Key Points
Question
Does daily emollient application from age 9 weeks to 24 months help to prevent atopic dermatitis (AD) in a population unselected for risk?
Findings
In this randomized, pragmatic, decentralized clinical trial of 1247 infant-parent dyads, those who were assigned to the daily moisturizer group had a lower cumulative incidence of AD compared with the standard of care group.
Meanings
The trial results suggest that applying emollient daily for infants may be a feasible way to reduce the incidence of AD.
Abstract
Importance
Atopic dermatitis (AD) imposes a global health burden for children and is a risk factor for developing food allergy and asthma. Few studies have evaluated emollient intervention for primary AD prevention in infants not selected for risk.
Objective
To determine whether emollient intervention in infants not selected for risk reduces AD incidence by age 24 months.
Design, Setting, and Participants
A randomized, decentralized pragmatic clinical trial was conducted that involving 1247 infant-parent dyads recruited from 25 community-based pediatric and family medicine clinics that are members of 4 statewide practice-based research networks. Participants were recruited from July 2018 to February 2021, with follow-up completed through February 2023.
Intervention
Dyads were randomized to 1 of 2 groups: a daily full-body emollient application daily moisturizer group starting by age 9 weeks or a control group that refrained from emollient use.
Main Outcomes and Measures
The primary outcome was physician-diagnosed AD recorded in the patient’s medical record by age 24 months. Participants completed quarterly electronic surveys to report adverse events and alert the team if an AD diagnosis had been made. Trained research coordinators abstracted participants’ medical records.
Results
Of 1247 infants, 553 (44.3%) were female, and the mean (SD) age at randomization was 23.9 (16.3) days. At 24 months, the cumulative incidence of AD was 36.1% (SE, 2.1) in the daily moisturizer group and 43.0% (SE 2.1) in the control group, with a relative risk (RR) of 0.84 (95% CI, 0.73-0.97; P = .02), and the magnitude of effect was larger in the population not at high risk of AD (RR, 0.75; 95% CI, 0.60-0.90; P = .01). The protective effect was significantly modified by the presence of a dog in the home (RR, 0.68; 95% CI, 0.50-0.90; P = .01). There were no between-group differences in cutaneous adverse events.
Conclusions and Relevance
This randomized clinical trial found that daily emollient application beginning before age 9 weeks in a representative US population not selected for risk reduced the cumulative incidence of AD at age 24 months. Implementing this approach to pediatric skin care may be a feasible way to reduce the burden of AD in US communities.
Trial Registration
ClinicalTrials.gov Identifier: NCT03409367
This randomized clinical trial examines whether emollient intervention in infants not selected for risk reduces atopic dermatitis incidence by age 24 months.
Introduction
Pediatric atopic dermatitis (AD) imposes a substantial community health care burden in US primary care clinics and represents a global health burden.1,2 Children who develop AD early in life carry a risk of developing allergic comorbidities, sleep disturbance due to pruritus, behavioral challenges, and mental health disorders and experiencing bullying.3 Recent studies have revealed that cutaneous inflammatory biomarkers precede AD development, suggesting the skin to be an important initiating site of the disease.4 Loss-of-function FLG variants, the strongest genetic risk factor for AD, can impair skin barrier function before the development of AD, indicating that the skin may initiate AD through impaired barrier function.5 Thus, protecting the skin barrier has been central to several AD prevention studies.
More than 10 randomized clinical trials enhancing the skin barrier to prevent AD have been performed, with conflicting results.6 Most trials have been conducted in high-risk populations and not in community primary care settings, a first point of care for most infants. Studies evaluating full-body emollient intervention for the primary prevention of AD in a population not selected for risk are lacking. The objective of this current study, the Community-Based Assessment of Skin Care, Eczema, and Allergies (CASCADE trial), was to determine whether once-daily, full-body emollient initiated within the first 9 weeks of life can reduce the cumulative incidence of AD in a community-based population not selected for risk.
