A Community-based Assessment of Skin Care, Allergies, and... | NCT03409367

ID	Type	Description	Link
1R01AR071057-01A1	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
University of Wisconsin, Madison	OTHER
University of Colorado, Denver	OTHER
Duke University	OTHER
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Description Module

Detailed Description

AD affects over 9 million children in the U.S. and ranks first among all skin conditions in global disability burden. AD often heralds the development of several comorbidities including asthma, food allergy, skin infections and neurodevelopmental disorders. Because of the significant socioeconomic impact of atopic dermatitis and its effect on the quality of life of children and families, there have been decades of research focused on prevention with limited success. Recent advances in cutaneous biology identify epidermal defects and skin barrier dysfunction to be the key initiators of atopic dermatitis and possibly allergic sensitization. Our central hypothesis is that emollient therapy from birth can prevent the development of AD. The findings of this trial will support the development of evidence-based skin care clinical guidelines for infants that currently do not exist. Recently, our international multi-centered clinical trial found enhancing early skin barrier function with daily emollient use from birth significantly reduces the risk of AD development in high-risk populations by 50%. With CASCADE, we extend this work into the community setting and into newborns unselected for risk, so results will be immediately applicable to the population at large and will establish a new standard of care for all newborns.

The specific aims are as follows:

Perform a community-based pragmatic randomized controlled trial investigating whether daily full-body emollient application starting in the first 2 months of life prevents atopic dermatitis in a real-world setting. The population for this trial consists of newborns between 0-2monthsof age, not selected for risk. Recruitment of families will occur during the course of routine care within primary care offices that are members of practice-based research networks(PBRNs).The intervention includes general skin care recommendations plus full-body daily lipid-rich emollient use. The control population will receive general skin care advice only and refrain from daily emollient use. The primary outcome will be the cumulative incidence of atopic dermatitis at age 24 months as determined by blinded clinicians trained in the diagnosis of AD. Key secondary clinical outcomes include time to disease onset and incidence of self-reported food allergy and wheeze using parental questionnaires.
As an exploratory aim, determine whether a family history of allergic disease and key early life exposures such as pet ownership modify the preventive effect of emollient therapy on atopic dermatitis. While the primary objective of this clinical trial is to determine the effectiveness of an emollient intervention in a real-world setting, data will be gathered on allergy history in the family and pet ownership-variables that may modify the effect of emollient therapy. Future implementation studies may target subpopulations found most likely to benefit from emollient intervention.

Twenty-five primary care clinics that participate in PBRNs from Oregon, Colorado, Wisconsin and North Carolina are the setting for the study protocol. The expected results from this project would represent a major public health breakthrough with the potential for reducing the atopic disease burden on a global scale.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Daily Emollient	Experimental	Parent-infant dyads assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until the infant is 24 months old. Parents select one of five emollients to be mailed to the dyad's home at enrollment and approximately every six months for the duration of the study. These emollients include (1) CeraVe Healing Ointment, (2) Vaseline, (3) Cetaphil cream, (4) CeraVe cream, and (5) Vanicream.	Other: Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream
Natural Skin	No Intervention	Parent-infant dyads assigned to the control arm receive educational materials promoting general infant skin care guidelines only and are asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream	Other	Lipid-rich emollient serving as skin barrier	Daily Emollient

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Provider-diagnosed Atopic Dermatitis	The cumulative incidence of AD as recorded in health records. Trained clinicians will assess for AD at each clinic visit and record in the health record.	up to 24 months

Secondary Outcomes

Measure	Description	Time Frame
Parent Report of Atopic Dermatitis	Parent or guardian reports that a clinician has diagnosed their child with atopic dermatitis (eczema) at any quarterly contact up to 24 months of age.	up to 24 months
Atopic Dermatitis by UK Working Party Criteria

