    Whey Hydrolyzed Formula
    All of 13 children with mild topical IgE- mediated CMA (group A: positive SPT to cow's milk, negative to whey and CAS hydrolyzed formulas) tolerated a whey hydrolysate formula (Good Start) when fed for at least 2 weeks (1)
    (1) Schwartz et al. 1991
    Whey Hydrolyzed Formula
    1 ultrafiltrated (<8 kDa) whey hydrolysate infant formula could be administered safely to 66 children with CMA (elimination/challenge procedure)
    (1) Halken et al. 1993a
    Casein / Whey Hydrolyzed Formula
    1 CAS-whey hydrolyzed infant formula tested by PBMC proliferation in 10 children with CMA: no significant T-cell activation (1)
    (1) Eigenmann et al. 1995
    Casein / Whey Hydrolyzed Formula
    Hydrolysate well tolerated by 31/33 cow's milk allergic children (1)
    (1) Martin-Esteban et al. 1998
    Several Infant Formulas
    32 children with proven CMA (two-center study):
    Formula SPT positive oral challenge tolerance
    extensive hydrolysate whey formula (Nutrilon Pepti) 19% 97%
    extensive hydrolysate whey formula (Profylac) 15% 94%
    partial hydrolysate whey formula (Nan HA) 32% 64%
    (1) Giampietro et al. 2001

