Formulas containing hydrolysed protein for prevention of allergic disease in infants

Review question

Does feeding infants with a formula containing hydrolysed protein result in decreased risk of developing allergic disease such as asthma, dermatitis/eczema, hay fever and food allergy during infancy and childhood?

Background

Allergic disease is responsible for a substantial health burden among infants, children and adults. Early dietary intake may influence the development of allergic disease. When babies are not exclusively breast fed, use of hydrolysed formula instead of ordinary cow's milk formula may reduce allergic disease among babies and children, although additional studies are needed to confirm this. Infant formulas have been designed to lower the chance of infants developing allergic disease. These include hydrolysed cow's milk and soy milk formulas. Hydrolysed formulas break down milk proteins into smaller, potentially less allergy-producing proteins.

Results

This review of trials found no evidence to support feeding with a hydrolysed formula to prevent allergic disease in preference to exclusive breast feeding. This review also found that for infants who are unable to be exclusively breast fed, there is no evidence that prolonged infant feeding with a hydrolysed formula compared with a cow's milk is associated with any difference in allergic disease, asthma, eczema, rhinitis, food allergy or cow's milk formula at any time point. However, limited data in infants who are exclusively formula fed suggest that feeding with a hydrolysed formula instead of a cow's milk formula may reduce infant allergic disease. Concerns regarding quality of the evidence and consistency of the results indicate that continued study is needed. The evidence in this review comes from literature searches updated until November 2017.

Conclusions

We found no substantial evidence to support short-term or prolonged feeding with a hydrolysed formula compared with a cow's milk formula for prevention of allergic disease in infants unable to be exclusively breast fed.

Authors' conclusions: 

We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergic disease. Very low-quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA. Further trials are recommended before implementation of this practice.

We found no evidence to support prolonged feeding with a hydrolysed formula compared with a CMF for prevention of allergic disease in infants unable to be exclusively breast fed.

Read the full abstract...
Background: 

Infant formulas containing hydrolysed proteins have been widely advocated for preventing allergic disease in infants, in place of standard cow’s milk formula (CMF). However, it is unclear whether the clinical trial evidence supports this.

Objectives: 

To compare effects on allergic disease when infants are fed a hydrolysed formula versus CMF or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective, including extensively or partially hydrolysed formula (EHF/PHF). To determine whether infants at low or high risk of allergic disease, and whether infants receiving early short-term (first few days after birth) or prolonged formula feeding benefit from hydrolysed formulas.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 11), MEDLINE (1948 to 3 November 2017), and Embase (1974 to 3 November 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles and previous reviews for randomised controlled trials and quasi-randomised trials.

Selection criteria: 

We searched for randomised and quasi-randomised trials that compared use of a hydrolysed formula versus human milk or CMF. Outcomes with ≥ 80% follow-up of participants from eligible trials were eligible for inclusion.

Data collection and analysis: 

Two review authors independently selected trials, assessed trial quality and extracted data from the included studies. Fixed-effect analyses were performed. The treatment effects were expressed as risk ratio (RR) and risk difference (RD) with 95% confidence intervals and quality of evidence using the GRADE quality of evidence approach. The primary outcome was all allergic disease (including asthma, atopic dermatitis, allergic rhinitis and food allergy).

Main results: 

A total of 16 studies were included.

Two studies assessed the effect of three to four days infant supplementation with an EHF while in hospital after birth versus pasteurised human milk feed. A single study enrolling 90 infants reported no difference in all allergic disease (RR 1.43, 95% CI 0.38 to 5.37) or any specific allergic disease up to childhood including cow's milk allergy (CMA) (RR 7.11, 95% CI 0.35 to 143.84). A single study reported no difference in infant CMA (RR 0.87, 95% CI 0.52 to 1.46; participants = 3559). Quality of evidence was assessed as very low for all outcomes.

No eligible trials compared prolonged hydrolysed formula versus human milk feeding.

Two studies assessed the effect of three to four days infant supplementation with an EHF versus a CMF. A single study enrolling 90 infants reported no difference in all allergic disease (RR 1.37, 95% CI 0.33 to 5.71; participants = 77) or any specific allergic disease including CMA up to childhood. A single study reported a reduction in infant CMA of borderline significance (RR 0.62, 95% CI 0.38 to 1.00; participants = 3473). Quality of evidence was assessed as very low for all outcomes.

Twelve studies assessed the effect of prolonged infant feeding with a hydrolysed formula compared with a CMF. The data showed no difference in all allergic disease in infants (typical RR 0.88, 95% CI 0.76 to 1.01; participants = 2852; studies = 8) and children (typical RR 0.85, 95% CI 0.69 to 1.05; participants = 950; studies = 2), and no difference in any specific allergic disease including infant asthma (typical RR 0.57, 95% CI 0.31 to 1.04; participants = 318; studies = 4), eczema (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 2896; studies = 9), rhinitis (typical RR 0.52, 95% CI 0.14 to 1.85; participants = 256; studies = 3), food allergy (typical RR 1.42, 95% CI 0.87 to 2.33; participants = 479; studies = 2), and CMA (RR 2.31, 95% CI 0.24 to 21.97; participants = 338; studies = 1). Quality of evidence was assessed as very low for all outcomes.

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