Other Outcomes

Measure	Description	Time Frame
Provider-diagnosed Atopic Dermatitis - Low-risk Population	Subgroup population: In the subgroup of participants who did not report atopic dermatitis in a first-degree relative, diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records	up to 24 months
Provider-diagnosed Atopic Dermatitis - High-risk Population

Eligibility Module

Name	Affiliation	Role
Eric Simpson, MD	Oregon Health and Science University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Colorado-Denver		Denver	Colorado	80045	United States
Duke University

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
40699587	Derived	Simpson EL, Michaels LC, Ramsey K, Fagnan LJ, Nease DE, Henningfield M, Dolor RJ, Lapidus J, Martinez-Ziegenfuss X, Vu A, Ferrara L, Zuckerman KE, Morris CD, Williams HC; CASCADE Consortium. Emollients to Prevent Pediatric Eczema: A Randomized Clinical Trial. JAMA Dermatol. 2025 Jul 23;161(9):957-65. doi: 10.1001/jamadermatol.2025.2357. Online ahead of print.
32131885	Derived	Eichner B, Michaels LAC, Branca K, Ramsey K, Mitchell J, Morris CD, Fagnan LJ, Dolor RJ, Elder N, Hahn DL, Nease DE, Lapidus J, Cibotti R, Block J, Simpson EL. A Community-based Assessment of Skin Care, Allergies, and Eczema (CASCADE): an atopic dermatitis primary prevention study using emollients-protocol for a randomized controlled trial. Trials. 2020 Mar 4;21(1):243. doi: 10.1186/s13063-020-4150-5.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 4, 2021	Sep 17, 2024

Masking Info

Arm/Group Information

ID	Title	Description
BG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
BG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and to refrain from emollient use unless dry skin develops (current standard of care guidelines).
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Provider-diagnosed Atopic Dermatitis

The cumulative incidence of AD as recorded in health records. Trained clinicians will assess for AD at each clinic visit and record in the health record.

Diagnosis of atopic dermatitis recorded by primary care clinicians in health records by 24 (+/- 3) months of age. Multiple imputation of 199 missing outcomes (92 intervention, 107 control). All ITT with multiple imputation for participants with absent outcome data. Numbers represent participants per randomized arm, regardless of adherence to instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.

Posted

Number

Participants with imputed values

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Units	Counts
Participants	OG000603 OG001625

Title

Denominators

Categories

Title	Measurements
	OG000217.7 OG001268.5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that the cumulative incidence of atopic dermatitis does not differ between the Daily Emollient and Natural Skin arms, or that the risk ratio is equal to 1.	Regression, log-binomial		0.019		Risk Ratio (RR)	0.84			2-Sided	95	0.73	0.97			Adjusted for family history of atopy (stratified randomization) and primary care site. Adjusted for multiple imputations.		Equivalence	The risk ratio is equal to 1.

Secondary

Parent Report of Atopic Dermatitis

Parent or guardian reports that a clinician has diagnosed their child with atopic dermatitis (eczema) at any quarterly contact up to 24 months of age.

Multiple imputation of 111 outcomes considered missing when parent did not respond at 21 or 24 months and no diagnosis had been reported at earlier contacts. All ITT with multiple imputation for 9% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.

Posted

Number

Participants with imputed values

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Atopic Dermatitis by UK Working Party Criteria

Parental report of AD using UK Working Party criteria. Parent responds "yes" to all parts of a modified version of the UK Working Party criteria at 12 and/or 24 month. Criteria include an itchy rash in flexural areas, generally dry skin, and asthma or hay fever in a first-degree relative.

Multiple imputation of 148 outcomes considered missing when parent did not respond at 24 months and the previous 12-month contact was not positive for AD by these criteria. All ITT with multiple imputation for 12% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.

Posted

Number

Participants with imputed values

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Atopic Dermatitis by Children's Eczema Questionnaire

AD as diagnosed by the Children's Eczema Questionnaire (CEQ). Parent response to 3 CEQ questions is consistent with AD at 12 and/or 24 months of age.

