Skin care interventions in infants for preventing eczema and food allergy.

Abstract

Eczema and food allergy are common health conditions that usually begin in early childhood and often occur in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth iseffective for preventing eczema or food allergy. Primary objective To assess the effects of skin care interventions such as emollients for primary prevention of eczema and food allergy in infants. Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventionsthat are associated with the greatest treatment benefit or harm for both eczema and food allergy. We performed an updated search of the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase in September 2021. We searched two trials registers in July 2021. We checked the reference lists of included studies and relevant systematic reviews, and scanned conference proceedings to identify further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTsof skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthyterm (> 37 weeks)infants (≤ 12 months) without pre-existingeczema,food allergy, or other skin condition.Eligible comparisons werestandard care in the localityor no treatment.Types of skin care interventions could includemoisturisers/emollients; bathing products; advice regarding reducing soap exposure andbathing frequency; and use of water softeners. No minimum follow-up was required. This is a prospective individual participant data (IPD) meta-analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomeswere cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E-mediatedfood allergy by one to three years, both measured at the closest availabletime point to two years.Secondary outcomes includedadverse events during the intervention period; eczema severity (clinician-assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen. We identified 33RCTs comprising 25,827participants. Of these, 17 studies randomising 5823 participants reported information on one or more outcomes specified in thisreview. We included 11 studies, randomising 5217 participants, in one or more meta-analyses (range 2 to 9studies per individual meta-analysis), with 10 of these studies providing IPD; the remaining 6 studies were included in the narrative results only. Most studies were conducted at children's hospitals. Twenty-five studies, including all those contributing data to meta-analyses, randomisednewborns up to age three weeks to receive a skin care interventionorstandard infant skin care. Eight of the 11 studies contributing to meta-analyses recruited infants at high risk of developing eczema or food allergy, althoughthe definition of high risk varied between studies.Durations of intervention and follow-up ranged from 24 hours to threeyears. All interventions were compared againstno skin care intervention or local standard care.Of the 17 studies that reported information on our prespecified outcomes, 13 assessed emollients. We assessed most of the evidence in the review as low certainty and had some concerns about risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so.We assessed the evidence for the primary food allergy outcome as high risk of bias due to the inclusion of only one trial,where findings varied based on different assumptions about missing data. Skin care interventions during infancy probably do not change the risk of eczema by one to three years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; risk difference 5 more cases per 1000 infants, 95% CI 28 less to 47 more; moderate-certainty evidence; 3075 participants,7 trials) or time to onset of eczema (hazard ratio0.86, 95% CI 0.65 to 1.14; moderate-certainty evidence; 3349 participants, 9 trials). Skin care interventions during infancy may increase the risk of IgE-mediated food allergy by one to three years of age (RR 2.53, 95% CI 0.99 to 6.49; low-certainty evidence; 976 participants,1 trial) but may not change risk of allergic sensitisation to a food allergen by age one to three years (RR 1.05, 95% CI 0.64 to 1.71; low-certainty evidence; 1794 participants,3 trials). Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low-certainty evidence; 1171 participants,1 trial); however, this was only seen for cow's milk, and may be unreliable due to over-reporting of milk allergy in infants.Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.33, 95% CI 1.01 to 1.75; risk difference 17 more cases per 1000 infants, 95% CI one more to 38 more; moderate-certainty evidence; 2728 participants,6 trials) and may increase the risk of infant slippageover the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low-certainty evidence; 2538 participants, 4 trials) and stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low-certainty evidence; 343 participants,4 trials), although CIs for slippages and stinging/allergic reactions were wide and include the possibility of no effect or reduced risk. Preplanned subgroup analyses showedthat the effects of interventions were not influenced by age, duration of intervention, hereditary risk, filaggrin (FLG) mutation, chromosome 11 intergenic variant rs2212434,or classification of interventiontypefor risk of developing eczema.We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and eczema or food allergy development. Based on low- to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection. Further study is needed to understand whether different approaches to infant skin care might prevent eczema or food allergy.