ArticlesSkin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial
Introduction
Atopic dermatitis, a chronic inflammatory disease of the skin, affects 5–30% of children1, 2 and has an impact on patient and family quality of life.3 Most children with atopic dermatitis present with pruritus, dry skin, and eczematous rash before age 1 year;4 reduced skin barrier function, a pathophysiological hallmark of atopic dermatitis,5 has been observed in neonates.6 In addition to anti-inflammatory therapy, emollient use has been the primary strategy in the management of atopic dermatitis because it enhances the skin barrier against irritants and maintains skin moisture.7, 8, 9 Emollients can be applied as leave-on cream or ointments, or used as soap replacement or bath additives. Bath additives have been widely prescribed for many years in infants and young children as additional treatment for dry skin and eczema, despite few studies assessing its efficacy.10 A pragmatic randomised clinical trial of 483 children with established atopic eczema showed no evidence of clinical benefit of bath oil emollient additives as an addition to standard management.9 However, the potential of enhancing the skin barrier by emollient bath additives to prevent atopic dermatitis has not been assessed beyond a small open-label pilot study in children with dry skin at age 6 weeks, whose findings indicated that regular bath emollient at a high concentration significantly reduced dry skin, but not atopic dermatitis by age 6 months.11 Two pilot studies from 2014 showed reduced atopic dermatitis with daily leave-on emollients that were applied to high-risk infants. Horimukai and colleagues12 defined high-risk infants as those with a parent or sibling with atopic dermatitis, and Simpson as colleagues13 as those with a parent or sibling with atopic dermatitis, asthma, or allergic rhinitis.
Infants with atopic dermatitis are also at increased risk of food allergy,14 asthma, and rhinitis,4 giving rise to the concept of the atopic march.15, 16, 17 The concept of epicutaneous sensitisation through an impaired skin barrier18 has been supported by the increased risk of food allergy observed in children aged 2 years with reduced skin barrier when they were 2 days old, even in the absence of early atopic dermatitis.19 Therefore, primary allergy prevention should ideally start early and target skin barrier enhancement for reducing atopic dermatitis20, 21 and inducing tolerance to foods through the alimentary tract.22
The Preventing Atopic Dermatitis and ALLergies in childhood (PreventADALL) study is the first large, pragmatic, population-based, randomised clinical trial combining two interventions of skin emollient and early complementary feeding aiming to prevent atopic dermatitis by age 12 months and food allergy by age 36 months.23 The present study primarily aimed to determine if either regular skin emollients or early complementary feeding could prevent atopic dermatitis by age 12 months.
Section snippets
Study design and participants
The PreventADALL study is an investigator-initiated, 2×2, multicentre, randomised controlled superiority trial done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway, and Karolinska University Hospital, Stockholm, Sweden. All women attending the routine 18-week ultrasound pregnancy screening at one of the three sites or in the region of Stockholm between Dec 9, 2014, and Oct 31, 2016, were invited to participate.23
All newborn babies of women recruited during pregnancy and
Results
We recruited 2697 women with 2701 pregnancies from whom 2397 newborn infants were enrolled from April 14, 2015, through to April 11, 2017, and randomly assigned to either the no intervention group (n=597), skin intervention group (n=575), food intervention group (n=642), or the combined intervention group (n=583). One participant in the no intervention group withdrew consent and was not included in the intention-to-treat data analyses for the primary outcome (figure 1).
Baseline characteristics
Discussion
In this large, randomised, primary prevention pragmatic clinical trial in a general infant population, development of atopic dermatitis by age 12 months was not prevented by regular use of bath oil additives and face-emollient cream on at least 4 days per week from 2 weeks of age, nor by early complementary feeding introduced from age 12 weeks. The effects of interventions were not influenced by parental atopy.
Our novel finding that atopic dermatitis was not prevented by emollient bath
Data sharing
Data are stored at the Service for Sensitive Data database at the University of Oslo. The PreventADALL study is an ongoing study that has been approved for data collection until 2044.
References (34)
Public health burden and epidemiology of atopic dermatitis
Dermatol Clin
(2017)- et al.
Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys
Lancet
(2006) - et al.
The burden of atopic dermatitis: summary of a report for the National Eczema Association
J Invest Dermatol
(2017) - et al.
Multifactorial skin barrier deficiency and atopic dermatitis: essential topics to prevent the atopic march
J Allergy Clin Immunol
(2016) - et al.
Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year
J Allergy Clin Immunol
(2015) - et al.
Can early skin care normalise dry skin and possibly prevent atopic eczema? A pilot study in young infants
Allergol Immunopathol (Madr)
(2014) - et al.
Application of moisturizer to neonates prevents development of atopic dermatitis
J Allergy Clin Immunol
(2014) - et al.
Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention
J Allergy Clin Immunol
(2014) - et al.
Does atopic dermatitis cause food allergy? A systematic review
J Allergy Clin Immunol
(2016) - et al.
The allergy march: from food to pollen
Environ Toxicol Pharmacol
(1997)
Predicting the atopic march: results from the Canadian Healthy Infant Longitudinal Development Study
J Allergy Clin Immunol
The atopic march: critical evidence and clinical relevance
Ann Allergy Asthma Immunol
Skin barrier impairment at birth predicts food allergy at 2 years of age
J Allergy Clin Immunol
The skin as a target for prevention of the atopic march
Ann Allergy Asthma Immunol
Prevention of food allergy
J Allergy Clin Immunol
The effectiveness of using a bath oil to reduce signs of dry skin: a randomized controlled pragmatic study
Int J Nurs Stud
How should an incident case of atopic dermatitis be defined? A systematic review of primary prevention studies
J Allergy Clin Immunol
Cited by (168)
Preclinical Atopic Dermatitis Skin in Infants: An Emerging Research Area
2024, Journal of Investigative DermatologyFeast for thought: A comprehensive review of food allergy 2021-2023
2024, Journal of Allergy and Clinical ImmunologyEarly skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants
2024, Journal of Allergy and Clinical ImmunologyConstant vigilance! Managing threats to the skin barrier
2024, Annals of Allergy, Asthma and Immunology