Multiple imputation of 136 outcomes considered missing when parent did not respond at 24 months and the previous 12-month contact was not positive for AD by these criteria. All ITT with multiple imputation for 11% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.

Posted

Number

Participants with imputed values

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Atopic Dermatitis With Prescription or Over-the-counter Therapies in Chart

Cumulative incidence of provider-diagnosed AD requiring prescription or over-the-counter therapies from chart review. Health records at primary care practice includes both a diagnosis of AD and prescription and/or over-the-counter (OTC) therapies. Prescription therapies could be steroids, calcineurin inhibitors, crisaborole, or antibacterials. OTC therapies could be steroids or antihistamines.

Multiple imputation of 199 missing outcomes. All ITT with multiple imputation for 16% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.

Posted

Number

Participants with imputed values

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Atopic Dermatitis With or Without Prescription or Over-the-counter Therapies in Chart (Ordinal)

Ordinal coding of diagnosis of atopic dermatitis (eczema) in primary care health records, coded as none, eczema without prescription or over-the-counter (OTC) topical therapies, eczema with OTC only, or eczema with prescription therapies. Prescription therapies could be steroids, calcineurin inhibitors, crisaborole, or antibacterials. OTC therapies could be steroids or antihistamines.

All ITT with multiple imputation for 16% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.

Posted

Number

Participants with imputed values

Up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Prescribed or Over-the-counter Topical Skin Medication by Parent Report

Ordinal formulation of parent report: no AD, AD not treated with steroidal or non-steroidal cream or ointment ("therapy"), AD treated with over-the-counter (OTC) therapy, AD treated with prescription therapy. AD could be reported on annual questionnaires or quarterly contacts. Therapies reported on annual questionnaires.

Participants with (a) a parent report of provider diagnosis from an annual questionnaire or quarterly contact or (b) if no diagnosis, a parent response to a quarterly or annual contact at 21 to 24 months. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Number

participants

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Skin Infections Diagnosed and Recorded in Chart Review

Chart outcome for provider diagnosis or medications associated with skin infections, including topical antibiotics. Skin infection diagnoses include impetigo, candida, wart/verruca, molluscum, or herpes simplex.

All participants with (a) at least one primary care visit between 20 and 27 months of age or (b) a skin infection diagnosis earlier than 20 months. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Count of Participants

Participants

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Provider-diagnosed Asthma

Health records at primary care practice include at least one diagnosis of asthma.

All participants with (a) at least one primary care visit between 20 and 27 months of age or (b) asthma diagnosis earlier than 20 months. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Number

participants

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Units	Counts
Participants

Secondary

Severity of AD Symptoms Using POEM

Patient-Oriented Eczema Measure (POEM) score, elicited from families of infants who reported AD diagnosis at this or any previous contact or whose CEQ response indicated AD. The POEM has seven items and ranges from 0 to 28, with higher scores reflecting more severe symptoms of AD.

Respondents to 12-month questionnaires who reported a provider diagnosis of AD in the same questionnaire or at a quarterly contact, or whose response to the CEQ indicated AD. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Median

Inter-Quartile Range

score on a scale

12 months of age

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Severity of AD Symptoms Using POEM

Respondents to 24-month questionnaires who reported a provider diagnosis of AD in the same or previous annual questionnaire or at a quarterly contact, or whose response to the CEQ indicated AD. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Median

Inter-Quartile Range

score on a scale

24 months of age

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Severity of AD Symptoms Using IDQoL

Symptom severity as reflected by the Infant Dermatology Quality of Life Instrument (IDQoL) elicited from families of infants who reported AD diagnosis at this or any previous contact or whose CEQ response indicated AD. The IDQoL has 12 items and ranges from 0-37 with higher scores reflecting greater adverse effect of AD on quality of life

Posted

Median

Inter-Quartile Range

score on a scale

12 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Severity of AD Symptoms Using IDQoL

Respondents to 24-month questionnaires who reported a provider diagnosis of AD in the same questionnaire or at a quarterly contact, or whose response to the CEQ indicated AD. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Median

Inter-Quartile Range

score on a scale

24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Secondary

Food Allergy Symptoms

Parent reports immediate food allergy reaction in child at 12- or 24-month questionnaire, or both.