    Skin Tests and in vitro Tests of Infant Formulas
     
    Allergens in Infant Formulas Content / Products References
    Hydrolyzed Formulas
    26 children with CMA (age of 1.3 to 13.8 years) 
    Positivity in SPT with
    a) whey hydrolyed formula 69%
    b) extensively hydrolyzed CAS formula 38%
    Schwartz et al. 1989
    Hydrolyzed Formulas
    45 children with CMA (age of 3 months to 16 years) 
    Positivity in SPT (n=34-41) with
    a) partially and extensively hydrolysed whey formulas: Beba 24% and Profylac 15%
    b) extensively hydrolysed CAS formulas: 2.5% each (Alimentum and Nutramigen)
    Positivity in RAST with Beba 24%, other hydrolyzed formulas 7-13%
    Relative IgE- binding potency <0.06% for all tested formulas (RAST inhibition)
    Detectable amounts of bovine beta-LG in Beba 200 µg/g dry weight, other hydrolysed formulas 0.006-0.066 µg/g (ELISA)
    Oldaeus et al. 1991
    Hydrolyzed Formulas
    15 children with CMA (age of 3 to 13 years) 
    Positivity in SPT with
    a) partially and extensively hydrolyed whey formulas: Beba 47% and Alfare 6.7% (1/15)
    b) extensively hydrolyzed CAS formulas: Nutramigen 0%
    (regular cow's milk formula 87%)
    Oldaeus et al. 1992
    Hydrolyzed Formulas
    7 different infant formulas
    Detectable amounts of bovine beta-LG in hydrolyzed formulas from cows' milk whey or CAS, and from bovine collagen and soy in (range 0.0056 to 200 µg/g dry weight, 0.84 to 31200 ng/mL ready-to-use product) Makinen-Kiljunen & Sorva 1993
    Hydrolyzed Formulas
    13 children with CMA
    Serum IgE against protein hydrolysates in 6 children Plebani et al. 1990
    Hydrolyzed Formulas
    children with CMA
    6 hydrolyzed formulas tested: certain hydrolysates induced positive skin reactions and allergic symptoms after oral challenge; CAS hydrolysates had the least residual allergenic activity Rugo & Wahn 1992
    Wahn et al. 1992
    Hydrolyzed Formulas
    16 children with CMA
    1 and 2 positive results to 2 extensively hydrolysed CAS formulas; 7 positive results to a extensively hydrolysed whey formula (RAST) Dean et al. 1993
    Hydrolyzed Formulas
    1 girl with CMA (at age of 12 months)
    Positive SPT to a) extensively hydrolysed whey formula (Profylac) and b) extensively hydrolysed CAS formula (Nutramigen) Nilsson et al. 1999
    Whey Hydrolyzed Formula
    1 ultrafiltrated (<8 kDa), extensively hydrolysed whey infant formula
    35 patients with IgE- mediated
    reactions: 6% had positive SPT, 11% positive RAST against formula (no reactions in oral challenge test)
    Halken et al. 1993a
    Whey Hydrolyzed Formula
    1 ultrafiltrated, extensively hydrolysed whey infant formula
    5 children with CMA:
    Hydrolysate positive in 4/5 patients in SPT, inhibition of IgE-binding to cow's milk proteins  by the formula ranged from 51-96%;
    Peptides of > 2600 Da positive in SPT and RAST inhibition; peptides of < 1400 Da negative in SPT
    but still able to inhibit to a small extent IgE- binding to the hydrolysate (SEC, SPT, RAST)
    Van Hoeyveld et al. 1998
    Casein Hydrolyzed Formula
    10 children with CMA
    Proliferative responses of PBMCs to hydrolysate formula: higher in 3 patients whose symptoms were not reduced by CAS hydrolysate formula Nishida et al. 1995
    Hydrolyzed Infant Formulas
    a) extensively hydrolyzed CAS formula
    b) extensively hydrolyzed whey formula
    c) partially hydrolyzed whey formula
    20 children with CMA (age of 15 to 76 months); positive SPT and specific RASTto 
    a) in 15% and 15%,
    b) in 15% and 20%
    c) in 45% and 65%, respectively
    Ragno et al. 1993
    Hydrolyzed Infant Formulas
    a) non hydrolysed formula
    b) whey-based formula
    c) whey-based and ultra-filtrated formula
    d) CAS/whey-based formula
    12 children with CMA:
    All hydrolysed formulas showed reduced IgE- binding capacity; 25% of patients sera showed IgE- binding to b) and c), and 42% to d);
    b) and d) contained bovine serum albumin, beta-LG, CAS and their fragments (3-67 kDa)
    c) contained CAS fragments (3-6 kDa) and beta-LG and its fragments (6-18 kDa)
    (RAST, immunoblot)
    Gortler et al. 1995
    Hydrolyzed Infant Formulas
    11 whey and 1 CAS hydrolysed formulas
    Inhibition of IgE binding to 
      positive samples inhibition
    alpha-LA 12 18-93%
    beta-LG 12 2-84%
    BSA 6 2-75%
    bovine IgG 8 3-72%
    CAS 11 3-89%
     (RAST inhibition)

    (1) van Beresteijn et al. 1995
    Hydrolyzed Infant Formulas
    9 whey or CAS hydrolysed formulas
    CAS- specific mAb: 0.05-0.67% CAS components in all partly and 2 extensively whey hydrolysate formulas, not detectable in 2 extensively CAS hydrolysate and the amino acid based formulas (SDS-PAGE immunoblot, ELISA inhibition) (1) Restani et al. 1995, 1996
    (2) Plebani et al. 1997
    Extensively Hydrolyzed Formulas
    children with CMA
    IgE-binding to residual protein fractions
    less than 20 kDa in several extensively hydrolyzed cow milk- based formulae (RAST inhibition)
    Hoffman & Sampson 1997
    Several Infant Formulas
    a) partially hydrolysed whey formula
    b) partially hydrolysed whey/CAS formula
    c) soy/pork collagen hydrolysate
    d) amino acid formula
    20 cow's milk allergic children (mean age 1.6 years):
    Inhibition of IgE- binding to cow's milk by cow's milk > a > b > c > d (RAST inhibition); SPT to d) all negative
    Niggemann et al. 1999a
    Several Infant Formulas
    12 different partially and extensively hydrolyzed cow's milk formulas
    Proteins with Mr of 7 to >30 kDa detected by gel filtration; proteins with Mr >20 kDa even detected in extensively hydrolyzed formulas by SDS-PAGE; residual beta-LG detected in all products by ELISA;  by immunoblot and dot-immunoblot with antibodies against total whey, caseins, or Kunitz soybean trypsin inhibitor antigenic material mainly detected in partially hydrolyzed products Rosendal & Barkholt 2000
    Human Milk Cow's milk proteins see 11 Allergen Sources

