Hydrolyzed milk formula for prevention of allergy, an updated meta analysis

Hydrolyzed Milk Formula for Prevention of Allergy: an updated meta analysis

Prof Ariyanto Harsono MD PhD SpA(K)

Prof Ariyanto Harsono MD PhD SpA(K) 2

Background

Allergies and food reactions are common and may be associated with foods including adapted cow’s milk formula. Formulas containing hydrolyzed proteins have been used to treat infants with allergy or food intolerance. However, it is unclear whether hydrolyzed formula can be advocated for prevention of allergy and food intolerance in infants without evidence of allergy or food intolerance.


Objectives

To determine the effect of feeding hydrolyzed formulas on allergy and food intolerance in infants and children compared to adapted cow’s milk or human breast milk.


Selection criteria

Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow’s milk formula.

Trials with >80% follow up of participants were eligible for inclusion.


Data collection and analysis

Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author.

Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model.


Results

Two trials compared early, short term hydrolyzed formula to human milk feeding. No significant difference in infant allergy or childhood cow’s milk allergy (CMA) were reported. No eligible trial compared prolonged hydrolyzed formula to human milk feeding. Two trials compared early, short term hydrolyzed formula to cow’s milk formula feeding. No significant benefits were reported. One large quasi random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00).


Ten eligible studies compared prolonged feeding with hydrolyzed formula versus cow’s milk formula in high risk infants. Meta-analysis found a significant reduction in infant allergy (seven studies, 2514 infants; typical RR 0.79, 95% CI 0.66, 0.94), but not in the incidence of childhood allergy (two studies, 950 infants; typical RR 0.85, 95% CI 0.69, 1.05). There was no significant difference in infant eczema (eight studies, 2558 infants, typical RR 0.84, 95% CI 0.68, 1.04), childhood eczema incidence (two studies, 950 infants, typical RR 0.83, 95% CI 0.63, 1.10), childhood eczema prevalence (one study, 872 infants; RR 0.66, 95% CI 0.43, 1.02), or infant or childhood asthma, rhinitis and food allergy.


One study reported a significant reduction in infants with CMA with confirmed atopy (RR 0.36, 95% CI 0.15, 0.89). Subgroup analysis of trials blinded to formula found no significant difference in infant allergy (four studies, 2156 infants; typical RR 0.87, 95% CI 0.69, 1.08) or childhood allergy incidence (one study, 872 infants; RR 0.91, 95% CI 0.73, 1.14). No eligible trial examined the effect of prolonged hydrolysed formula feeding on allergy beyond early childhood. There is evidence that preterm or low birthweight infants fed a hydrolysed preterm formula have significantly reduced weight gain, but not in other growth parameters (head circumference or length). Studies in term infants report no adverse effects on growth.


Subgroup analysis of trials of partially hydrolyzed versus cow’s milk formula found a significant reduction in infant allergy (six studies, 1391 infants; typical RR 0.79, 95% CI 0.65, 0.97) but not childhood allergy, or infant or childhood asthma, eczema or rhinitis. Methodological concerns were the same as for the overall analysis. Analysis of trials of extensively hydrolyzed formula versus cow’s milk formula found no significant differences in allergy or food intolerance. Infants fed extensively hydrolyzed formula compared with partially hydrolyzed formula had a significant reduction in food allergy (two studies, 341 infants; typical RR 0.43, 95% CI 0.19, 0.99), but there was no significant difference in all allergy or any other specific allergy incidence.


Comparing extensively hydrolyzed casein containing formula with cow’s milk formula, one study (431 infants) reported a significant reduction in childhood allergy incidence (RR 0.72, 95% CI 0.53, 0.97). Meta-analysis found a significant reduction in infant eczema (three studies, 1237 infants; typical RR 0.71, 95% CI 0.51, 0.97). One study reported a significant reduction in childhood eczema incidence (RR 0.66, 95% CI 0.44, 0.98) and prevalence (RR 0.50, 95% CI 0.27, 0.92).

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Discussion

Partially Hydrolyzed Formula: How it should be.US Nutrition guidelines*Should contain a small amount of cow’s protein* The purpose is to induce immune tolerance,

not the elimination of SS or prevent new sensitization

* Must contain little bit of casein and whey that going on to induce tolerance to both.

Prof DR Dr Ariyanto Harsono SpA(K)

Induction of Oral Tolerance

T-cells regulation: 1. Intra Epithelial Lymphocytes: extrathymically derived, have limited TCR repertoir, capable of recognizing common microbiologic Antigens, and demonstrate predominantly cytolytic functions

2. Lamina Propria Lymphocytes: thymicaly derived, contributes to limiting TCR/CD3-mediated signals in the mucosa.


IEL

LPL

CD23

Anergy/Tolerance: Formula HA

: Imunoterapi: Probiotik



Two trials compared a short period of early supplemental or sole hydrolyzed formula to human milk feeding and found no significant reduction in infant allergy or CMA incidence up to childhood. No eligible trials were found that compared prolonged feeding with a hydrolyzed formula to human milk feeds for the prevention of allergy or food intolerance.


Meta-analysis of seven trials reporting 2514 infants found a significant reduction in infant allergy from use of a hydrolyzed formula compared to a cow’s milk formula in infants at high risk of allergy. Hydrolyzed infant formula would need to be given to 25 infants (95%CI 12.5, 100) to prevent one infant developing allergy.


Additional subgroup analyses were performed to determine if there were differences in effects between different types of hydrolyzed protein (100% whey or casein containing formulas). Most trials of partially hydrolyzed formulas used partially hydrolyzed 100% whey formula with analyses finding a significant reduction in infant allergy (six studies, 1391 infants), but no significant difference in childhood allergy (two studies, 510 infants), infant or childhood asthma, eczema or rhinitis.


C O N C L U S I O N SThere is no evidence to support feeding with a hydrolyzed formula

compared to exclusive breast feeding for the prevention of allergy or food intolerance. Until high quality trials are performed that compare prolonged hydrolyzed formula feeding to breast or expressed human milk feeding, hydrolyzed formula should not be routinely offered to infants for the prevention of allergy or food intolerance in preference to breast milk. There is no evidence of benefit from the use of a hydrolyzed formula in preference to human milk for early, short term feeding in low risk infants. In infants at high risk of allergy who cannot be exclusively breast fed, there is limited evidence that prolonged supplementation with hydrolyzed formula as opposed to cow’s milk formula reduces the risk of allergy. However, there was no significant difference in rates of asthma, eczema or rhinitis.


Effects on allergy did not persist in subgroup analysis of trials of adequate methodology or where allergy was proven with testing. There is limited evidence that use of a partially hydrolyzed formula may prevent CMA, and that use of an extensively hydrolyzed formula is better than a partially hydrolyzed formula at preventing food allergy, although no differences were found for all allergy, asthma, eczema or rhinitis. There is limited evidence that use of an extensively hydrolyzed casein formula prevents allergy, predominately eczema.

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Hydrolyzed milk formula for prevention of allergy, an updated meta analysis

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