Rationale

The effects of maternal alcohol use on offspring represent a substantial yet modifiable public health concern. The potential association between maternal alcohol use, a modifiable risk factor and atopic dermatitis, a common childhood disorder, necessitates thorough investigation and highlights a critical opportunity for preconception and antenatal interventions. A prior systematic review by Overgaard et al. [19] suggested a preliminary association reporting a small but statistically significant positive association between maternal alcohol use during pregnancy and the development of AD in offspring. However, this review was limited by a small number of observational studies and mainly relied on binary exposure definitions (drinker vs. abstainer) without accounting for potential dose-response relationships or key exposure dimensions such as preconception alcohol use, trimester-specific exposure, and dose-frequency patterns of maternal alcohol use. Since then, the evidence has remained limited, with recent studies reporting inconsistent findings. For instance, Manjunath and Silverberg [20] reported no significant association between maternal alcohol use during pregnancy and childhood AD, while earlier cohort studies have suggested a potential positive association. In addition, variability in diagnostic criteria and broader methodological differences further limit comparability across studies. Alongside these inconsistencies, the current literature remains too diverse for a traditional systematic review aimed at establishing a definitive cause-and-effect relationship. Therefore, a scoping review methodology is the most appropriate approach to comprehensively examine exposure patterns, outcome characteristics, and hypothesised mechanisms in human studies. The primary aim of this review is to map the scope, range, and key characteristics of the existing research on the association between maternal alcohol exposure (including preconception and pregnancy) and atopic dermatitis in offspring.

A. Identifying the research question

Objectives:

• To assess the association between maternal alcohol exposure (timing, dose, pattern) and atopic dermatitis in the offspring
• To identify and map the hypothesized biological mechanisms underlying the association between maternal alcohol exposure and atopic dermatitis in the offspring
• To map the scope and characteristics of the current literature on maternal alcohol exposure and atopic dermatitis in the offspring to inform future research and policy

The review question was developed after discussion with the research team and a comprehensive assessment of existing literature on maternal alcohol use and risk of atopic dermatitis in offspring. The following research questions were formulated.

1. a. Is there an association between maternal alcohol exposure and atopic dermatitis in the offspring?
2. b. Does frequency and quantity of maternal alcohol consumption modify the risk of atopic dermatitis in offspring?
3. c. What biological mechanisms have been reported or hypothesised to link maternal alcohol exposure to the development of atopic dermatitis in offspring?

This scoping review will use the PEO framework to conceptualise the research questions and objectives as described in Table 1.

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Table 1. PEO framework.

https://doi.org/10.1371/journal.pone.0354140.t001

B. Identification of relevant studies

The search strategy was initially developed for the PubMed database using the PEO framework and a combination of controlled vocabulary and free-text terms. Following peer review and validation, the strategy was adapted for each database and reviewed for accuracy, syntax, and reproducibility. Validation will include checking whether known relevant studies are retrieved by the final search strategy and documenting all final database-specific search strings in the appendix. Searches will be conducted in PubMed, Embase via Ovid, Scopus, CINAHL via EBSCOhost, and Web of Science Core Collection from database inception to the final search date. Database-specific search strategies will incorporate appropriate controlled vocabulary and free-text terms according to the PEO framework, as listed in Table 1. PubMed uses MeSH terms; Embase via Ovid uses Emtree subject headings; and Scopus and Web of Science use database-specific title, abstract, keyword, and proximity syntax. The full PubMed search strategy is presented in Table 2, and the search strategies for all other databases are provided in S1 Appendix. In addition, grey literature, including clinical trial registries, dissertations and theses, and relevant public health agency reports, will be searched. Trial registries will include ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and the Clinical Trials Registry–India. Dissertations and theses will be searched through ProQuest Dissertations and relevant institutional/open-access repositories. Records identified from grey literature sources will be imported into the reference-management software, where possible, deduplicated, and screened using the same PEO-based eligibility criteria as those used for bibliographic database records. If export is not possible, search results will be documented manually in the grey literature search log. Additionally, the reference lists of all included studies shall be hand-searched to identify any potentially eligible articles. Studies meeting the predefined inclusion criteria will be included in the review.

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Table 2. Search strategy for PubMed database.

https://doi.org/10.1371/journal.pone.0354140.t002

C. Selection of the eligible studies

Two independent reviewers shall be involved in the search and screening of eligible articles as described in the PRISMA-ScR flow diagram (S1 Fig). Initial screening of titles and abstracts will be conducted using the PEO framework, as outlined in Table 1, to conceptualise the eligibility criteria.

Outcome: Atopic dermatitis.

Studies must report on the diagnosis of atopic dermatitis, or eczema, using established diagnostic criteria, such as the UK Working Party Criteria, Hanifin and Rajka Criteria or clinical diagnosis by a dermatologist, paediatrician, or a physician, based on symptoms, histological and laboratory findings or history by parent/guardian or registry data.

