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Use Of Infant Formulae In The Treatment
           And Prevention Of Atopic Disease
Written by Dr Cassim Motala

The treatment of CowпїЅs Milk Allergy (CMA) is complete avoidance of cowпїЅs milk protein.  Milk avoidance is relatively easy in early life, but an appropriate substitute for human milk is mandatory in infants with CMA who are not breast-fed.  Breast-feeding is generally believed to protect against development of atopic diseases in high-allergic-risk infants. 

When breast-feeding is not possible, not adequate or when the mother prefers early weaning, a пїЅhypoallergenic formulaпїЅ is recommended for infants who are at high risk for developing allergy.  For a formula to be regarded as пїЅhypoallergenicпїЅ, it should be significantly less allergenic than standard infant formulas that are derived from cowпїЅs milk. 

The American Academy of Pediatrics Nutritional Committee has stipulated that such formulae should be tolerated by 90% of children with cowпїЅs milk allergy with 95% confidence.1

In addition, a пїЅhypoallergenicпїЅ formula should ideally be nutritionally adequate, acceptable in taste, easily available, easily prepared if not пїЅready to feed,пїЅ and reasonably priced. 

 

Currently available formulae which are available in South Africa as alternatives to breast-feeding for prevention and treatment of certain atopic diseases include soya (Infasoy, Isomil, extensively hydrolyzed casein (Nutamigen, Pregestemil), extensively hydrolyzed whey (Alfare and partially hydrolyzed whey (Nan-HA).  The relative cost of these formulae are listed in Table I.

Table I.  Relative cost of various formulae
                 Retail prices as at 31 August 1997

Soya protein
Isomil
Infasoy

500 g
500 g

R19.07
R20.90

Partial hydrolysed whey
Nan HA

400 g

R26.28

Extensively hydrolysed whey
Alfare

400 g

R91.48

Extensively hydrolysed casein
Nutramigen
Pregestemil

450 g
450 g

R55.99
R94.91

Soya formula
Soya formula has long been recommended by some authorities as a substitute for human or cowпїЅs milk based on the studies by Glaser and Johnstone.2  However, allergy to soya is frequently encountered in subjects allergic to cowпїЅs milk.  Many of these patients in fact can tolerate soya, as judged from challenge tests.4 

The prevalence of soya  allergy varies depending on the type of allergic reaction to cowпїЅs milk.  In patients with IgE-mediated reactions to cowпїЅs milk (manifestations: urticaria, eczema, abdominal pains, vomiting, diarrhoea, asthma, allergic rhinitis, anaphylaxis) about 15% of these will later also develop an allergic reaction to soya protein.3 

In contrast in patients with non-IgE mediated reactions to cowпїЅs milk (manifestations: enterocolitis, colitis, failure to thrive) over 50% of these children will develop allergy to soya protein.3  Children with IgE-mediated cowпїЅs milk allergy and soya protein allergy tend to manifest sensitivity to both proteins at the time of initial diagnosis.3  Soya formula would be an appropriate formulae to use for the treatment of IgE-mediated cowпїЅs milk allergy but not for non-IgE mediated reactions.

 

The possible allergy-preventive effect of soya formula is contentious.  In on study,5 no allergy-preventive effect was observed when soya formula was compared with cowпїЅs milk formula at weaning in offspring of two atopic parents.  In another study, the use of soya for allergy prevention was recommended, even though a case of soya anaphylaxis occurred.6  Soya allergy tends to be more prolonged than cowпїЅs milk allergy.  It also seems more difficult for soya allergic subjects to avoid soya than for cowпїЅs milk allergic subjects to avoid milk because of extensive use of soya in the food industry.  Hence, soya formula is not routinely recommended for preventive purposes in high-allergy-risk infants.7

Extensively hydrolyzed formula
Extensively hydrolyzed casein formulae such as Nutramigen and Pregestemil are currently recommended for children with established cowпїЅs milk allergy, and for preventive purposes in high-allergy-risk infants when a substitute for breast-milk is needed.  These formulae rarely elicit anaphylactic reactions in milk-allergic subjects.8-11

 In one allergy-preventive study, Pregestemil appeared to reduce the occurrence of atopic eczema by the age of 4 years but had no effect on the prevalence of asthma.12  An extensively hydrolyzed whey formula (e.g. Alfare) is also recommended for treatment of CMA for preventive purposes.  Its efficacy appears to be similar to that of Nutramigen.13   The two main drawbacks of the extensively hydrolyzed milk-based products are their expense and rather unpleasant taste.  The cost is almost three to four times that of conventional formulae (Table I).

