Strengths and limitations of this study
We aim to map the existing literature related to pregnancy outcomes and vitiligo.
To the best of our knowledge, this is the first scoping review in this subject.
This information could provide valuable insights for future original and secondary studies.
We will not assess the risk of bias or the quality of evidence for the studies included in our review.
Our search will be limited to two databases: Scopus and PubMed. Other databases and grey literature will not be considered due to limitations in resources and time.
Introduction
Vitiligo is a chronic systemic disease characterised by hypopigmented macules resulting from the partial or complete loss of melanocytes in the affected skin. 1 It affects both men and women equally at any age, but it most commonly appears between the ages of 10 and 30. 2 It is estimated that vitiligo affects 0.5%–2% of the general population. 3 The exact cause of vitiligo is still being studied, but it is believed to involve a combination of genetic and environmental factors. These include genetic and metabolic influences, oxidative stress, autoimmune responses, inflammation, mechanisms that lead to the detachment of melanocytes, both innate and adaptive immune responses and abnormalities in cell separation. 1 4 5 Recent evidence suggests that this disease is an autoimmune condition, while mechanisms linked to genetic factors are still being examined. 6
Vitiligo profoundly impacts patients’ mental health and significantly affects their daily lives. 7 Pregnancy and childbirth can present significant challenges for women with vitiligo due to the potential exacerbation of the disease and the associated complications for both mother and fetus. 8 Vitiligo is associated with other systemic autoimmune disorders, including autoimmune thyroid disease, systemic lupus erythematosus (SLE), rheumatoid arthritis and type 1 diabetes mellitus. 9 10 Like many other autoimmune and inflammatory diseases, patients with vitiligo often use immunosuppressants and anti-inflammatory medications, which can lead to complications during pregnancy. 11 13 Impaired immune responses, such as the induction of Th1 and Th17 responses, could contribute to pregnancy complications in patients with vitiligo. 14 15 Vitiligo may be associated with adverse pregnancy outcomes (APOs), including recurrent miscarriage, prematurity, intrauterine growth retardation and pre-eclampsia. 15 16
APOs refer to complications that occur during pregnancy, delivery or the postpartum period and can affect the health of both mothers and their babies. 17 These outcomes are particularly prevalent in developing countries. 18 The most severe APO is the death of the mother or child, which is most common in developing countries. 18 Research indicates that certain autoimmune diseases, such as SLE and inflammatory bowel disease (IBD), may be associated with complications during pregnancy. 19 20 These complications may include low birth weight, intrauterine growth restriction, infant mortality, premature birth, pre-eclampsia and eclampsia, high blood pressure, frequent spontaneous abortions, premature birth 21 22 and can vary from one disease to another. For instance, lupus is associated with increased mortality during pregnancy, while psoriasis is linked to a higher risk of repeated abortions, chronic hypertension and caesarean deliveries. 23 24 So far, more than 80 different types of autoimmune diseases have been identified. 25 Given that autoimmune diseases are more prevalent in women 26 and often occur before or during their reproductive years, it is crucial to evaluate their impact on pregnancy. 8 The incidence of autoimmune diseases is rising globally. 27 As a result, the number of pregnant women suffering from autoimmune diseases is increasing. Research on autoimmune diseases during pregnancy and their impacts is crucial, offering knowledge that benefits both mothers and their babies.
Numerous systematic reviews have been conducted on the association between autoimmune diseases and APOs. 21 28 29 Some studies suggest that autoimmune diseases such as lupus and IBD may be associated with APOs. However, additional research is needed to clarify the relationship between multiple sclerosis and its effect on pregnancy. 1920 30 32 It is also important to note that some findings regarding the association between autoimmune diseases and APOs are inconsistent. 33 34
Research on pregnancy outcomes in patients with vitiligo is limited. Moreover, there is controversy regarding the association between vitiligo and APOs. 15 16 35 This requires conducting studies on this issue. To clearly outline the scope and range of existing literature, it is essential to conduct secondary studies, such as a scoping review. This type of review helps identify the concepts explored in various studies, examine their methodologies and highlight knowledge gaps and limitations. To date, no scoping review has been conducted on APOs in patients with vitiligo. 25 We aim to conduct a scoping review to map related evidence. This study offers valuable information and data for other secondary studies, such as systematic reviews, as well as for clinical purposes and applications.
Our main objectives are as follows:
To identify the extent and range, nature of related studies.
To summarise research findings, including APOs in patients with vitiligo and associated factors.
To find out research gaps in the existing studies.
To suggest future research directions that address these knowledge gaps.
To determine the value of undertaking a comprehensive systematic review.
