Early initiation of short-term emollient use for the prevention of atopic dermatitis in high-risk infants-The STOP-AD randomised controlled trial

Abstract

Background: Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high-risk infants at 12 months.

Methods: This was a single-center, two-armed, investigator-blinded, randomized controlled clinical trial (NCT03871998). Term infants identified as high risk for AD (parental history of AD, asthma or allergic rhinitis) were recruited within 4 days of birth and randomised 1:1 to either twice-daily emollient application for the first 8 weeks of life (intervention group), using an emollient specifically formulated for very dry, AD-prone skin, or to standard routine skin care (control group). The primary outcome was cumulative AD incidence at 12 months. AD <6 months was diagnosed based on clinical presence of AD. The UK Working Party Diagnostic Criteria were applied when diagnosing AD between 6 and 12 months.

Results: Three hundred twenty-one were randomised (161 intervention and 160 control), with 61 withdrawals (41 intervention, 20 control). The cumulative incidence of AD at 12 months was 32.8% in the intervention group vs. 46.4% in the control group, p = 0.036 [Relative risk (95%CI): 0.707 (0.516, 0.965)]. One infant in the intervention group was withdrawn from the study following development of a rash that had a potential relationship with the emollient. There was no significant difference in the incidence of skin infections between the intervention and control groups during the intervention period (5.0% vs. 5.7%, p > 0.05).

Conclusions: This study has demonstrated that early initiation of daily specialized emollient use until 2 months reduces the incidence of AD in the first year of life in high-risk infants.

Keywords: atopic dermatitis; emollient; prevention; randomized controlled trial; skin barrier.

FIGURE 1

Trial profile. *Two infants in the control group were no longer eligible due to receiving phototherapy for jaundice after randomization. The primary outcome was the cumulative incidence of atopic dermatitis at 12 months. CW = Consent withdrawn, LTFU = Lost to follow‐up.

FIGURE 2

Point prevalence and cumulative incidence of AD at 12 months in the intervention and control groups. The point prevalence of AD was calculated based on the number of infants in each group who met the UK Working Party Diagnostic Criteria for atopic dermatitis at 12 months (intervention: 24/117, control: 52/136), as assessed by the blinded investigator. The cumulative incidence of AD was calculated based on the number of infants diagnosed with AD at any point in the first 12 months (intervention: 24/117, control: 52/136). AD = atopic dermatitis.

FIGURE 3

Kaplan–Meier plot of the proportion of infants in the intervention and control group without AD during the first 12 months of life. The intervention group maintained AD‐free skin for a longer period in the first 12 months than the control group (p = 0.016, log‐rank test). AD = atopic dermatitis.

FIGURE 4

(A, B) Cumulative incidence of AD at 6 and 12 months in a LoF FLG mutation carriers and wildtype stratified by study treatment (B) intervention and control groups stratified by FLG status. The cumulative incidence of AD was calculated based on the number of infants diagnosed with AD at any point in the first 6 and 12 months. There was a non‐significant trend towards a reduced incidence of cumulative AD incidence at 12 months in the intervention group for both FLG groups, with a greater effect size in the LoF FLG group [RR (95% CI): 0.524 (0.265, 1.036) vs. 0.722 (0.502, 1.038)]. LoF = Loss‐of‐function, FLG = gene encoding filaggrin, AD = atopic dermatitis.