    13.3 Infant Formulas for Allergy Prophylaxis

    It should be noticed that multiple parameters are involved in (food) allergy prevention. Nutritional intervention and environmental allergen avoidance are factors in allergy prevention. The role of infant formulas is controversial because the results of several studies have not been reproduced and the objective experimental conditions are difficult to achieve and maintain when studying human subjects. Please notice the disclaimer !
     
    Prevention of Feeding / Formula References
    Atopic Disease
    328 children with a positive family history of allergy (15 years follow up) 
    Breast fed infants were found to have approximately one-half the incidence of atopy of cow's milk or soy based formula fed infants  Gruskay 1982
    Atopic Disease
    101 newborn infants of atopic parents
    (total serum IgE)
    Development of atopic disease in
    Breast-fed group:
    38% with IgE > 0.8 U/ml
    12% with IgE < 0.8 U/ml 
    Soy-fed group:
    33% with IgE > 0.8 U/ml
    16% with IgE < 0.8 U/ml
    Cow's milk-fed group:
    90% with IgE > 0.8 U/ml
    17% with IgE < 0.8 U/ml
    Businco et al. 1983b
    Atopic Eczema
    97 brest fed and 124 non brest fed infants
    Development of atopic eczema
    Breast-fed group:
    22%  (restricted maternal diet)
    48% (no restricted maternal diet)
    Soy-fed group:  in 63%
    Cow's milk-fed group: in 70%
    CAS hydrolysate-fed group:  in 21%
    Chandra et al. 1989a
    Atopic Disease
    72 infants with family history of atopy (each group)*
    Incidence of atopic eczema, wheezing, rhinitis, gastrointestinal symptoms, or colic
    Breast-fed group: in 20%
    Soy-fed group:  in 37%
    Cow's milk-fed group:  in 36%
    Partially hydrolysed whey-fed group: in 7%
    Cumulative incidence of atopic disease:
    breast-fed and whey hydrolysate-fed group < cow's milk and soy-formula fed group
    Chandra et al. 1989b
    Chandra & Hamed 1991
    Chandra 1997
    Atopic Disease
    155 infants with family history of atopy
    Incidence of atopic symptoms (at 18 months)
    Extensively CAS hydrolysate fed group: in 51%
    Partially hydrolysate fed group: in 64%
    Regular cow's milk formula fed group: in 84%
    Oldaeus et al. 1997
    Atopic Disease, Cow's Milk Allergy
    91 high risk infants (follow-up to 18 months of age)
    Development of atopic diseases similar in all groups; development of cow's milk allergy / intolerance:
    Exclusively breast fed group: none
    Regular cow's milk formula fed group:
    in 3 infants with skin symptoms
    Ultrafiltered, extensively hydrolysed whey-fed group: none
    Odelram et al. 1996
    Atopic Disease, Humoral Response
    high risk infants (formula fed >3 months)
    a) 31 fed with extensively CAS hydrolyzed formula
    b) 29 fed with partially hydrolyzed formula
    c) 34 fed with regular cow's milk formula
    Development of any atopic disease:
    a) in 29%, b) in 38%, c) in 50% (at 9 months)
    a) in 35%, b) in 48%, c) in 62% (at 18 months)
    associated to detection of spec. IgE and high spec. IgG responses
    Cow's milk specific IgE:
    a) in 6.5%, b) in 10%, c) in 65%
    beta-LG specific IgG:
    a < b < c
    Oldaeus et al. 1999
    Atopic Dermatitis, Cellular and Humoral Response
    72 infants from families with atopic symptoms
    a) fed with extensively hydrolyzed formula
    b) fed with partially hydrolyzed formula
    c) breast fed (not received any formula at 6 months of age)
    Development of atopic dermatitis:
    no differences in numbers and severity among groups during first 12 months
    PBMC proliferation:
    significantly decreased proliferation to CAS in b) as compared to c) at 6 months of age
    Cow's milk specific IgE:
    a) in 9.5%, b) in 0%, c) in 13% at 6 months of age
    CAS specific IgG levels:
    b > a at 12 months of age
    Nentwich et al. 2001
    Cow's Milk Allergy
    21 infants with gastrointestinal symptoms of cow's milk and/or soy protein intolerance
    Fed with whey protein hydrolysate formula: improvement of symptoms Merrit et al. 1990
    Cow's Milk Allergy
    158 high-risk infants (1 year of age, prospective study)
    Development of cow's milk allergy / intolerance:
    Exclusively breast-fed group:  in 1/20
    Extensively hydrolysed CAS formula-fed group: in 1/59
    Extensive whey hydrolysate-fed group: in 3/62
    (no symptoms to formulas occurred)
    Halken et al. 1993b
    Cow's Milk Allergy
    58 formula-fed "at risk" infants (all children not breast-fed, formulas fed for first 6 months of life)
    Development of cow's milk allergy / intolerance
    at age of 6, 12, 36, and 60 months:
    Regular cow's milk formula fed group:
    in 43%, 53%, 57%, and 60%
    Partially whey hydrolysate-fed group:
    in 7%, 21%, 25%, and 29%
    Vandenplas et al. 1995
    Cow's Milk Allergy
    unselected healthy, full-term infants
    a) 1789 fed with cow's milk formula
    b) 1859 with pasteurized human milk
    c) 1737 with extensively hydrolysed whey formula 
    d) 824 exclusively breast-fed
    18 to 34 months follow-up
    Cumulative incidence of CMA:
    in a) 2.4%, b) 1.7%, c) 1.5%, d) 2.1% of infants
    Saarinen et al. 1999a
    Saarinen et al. 2000
    Cow's Milk Allergy
    478 infants with high-risk of atopy fed during the first 4 months of life:
    a) 232 exclusively breast-fed
    b) 79 extensively hydrolyzed casein formula
    c) 82 extensively hydrolyzed whey formula
    d) 85 partially hydrolyzed whey formula
    (study period 1994-95)

