Chalmers 2020.

Study characteristics
Methods	Study design: multi‐centre, pragmatic, parallel‐group, randomised controlled trial Recruitment: 19 Nov 2014 and 18 Nov 2016 Treatment arms: 2 AD follow‐up: participant follow‐up was 2 years, including follow‐up at 2 weeks (by telephone), and at 3, 6, 12, and 18 months (online or postal questionnaire), and at a 2‐year face‐to‐face appointment FA and inhalants follow‐up: 2 years
Participants	Randomised: N = 1394 (emollient n = 693, control n = 701) Inclusion criteria:  Term infants (at least 37 weeks’ gestation)  At least 1 first‐degree relative with parent‐reported eczema, allergic rhinitis, or asthma diagnosed by a doctor Mother aged 16 years or older Consenting adult with the ability to understand English Exclusion criteria:  Preterm birth (birth before 37 weeks’ gestation) Sibling (including twin) randomly assigned in the trial Severe widespread skin condition that would make detection or assessment of eczema difficult Serious health issue that would make it difficult for the family to take part in the trial Condition that would make use of an emollient inadvisable
Interventions	Both groups received advice on general skin care in booklet and video formats at the time of randomisation (Appendix pp 11 to 21). The skin care guidance provided advice to use mild cleansers and shampoos specifically formulated for infants, and to avoid soap, bubble bath, and baby wipes. Infants were randomly assigned to a group within a maximum of 21 days after delivery, and randomisation was stratified by recruiting centre and number of first‐degree relatives with atopic disease (1, 2, or > 2) Intervention: adherence was captured at each questionnaire time point during year 1 (3, 6, and 12 months) by asking parents about emollient use since the last questionnaire (Appendix p 4), and was defined in the protocol as satisfactory in the intervention group if emollients were applied at least 3 to 4 times per week to most of the child’s body (defined as at least 2 of face and neck, arms and legs, or trunk). A similar definition was used for contamination in the control group Parents were advised to apply emollient to the whole body of their child at least once daily (excluding the scalp) until the child reached 1 year of age. They were also advised to apply emollient after every bath, even if they had already applied the emollient that day. Daily application was advised to encourage regular use of emollient several times a week, but because the study was designed to reflect how the intervention might be delivered in normal practice, no prompts or reminders were sent to parents The guidance given to those in the emollient group also showed parents how to apply emollients correctly by dotting over the skin and using gentle downward strokes rather than rubbing in, and contained warnings about the skin being slippery after application and the need to clean up spillages from the floor to avoid slipping Comparator: best practice skin care advice only Moisturiser/Emollient: Doublebase Gel (Dermal Laboratories, Herts, UK) or Diprobase Cream (Bayer, Berks, UK)
Outcomes	Primary outcome: diagnosis of eczema over the past year (defined by the UK Working Party refinement of Hanifin and Rajka diagnostic criteria for eczema) assessed by research nurses masked to treatment allocation at age 2 years Secondary outcomes: other eczema definitions ‐ i.e. presence of eczema between birth and 2 years of age (assessed by any parental report of a clinical diagnosis of eczema (up to 2 years) and parent completion of UK Working Party criteria at 1 and 2 years); presence of visible eczema at 2 years recorded by a nurse who was masked to treatment allocation; time to onset of eczema (based on first parent report of clinician diagnosis and time of first topical corticosteroid or immunosuppressant prescription); clinician‐reported and patient‐reported severity of eczema (Eczema Area and Severity Index (EASI) at 2 years and Patient‐Oriented Eczema Measure [POEM] at 1 and 2 years). Other secondary outcomes were presence of other allergic diseases (i.e. parent‐reported wheezing and allergic rhinitis (between 1 and 2 years); allergic sensitisation (masked skin prick tests) to milk, egg, peanut, cat dander, grass pollen, or dust mite at 2 years; parent‐reported food allergy and parental report of clinical diagnosis of food allergy at 1 and 2 years; and allergy to milk, egg, or peanut at 2 years confirmed by oral food challenge; for cases in which no oral food challenge was done, an expert allergy panel was asked to allocate treatment  Adverse events: safety outcomes were parent‐reported skin infections (parents were asked what the doctor called the infection) and emollient‐related infant slippages during the intervention period (year 1). Skin infections and slippages were collected via 3, 6, and 12 month questionnaires. No other adverse event information was collected
Identification	Country: UK Setting: 12 hospitals and 4 primary care sites across the UK  Sponsorship source: this study was sponsored by the University of Nottingham, was co‐ordinated by the Nottingham Clinical Trials Unit (CTU), and was funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment  Programme
Declarations of interest	The main funder (NIHR Health Technology Assessment) was involved in refining the trial design through the funding peer review process but had no role in data collection, data analysis, data interpretation, or writing of the report. Funders of the food allergy outcomes and skin prick tests (Goldman Sachs Gives and Sheffield Children’s Hospital Research Fund) had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript HCW, AAM, and LEB had full access to all data in the study, and HCW had final responsibility for the decision to submit for publication
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