Before the formal screening process, the two independent reviewers will conduct a pilot test using a random sample of approximately 50–100 titles and abstracts. This will ensure both reviewers understand and consistently apply the PEO eligibility criteria. Any discrepancies arising during this pilot phase will be resolved through discussion, and the inclusion criteria will be refined as necessary. The titles and abstracts identified from the search will be imported into the Rayyan software to facilitate blinded, independent screening and to track the selection process as per the PRISMA-ScR. Following the initial screening, the full text of potentially eligible articles will be retrieved and independently reviewed against the eligibility criteria summarised in Table 3. Disagreements during the full-text review will first be addressed through discussion and consensus between the two reviewers. A third reviewer will be included if consensus cannot be reached about the discrepancies. The reasons for the exclusion of any full-text articles will be documented and reported in the final review. The selection process will be mapped as per PRISMA-ScR [21].

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Table 3. Eligibility criteria.

https://doi.org/10.1371/journal.pone.0354140.t003

D. Charting the data

The data extraction process will utilise a standardised, electronic form in Microsoft Excel. Before full-scale data extraction, the charting form will be applied to a pilot sample of 5 included studies to assess inter-rater reliability, thereby ensuring clarity, consistency, and completeness in capturing the required variables. Refinements to the form will be made based on this pilot testing. One author shall extract the data, and the second author shall verify it against the original article. The verification ensures a comprehensive check for accuracy and completeness of the extracted data. A draft charting table (Table 4) will be developed to record the data obtained from each study. The second reviewer confirms all data fields in the charting table. Any discrepancies identified during verification will be resolved through discussion between the two authors.

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Table 4. Data Charting.

https://doi.org/10.1371/journal.pone.0354140.t004

E. Collating, summarising and reporting the results

The overview and characteristics of the eligible studies will be tabulated and summarised, including the author, year of publication, place of study, study design, study aim, and sample size. The included studies examining the risk of AD in offspring will be grouped according to maternal use of alcohol during the preconception period and during pregnancy. A narrative summary will integrate the following study characteristics and findings.

1. i. Exposure and outcome measurement: Maternal alcohol use (exposure) and atopic dermatitis (outcome) will be examined in each included study. To address potential heterogeneity, the diagnostic criteria used for atopic dermatitis, age at outcome assessment, and methods used to quantify maternal alcohol exposure, including dose, duration, frequency, timing, and pattern of use, will be extracted and mapped during data charting and synthesis. This will facilitate comparison of outcome definitions and exposure measurements across studies. Dose–response mapping will focus on how the frequency and quantity of maternal alcohol consumption (e.g., light, moderate, or heavy use, or specific grams of alcohol) were measured and whether these variables were reported to modify the risk of AD in offspring.
2. ii. Summary of key findings: The key findings will be summarised based on whether studies reported statistically significant positive association, no association, or an inverse association between maternal alcohol exposure and AD risk in offspring. For studies assessing antenatal alcohol exposure, the timing or trimester of exposure will also be noted and summarised.
3. iii. Hypothesized biological mechanism: The reported biological mechanisms associated with maternal alcohol exposure and atopic dermatitis in offspring, as discussed within the included studies, will be explored.
4. iv. Confounding factors: Confounding factors adjusted in the included studies, such as family history of atopy, environmental exposures, maternal smoking, and other related covariates, will be summarised.

The knowledge gap in current literature on aspects such as the specific trimester of highest risk, chronic alcohol exposure risk, lack of standardised measures for alcohol consumption, including biomarker testing and lack of longitudinal studies tracking AD incidence will be reported.

The anticipated timeline for the review is as follows:

• Search Strategy & Execution: To be finalised and executed in July 2026.
• Record screening: Title, abstract, and full-text screening are expected to be completed by August 2026.
• Data extraction and charting: Expected to be completed by December 2026, along with the synthesis of results.

F. Consultation

The sixth stage of the JBI scoping review methodology, consultation, will be incorporated to maximise the relevance and applicability of the review findings, provide additional insights, and facilitate their dissemination. A purposive sample of approximately 5–10 experts relevant to the review topic will be invited to participate. These may include specialists and researchers in allergy and immunology, psychiatrists, obstetricians, paediatricians, and dermatologists. Participants will be identified through professional networks and academic institutions. Following the preliminary synthesis of the review findings, participants will receive a summary of the results and be invited to provide feedback through structured discussions, online meetings, or written responses. Feedback will focus on the clinical relevance of the findings, interpretation of evidence gaps, and implications for future research, clinical practice, and public health. The consultation findings will be used to contextualise and refine the interpretation of the review results, thereby enhancing the review’s practical relevance.