Methods
This study was approved by a central institutional review board at the University of Utah, with institutional review boards at the University of Wisconsin, University of Colorado, Duke University, and Oregon Health & Science University agreeing to rely on the University of Utah. Follow-up was completed through 2023. Study reporting adhered to the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline 2022 statement.7
The CASCADE trial was a randomized, parallel-group, controlled, single-blind, pragmatic 24-month clinical trial with a decentralized outcomes reporting structure. Decentralized trials minimize or eliminate the need for participants to travel to a centralized study center. Data were collected using remote or electronic methods, and interventions are distributed by mail or email.8 The trial protocol (Supplement 1) and key participant-facing communications were reviewed and approved by a community advisory committee composed of primary care clinicians and patient advocates. Key elements of the trial have been previously published.9 Parent-infant dyads were recruited from 25 primary care clinics from 4 US states and enrolled during scheduled well child clinic visits using an electronic tablet or personal electronic device. Inclusion criteria included that child were aged 0 to 8 weeks and parents/guardians communicated in English or Spanish and had email and internet connectivity. Exclusion criteria included infants with a prior eczema diagnosis who were extremely premature (<25 weeks’ gestation) or had a very low birth weight (<1000 g), an immunodeficiency syndrome, or a sibling in the study. Eligible parents and guardians used Research Electronic Data Capture (REDCap) to provide electronic informed consent, complete the baseline questionnaire, and be randomized into the daily moisturizer (intervention) or the control arm.
Randomization and Blinding
Participants were randomized in a 1:1 allocation ratio as stratified by primary care clinic and history of AD in a first-degree family member. Randomization sequences with blocks of 4 were created by the biostatistician (K.R.) using a computer-based random number generator to assign arms 1 and 2. The data coordinating center programmed the REDCap randomization module and determined which number designated the treatment or control arm.
Intervention
All parents received general skin care instructions that suggested bathing their child twice per week with a gentle cleanser according to contemporary guidelines10 that have now been updated.11 Participants in the daily moisturizer arm selected an emollient from 5 bland emollient options that were mailed to the participant’s home every 6 months. Included emollients were selected for their ability to improve skin barrier function and lack of irritants and common allergens.12,13,14 These choices were confirmed as common and appropriate recommendations by 8 pediatric dermatologists or pediatric eczema experts at 3 universities and 1 private practice. Participants assigned to the daily moisturizer group were instructed to use the supplied emollient and apply to the entire body once daily. The scalp and diaper area could be excluded from emollient use if preferred by the family. In the control group, participants were instructed to refrain from routine frequent emollient use. The emollient could be used intermittently for dry skin in the control group if deemed necessary by the family.
Primary Outcome
The primary outcome was the cumulative incidence of AD at age 2 years as determined by a credentialed health care clinician and recorded in the health care record. Clinicians involved in the study were trained in AD diagnosis with comprehension checks.15 Structured health record audits were completed by trained assessors who were masked to the study arm to collect the primary outcome.
Secondary Outcomes
Health record auditors collected information on AD diagnosis, skin infections, hay fever/allergic rhinitis, asthma, wheeze, food allergy testing, adverse events secondary to skin products, and serious adverse events at 24 months (21-27 months). Quarterly and annual surveys gathered information on emollient use frequency in both groups, alternate AD definitions, reported clinician-diagnosed food allergy, skin care–related adverse events, and any serious adverse events.
Alternate AD definitions were gathered. The UK Working Party (UKWP) AD assessment was modified to remove the visible flexural eczema evaluation as originally designed.16,17 Children’s Eczema Questionnaire scores were collected and had validation in children younger than 4 years, whereas the UKWP criteria do not.18 The third approach asked whether a clinician had diagnosed AD for the child, a question that was validated in other studies.19 Participants who reported a diagnosis of AD by their clinician or met Children’s Eczema Questionnaire criteria were asked to complete the Patient-Oriented Eczema Measure and the Infant Dermatology Quality of Life.20,21
Statistical Analysis
Statistical analyses were performed by K.R. and supervised by J.L. The assumption was that the control group cumulative incidence of AD by age 2 years would be 24% based on literature review and our own work.2,22 We hypothesized that the intervention would provide a 30% reduction in risk based on results from previous studies of emollients. Because an interim analysis was planned (Supplement 2), the O’Brien-Fleming group sequential spending function was used to set the overall type 1 error at 0.05 and found that a total of 982 infants (491 per arm) were required to detect differences between the arms. Allowing for an approximate 20% loss to follow-up, we planned to recruit 1250 dyads (625 per arm). The final analysis used a type 1 error threshold of 0.05.