Method
A scoping review is a type of secondary study that is particularly effective for identifying research priorities and formulating future investigations. 36 It provides a comprehensive overview of the key concepts within a particular research area. By conducting a scoping review, we can map existing evidence, identify gaps in the literature and review research studies based on their geographic locations and sources. 36 39 This study will be conducted using the framework developed by Hilary Arksey and Lisa O’Malley (2005), 37 which consists of the following five stages:
Identifying the research question.
Identifying relevant studies.
Study selection.
Charting the data.
Collating, summarising and reporting the results.
Stage 1: identification of the research question
This stage focuses on formulating research questions to guide the review. The primary objective of our study is to define the extent of relevant literature published in the Scopus and PubMed databases from 1 January 2000 to 1 January 2025. We aim to answer the following research questions:
What is the extent and range of research related to APOs in patients with vitiligo?
What are the levels of evidence presented in the published articles?
What types of pregnancy outcomes and associated factors have been evaluated in the studies?
What knowledge gaps exist in the topic area?
What future research is needed to address these knowledge gaps?
Stage 2: identifying relevant studies
In the second stage of the review, relevant studies will be identified by defining the eligibility criteria and employing search strategies. We will focus on published studies available in English from 1 January 2000 to 1 January 2025. The participants will be pregnant women with vitiligo. The parameters of interest will be the adverse outcomes of pregnancy in these patients. All original studies, regardless of study design, and reviews evaluating pregnancy outcomes in vitiligo will be included, while the grey literature will be excluded.
A list of maternal and fetal complications aimed to be investigated is presented in box 1 .
Adverse pregnancy outcomes
Maternal outcomes
Pre-eclampsia/eclampsia
Fetal loss
Abortion, miscarriage
Gestational diabetes
Gestational hypertension
Hyperemesis gravidarum
Obstetric haemorrhage
Placenta previa
Placenta accreta
Oligohydramnios
Maternal death
Amniotic embolism
Ectopic pregnancies
Fetal/neonatal outcomes
Preterm birth
Infants who were small for gestational age
Infants with low birth weight
Neonatal Intensive Care Unit (NICU) admission
Intrauterine growth restriction
Stillbirth
Neonatal death
Vasa previa
Fetal membranes, premature rupture
Perinatal death
Pre-term delivery
Placenta previa
The search keywords will include “vitiligo AND pregnancy outcomes”. After the initial search, all MeSH terms, key concepts and their synonyms will be combined to create search strings. These strings will be applied across the selected databases. An example of the search strategy for the PubMed database is presented: (“Pregnancy outcome” OR “high-risk Pregnancy” OR “Obstetric Labor” OR “Morbidly Adherent Placenta” OR “labor complications” OR “maternal outcomes” OR abortion OR Oligohydramnios OR “Postpartum hemorrhage” OR “Premature Rupture” OR “Preterm delivery” OR Hypertension OR “Placental abruption” OR “Maternal Death” OR “neonatal death” OR “preterm birth” OR Preeclampsia OR “perinatal outcomes”) AND vitiligo. A detailed search strategy used in the PubMed database is illustrated in the online supplemental table .
Stage 3: selecting the studies
At this stage, studies will be screened and selected. All published literature identified from the search will be imported into EndNote software, where duplicates will be removed. Two independent reviewers will screen the titles and abstracts of the manuscripts to select the relevant articles. The full texts will be assessed to confirm their relevance. Any disagreement will be resolved through discussion and consensus. Additionally, we will present the search results using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. 40
Stage 4: charting the data
In this stage, data charting will be conducted, involving the extraction of the key concepts and data from the selected articles. Two reviewers will independently chart data from all included manuscripts. Any uncertainties or inconsistencies will be resolved by consensus. A data extraction form will be used to collect the required information, including author(s), year of publication, level of evidence, study aims and purpose, study population, sample size, the methodological features, outcomes and key findings, type of interventions, comorbidities and other relevant parameters.
Stage 5: collating, summarising and presenting the results
In stage 5, collating and summarising data will be done. The objective of this study is to explore a broad range of research on the effects of vitiligo on pregnancy outcomes. We will analyse both the abstracts and full texts of the included articles to gather the necessary information and determine the extent and range of the studies. A narrative synthesis method will be employed to summarise and report the findings. The data will be presented using different strategies, including tables and graphs. This information will be used to discover the research gaps in the field. Additionally, we will compare our findings with the latest related guidelines or the results of published systematic reviews and meta-analyses.
Consultation
In line with the recommendations of Levac et al , this stage will focus on facilitating the knowledge transfer of preliminary data and identifying effective dissemination strategies. We will conduct consultations with relevant health professionals, including midwives, paediatric nurses, obstetricians, paediatricians and dermatologists. During these consultations, we will present our proposal and preliminary findings. We will seek their feedback and comments to enhance the quality and practical value of the study. The feedback we receive will be used to improve the data collection section, thereby increasing the practical and clinical utility of the study.