 

Partially hydrolyzed formulae
Because of the high costs and the poor taste of extensively hydrolyzed formulae (eHF), a partially hydrolyzed formulae (pHF) based on various cowпїЅs milk proteins has been developed.  In contrast to eHF, pHF contains a high proportion of non-degraded or partly degraded proteins in the molecular weight range 8-40.10  Of note is that certain pHF contain lactose (e.g. Nan-HA) and should therefore not be used in infants with lactose intolerance. 

The allergenicity of pHF varies14 and severe reactions have been reported in children with establised cowпїЅs milk allergy who were fed a partially hydrolyzed whey protein formulae.15,16  Hence, it is recommended that pHF must be avoided in infants with diagnosed cowпїЅs milk allergy. 

The preventive effect of pHF on allergy development remains an open question.  Several studies have shown that feeding pHE to high-risk infants from birth to 6 months was associated with a lower incidence of atopic disease, including eczema and asthma.17-24  The results of these studies have been reviewed.25  The recent prospective, double-blind study by Chandra23 found that infants fed exclusively on pHF for the first 6 months after birth had a significantly lower cumulative incidence and period prevalence of atopic eczema and asthma until age 5 years.  Similar results were obtained by Van den Plas et al.24 and Wilhelms et al.21 Marini et al.22 confirmed that the incidence of atopic symptoms was lowest among infants in the pHF group, with the follow-up until age 3 years.  Confirmation of the results of these studies by a prospective, multicentred, controlled trial by non-biased observers is needed.  Such a study should compare the relative efficacies of pHF versus eHF in allergy prevention and be carried out beyond 5 years to help clarify the issue of true prevention.

Elemental formulae
Elemental formulae, which consist of synthetic amino acids (least antigenic) can be used as alternatives to human milk in the treatment of CMA.  The only elemental formulae available in South Africa is Alitraq (Ross/Abbott Laboratories).  Alitraq is a liquid product specifically formulated for metabolically stressed patients with impaired gastrointestinal tract function.  Alitraq is an adult element formula but can be correctly diluted and used in the paediatric situation if this becomes necessary.

 

GoatпїЅs milk
GoatпїЅs milk is not considered пїЅhypoallergenicпїЅ.  In vitro and in vivo studies showed very strong cross-reactivity between proteins in cowпїЅs milk and thos in goatпїЅs milk.2627  Thus, goatпїЅs milk is not recommended in the treatment of CMA, or for prevention of atopy.

Summary
Currently, eHF, casein hydrosylate in particular, is recommended as a first-line substitute for human milk in the treatment of CMA and for prevention of atopy in high risk infants.  In practice, there are major inconveniences in feeding caseing hydrosylates  these formulae have an unpleasant taste, they are very expensive and they are not widely available.

A soya formula is an acceptable alternative to eHF in patients with diagnosed IgE-mediated CMA but, not for non-IgE mediated CMA or for preventive purposes.  PHF is not recommended for treatment of CMA but may have a role in prevention of atopy in high-risk infants, especially when cost (the cost of pHF is almost comparable to that of standard cowпїЅs milk formula), availability and palatability are taken into consideration.  Current data suggests that exclusive feeding for 6 months with casein hydrosylate or a partial whey hydrosylate has similar benefits to exclusive breast-feeding for prevention of allergic disease in early life in at-risk infants.

REFERENCES

    1. Committee on Nutrition of the American Academy of Pediatrics.  Hypoallergenic formulas.  Pediatrics 1989; 83: 1068-1069.

    2.Kleinman RE, Bahna S, Powell GF, Sampson NA.  Use of infant formulas in infants with cowпїЅs milk allergy.  A review and recommendations.  Pediatr Allergy Immunol  1991; 2: 146-155.

    3.Glaser J, Johnstone D.  Prophylaxis of allergenic disease in the newborn.  J Am Med Assoc 1953; 153: 620-622.

    4.Giampietro P, Ragno V, Daniele S, Cantani A, Ferrara M, Businco L.  Soy hypersensitivity in children with food allergy.  Ann Allergy 1992; 69: 143-146.

    5.Kjellman N-IM, Johnsson S.  Soy versus cowпїЅs milk in infants with a biparental history of atopic disease:  development of atopic disease and immunoglobulins from birth to 4 years of age.  Clin Allergy 1979; 9: 347-358.

    6.Bardare M, Vaccari A, Allievi E, et al.  Influence of dietary manipulating on incidence of atopic disease in infants at risk.  Ann Allergy 1993; 71: 366-371.