In the primary analysis, the risk of diagnosed AD by age 2 years in the intervention was compared with the control groups under an intention-to-treat assumption and missing outcomes were imputed using multiple imputation. The relative risk (RR) was estimated using a generalized linear model with a binomial distribution and log link and reported P values from a 2-sided Wald test at the .05 level of significance. Risk differences are presented using the margins and mimrgns commands in Stata, version 18 (StataCorp).
Missing values, including outcomes, were imputed using multiple imputation by chained equations. The number of imputation sets was determined by 100*(missingness fraction of the primary outcome).23 Additional details are provided in Supplement 2, including alternate AD diagnoses, secondary outcome analyses, and sensitivity analyses.
We investigated differences in treatment effects in subgroups with risk or protective associations with AD. Subgroups included family history of atopy, dry climate, interaction with pets and farm animals at baseline, child’s age at randomization, more frequent bathing, and cesarean delivery.
Results
Population
From July 2018 to February 2021, 1872 infant-parent dyads were screened, and 1247 were randomized. (Figure 1; eTable 1 in Supplement 3). Baseline characteristics (Table) were balanced between the study arms. The racial and ethnic composition of the study population closely reflected the ethnic and racial makeup of the US.24 A total of 342 participants (27.9%) were enrolled from practices in rural areas (as described by the practice).
Figure 1. CONSORT Flow Diagram of the Progress of the Participants Throughout the Trial.
Table. Baseline Characteristics.
| Characteristic | No. (%) | Difference | ||
|---|---|---|---|---|
| Daily moisturizer (n = 603) | Control (n = 625) | Total (N = 1228) | ||
| Atopy in parent or sibling | ||||
| Yes | 296 (49.1) | 303 (48.5) | 599 (48.8) | 0.012 |
| No/do not know | 307 (50.9) | 322 (51.5) | 629 (51.2) | |
| State | ||||
| Colorado | 132 (21.9) | 136 (21.8) | 268 (21.8) | 0.025 |
| North Carolina | 146 (24.2) | 154 (24.6) | 300 (24.4) | |
| Oregon | 222 (36.8) | 224 (35.8) | 446 (36.3) | |
| Wisconsin | 103 (17.1) | 111 (17.8) | 214 (17.4) | |
| Sexa | ||||
| Female | 279 (46.3) | 274 (43.9) | 553 (45.1) | 0.047 |
| Male | 324 (53.7) | 350 (56.1) | 674 (54.9) | |
| Age at randomization, mean (SD), d | 23.9 (16.0) | 24.0 (16.6) | 23.9 (16.3) | 0.009 |
| Moisturizer use before enrollment | ||||
| Yes | 391 (65.4) | 382 (62.4) | 773 (63.9) | 0.062 |
| No | 207 (34.6) | 230 (37.6) | 437 (36.1) | |
| If yes, days per week, mean (SD) | 2.6 (2.1) | 2.8 (2.1) | 2.7 (2.1) | 0.095 |
| Domestic animals | ||||
| Dogs | 334 (55.4) | 317 (50.8) | 651 (53.1) | 0.092 |
| Cats | 168 (27.9) | 179 (28.7) | 347 (28.3) | 0.018 |
| Farm animals | 28 (4.6) | 27 (4.3) | 55 (4.5) | 0.015 |
| Ethnicitya | ||||
| Hispanic or Latino | 144 (24.8) | 141 (23.5) | 285 (24.1) | 0.030 |
| Not Hispanic or Latino | 437 (75.2) | 459 (76.5) | 896 (75.9) | |
| Racea,b | ||||
| American Indian or Alaska Native | 24 (4.2) | 7 (1.2) | 31 (2.7) | 0.185 |
| Asian | 39 (6.8) | 38 (6.4) | 77 (6.6) | 0.013 |
| Black | 72 (12.5) | 72 (12.2) | 144 (12.3) | 0.008 |
| Native Hawaiian or Pacific Islander | 5 (0.9) | 5 (0.8) | 10 (0.9) | 0.002 |
| White | 497 (86.1) | 523 (88.6) | 1020 (87.4) | 0.076 |
| Otherc | 6 (1.0) | 3 (0.5) | 9 (0.8) | 0.061 |
| Educationa | ||||
| Did not finish high school | 26 (4.5) | 23 (3.8) | 49 (4.1) | 0.150 |
| High school degree or GED | 98 (16.8) | 127 (21.2) | 225 (19.0) | |
| Some college education | 160 (27.4) | 137 (22.9) | 297 (25.1) | |
| 4-y College degree | 120 (20.5) | 136 (22.7) | 256 (21.7) | |
| Professional degree | 180 (30.8) | 175 (29.3) | 355 (30.0) | |
| Primary care practice settingd | ||||
| Urban | 209 (34.7) | 223 (35.7) | 432 (35.2) | 0.028 |
| Suburban | 227 (37.6) | 227 (36.3) | 454 (37.0) | |
| Rural | 167 (27.7) | 175 (28.0) | 342 (27.9) | |
Abbreviation: GED, general education development.