Patient and public involvement
There is no patient involvement.
Ethics and dissemination
Since the objective of a scoping review is to synthesise information from publicly available literature, this study will not require approval from the research ethics board. The results of this review will be discussed with a clinical consultant before dissemination through peer-reviewed publications and presentations at relevant conferences.
This study was approved by the Ethics Committees of Khoy University of Medical Sciences (approval No: IR.Khoy.Rec.1403. 032).
Supplementary material
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ( https://doi.org/10.1136/bmjopen-2024-098022 ).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
References
1 Bergqvist C Ezzedine K Vitiligo: A Review Dermatology (Basel) 2020 236 571 92 10.1159/000506103 32155629
2 Nicolaidou E Antoniou C Miniati A et al Childhood- and later-onset vitiligo have diverse epidemiologic and clinical characteristics J Am Acad Dermatol 2012 66 954 8 10.1016/j.jaad.2011.07.010 21982634
3 Silverberg NB The Epidemiology of Vitiligo Curr Derm Rep 2015 4 36 43 10.1007/s13671-014-0098-6
4 Picardo M Taïeb A Vitiligo Springer 2019
5 Ezzedine K Lim HW Suzuki T et al Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference Pigment Cell Melanoma Res 2012 25 E1 13 10.1111/j.1755-148X.2012.00997.x PMC3511780 22417114
6 Spritz RA Andersen GHL Genetics of Vitiligo Dermatol Clin 2017 35 245 55 10.1016/j.det.2016.11.013 28317533 PMC5362127
7 Ezzedine K Grimes PE Meurant J ‐M. et al Living with vitiligo: results from a national survey indicate differences between skin phototypes Br J Dermatol 2015 173 607 9 10.1111/bjd.13839 25892476
8 Abdelhafez MMA Ahmed KAM Ping Pang NT et al Vitiligo and pregnancy: How do each affect the other? Ann Med Surg (Lond) 2021 70 102833 10.1016/j.amsu.2021.102833 34540219 PMC8437779
9 Gill L Zarbo A Isedeh P et al Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study J Am Acad Dermatol 2016 74 295 302 10.1016/j.jaad.2015.08.063 26518171
10 Choi CW Eun SH Choi KH et al Increased risk of comorbid rheumatic disorders in vitiligo patients: A nationwide population‐based study J Dermatol 2017 44 909 13 10.1111/1346-8138.13846 28370282
11 Weber‐Schoendorfer C Chambers C Wacker E et al Pregnancy Outcome After Methotrexate Treatment for Rheumatic Disease Prior to or During Early Pregnancy: A Prospective Multicenter Cohort Study Arthritis Rheumatol 2014 66 1101 10 10.1002/art.38368 24470106
12 Dai F-F Hu M Zhang Z et al TNF-α/anti-TNF-α drugs and its effect on pregnancy outcomes Expert Rev Mol Med 2022 24 e26 10.1017/erm.2022.18 35687009 PMC9884758
13 Perez-Bootello J Cova-Martin R Naharro-Rodriguez J et al Vitiligo: Pathogenesis and New and Emerging Treatments IJMS 2023 24 17306 10.3390/ijms242417306 38139134 PMC10743634
14 Zhen Y Yao L Zhong S et al Enhanced Th1 and Th17 responses in peripheral blood in active non-segmental vitiligo Arch Dermatol Res 2016 308 703 10 10.1007/s00403-016-1690-3 27687555
15 Hung C-T Huang H-H Wang C-K et al Pregnancy outcomes in women with vitiligo: A Taiwanese nationwide cohort study PLoS ONE 2021 16 e0248651 10.1371/journal.pone.0248651 33750961 PMC7984608
16 Park KY Kwon HJ Wie JH et al Pregnancy outcomes in patients with vitiligo: A nationwide population-based cohort study from Korea J Am Acad Dermatol 2018 79 836 42 10.1016/j.jaad.2018.02.036 29477741
17 Crump C Sundquist J Sundquist K Adverse Pregnancy Outcomes and Long-Term Mortality in Women JAMA Intern Med 2024 184 631 10.1001/jamainternmed.2024.0276 38619848 PMC11019441
18 Kramer MS The Epidemiology of Adverse Pregnancy Outcomes: An Overview J Nutr 2003 133 1592S 1596S 10.1093/jn/133.5.1592S 12730473
19 He WR Wei H Maternal and fetal complications associated with systemic lupus erythematosus: an updated meta-analysis of the most recent studies (2017–2019) Medicine (Baltimore) 2020 99 e19797 10.1097/MD.0000000000019797 32311994 PMC7440247
