A randomised controlled trial in 12 hospitals and four primary care sites across the UK found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections.
Eczema (additionally termed atopic dermatitis or atopic eczema) affects about one in five children, is increasing in prevalence, and confers a high disease burden for individuals and their carers. Eczema usually starts in infancy, and persistence into adulthood is common. Children with eczema are more likely to develop other atopic conditions including food allergies, asthma, and allergic rhinitis. According to researchers led by Professor Hywell C Williams at the Centre of Evidence Based Dermatology, University of Nottingham, because eczema usually precedes the development of food allergy, and early onset eczema is strongly associated with food allergy, prevention of eczema could prevent the development of food allergy.,
Eczema is associated with loss-of-function mutations in FLG, the gene encoding filaggrin – a multi-functional protein that contributes to skin barrier integrity. This suggests that an impaired skin barrier could be a key defect in eczema development.
Sensitisation to food allergens can occur via a defective skin barrier. Several observations support the rationale for emollients as a primary prevention intervention for eczema. Skin barrier dysfunction is apparent soon after birth and precedes eczema development, providing an opportunity for strategies to improve skin hydration and barrier function., Emollients render the skin less susceptible to irritants such as soaps and detergents that could initiate eczema, can reduce percutaneous sensitisation by food antigens,, and can prevent flares of eczema (secondary prevention).
Two small randomised pilot trials provided evidence that eczema prevention through emollients might be possible. One study of 124 infants at high risk of eczema born in the UK and the US showed that 22% of infants advised to use daily emollients developed eczema by age 6 months compared with 43% in controls (relative risk [RR] 0·50, 95% CI 0·28–0·90).
The second study included 118 high-risk infants in Japan and showed that 32% of infants in the intervention group had eczema after 32 weeks versus 47% in the control group (hazard ratio 0·48, 95% CI 0·27–0·86). These strong efficacy signals from two small studies underpinned the decision of our funders to support a large-scale pragmatic trial to assess whether this intervention was effective when tested in normal practice.
Background: Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children.
Methods: We did a multicentre, pragmatic, parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via antenatal or postnatal services for recruitment of term infants (at least 37 weeks’ gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment.
Findings: 1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 [95% CI 0·78 to 1·16], p=0·61; adjusted risk difference –1·2% [–5·9 to 3·6]). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09).
Interpretation: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn.
Funding: National Institute for Health Research Health Technology Assessment.
Joanne R Chalmers, Rachel H Haines, Lucy E Bradshaw, Alan A Montgomery, Kim S Thomas, Sara J Brown, Matthew J Ridd, Sandra Lawton, Eric L Simpson, Michael J Cork, Tracey H Sach, Carsten Flohr, Eleanor J Mitchell, Richard Swinden, Stella Tarr, Susan Davies-Jones, Nicola Jay, Maeve M Kelleher, Michael R Perkin, Robert J Boyle, Hywel C Williams