Respondents who answered items about immediate food allergy symptoms. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Number

participants

12 months, 24 months or both

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Units	Counts
Participants

Secondary

Food Allergy Diagnosis With Positive Test

Parent reports a provider diagnosis of and a positive test for food allergy at 12- or 24-month questionnaire, or both.

Respondents who answered items about immediate food allergy symptoms. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Number

participants

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Units	Counts
Participants

Secondary

Primary Outcome of Provider-diagnosed Atopic Dermatitis

Diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records up to 12 months of age (rather than 24 months).

Infants with diagnosis of atopic dermatitis at <=12 months or with no diagnosis and at least one primary care visit in the health record after 9 months of age. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Count of Participants

Participants

up to 12 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Units	Counts

Secondary

Provider-diagnosed Atopic Dermatitis at 18 Months

Diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records up to 18 months of age.

Infants with diagnosis of atopic dermatitis at <=18 months or with no diagnosis and at least one primary care visit in the health record after 15 months of age. Numbers represent participants according to arm randomized, regardless of adherence to study instructions.

Posted

Count of Participants

Participants

up to 18 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Units	Counts

Other Pre-specified

Provider-diagnosed Atopic Dermatitis - Low-risk Population

Subgroup population: In the subgroup of participants who did not report atopic dermatitis in a first-degree relative, diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records

All ITT with multiple imputation for 19% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.

Posted

Number

Participants with imputed values

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Other Pre-specified

Provider-diagnosed Atopic Dermatitis - High-risk Population

Subgroup population: In the subgroup of participants who reported atopic dermatitis in a first-degree relative, diagnosis of atopic dermatitis (eczema) recorded by primary care providers in health records

All ITT with multiple imputation for 13% of participants with absent outcome data. Numbers represent participants according to arm randomized, regardless of adherence to study instructions. Counts were summarized over 15 multiple imputation datasets generated by chained equations using baseline and follow-up survey responses.

Posted

Number

Participants with imputed values

up to 24 months

ID	Title	Description
OG000	Daily Emollient	Parents assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier
OG001	Natural Skin	Parents assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Daily Emollient	Daily Emollients: Infants assigned to the intervention arm receive a lipid-rich emollient and educational materials promoting once daily full-body emollient use until infant age 24 months. Participant choice of over-the-counter emollients: Vaseline, Vanicream, CeraVe Healing Ointment, CeraVe cream, Cetaphil cream: Lipid-rich emollient serving as skin barrier.	1	614	25	614	134	614
EG001	Natural Skin	Natural Skin: Infants assigned to the control arm receive educational materials promoting general infant skin care guidelines only and asked to refrain from emollient use unless dry skin develops (current standard of care guidelines).	1	633	39	633	155	633