    7.Bruijnzeel-Koomen C, Ortolani C, Aask et al. Position paper: Adverse reactions to food.  Allergy 1995; 50: 623-635.

    8.Beck SA.  Probable allergic reactions to casein hydrosylate.  J Allergy Clin Immunol 1989; 84: 272.

    9.Saylor JD, Bahna SL.  Anaphylaxis to casein hydrosylate formula.  J Pediatr 1991; 118: 71-74.

    10.Oldaeus G, Bjorksten B, Einarsson R, Kjellman N-IM.  Antigenicity and allergenicity of cow milk hydrosylates intended for infant feeding.  Pediatr Allergy Immunol 1991; 4: 156-164.

    11.Businco L, Cantani A, Longhi AL, Giampietro PG.  Anaphylactic reactions to cowпїЅs milk whey hydrosylate (Alfa-Re Nestle) in infants with cowпїЅs milk allergy.  Ann Allergy 1989; 62: 333-335.

    12.Mallet E, Henscq A.  Longterm prevention of allergic disease by using protein hydrosylate formula in at-risk infants.  J Pediatr 1992; 121:S95-S100.

    13.Halken S, Host A, Hanson L, Osterballe O.  Preventive effect of feeding high-risk infants a casein hydrosylate formula or an ultrafiltrated whey hydrosylate formula.  A prospective-randomized, comparative clinical study.  Pediatr Allergy Immunol 1993; 4: 173-181.

    14.Oldaeus G, Bradley CK, Bjorksten B, Kjellman N-IM.  Allergenicity screening of пїЅhypoallergenicпїЅ milk-based formulas.  J Allergy Clin Immunol 1992; 90: 133-135.

    15.Ellis M, Short J, Heiner D.  Anaphylaxis after ingestion of a recently introduced hydrolysed whey protein formula.  J Pediatr 1991; 118: 74-77.

    16.Ragno V, Giampetro P, Bruno G, Businco L.  Allergenicity of milk protein hydrosylate formulae in children with cowпїЅs milk allergy.  Eur J Pediatr 1993; 152: 760-762.

    17.Vandenplas Y, Deneyer M, Sacre L, Loeb H.  Preliminary data on field study with a new hypoallergenic formula.  Eur J Pediatr 1988; 148: 274-277.

    18.Chandra RK, Singh G, Shidhara B.  Effect of feeding whey hydrosylate, soy, and conventional cow milk formulas on incidence of atopic disease in high-risk infants.  Ann Allergy 1989; 63: 102-106.

    19.Chandra RK, Hamed A.  Cumulative incidence of atopic disorders in high-risk infants fed whey hydrosylate, soy, and conventional cow milk formulas.  Ann Allergy 1991; 67: 129-132.

    20.Vandenplas Y, Hauser B, Van den Borre C, Sacre L, Dab J.  Effect of whey hydrosylate prophylaxis of atopic disease.  Ann Allergy 1992; 68: 419-424.

    21.Wilhelms R, Duchateau J, Magrez P, Denis R, Casimir G.  Influence of hypoallergenic formula on the incidence of early allergic manifestations in infants predisposed to allergic diseases.  Ann Allergy 1993; 71:147-150.

    22.Marini A, Agosti M, Motta G, et al.  Effects of dietary and environmental prevention programme on the incidence of allergic symptoms in high-risk infants: three yearsпїЅ follow-up.  Acta Paediatrica 1996; 85 (Supplement 414): 1-22.

    23.Chandra A.  Five-year follow-up at high-risk-infants with family history of allergy who were exclusively breast-fed or fed partial whey hydrosylate, soy and conventional cowпїЅs milk formulas.  J Pediatr Gastroenterol Nutr 1997; 24: 380-388.

    24.Vandenplas Y, Hauser B, Van den Borre C, et al.  The long-term effect of partial whey hydrosylate formula on the prophylaxis of atopic disease.  Eur J Pediat 1995; 154: 488-494.

    25.Collin-Williams C.  Current status of hydrosylates in the prevention of allergy.  In: Chandra RK, ed Nutrition and Immunology.  St JohnпїЅs Newfoundland: ARTS Biomedical, 1992; 379-390.

    26.Saperstein S.  Antigenicity of the whey proteins in evaporated cowпїЅs milk and whole goatпїЅs milk.  Ann Allergy 1960; 18: 765-773.

    27.Crawford LV, Grogan ET.  Allergenicity of cowпїЅs milk proteins.  IV.  Relationship to goatпїЅs milk proteins as studied by serum-agar precipitation.  J Pediatr 1961 1961; 59: 347-350.

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