Title: Skin care interventions for preventing eczema and food allergy: a systematic review and individual participant data meta-analysis
Funder: Department of Health and Social Care

Abstract: Background: allergic conditions such as asthma, eczema, allergic rhinitis and food allergy affect around 1 in 3 children and young people, and cost the NHS over &pound;1 billion per annum. Previous work suggests that a damaged skin barrier may be the cause of some allergic conditions, especially eczema and food allergy. Sensitisation to food allergens, the process through which people become allergic to food, is now thought to occur through the skin rather than the intestine, in at least some people. If this is the case, then using simple measures to prevent skin damage or inflammation in the first year of life may be effective for preventing both eczema and food allergy. Hypothesis: interventions that aim to enhance skin barrier function during the first year of life will lead to reduced eczema and food allergy beyond the intervention period. Inclusion criteria: we will include randomised controlled trials whose intervention period is during the first year of life, before infants develop a clinically manifest allergic condition such as eczema. We will include trials which compare skin care interventions designed to increase skin barrier function, reduce dryness or reduce subclinical inflammation, with no treatment, standard care or other interventions designed to improve the skin barrier, or reduce dryness or inflammation. Outcomes: we will analyse outcomes reported at least 4 weeks after cessation of the intervention period. Eczema, food allergy, asthma, rhinitis, adverse events, quality of life and health economic outcomes will be evaluated. The primary outcomes are eczema and food allergy, analysed at 2 years of age. Eczema will be evaluated using the UK working party criteria, Hanifin and Rajka criteria or a modification of such criteria, or doctor diagnosis or investigator assessment when these criteria are not available. Food allergy will be evaluated using oral food challenge, or doctor diagnosis or clinical assessment for any trials where oral food challenge data are not available. Search: Cochrane Skin Group search methodology will be used to identified potentially eligible trials, including a search of trial registries, contact with industry and experts in the field to identify ongoing or unpublished trials. Title screening and data extraction will be conducted in duplicate. The Cochrane Risk of Bias tool will be used to assess risk of bias in included trials. Data analysis: the primary analysis will use all available data, either collected retrospectively or prospectively, as individual participant data or summary (aggregate) according to availability of data from the included trials. Secondary analysis will be a one-stage analysis of individual participant data from all prospectively included studies, with trial as a factor. Pre-specified subgroup analyses will explore outcomes according to participant characteristics, type and timing of intervention. Where feasible, adherence to treatment will be examined. Sensitivity analyses will exclude studies at high risk of bias, and studies using unvalidated outcome assessment tools. Random effect models will be used for meta-analysis - treatment will be a fixed effect, and trial and other clustered data will be included as random effects. Impact: findings will increase our certainty whether skin care interventions in infancy prevent eczema or food allergy, and will allow infant skin care guidelines to be written in a targeted way with more confidence and precision.

Lay abstract: Eczema and food allergy are common long-term health conditions, especially in young people. These conditions used to be less common than they are now, and they are seen more often in high-income countries such as England than in some other areas of the world. These variations over time and place suggest that factors in the environment influence whether or not a child develops eczema and food allergy, so it might be possible to prevent these conditions by changing the environment. Recent research has pointed to a faulty skin barrier in the first days or months of life as a cause of eczema and food allergy. So it may be possible to prevent eczema and food allergy using moisturisers that boost the defective skin barrier. This research study will show whether or not moisturisers and other approaches for improving the skin barrier of babies during the first year of life can prevent eczema or food allergy. Several trials, including one large NHS-funded trial, are looking at this question, but the individual trial results will still leave some uncertainties. Combining the results of all these trials means we can be much more certain about the conclusions. We will also be able to see whether moisturisers work better for some groups of babies than others, and whether they are safe for all babies. Our study results will give parents and the NHS much better information about the possible benefits or risks of different approaches to infant skin care.

Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: SKIN;INFLAMMATORY AND IMMUNE SYSTEM