Percentages were calculated using nonmissing responses in the denominator. Responses were considered missing if respondents indicated that they preferred not to answer questions about the sex (n = 1), ethnicity (n = 47), or race (n = 61) of their child or about their own education level (n = 46).
Race percentages sum to more than 100 because respondents could indicate more than 1 category.
Responses of other were recategorized when possible. The remaining 9 responses selected other but left the additional description blank, so they could not be categorized.
As reported by practice representative at the study start.
Intervention
At baseline, emollient option 4 was the most commonly selected emollient (eTable 2 in Supplement 3) in the daily moisturizer group (272 [45.0%]), but switching between emollients was common (eFigure 1 in Supplement 3). At quarterly contacts, more than 50% of the daily moisturizer group reported 7 applications per week (range of 49% to 58%, or 261 of 528 responses at 24 months to 244 of 424 responses at 15 months), whereas more than 50% of the control group reported 0 to 1 applications per week (range of 67% to 77%, or 369 of 549 responses at 12 months and 356 of 465 responses at baseline; Figure 2; eTable 3 in Supplement 3).
Figure 2. Parent-Reported Moisturizer Use Over Time by Study Arm.
Moisturizer, n = 603 infants; control, n = 625 infants.
The annual survey completion rate was 90.1% for the 12-month survey and 88.3% for the 24-month survey. Fewer than 20% of participants in both study arms had missing primary outcomes (Figure 2).
Primary End Point and Sensitivity Analyses
At 2 years, the cumulative incidence of AD per adjudicated primary care clinician–reported health record diagnosis (primary outcome) in the daily moisturizer group was 36.1% (SE, 2.1%) and 43.0% (SE, 2.1%) in the control group (Figure 3). The cumulative incidence of AD in the daily moisturizer group was significantly lower than the control group (RR, 0.84; 95% CI, 0.73-0.97; P = .02). The results were consistent with a protective effect of emollients for all case definitions, except for the UKWP criteria, which has not been validated for children (Figure 4). The study was not powered to detect differences in AD incidence by emollient type, and discerning the relative potency of each emollient for AD protection was not possible (eFigure 2 in Supplement 3) given emollient switching.
Figure 3. Cumulative Incidence, Risk Difference, and Relative Risk of Atopic Dermatitis (AD) by Age 24 Months by the Primary Definition of Documentation in Health Records and Alternative Methods to Ascertain AD.
Moisturizer arm, n = 603 infants; standard of care arm, n = 625 infants. Intent-to-treat analysis with multiple imputation for missing outcomes. OTC indicates over the counter; UKWP, UK Working Party.
Figure 4. Cumulative Incidence, Risk Difference, and Interaction for the Risk of Atopic Dermatitis (AD) by Age 24 Months for Subgroups.
Moisturizer arm, n = 603 infants; control arm, n = 625 infants. Intent-to-treat analysis with multiple imputation for missing outcomes.
Effect Modification
Having a first-degree blood relative with atopic disease (ie, high risk) was associated with a weaker intervention effect than for children at lower risk, although the interaction was not statistically significant (Figure 4). Among children at low risk, the cumulative incidence in the control arm was 43.4% compared with 33.2% in the intervention, a statistically significant −10.1% risk difference (RD; 95% CI, –18.1 to –2.2). Among children at high risk, the control arm had a similar cumulative incidence (42.5%), but the RD associated with the intervention was only −3.4% (95% CI, −11.9 to 5.1). The protective effect of emollient was significantly modified by dog ownership, with a stronger protective effect of the intervention observed in this subset of families (RD, −14.2; 95% CI, −23.2 to –4.6) than in those without any pets (RD, 0.3; 95% CI, −9.6 to 10.3).
