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Meta-Analysis
. 2016 Mar 8:352:i974.
doi: 10.1136/bmj.i974.

Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis

Robert J Boyle  1 , Despo Ierodiakonou  2 , Tasnia Khan  3 , Jennifer Chivinge  3 , Zoe Robinson  3 , Natalie Geoghegan  3 , Katharine Jarrold  3 , Thalia Afxentiou  3 , Tim Reeves  4 , Sergio Cunha  5 , Marialena Trivella  6 , Vanessa Garcia-Larsen  4 , Jo Leonardi-Bee  7
Affiliations
Meta-Analysis

Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis

Robert J Boyle et al. BMJ. .

Abstract

Objective: To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease.

Design: Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool.

Data sources: Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015.

Eligibility criteria for selecting studies: Prospective intervention trials of hydrolysed cows' milk formula compared with another hydrolysed formula, human breast milk, or a standard cows' milk formula, which reported on allergic or autoimmune disease or allergic sensitisation.

Results: 37 eligible intervention trials of hydrolysed formula were identified, including over 19,000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows' milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I(2)=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I(2)=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I(2)=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could allergy to cows' milk.

Conclusion: These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants.

Review registration: PROSPERO CRD42013004252.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare: RJB, VG-L, JL-B and DI received support from the UK Food Standards Agency for the submitted work. No other support was received from any organisation for the submitted work. The authors have no financial relationships with any organisations that might have an interest in the submitted work in the previous three years. RJB was a co-investigator and author of one of the trials included in this systematic review. The authors report no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Summary of risk of bias and conflict of interest in included studies reporting allergic outcomes and type 1 diabetes mellitus, showing proportion of studies with high, low, or unclear risk of bias in each domain
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Fig 2 Summary of treatment effects of hydrolysed formula on different outcome measures. Data shown are mean risk ratios (for allergic rhinitis at age 0-4; food allergy; allergic sensitisation; diabetes) or odds ratios (all other outcomes) with 95% confidence intervals for partially hydrolysed formula compared with standard cow’s milk formula
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Fig 3 Summary of treatment effects of hydrolysed formula on different outcome measures. Data shown are mean risk ratios (for allergic rhinitis at age 0-4; food allergy; allergic sensitisation; diabetes) or odds ratios (all other outcomes) with 95% confidence intervals for extensively hydrolysed formula compared with standard cows’ milk formula
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Fig 4 Evidence from randomised or quasi-randomised controlled trials for partially hydrolysed formula and extensively hydrolysed formula compared with standard cows’ milk formula for prevention of eczema in children aged ≤4
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Fig 5 Evidence from randomised controlled trials for partially hydrolysed formula and extensively hydrolysed formula compared with standard cow’s milk formula, and recurrent wheezing at age ≤4
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Fig 6 Evidence from randomised controlled trials for partially hydrolysed formula and extensively hydrolysed formula compared with standard cow’s milk formula, and allergic sensitisation to cows’ milk
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Fig 7 Evidence from randomised controlled trials for extensively hydrolysed formula compared with standard cows’ milk formula, and type 1 diabetes mellitus
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Fig 8 Funnel plots for pooled analysis of “any hydrolysed formula” and risk of eczema showing evidence of publication bias/small study effects at age ≤4 (Egger’s test P=0.019)
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Fig 9 Funnel plots for pooled analysis of “any hydrolysed formula” and recurrent wheeze showing evidence of publication bias/small study effects at age ≤4 (Egger’s test P=0.021)
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Comment in

References

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