20 O’Toole A Nwanne O Tomlinson T Inflammatory Bowel Disease Increases Risk of Adverse Pregnancy Outcomes: A Meta-Analysis Dig Dis Sci 2015 60 2750 61 10.1007/s10620-015-3677-x 26070523
21 Blagojevic J AlOdhaibi KA Aly AM et al Pregnancy in Systemic Sclerosis: Results of a Systematic Review and Metaanalysis J Rheumatol 2020 47 881 7 10.3899/jrheum.181460 31474594
22 Essouma M Nkeck JR Motolouze K et al Outcomes of pregnancy and associated factors in sub-Saharan African women with systemic lupus erythematosus: a scoping review Lupus Sci Med 2020 7 e000400 10.1136/lupus-2020-000400 32540928 PMC7295444
23 Sangah AB Jabeen S Hunde MZ et al Maternal and fetal outcomes of SLE in pregnancy: a literature review J Obstet Gynaecol 2023 43 2205513 10.1080/01443615.2023.2205513 37154805
24 Ben-David G Sheiner E Hallak M et al Pregnancy outcome in women with psoriasis J Reprod Med 2008 53 183 7 18441722
25 Singh M Wambua S Lee SI et al Autoimmune diseases and adverse pregnancy outcomes: an umbrella review The Lancet 2023 402 S84 10.1016/S0140-6736(23)02128-1 37997130
26 Angum F Khan T Kaler J et al The Prevalence of Autoimmune Disorders in Women: A Narrative Review Cureus 2020 12 10.7759/cureus.8094 PMC7292717 32542149
27 Lerner A Jeremias P Matthias T The world incidence and prevalence of autoimmune diseases is increasing Int J Celiac Dis 2015 3 151 5
28 Dong Y Yuan F Dai Z et al Preeclampsia in systemic lupus erythematosus pregnancy: a systematic review and meta-analysis Clin Rheumatol 2020 39 319 25 10.1007/s10067-019-04823-8 31754886
29 Huang W Wu T Jin T et al Maternal and fetal outcomes in pregnant women with rheumatoid arthritis: a systematic review and meta-analysis Clin Rheumatol 2023 42 855 70 10.1007/s10067-022-06436-0 36357630
30 Tandon P Govardhanam V Leung K et al Systematic review with meta‐analysis: risk of adverse pregnancy‐related outcomes in inflammatory bowel disease Aliment Pharmacol Ther 2020 51 320 33 10.1111/apt.15587 31912546
31 Wei S Lai K Yang Z et al Systemic lupus erythematosus and risk of preterm birth: a systematic review and meta-analysis of observational studies Lupus (Los Angel) 2017 26 563 71 10.1177/0961203316686704 28121241
32 Arafa A Wang X Dong J-Y et al Does multiple sclerosis increase the risk of preeclampsia? A systematic review and meta-analysis Hypertens Pregnancy 2021 40 180 5 10.1080/10641955.2021.1921792 33999737
33 Banner H Niles KM Ryu M et al Myasthenia gravis in pregnancy: Systematic review and case series Obstet Med 2022 15 108 17 10.1177/1753495X211041899 35845224 PMC9277733
34 Maguire S O’Dwyer T Mockler D et al Pregnancy in axial spondyloarthropathy: A systematic review & meta-analysis Semin Arthritis Rheum 2020 50 1269 79 10.1016/j.semarthrit.2020.08.011 33065422
35 Horev A Weintraub AY Sergienko R et al Pregnancy outcome in women with vitiligo Int J Dermatology 2011 50 1083 5 10.1111/j.1365-4632.2010.04839.x 22126869
36 Anderson S Allen P Peckham S et al Asking the right questions: Scoping studies in the commissioning of research on the organisation and delivery of health services Health Res Policy Sys 2008 6 1 12 10.1186/1478-4505-6-7 PMC2500008 18613961
37 Arksey H O’Malley L Scoping studies: towards a methodological framework Int J Soc Res Methodol 2005 8 19 32 10.1080/1364557032000119616
38 Peters MD Godfrey CM Khalil H et al Guidance for conducting systematic scoping reviews JBI Evidence Implementation 2015 13 141 6 10.1097/XEB.0000000000000050 26134548
39 Mays N Roberts E Popay J Synthesising research evidence Studying the organisation and delivery of health services Routledge 2004 200 32
40 Moher D Liberati A Tetzlaff J et al Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement Int J Surg 2010 8 336 41 10.1016/j.ijsu.2010.02.007 20171303