Secondary Outcomes
Skin infections occurred at slightly lower rates in the daily moisturizer group than the control group (19.8% vs 21.1%; RR, 0.94; 95% CI, 0.74-1.20) with no statistical difference between groups (eTable 5 in Supplement 3). Parental report of food allergy, defined as a reaction to a food within 90 minutes plus a typical type 1 reaction, such as vomiting or hives, was lower in the daily moisturizer group than in the control group, with no significant differences between groups (10.7% vs 14.2%; RR, 0.76; 95% CI, 0.55-1.04). In those with AD, the median scores reflected mild disease for Patient-Oriented Eczema Measure and the Infant Dermatology Quality of Life, with a large range of disease severity (eFigure 3 and eTable 3 in Supplement 3). There were no clinically meaningful differences between groups in disease severity by either instrument.
Safety
There were no differences in cutaneous skin product–related adverse event (AE) rate proportions between the 2 groups (eTable 6 in Supplement 3). Rash was the most frequently parent-reported AE, and most AEs were mild to moderate in severity. While rashes were reported to be related to skin care product use, the exact etiology could not be precisely defined due to the limitations of participant-described AEs. There were no treatment-related severe AEs.
Discussion
In this community-based study and randomized clinical trial, a protective effect of daily full-body bland emollient application was observed at age 2 years in an unselected population. The use of emollients reduced the risk of AD at age 2 years by 16%, which equated to a number needed to treat of 15. These results were consistent across multiple definitions of AD, including AD requiring prescription therapy. The magnitude of the effect of the intervention was stronger in infants without an atopic history in the family (24% reduction) and those reporting having a dog in the household. The intervention appeared safe and feasible. Given the current and frequent use of moisturizers by the US population,25,26 this intervention may represent a practical and safe approach to reducing the burden of AD in US communities.
The results of this study add to a growing body of evidence regarding the potential role of emollient therapy in preventing AD. A Cochrane individual participant-level meta-analysis did not find skin care interventions, taken together, to be protective against AD development, which included interventions that were not strictly emollient interventions.6 Two additional systematic reviews reported a protective effect of emollients in high-risk populations, with RRs estimated to be 0.74 to 0.75.27,28 Methodological concerns regarding 1 of these reviews have been published.29 To our knowledge, only 2 individual studies evaluating populations not selected for risk have been performed. However, these studies did not test full-body emollients; one used bath oils and one used facial application of emollient only.30,31 Thus, the CASCADE trial is unique in that it evaluated full-body direct emollient application for the prevention of AD in a population not selected for risk.
The finding that an emollient intervention reduces the risk of AD to a greater degree in participants without a family history of atopic disease is a novel finding. One explanation for this observation may be that children with a strong atopic family history, which includes AD, asthma, and hay fever, may have disease that is primarily driven by immune dysregulation, including genetic causes, whereas those without an atopic family history may have AD initiated by skin barrier insults, such as irritation from water, soap, a dry indoor or outdoor climate, and additional unknown genetic factors; thus, they are more amenable to skin barrier repair. Behaviors within families with atopic conditions may favor practices that reduce skin and allergy issues, such as more care in bathing practices and avoidance of irritants and allergens, behaviors that were not captured systematically in our study but that may blunt the effect of moisturizer use in this subgroup. A study of prenatal antibiotic exposures found more of an effect on risk of AD in offspring in low-risk families than higher risk for unclear reasons but suggests that family history may modify effects of various exposures.32 Future studies should ideally measure markers of immune dysregulation and known genetic risk alleles if feasible.
Another novel finding was the significant modification of the effect of emollients by household dog ownership status. Data regarding AD risk and pet ownership are conflicting but appear to provide a protective effect.33 A recent birth cohort study from Japan (n = 1440) found that pet ownership was associated with reduced AD incidence only in infants without an FLG variant. This suggests that a child’s skin barrier status can alter the effects of household pet exposure.34 This is consistent with our results that found dog ownership to enhance the protective effect of emollients, although the exact mechanisms underlying this observation requires further study.
Our findings suggested that the routine use of emollients for prevention may be a feasible approach for families. Interestingly, 64% of participants reported using emollients before study enrollment. These findings were consistent with a previous survey from Oregon.25 This suggests that routine emollient use is part of infant skin care routines for many households in the US. The composition of the emollient likely makes a difference in efficacy, as differences have been observed in skin barrier assessments between ceramide and non–ceramide-containing moisturizers.35 Two of the 5 emollients in the study contained ceramides. Some emollients may even harm the skin barrier and theoretically promote AD.36,37
The overall prevalence of AD was higher than expected at approximately 43% by age 2 years. Rates close to this magnitude were reported in a recent cohort in Scandinavia (n = 1834) that were reported to be 34.2% at age 1 year.38 As in our study, this cohort found that the UKWP criteria prevalence was lower due to a lack of fulfilling the itch criteria. The sensitivity and specificity of each definition in the CASCADE cohort are undergoing analysis to better understand discrepancies and will be the subject of a future article. The protective effect was observed with similar magnitude across all disease definitions. The use of multiple definitions of AD may be useful in future studies.
The study identified no safety signals of concern with the emollient interventions. Fewer cases of contact dermatitis and rash were observed in the daily moisturizer arm, suggesting that emollient use may protect against conditions, such as irritant contact dermatitis and diaper dermatitis. A previous large randomized controlled study found possible increases in skin infection and food allergy with emollient use.39 These trends were not observed in our study, and the rates of both events were numerically lower in the daily moisturizer group.
The ultimate goal of this line of research is to develop skin care guidelines for families with young children that best protect against AD development. Reducing the burden of AD may also mitigate the risk of developing allergic comorbidities that are shown to be more prevalent in children with early-onset AD.40 There are some data to suggest that systemic allergic responses may initiate from skin inflammation. Certain inflammatory serum biomarkers elevated in atopic diseases decrease following skin-directed therapies.41 Thus, promoting daily emollient use may have benefits not only on AD development but also allergic diseases as a whole. Longer-term follow-up is needed to determine whether the reduction of AD translates to measurable reductions in the incidence of allergic comorbidity.
Strengths and Limitations
This study had several strengths. To our knowledge, this was the first randomized clinical trial that used primary care practice–based research networks studying an intervention for a dermatologic condition. The decentralized structure eased the study burden on participants, allowed enrollment of a diverse study population, and led to low attrition rates.
Limitations of the study included a lack of understanding that emollient may be best to achieve effective prevention of AD, no genetic testing, and no formal food allergy testing. In addition, daily full-body moisturizer may be cost-prohibitive for some families, difficult to apply, cause contact dermatitis, or have unknown adverse effects from absorption of ingredients, such as parabens, with long-term use.42 Emollients were provided free of charge for this study; thus it may not be generalizable to the current US population.
Conclusions
This randomized clinical trial found that full-body emollient application starting during the first 2 months of life reduced the risk of AD development, especially in those without a family history of AD and who had a dog in the household. Further work will be needed on the cost-effectiveness of this approach and implementation strategies. The effect of this approach on allergic comorbidities is also a high priority for future work.
Trial protocol
Statistical analysis plan
eTable 1. Characteristics of participating clinics
eTable 2. Baseline emollients received, intervention arm only
eFigure 1. Emollient changes during study participation (intervention arm n=603)
eTable 3. Detailed data of adherence
eFigure 2. Risk differences by emollient shipped at enrollment compared to none
eFigure 3. POEM and IDQoL scores with median and quartiles at 12 and 24 months among respondents who reported a provider diagnosis or met CEQ criteria
eTable 4. POEM/IDQoL numbers and difference calculations
eTable 5. Secondary outcomes (skin infections, food allergy, asthma)
eTable 6. Participants reporting adverse events, defined as a reaction to a skin care product
Nonauthor collaborators
Data sharing statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Trial protocol
Statistical analysis plan
eTable 1. Characteristics of participating clinics
eTable 2. Baseline emollients received, intervention arm only
eFigure 1. Emollient changes during study participation (intervention arm n=603)
eTable 3. Detailed data of adherence
eFigure 2. Risk differences by emollient shipped at enrollment compared to none
eFigure 3. POEM and IDQoL scores with median and quartiles at 12 and 24 months among respondents who reported a provider diagnosis or met CEQ criteria
eTable 4. POEM/IDQoL numbers and difference calculations
eTable 5. Secondary outcomes (skin infections, food allergy, asthma)
eTable 6. Participants reporting adverse events, defined as a reaction to a skin care product
Nonauthor collaborators
Data sharing statement