    Group a) children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas groups b), c), and d) were
    identical concerning environmental factors

    Followed-up at the age of 12 and 18 months:

    Cumulative incidence of confirmed CMA:
    a) 1.3%, b) and c) 0.6%, and d) 4.7% of infants

    Cumulative incidence of parental-reported CMA:
    b) 2.5, c) 0%, and d) 7.1% of infants

    No significant differences in b), c), and d) regarding the cumulative incidence of atopic dermatitis or respiratory symptoms

    Halken et al. 2000
    Humoral Response
    infants at risk of atopy (age of 6 months)
    a) breast fed group
    b) regular cow's milk formula fed group
    c) partially whey hydrolysate fed group
    IgE, IgG, and IgG subclasses:
    lower total IgE, cow's milk specific IgG, and alpha- lactalbumin and beta- lactoglobulin specific IgG4 in a) and c) than in b)
    (no significant differences at 5 days of age)
    Chirico et al. 1997
    Humoral Response
    129 unselected infants
    a) breast fed
    b) cow's milk formula fed
    c) CAS hydrolysate fed
    during the first 3 days of life, otherwise exclusively breast fed
    Follow-up for 2 years:
    Exposure to cow’s milk stimulated cow's milk proteins specific IgG production, while feeding with a CAS hydrolysate was associated with low specific IgG levels
    Juvonen et al. 1999
    * Studies may be experimental, unproved, or controversial. Please notice the disclaimer !



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