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Acute leukemia, acute myeloid leukemia NOS, eosinophilic pustular folliculitis	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment		EG0000 events0 affected614 at risk EG0013 events3 affected633 at risk
Laryngomalacia, Kabuki make-up syndrome, macrocephaly	Congenital, familial and genetic disorders	MedDRA (24.1)	Systematic Assessment		EG0001 events1 affected614 at risk EG0012 events2 affected633 at risk
Gastritis acute, gastroenteritis, gastrointestinal disorder NOS, oropharyngeal dysphagia, vomiting	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment		EG0001 events1 affected614 at risk EG0015 events5 affected633 at risk
Intussusception, inguinal hernia	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment		EG0001 events1 affected614 at risk EG0011 events1 affected633 at risk
Periodic Fever Syndrome	General disorders	MedDRA (24.1)	Systematic Assessment		EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk
Pyrexia	General disorders	MedDRA (24.1)	Systematic Assessment		EG0001 events1 affected614 at risk EG0011 events1 affected633 at risk
Milk allergy	Immune system disorders	MedDRA (24.1)	Systematic Assessment		EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk
Bronchitis viral, COVID-19, influenza, pneumonia, rhinovirus NOS, thrush, viral infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment		EG0004 events4 affected614 at risk EG0016 events6 affected633 at risk
Asphyxia	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment		EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk
Chemical burn of esophagus	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment		EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk
Skull fracture NOS, subdural haematoma	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment		EG0002 events2 affected614 at risk EG0010 events0 affected633 at risk
Dehydration, failure to thrive	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment		EG0000 events0 affected614 at risk EG0012 events2 affected633 at risk
Sagittal craniosynostosis	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment		EG0001 events1 affected614 at risk EG0010 events0 affected633 at risk
Choledochal cyst, neuroblastoma, Langerhans cell histiocytosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (24.1)	Systematic Assessment		EG0002 events2 affected614 at risk EG0011 events1 affected633 at risk
Autism spectrum disorder	Nervous system disorders	MedDRA (24.1)	Systematic Assessment		EG0001 events1 affected614 at risk EG0013 events3 affected633 at risk
Brain empyema, epilepsy NOS, episodic ataxia, febrile seizure, neonatal seizure disorder	Nervous system disorders	MedDRA (24.1)	Systematic Assessment		EG0003 events3 affected614 at risk EG0014 events4 affected633 at risk
Meningitis bacterial	Nervous system disorders	MedDRA (24.1)	Systematic Assessment		EG0000 events0 affected614 at risk EG0012 events2 affected633 at risk
Urinary tract infection	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment		EG0001 events1 affected614 at risk EG0011 events1 affected633 at risk
Breath holding spells, bronchial hyper-reactivity, bronchiolitis, croup infectious, RSV, URI	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment		EG0009 events9 affected614 at risk EG00117 events16 affected633 at risk
Cleft palate repair, Nissen fundoplication	Surgical and medical procedures	MedDRA (24.1)	Systematic Assessment		EG0001 events1 affected614 at risk EG0011 events1 affected633 at risk
Subgaleal haemorrhage	Vascular disorders	MedDRA (24.1)	Systematic Assessment		EG0000 events0 affected614 at risk EG0012 events1 affected633 at risk
Hospitalization	Investigations	MedDRA (24.1)	Systematic Assessment	Hospitalization reported, no further information available	EG0001 events1 affected614 at risk EG0010 events0 affected633 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Eosinophilic pustular folliculitis	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk
Allergic reaction NOS, urticaria	Immune system disorders	MedDRA (24.1)	Systematic Assessment	EG0002 events2 affected614 at risk EG0014 events4 affected633 at risk
Acne infantile	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events2 affected614 at risk EG0013 events3 affected633 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG00035 events30 affected614 at risk EG00146 events40 affected633 at risk
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0016 events6 affected633 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0008 events7 affected614 at risk EG0018 events7 affected633 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG00026 events22 affected614 at risk EG00138 events26 affected633 at risk
Eczema exacerbated	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0013 events3 affected633 at risk
Keratosis	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0010 events0 affected633 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG000122 events89 affected614 at risk EG001127 events99 affected633 at risk
Scarlet fever	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0003 events3 affected614 at risk EG0013 events3 affected633 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk
Skin infection / Staphylococcal skin infection	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0012 events2 affected633 at risk
Skin sensitization	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 events1 affected614 at risk EG0011 events1 affected633 at risk
Viral rash	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 events0 affected614 at risk EG0011 events1 affected633 at risk

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D003872	Dermatitis
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D017443	Skin Diseases, Eczematous
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases