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Health outcomes in international migrant children: Protocol for a systematic review

Journal: BMJ Open ManuscriptFor ID peerbmjopen-2020-041173 review only Article Type: Protocol

Date Submitted by the 01-Jun-2020 Author:

Complete List of Authors: Armitage, Alice; UCL, Institute of Child Health Heys, Michelle; University College London Institute of Child Health, University College London Institute of Child Health Lut, Irina; UCL, Institute of child health Hardelid, Pia; UCL Institute of Child Health, Centre for Paediatric Epidemiology and Biostatistics

PAEDIATRICS, Health policy < HEALTH SERVICES ADMINISTRATION & Keywords: MANAGEMENT, PUBLIC HEALTH

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4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 7 8 9 I, the Submitting Author has the right to grant and does grant on behalf of all authors of the Work (as defined 10 in the below author licence), an exclusive licence and/or a non-exclusive licence for contributions from authors 11 who are: i) UK Crown employees; ii) where BMJ has agreed a CC-BY licence shall apply, and/or iii) in accordance 12 with the terms applicable for US Federal Government officers or employees acting as part of their official 13 duties; on a worldwide, perpetual, irrevocable, royalty-free basis to BMJ Publishing Group Ltd (“BMJ”) its 14 licensees and where the relevant Journal is co-owned by BMJ to the co-owners of the Journal, to publish the 15 Work in this journal and any other BMJ products and to exploit all rights, as set out in our licence. 16 17 The Submitting Author accepts and understands that any supply made under these terms is made by BMJ to 18 the Submitting Author Forunless you peer are acting as review an employee on behalf only of your employer or a postgraduate 19 student of an affiliated institution which is paying any applicable article publishing charge (“APC”) for Open 20 Access articles. Where the Submitting Author wishes to make the Work available on an Open Access basis (and 21 intends to pay the relevant APC), the terms of reuse of such Open Access shall be governed by a Creative 22 Commons licence – details of these licences and which Creative Commons licence will apply to this Work are set 23 out in our licence referred to above. 24 25 Other than as permitted in any relevant BMJ Author’s Self Archiving Policies, I confirm this Work has not been 26 accepted for publication elsewhere, is not being considered for publication elsewhere and does not duplicate 27 material already published. I confirm all authors consent to publication of this Work and authorise the granting 28 of this licence. 29 30 31 32 33 34 35

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44 on September 27, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 | P a g e 1 2 3 DR ALICE ARMITAGE (Orcid ID: 0000-0001-6972-3651)

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 7 Article type: Protocol for systematic review 8 9 10 11 12 13 Health outcomes in international migrant children: 14 Protocol for a systematic review 15 16 17 18 For peer review only 19 20 21 22 Authors: Alice Armitage1, Michelle Heys1, Irina Lut1, Pia Hardelid1 23 24 25 26 Email addresses: [email protected], [email protected], [email protected], 27 [email protected] 28 29 30 1 31 Guarantor: Pia Hardelid 32 33 34 1. Population, Policy & Practice Dept, UCL GOS Institute of Child Health, Faculty of Pop 35 Health Sciences, UCL 36 http://bmjopen.bmj.com/ 37 38 39 Correspondence to: 40 41 Dr Alice Armitage 42 UCL Great Ormond Street Institute of Child Health 43 30 Guilford St, Holborn, London WC1N 1EH

44 Tel: 020 7242 9789 on September 27, 2021 by guest. Protected copyright. 45 [email protected] 46 47 rythemaassociated multiforme with COVID-19 and Kawasaki infection disease in children 48 Keywords: Transients and migrants, Global health, Pediatrics, Population Health, Systematic 49 Review 50 51 52 53 Tables: 1 54 Figures: 0 55 56 Appendices: 1 57 58 59 Word count: 2680 60

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4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 Abstract 7 Introduction 8 Migration status is a key determinant of health, but health outcomes among migrant children 9 and young people (CYP), i.e. those aged under 18 years, are poorly understood. A ‘healthy- 10 11 migrant’ effect has been demonstrated among adults, but evidence for the presence of the 12 same effect in CYP is lacking. No large studies or reviews exist reporting comprehensive or 13 holistic outcomes among migrant CYP. We aim identify and synthesise original quantitative 14 research on health of migrant CYP to explore the relations between migration status and 15 16 health outcomes. 17 18 Methods and analysisFor peer review only 19 A search of Pubmed/Medline, Embase and Cochrane and grey literatures sites will be 20 undertaken for any original quantitative research on health outcomes of migrant CYP 21 22 published from 01/01/2000 onwards. Outcomes will be categorised as: mortality, 23 communicable diseases, non-communicable diseases, nutritional status, mental health, 24 disability, vaccine coverage, and accidental and non-accidental injuries (including assault and 25 abuse). Search results will be screened against inclusion criteria and presented in a PRISMA 26 27 flow diagram. 28 29 The Newcastle-Ottawa Scale (NOS) assessment tool will be used to assess study quality. If 30 feasible, depending on study availability data heterogeneity (explored using I2 statistic), 31 32 results will be pooled for meta-analysis. If sufficient data are available, a priori defined sub- 33 group analyses will be undertaken. A narrative quantitative synthesis will be presented, 34 taking account of study quality and assessed risk of bias. 35

36 http://bmjopen.bmj.com/ 37 Ethics and dissemination 38 Formal ethical approval will not be sought as we will be accessing data already in the public 39 domain. This review will be submitted for publication in a high impact journal and presented 40 at international conferences. The results of this work will be shared with the groups of 41 migrant children as part of an ongoing engagement project. 42 43 This protocol has been submitted to the International Prospective Register for Systematic

44 on September 27, 2021 by guest. Protected copyright. 45 Reviews (PROSPERO), registration number is awaited. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 Strengths and limitations of this study 7 8 This protocol is written in line with PRISMA-P reporting guidelines for systematic review 9 protocols1. 10 11 This systematic review will address a clear research gap on health outcomes of migrant 12 children and young people (CYP). 13 14 Well-established systematic review methodology will allow evidence-based 15 16 recommendations for policy around migrant children based on available data and identify key 17 gaps in the research evidence. 18 For peer review only 19 Review conclusions are likely to be limited by the quality and quantity of available studies. 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

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44 on September 27, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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4 | P a g e 1 2 3 Introduction

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 Migration status is known to be a key determinant of health2. There is no international 6 consensus on the definition of migrant; here we use the term to describe international 7 8 migrants, as suggested by the United Nations definition: ‘someone who changes his or her 9 country of usual residence, irrespective of the reason for migration or legal status’3. This 10 includes refugees and asylum seekers, as well as economic migrants and international 11 students3. Adult migrants may be young and healthy, and a ‘healthy-migrant’ effect, whereby 12 13 migrants have better health status than the population of the host country, has been 4 14 demonstrated . 15 16 Migrant populations may experience poverty, social inequality or persecution at their 17 destination, which could compound physical and mental health burdens associated with 18 country of origin, reasonsFor for peer displacement review and circumstances only of their journey. Children and 19 young people (CYP: those under the age of 18) are further impacted by the health of their 20 21 caregivers, and by their inherent physical and social vulnerabilities, particularly to 22 malnutrition, communicable diseases, disrupted education, violence and exploitation 5-8. 23 Unlike adults migrating for work or education, who are likely to be healthy, CYP are 24 significantly less likely to be the drivers of their own migration. It is not yet known whether 25 26 these factors outweigh the ‘healthy-migrant’ effect observed in adult migrants. 27 28 Many high income countries place restrictions on migrant CYP’s entitlement to health 9 29 services , and unmet health needs in CYP are known to be associated with poor adult 30 health10. However, health needs, and associated health outcomes, among migrant CYP are 31 poorly understood11 and infrequently reported in the literature, preventing a population-based 32 approach to planning health services. This is in part due to poor quality and quantity of data 33 34 on this topic. Routinely collected healthcare data sets rarely include migration status. Most 35 studies on the health of migrants only have children as a subgroup. There is a lack of data on

36 migrant health spanning larger geographical regions and crossing borders, barriers to data http://bmjopen.bmj.com/ 37 linkage, and an associated lack of large scale studies or reviews12. The lack of healthcare 38 12 39 data on migrant CYP has been identified as an unmet research need , as well as a rights of 40 the child issue13. 41 42 A recent systematic review on mortality of international migrants provided evidence that, on 43 average, international migrants have lower mortality than the host population4. However, 44 on September 27, 2021 by guest. Protected copyright. 45 mortality from specific causes, such as violence and infectious diseases, was higher among 46 migrants4. This systematic review also highlighted a lack of data on the health of vulnerable 47 migrant groups such as asylum seekers, refugees and undocumented migrants4, and authors 48 49 cautioned against generalising results to these groups. 50 51 Other comprehensive systematic review evidence addresses perinatal outcomes among 52 migrants, indicating increased maternal mortality, preterm birth and congenital abnormalities, 53 as well as barriers to access and use of healthcare14. Systematic review evidence from 2018 54 demonstrates that migrant children use healthcare services less than non-migrant populations, 55 with the exception of emergency services, although their rate of hospital admission is 56 15 57 higher . There have been no comprehensive systematic reviews on a range of migrant child 58 health outcomes across the life course either internationally or in the UK. Following a 59 PROSPERO search, no similar review is planned at present. 60

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4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 The proposed systematic review will therefore address a clear evidence gap. 6 7 8 Aims and objectives of systematic review 9 The aim of the systematic review will be to summarise the available evidence base regarding 10 11 a range of key health outcomes of migrant CYP across the life course. 12 13 Our specific objectives are to: 14 15 16 1) Identify global original quantitative research on health outcomes for migrant CYP, and to 17 compare this to CYP in the host population where data are available. Where there is no 18 control group or theFor control grouppeer are another review migrant group, only the studies will be included in 19 the quantitative narrative synthesis. 20 21 2) Undertake meta-analyses of specific health outcomes if the data allow, e.g. mortality, 22 vaccination coverage (see eight domains listed below). Similarly, if sufficient data are 23 24 available, subgroup analyses, decided a priori, will include break-down of health outcomes 25 by: 26 27  Age group (1-4, 5-9, 10-17), 28  Reason for migration (refugee, asylum seeker, child of economic migrants, student) 29  Migrant destination (World Bank income group16) 30 31  Study quality as assess by NOS scale tool17 (see below). 32 33 Table 1. Research question in PICOS format 34 35 i. Population, or Children and young people (CYP), defined as those under the age of

36 participants and 18 http://bmjopen.bmj.com/ 37 conditions of 38 interest 39 40 ii. Interventions Migration status; any migrant CYP, i.e. living in a different country 41 42 or exposures from that of their birth. 43

44 iii. Comparisons CYP who have not migrated, described as ‘the host population’ on September 27, 2021 by guest. Protected copyright. 45 or control groups 46 47 iv. Outcomes of 1. Mortality (age group: 1-4, 5-9, 10-17), infants are excluded 48 49 interest unless clearly stated that they have migrated after birth, in which 50 case they will be included in 1-4 age group. 51 2. Communicable diseases (incidence/prevalence) 52 3. Non-communicable diseases 53 4. Over and under nutrition 54 5. Mental health outcomes 55 6. Disability 56 57 7. Vaccine coverage 58 8. Accidental and non-accidental injuries (e.g. assault and abuse) 59 60 v. Setting Studies in any setting and from any country will be included

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4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 vi. Study designs All studies presenting original data, including observational (cohort, 6 case-control and cross-sectional studies), systematic reviews, and 7 randomised controlled trials reporting quantitative data on health 8 outcomes in international migrant CYP. 9 10 11 12 Methods and analysis 13 14 This protocol is written with reference to the PRISMA-P reporting guidelines for systematic 15 review protocols1. 16 17 Eligibility 18 For peer review only 19 This systematic review will include published studies presenting original data on health 20 outcomes of migrant children and young people (CYP), i.e. those living in a different country 21 from that of their birth, including observational studies (cohort and case-control studies, and 22 cross-sectional surveys), systematic review and randomised controlled trials. Studies in any 23 24 setting and from any country will be included. 25 Only studies pertaining to first generation migrant children will be included, i.e. we would 26 27 not include studies on children born to parents who were originally migrants. In view of this, 28 and in view of existing systematic review evidence, studies will be excluded that pertain 29 exclusively to maternal and/or perinatal outcomes as these will not address the outcomes for 30 CYP who have themselves migrated. The perinatal period in this systematic review is 31 32 defined as birth up until the child’s first birthday unless is it explicitly stated that the child 33 migrated during this period. If studies specifically pertain to infants under 1 year who have 34 migrated then this data will be included and analysed within the 1-4 age group. We will 35 exclude studies that only include patients from intensive care or high dependency settings,

36 http://bmjopen.bmj.com/ 37 where health outcomes do not fall within defined areas (see below). In view of existing 38 systematic review evidence and the defined outcomes areas, we will not include studies 39 exclusively reporting hospital attendance or admission rates without other health outcomes 40 presented. We will also exclude research letters, studies where the abstract or full text is not 41 42 available, and studies where it is not possible to obtain an English translation. Restricting 43 systematic reviews to English language publications is routine practice and has been shown 18 44 not to significantly affect results regarding empirical studies . on September 27, 2021 by guest. Protected copyright. 45 46 Outcomes of interest 47 48 Following identification of studies, the outcomes will be grouped into the following eight 49 areas, chosen to represent key health outcomes across the life course. Outcomes are chosen 50 with reference to the Global Burden of Disease Study 201719 and to reflect the ‘survive and 51 thrive’, strategy of the sustainable development goals20. More emphasis has been placed on 52 health outcomes where quantitative data may be available, where definitions are recognised 53 internationally and where the outcomes are plausibly affected my migration status. For each 54 55 outcome a finite list of more common conditions has been chosen. 56 1. Mortality (By age group 1-4, 5-9, 10-17 years) 57 58 If data are available following identification of studies, mortality will be broken down by 59 60 age-group and compared to the host population. In view of perinatal studies being excluded

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7 | P a g e 1 2 3 and focus being on children who have themselves migrated we are excluded infant mortality

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 under the age of one year. 6 2. Communicable diseases (incidence/prevalence) 7 8 Systematic review evidence suggests that despite the healthy migrant effect rates of infectious 9 4 10 diseases are higher among migrant populations . The search strategy will focus on HIV, 11 Hepatitis B, Tuberculosis (active and latent), Sexually transmitted diseases (Chlamydia and 12 Gonorrhoea), Schistosomiasis and parasitic infections4. 13 14 3. Non-communicable diseases (NCDs) 15 16 With reference to the global data, the search strategy will focus on neoplasms, asthma and 17 other chronic respiratory conditions, epilepsy and Type 1 diabetes mellitus (T1DM). With 18 chronic conditions characterisedFor peer by occasional review exacerbations, only such as asthma, the focus will 19 20 be on exacerbations of asthma as opposed to baseline prevalence. 21 22 4. Over and under nutrition 23 Forced migration of children may be associated with periods of food insecurity both before 24 21 25 and during migration, with associated morbidity . Following migration to middle and high 26 income countries migrant children are at risk of becoming overweight or obese22. We are 27 therefore seeking to identify studies addressing both under and over nutrition in migrant 28 children. The search strategy will focus on terms around malnutrition, under-nutrition, 29 30 underweight, low BMI, high BMI, overweight and obesity. Micronutrient deficiencies, such 31 as vitamin deficiencies, requiring blood tests to identify, are considered outside the scope of 32 this review. 33 34 5. Mental health outcomes 35

36 Poor mental health is increasingly recognised as an unmet health need in childhood and http://bmjopen.bmj.com/ 37 adolescence and being identified as prevalent among migrant populations11 23. The search 38 strategy will focus on Post-traumatic stress disorder (PTSD), psychosis, depression, self-harm 39 40 and suicide. 41 42 6. Disability 43 Disability may be higher in migrant children from countries with poor health infrastructure 44 on September 27, 2021 by guest. Protected copyright. 21 24 45 and has been identified as a significant unmet health need among migrant children . The 46 search strategy will focus on hearing impairment, deafness, visual impairment, blindness, 47 cerebral palsy, autism, learning difficulties and/or developmental delay. 48 49 7. Vaccine coverage and uptake 50 51 Lack of access to preventative health care and disruption to healthcare access in migrant CYP 52 affects vaccination coverage. Following migration catch-up immunisation programmes 53 depend upon timely and coordinated healthcare in-put. The search strategy will focus on 54 55 immunisation, vaccination and specific vaccine-preventable pathogen targets (polio, 56 diphtheria, pertussis, measles, mumps, rubella, hepatitis B) combined with vaccine-specific 57 terms. 58 59 8. Accidental and non-accidental injuries (e.g. assault and abuse) 60

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8 | P a g e 1 2 3 Road traffic accidents and inter-personal violence are examples of accidental injuries that

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 may be associated with migration. It is know that migrant CYP are at increased risk of 6 assault and abuse both historically (in their country of origin and during transit) and 7 following migration21 25. Rates of sexual assault and abuse are also high, particularly among 8 forced migrants, and will be included in this category. The search strategy will focus on road 9 10 traffic accidents or injuries, interpersonal or domestic violence, physical or sexual assault or 11 abuse, sexual violence and rape. 12 13 Search Strategy 14 15 The electronic databases Pubmed/Medline, Embase and Cochrane will be searched with date 16 range from 01/01/2000 onwards. A grey literature search will also be undertaken including 17 the following websites: Organisation for Economic Co-operation and Development (OECD), 18 WHO Global HealthFor Observatory peer (GHO), review Health evidence only network, Health for 19 20 Undocumented Migrants and Asylum seekers (HUMA) Network and the International 21 Organization of Migration (IOM). We will also undertake reference checking for selected 22 manuscripts and search conference proceedings from international conferences relevant to 23 migrant child health. 24 25 The search strategy will use key words and index terms around migrant status, children and 26 young people (CYP) and the eight areas of health outcomes as described above. A draft 27 28 search strategy for Ovid Medline for Mortality is attached (Appendix 1). The finalised search 29 strategy for all outcomes will be published online and any amendments identified 30 (PROSPERO register). 31 32 Selection process 33 34 Search results will be exported to EPPI-4 software for screening and selection. Two 35 independent reviewers (AA and IL) will screen all titles and abstracts. Full manuscripts will 36 be screened when it is not clear from the title or abstract whether the study meet the inclusion http://bmjopen.bmj.com/ 37 38 criteria. Where there is disagreement between the two reviewers the study will be escalated 39 to a third reviewer (MH or PH) to resolve. Following the screening of full-text, articles will 40 be assessed for eligibility; a PRISMA flow diagram will be produced and the PRISMA 41 checklist followed26. 42 43 Data synthesis and analysis

44 on September 27, 2021 by guest. Protected copyright. 45 Data will be extracted and entered into a Microsoft Excel spreadsheet by a single reviewer 46 (AA or IL). We will extract the following data items: demographic features (age, sex and 47 48 country/countries of origin of CYP), study design, country/countries of arrival (study setting), 49 study period, study population, presence of control or comparator group, outcomes presented 50 (using pre-defined categories as listed above), outcome measures (rate ratio, hazard ratio or 51 odds ratio), follow-up period and funding source. 52 53 The Newcastle-Ottawa Scale(NOS)17 assessment tool will be used to assess the quality of 54 studies. The NOS scale assigned a ‘star system’ judging across three domains: the selection 55 56 of the study groups, the comparability of the groups; and the ascertainment of either the 57 exposure or outcome of interest for case-control or cohort studies respectively. The NOS 58 score for each study will be presented. A sensitivity analysis will be undertaken by rerunning 59 the meta-analyses excluding any low quality outliers on the NOS scale. 60

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9 | P a g e 1 2 3 The decision to include meta-analyse study results will depend on the availability of studies

4 2 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 pertaining to the various outcomes and heterogeneity of the data presented. The I statistic 6 will be used to explore heterogeneity of studies. A small number of studies (less than three) 7 or I2 of >75% will be adopted as the threshold for decision not to undertake meta-analysis27. 8 9 Studies presenting original data on one or more of the eight defined health outcomes will be 10 considered for inclusion in meta-analyses. Summary parameters for most outcomes are likely 11 to be rate ratio, hazard ratio or odds ratio. If appropriate, other measures such as prevalence 12 13 or vaccine uptake rates, will be will be used. Study results will be pooled for meta-analysis 14 using STATA version 14 using a random effects model (Der-Simonian and Laird method)28 15 and presented in forest plots. The likelihood of publication bias will be explored using funnel 16 plots if enough studies are identified. We acknowledge that if a small number of studies is 17 18 identified it may notFor be possible peer to assess review publication bias. only 19 20 If sufficient data are available, the following sub-group analyses will be undertaken: break- 21 down of health outcomes by age group (1-4, 5-9, 10-17 years), by migrant subgroup (refugee, 22 asylum seeker, child of economic migrants, student), by migrant destination (World Bank 23 income group16) and by study quality as assessed by the NOS scale tool17. 24 25 A quantitative narrative synthesis will be undertaken of studies that are not included in the 26 meta-analysis, guided by the Systematic review Without Metaanalysis (SwIM) guidelines29. 27 We will clearly set out why studies are not included in a meta-analysis; the diversity of 28 29 studies will be addressed (including populations, methodology and outcomes) and the 30 completeness of outcome data. Studies will be grouped for synthesis according to the 8 pre- 31 defined outcomes (Table 1). Any quantitative effect sizes presented (that have not been 32 amenable to meta-analysis) will be presented in tables. Statistics will not be combined for 33 presentation outside of the meta-analysis. Where the heterogeneity cannot be explored using 34 the I² tool, heterogeneity will be informally explored by ordering studies according to 35 characteristics including outcomes and population. Studies will be prioritised based on 36 http://bmjopen.bmj.com/ 37 assessed risk of bias, sample and effect size and relevance to the research question. For each 38 outcome a description of synthesised findings will be made including certainty of results 39 (with reference to p- values and confidence intervals where available), conclusions will take 40 account of quality of included studies and the assessed risk of bias. 41 42 Bias due to confounding must be considered when considering migration as a risk factor for 43 health outcomes: migration is inevitably correlated with race/ethnicity, poverty and 44 on September 27, 2021 by guest. Protected copyright. 45 educational level. Bias due to missing data, selection bias and reporting bias will also be 46 considered. 47 48 Ethics and dissemination 49 50 Formal ethical approval will not be sought in line with systematic review guidelines as we 51 will only be accessing data already in the public domain. This review will make up part of an 52 MD(Res) thesis. We will submit results for publication in a high impact peer reviewed 53 journal. Results will be presented at international conferences in the areas of migrant health 54 and paediatrics. The results of this review will be relevant for UK and international 55 56 stakeholders in the area of migrant child health. Funding has been secured for a separate 57 piece of work with unaccompanied asylum seeking children in the UK, a particularly 58 vulnerable group of migrant children. The results of this work will be shared with this group 59 as part of an ongoing engagement project. 60

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10 | P a g e 1 2 3 This protocol has been submitted to the International Prospective Register for Systematic 4 Reviews (PROSPERO) and revised based on their recommendations, registration number is BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 awaited. 7 Author’s contributions 8 9 The protocol was conceived by all authors, written by AA and reviewed by PH, MH and IL 10 prior to submission. PH is the guarantor of the review. 11 12 Funding sources/sponsors 13 14 This systematic review is being undertaken by a team at University College London, no 15 additional funding is available for this. MH is funded by East London NHS Foundation 16 Trust, London, UK. Research at the UCL Great Ormond Street Institute of Child Health is 17 supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. 18 For peer review only 19 We declare no known conflicts of interests. 20 21 References 22 23 1. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and 24 meta-analysis protocols (PRISMA-P) 2015 statement. Systematic reviews 25 2015;4(1):1. 26 2. Abubakar I, Aldridge RW, Devakumar D, et al. The UCL–Lancet Commission on 27 Migration and Health: the health of a world on the move. The Lancet 28 2018;392(10164):2606-54. 29 30 3. Perruchoud R. Persons falling under the Mandate of the International Organization for 31 Migration (IOM) and to Whom the Organization may Provide Migration Services. 32 International Journal of Refugee Law 1992;4(2):205-15. 33 4. Aldridge RW, Nellums LB, Bartlett S, et al. Global patterns of mortality in international 34 migrants: a systematic review and meta-analysis. The Lancet 2018;392(10164):2553- 35 66. 36 5. Manhica H, Almquist Y, Rostila M, et al. The use of psychiatric services by young adults http://bmjopen.bmj.com/ 37 38 who came to Sweden as teenage refugees: a national cohort study. Epidemiology and 39 psychiatric sciences 2017;26(5):526-34. 40 6. Buchanan A, Kallinikaki T. Meeting the needs of unaccompanied children in Greece. 41 International Social Work 2018:0020872818798007. 42 7. Chavez L, Menjívar C. Children without borders: A mapping of the literature on 43 unaccompanied migrant children to the United States. Migraciones internacionales 44 2017;5(18):71-111. on September 27, 2021 by guest. Protected copyright. 45 46 8. Kloning T, Nowotny T, Alberer M, et al. Morbidity profile and sociodemographic 47 characteristics of unaccompanied refugee minors seen by paediatric practices between 48 October 2014 and February 2016 in Bavaria, Germany. BMC public health 49 2018;18(1):983. 50 9. Stubbe Østergaard L, Norredam M, Mock-Munoz de Luna C, et al. Restricted health care 51 entitlements for child migrants in Europe and Australia. The European Journal of 52 53 Public Health 2017;27(5):869-73. 54 10. Hargreaves DS, Elliott MN, Viner RM, et al. Unmet health care need in US adolescents 55 and adult health outcomes. Pediatrics 2015;136(3):513-20. 56 11. Carrasco‐Sanz A, Leiva‐Gea I, Martin‐Alvarez L, et al. Migrant children's health 57 problems, care needs, and inequalities: European primary care paediatricians' 58 perspective. Child: care, health and development 2018;44(2):183-87. 59 60

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11 | P a g e 1 2 3 12. Kerbl R, Grois N, Popow C, et al. Pediatric Healthcare for Refugee Minors in Europe: 4 Steps for Better Insight and Appropriate Treatment: Elsevier, 2018. BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 13. Carballo M, Hargreaves S, Gudumac I, et al. Evolving migrant crisis in Europe: 7 implications for health systems. The Lancet Global Health 2017;5(3):e252-e53. 8 14. Heslehurst N, Brown H, Pemu A, et al. Perinatal health outcomes and care among asylum 9 seekers and refugees: a systematic review of systematic reviews. BMC medicine 10 2018;16(1):89. 11 15. Markkula N, Cabieses B, Lehti V, et al. Use of health services among international 12 migrant children–a systematic review. Globalization and health 2018;14(1):52. 13 14 16. Bank W. New Country Classifications by Income Level: 2018–2019. [TheDATABlog] 15 2018 16 17. Wells G. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non randomised 17 studies in meta-analyses. http://www ohri ca/programs/clinical_epidemiology/oxford 18 asp 2001 For peer review only 19 18. Morrison A, Polisena J, Husereau D, et al. The effect of English-language restriction on 20 21 systematic review-based meta-analyses: a systematic review of empirical studies. Int J 22 Technol Assess Health Care 2012;28(2):138-44. doi: 10.1017/s0266462312000086 23 [published Online First: 2012/05/09] 24 19. Roth GA, Abate D, Abate KH, et al. Global, regional, and national age-sex-specific 25 mortality for 282 causes of death in 195 countries and territories, 1980–2017: a 26 systematic analysis for the Global Burden of Disease Study 2017. The Lancet 27 2018;392(10159):1736-88. 28 29 20. Temmerman M, Khosla R, Bhutta ZA, et al. Towards a new global strategy for women’s, 30 children’s and adolescents’ health. bmj 2015;351:h4414. 31 21. Hjern A. Health of refugee and migrant children: Technical guidance, 2018. 32 22. Labree L, Van De Mheen H, Rutten F, et al. Differences in overweight and obesity 33 among children from migrant and native origin: a systematic review of the European 34 literature. Obesity reviews 2011;12(5):e535-e47. 35 23. Fazel M, Reed RV, Panter-Brick C, et al. Mental health of displaced and refugee children 36 http://bmjopen.bmj.com/ 37 resettled in high-income countries: risk and protective factors. The Lancet 38 2012;379(9812):266-82. 39 24. Woodland L, Burgner D, Paxton G, et al. Health service delivery for newly arrived 40 refugee children: a framework for good practice. J Paediatr Child Health 41 2010;46(10):560-67. doi: 10.1111/j.1440-1754.2010.01796.x 42 25. Kadir A, Battersby A, Spencer N, et al. Children on the move in Europe: a narrative 43 review of the evidence on the health risks, health needs and health policy for asylum 44 on September 27, 2021 by guest. Protected copyright. 45 seeking, refugee and undocumented children. BMJ paediatrics open 2019;3(1) 46 26. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews 47 and meta-analyses: the PRISMA statement. Int J Surg 2010;8(5):336-41. 48 27. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions: John 49 Wiley & Sons 2011. 50 28. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled clinical trials 51 52 1986;7(3):177-88. 53 29. Campbell M, McKenzie JE, Sowden A, et al. Synthesis without meta-analysis (SWiM) in 54 systematic reviews: reporting guideline. BMJ 2020;368:l6890. doi: 55 10.1136/bmj.l6890 56 57 58 59 60

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1 | P a g e 1 2 3 Appendix 1.

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 1 "Transients and Migrants"/ 7 8 2 "emigrants and immigrants"/ or undocumented immigrants/ 9 10 3 Refugees/ 11 12 13 4 "Emigration and Immigration"/ 14 15 5 (refugee* or migrant* or migrati* or immigrant* or immigrati* or transient* or asylum 16 seek* or displaced person* or displaced people or displaced child*).tw. 17 18 6 1 or 2 or 3 or 4 orFor 5 peer review only 19 20 21 7 adolescent/ or child/ or child, preschool/ or infant/ 22 23 8 pediatrics/ or pediatric emergency medicine/ 24 25 9 Minors/ 26 27 28 10 Puberty/ 29 30 11 (child* or preschool or pre-school or infan* or schoolchild* or school-child* or 31 schoolage* or school-age* or kid or kids or toddler* or teen* or boy* or girl* or pubert* or 32 pubescen* or prepubesc* or p?ediatric* or minor*).tw. 33 34 35 12 7 or 8 or 9 or 10 or 11

36 http://bmjopen.bmj.com/ 37 13 Epidemiologic studies/ 38 39 14 exp case control studies/ 40 41 15 exp cohort studies/ 42 43

44 16 Case control.tw. on September 27, 2021 by guest. Protected copyright. 45 46 17 (cohort adj (study or studies)).tw. 47 48 18 Cohort analy$.tw. 49 50 51 19 (Follow up adj (study or studies)).tw. 52 53 20 (observational adj (study or studies)).tw. 54 55 21 Longitudinal.tw. 56 57 58 22 Retrospective.tw. 59 60 23 Cross sectional.tw.

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2 | P a g e 1 2 3 24 Cross-sectional studies/

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 25 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 7 8 26 Randomized Controlled Trials as Topic/ 9 10 27 randomized controlled trial/ 11 12 13 28 Random Allocation/ 14 15 29 Double Blind Method/ 16 17 30 Single Blind Method/ 18 For peer review only 19 20 31 clinical trial/ 21 22 32 clinical trial, phase i.pt. 23 24 33 clinical trial, phase ii.pt. 25 26 34 clinical trial, phase iii.pt. 27 28 29 35 clinical trial, phase iv.pt. 30 31 36 controlled clinical trial.pt. 32 33 37 randomized controlled trial.pt. 34 35

36 38 multicenter study.pt. http://bmjopen.bmj.com/ 37 38 39 clinical trial.pt. 39 40 40 exp Clinical Trials as topic/ 41 42 43 41 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40

44 on September 27, 2021 by guest. Protected copyright. 45 42 (clinical adj trial$).tw. 46 47 43 ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. 48 49 50 44 PLACEBOS/ 51 52 45 placebo$.tw. 53 54 46 randomly allocated.tw. 55 56 57 47 (allocated adj2 random$).tw. 58 59 48 42 or 43 or 44 or 45 or 46 or 47 60

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3 | P a g e 1 2 3 49 41 or 48

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 50 case report.tw. 7 8 51 letter/ 9 10 52 historical article/ 11 12 13 53 50 or 51 or 52 14 15 54 49 not 53 16 17 55 25 or 54 18 For peer review only 19 20 56 6 and 12 and 55 21 22 57 mortality/ or "cause of death"/ or child mortality/ or fatal outcome/ or hospital mortality/ 23 or infant mortality/ or mortality, premature/ or survival rate/ 24 25 58 (mortalit* or case fatality rate* or death rate* or fatal outcome*).tw. 26 27 28 59 57 or 58 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 27, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 16 of 19 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 2 3 4 Reporting checklist for protocol of a systematic 5 6 7 review. 8 9 10 11 Based on the PRISMA-P guidelines. 12 13 14 15 Instructions to authors 16 For peer review only 17 Complete this checklist by entering the page numbers from your manuscript where readers will find 18 19 20 each of the items listed below. 21 22 23 Your article may not currently address all the items on the checklist. Please modify your text to 24 25 include the missing information. If you are certain that an item does not apply, please write "n/a" and 26 27 provide a short explanation. 28 29 30 Upload your completed checklist as an extra file when you submit to a journal. 31

32 http://bmjopen.bmj.com/ 33 In your methods section, say that you used the PRISMA-Preporting guidelines, and cite them as: 34 35 36 37 Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA. Preferred 38 39 Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement.

40 on September 27, 2021 by guest. Protected copyright. 41 Syst Rev. 2015;4(1):1. 42 43 44 Reporting Item Page Number 45 46 47 Title 48 49 50 Identification #1a Identify the report as a protocol of a systematic 1 51 52 53 review 54 55 56 Update #1b If the protocol is for an update of a previous N/A 57 58 systematic review, identify as such 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 2 Registration 3 4 5 #2 If registered, provide the name of the registry (such 10 6 7 as PROSPERO) and registration number 8 9 10 Authors 11 12 13 Contact #3a Provide name, institutional affiliation, e-mail 1 14 15 address of all protocol authors; provide physical 16 For peer review only 17 18 mailing address of corresponding author 19 20 21 Contribution #3b Describe contributions of protocol authors and 10, 1 22 23 identify the guarantor of the review 24 25 26 Amendments 27 28 29 #4 If the protocol represents an amendment of a N/A 30 31 previously completed or published protocol, identify 32 http://bmjopen.bmj.com/ 33 34 as such and list changes; otherwise, state plan for 35 36 documenting important protocol amendments 37 38 39 Support

40 on September 27, 2021 by guest. Protected copyright. 41 42 Sources #5a Indicate sources of financial or other support for the 10 43 44 review 45 46 47 48 Sponsor #5b Provide name for the review funder and / or 10 49 50 sponsor 51 52 53 Role of sponsor #5c Describe roles of funder(s), sponsor(s), and / or N/A 54 55 or funder institution(s), if any, in developing the protocol 56 57 58 Introduction 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 19 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 2 Rationale #6 Describe the rationale for the review in the context 4,5 3 4 of what is already known 5 6 7 Objectives #7 Provide an explicit statement of the question(s) the 5,6 8 9 review will address with reference to participants, 10 11 interventions, comparators, and outcomes (PICO) 12 13 14 15 Methods 16 For peer review only 17 18 Eligibility criteria #8 Specify the study characteristics (such as PICO, 5-8 19 20 study design, setting, time frame) and report 21 22 characteristics (such as years considered, 23 24 language, publication status) to be used as criteria 25 26 27 for eligibility for the review 28 29 30 Information #9 Describe all intended information sources (such as 8 31

32 sources electronic databases, contact with study authors, http://bmjopen.bmj.com/ 33 34 trial registers or other grey literature sources) with 35 36 37 planned dates of coverage 38 39

40 Search strategy #10 Present draft of search strategy to be used for at Supplementary on September 27, 2021 by guest. Protected copyright. 41 42 least one electronic database, including planned material (appendix 43 44 limits, such that it could be repeated 1) 45 46 47 Study records - #11a Describe the mechanism(s) that will be used to 8,9 48 49 50 data manage records and data throughout the review 51 52 management 53 54 55 Study records - #11b State the process that will be used for selecting 8,9 56 57 selection process studies (such as two independent reviewers) 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 through each phase of the review (that is, 2 3 screening, eligibility and inclusion in meta-analysis) 4 5 6 Study records - #11c Describe planned method of extracting data from 8 7 8 data collection reports (such as piloting forms, done independently, 9 10 11 process in duplicate), any processes for obtaining and 12 13 confirming data from investigators 14 15 16 Data items #12ForList and peer define all review variables for which only data will be 5-9 17 18 sought (such as PICO items, funding sources), any 19 20 pre-planned data assumptions and simplifications 21 22 23 24 Outcomes and #13 List and define all outcomes for which data will be 5-9 25 26 prioritization sought, including prioritization of main and 27 28 additional outcomes, with rationale 29 30 31 Risk of bias in #14 Describe anticipated methods for assessing risk of 8,9 32 http://bmjopen.bmj.com/ 33 individual studies bias of individual studies, including whether this will 34 35 36 be done at the outcome or study level, or both; 37 38 state how this information will be used in data 39 40 synthesis on September 27, 2021 by guest. Protected copyright. 41 42 43 Data synthesis #15a Describe criteria under which study data will be 9 44 45 46 quantitatively synthesised 47 48 49 Data synthesis #15b If data are appropriate for quantitative synthesis, 9 50 51 describe planned summary measures, methods of 52 53 handling data and methods of combining data from 54 55 56 studies, including any planned exploration of 57 58 consistency (such as I2, Kendall’s τ) 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 20 of 19 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 2 Data synthesis #15c Describe any proposed additional analyses (such 8,9 3 4 as sensitivity or subgroup analyses, meta- 5 6 regression) 7 8 9 Data synthesis #15d If quantitative synthesis is not appropriate, describe 9 10 11 the type of summary planned 12 13 14 15 Meta-bias(es) #16 Specify any planned assessment of meta-bias(es) 9 16 For peer review only 17 (such as publication bias across studies, selective 18 19 reporting within studies) 20 21 22 Confidence in #17 Describe how the strength of the body of evidence 9 23 24 cumulative will be assessed (such as GRADE) 25 26 27 evidence 28 29 30 None The PRISMA-P checklist is distributed under the terms of the Creative Commons Attribution 31

32 License CC-BY 4.0. This checklist can be completed online using https://www.goodreports.org/, a tool http://bmjopen.bmj.com/ 33 34 made by the EQUATOR Network in collaboration with Penelope.ai 35 36 37 38 39

40 on September 27, 2021 by guest. Protected copyright. 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from

Health outcomes in international migrant children: Protocol for a systematic review

Journal: BMJ Open ManuscriptFor ID peerbmjopen-2020-041173.R1 review only Article Type: Protocol

Date Submitted by the 12-Jan-2021 Author:

Primary Subject Global health Heading:

Secondary Subject Heading: Paediatrics, Mental health, Infectious diseases, Health policy

PAEDIATRICS, PUBLIC HEALTH, Paediatric infectious disease & immunisation < PAEDIATRICS, International health services < HEALTH http://bmjopen.bmj.com/ Keywords: SERVICES ADMINISTRATION & MANAGEMENT, Health policy < HEALTH SERVICES ADMINISTRATION & MANAGEMENT

on September 27, 2021 by guest. Protected copyright.

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1 2 3

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 27, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 | P a g e 1 2 3 DR ALICE JANE ARMITAGE (Orcid ID: 0000-0001-6972-3651)

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 7 Article type: Protocol for systematic review 8 9 10 11 12 13 Health outcomes in international migrant children: 14 Protocol for a systematic review 15 16 17 18 For peer review only 19 20 21 22 Authors: Alice Jane Armitage1, Michelle Heys2, Irina Lut3, Pia Hardelid4 23 24 25 26 Email addresses: [email protected], [email protected], [email protected], 27 [email protected] 28 29 30 1 31 Guarantor: Pia Hardelid 32 33 1. UCL, Institute of Child Health, 30 Guilford St, London, UK WC1N 1EH 34 2. University College London Institute of Child Health, University College London Institute 35 of Child Health, London, UK 36 http://bmjopen.bmj.com/ 37 3. UCL, Institute of child health, London, UK 38 4. UCL Institute of Child Health, Centre for Paediatric Epidemiology and Biostatistics 39 30 Guilford Street, London, UK WC1N 1EH 40 41 42 43 Correspondence to:

44 Dr Alice Jane Armitage on September 27, 2021 by guest. Protected copyright. 45 UCL Great Ormond Street Institute of Child Health, 30 Guilford St, Holborn, London WC1N 46 47 1EH, Tel: 020 7242 9789 48 [email protected] 49 rythemaassociated multiforme with COVID-19 and Kawasaki infection disease in children 50 Keywords: Transients and migrants, Global health, Pediatrics, Population Health, Systematic 51 52 Review 53 Tables: 1 54 55 Figures: 0 56 57 Appendices: 1 58 59 60 Word count: 3119

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2 | P a g e 1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 Abstract 7 Introduction 8 Migration status is a key determinant of health, but health outcomes among migrant children 9 and young people (CYP), i.e. those aged under 18 years, are poorly understood. A ‘healthy- 10 11 migrant’ effect has been demonstrated among adults, but evidence for the presence of the 12 same effect in CYP is lacking. No large studies or reviews exist reporting comprehensive or 13 holistic health outcomes among migrant CYP. We aim to identify and synthesise original 14 quantitative research on health of migrant CYP to explore the relations between migration 15 16 status and health outcomes. 17 18 Methods and analysisFor peer review only 19 A search of Pubmed/Medline, Embase and Cochrane and grey literatures sites will be 20 undertaken for any original quantitative research on health outcomes of migrant CYP 21 22 published from 01/01/2000 onwards. Outcomes will be categorised as: mortality, 23 communicable diseases, non-communicable diseases, nutritional status, mental health, 24 disability, vaccine coverage, and accidental and non-accidental injuries (including assault and 25 abuse). Search results will be screened against inclusion criteria and presented in a PRISMA 26 27 flow diagram. 28 29 The Newcastle-Ottawa Scale (NOS) assessment tool will be used to assess study quality. If 30 feasible, depending on study availability data heterogeneity (explored using I2 statistic), 31 32 results will be pooled for meta-analysis. If sufficient data are available, a priori defined sub- 33 group analyses will be undertaken. A narrative quantitative synthesis will be presented, 34 taking account of study quality and assessed risk of bias. 35

36 http://bmjopen.bmj.com/ 37 Ethics and dissemination 38 Formal ethical approval will not be sought as we will be accessing data already in the public 39 domain. This review will be submitted for publication in a high impact journal and presented 40 at international conferences. The results of this work will be shared with groups of migrant 41 children as part of an ongoing engagement project. 42 43 This protocol has been submitted to the International Prospective Register for Systematic

44 on September 27, 2021 by guest. Protected copyright. 45 Reviews (PROSPERO), registration number: CRD42020166305. 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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3 | P a g e 1 2 3

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 Strengths and limitations of this study 7 8 This protocol is written in line with PRISMA-P reporting guidelines for systematic review 9 protocols. 10 11 This systematic review will address a clear research gap on health outcomes of migrant 12 children and young people (CYP). 13 14 Well-established systematic review methodology will allow for evidence-based 15 16 recommendations for policy around migrant children based on available data and 17 identification of key gaps in the research evidence. 18 For peer review only 19 Review conclusions are likely to be limited by the quality and quantity of available studies. 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 27, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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4 | P a g e 1 2 3 Introduction

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 Migration status is known to be a key determinant of health1. There is no international 6 consensus on the definition of migrant; here we use the term to describe international 7 8 migrants, as suggested by the United Nations definition: ‘someone who changes his or her 9 country of usual residence, irrespective of the reason for migration or legal status’2. This 10 includes refugees and asylum seekers, as well as economic migrants and international 11 students2. Adult migrants may be young and healthy, and a ‘healthy-migrant’ effect, whereby 12 13 migrants have better health status than the population of the host country, has been 3 14 demonstrated . 15 16 Migrant populations may experience poverty, social inequality or persecution at their 17 destination, which could compound physical and mental health burdens associated with 18 country of origin, reasonsFor for peer displacement review and circumstances only of their journey. Children and 19 young people (CYP: those under the age of 18) are further impacted by the health of their 20 21 caregivers, and by their inherent physical and social vulnerabilities, particularly to 22 malnutrition, communicable diseases, disrupted education, violence and exploitation 4-7. 23 Unlike adults migrating for work or education, who are likely to be healthy, CYP are 24 significantly less likely to be the drivers of their own migration. Conversely, there may be 25 26 families who migrate to seek healthcare for CYP with chronic conditions. Therefore, it is not 27 yet known whether there will be the same ‘healthy-migrant’ effect in CYP as observed in 28 adult migrants. 29 30 Many high income countries place restrictions on migrant CYP’s entitlement to health 31 services8. Unmet health needs in CYP are known to be associated with poor adult health9. 32 However, health needs, and associated health outcomes, among migrant CYP are poorly 33 10 34 understood and infrequently reported in the literature, preventing a population-based 35 approach to planning health services. This is in part due to poor quality and quantity of data

36 on this topic. Routinely collected healthcare datasets rarely include migration status for http://bmjopen.bmj.com/ 37 children. Most studies on the health of migrants only include children as a subgroup, if 38 39 included at all. There is a lack of data on migrant health spanning larger geographical 40 regions and crossing borders, barriers to data linkage, and an associated lack of large scale 41 studies or reviews11. The lack of healthcare data on migrant CYP has been identified as an 42 unmet research need11, as well as a rights of the child issue12. 43

44 on September 27, 2021 by guest. Protected copyright. 45 A recent systematic review on mortality of international migrants provided evidence that, on 46 average, international migrants have lower mortality than the host population3. However, 47 mortality from specific causes, such as violence and infectious diseases, was higher among 48 3 49 migrants . This systematic review also highlighted a lack of data on the health of vulnerable 50 migrant groups such as asylum seekers, refugees and undocumented migrants3, and authors 51 cautioned against generalising results to these groups. Similarly, the majority of studies 52 reflect migration into high income countries with a noted evidence gap for data on migrants, 53 54 particularly refugees, in low- and middle- income countries. Health outcomes for migrants 55 from different geographical regions and countries are likely to be related to the 56 socioeconomic conditions of the origin and host countries. For example, a study of perceived 57 wellbeing in adolescent migrants living in Canada showed different rates of health complaints 58 13 59 based on country and region of origin . 60

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5 | P a g e 1 2 3 Other comprehensive systematic review evidence addresses perinatal outcomes among

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 migrants, indicating increased maternal mortality, preterm birth and congenital abnormalities, 14 6 as well as barriers to access and use of healthcare . Systematic review evidence from 2018 7 demonstrates that migrant children use healthcare services less than non-migrant populations, 8 with the exception of emergency services, although their rate of hospital admission is 9 15 10 higher . 11 12 As mortality is a relatively rare outcome in childhood, wider health outcomes are required to 13 reflect the impact of migration on health. Over the last decade, the life course approach to 14 health has been adopted by multiple international organisations, such as the World Health 15 16 16 Organisation , and is reflected in approaches such as the ‘survive and thrive’ strategy of the 17 sustainable development goals17. Rather than seeing health outcomes as discrete and 18 unrelated, this approachFor takes peer a comprehensive review and holistic only view of health. It allows for 19 early influences on risk factors for long-term conditions potentially presenting later in life 20 16 21 and the biopsychosocial model of child and adolescent health to be taken into account . 22 There have been no comprehensive systematic reviews on a range of migrant child health 23 outcomes across the life course either internationally or in the UK. Following a PROSPERO 24 search, no similar review is planned at present. 25 26 27 The proposed systematic review will therefore address a clear evidence gap.. We have 28 therefore designed this review to address comprehensive health outcomes across the life- 29 course of CYP (i.e. up to age 18), in addition to mortality. 30 31 32 Aims and objectives of systematic review 33 34 The aim of the systematic review will be to summarise the available evidence base regarding 35 a range of key health outcomes of migrant CYP across the childhood life course.

36 http://bmjopen.bmj.com/ 37 38 Our specific objectives are to: 39 40 1) Identify global original quantitative research on health outcomes for migrant CYP, and to 41 42 compare this to CYP in the host population where data are available. Where there is no 43 control group or the control group are another migrant group, the studies will be included in

44 the quantitative narrative synthesis. on September 27, 2021 by guest. Protected copyright. 45 46 2) Undertake meta-analyses of specific health outcomes if the data allow, e.g. mortality, 47 vaccination coverage (see eight domains listed below). Similarly, if sufficient data are 48 available, subgroup analyses, decided a priori, will include break-down of health outcomes 49 50 by: 51 52  Age group (1-4, 5-9, 10-17), 53  Reason for migration (refugee, asylum seeker, child of economic migrants, student) 54  Migrant country of origin and destination ( according World Bank national income 55 18 56 groups ) 57  Study quality as assessed by NOS scale tool19 (see below). 58 59 Table 1. Research question in PICOS format 60

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6 | P a g e 1 2 3 i. Population, or Children and young people (CYP), defined as those under the age of 4 participants and 18 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 conditions of 7 interest 8 9 ii. Interventions Migration status; any migrant CYP, i.e. living in a different country 10 or exposures from that of their birth. 11 12 13 iii. Comparisons CYP who have not migrated, described as ‘the host population’ 14 or control groups 15 16 iv. Outcomes of 1. Mortality (age group: 1-4, 5-9, 10-17), infants are excluded 17 interest unless clearly stated that they have migrated after birth, in which 18 Forcase theypeer will be includedreview in 1-4 age only group. 19 20 2. Communicable diseases (incidence/prevalence) 21 3. Non-communicable diseases 22 4. Over and under nutrition 23 5. Mental health outcomes 24 6. Disability 25 7. Vaccine coverage 26 8. Accidental and non-accidental injuries (e.g. assault and abuse) 27 28 29 v. Setting Studies in any setting and from any country will be included 30 31 vi. Study designs All studies presenting original data, including observational (cohort, 32 case-control and cross-sectional studies), systematic reviews, and 33 randomised controlled trials reporting quantitative data on health 34 35 outcomes in international migrant CYP.

36 http://bmjopen.bmj.com/ 37 38 39 Methods and analysis 40 This protocol is written with reference to the PRISMA-P reporting guidelines for systematic 41 20 42 review protocols . 43 Patient and public involvement

44 on September 27, 2021 by guest. Protected copyright. 45 No patient involved 46 47 Eligibility 48 49 This systematic review will include published studies presenting original data on health 50 outcomes of migrant children and young people (CYP), i.e. those living in a different country 51 from that of their birth, including observational studies (cohort and case-control studies, and 52 cross-sectional surveys), systematic review and randomised controlled trials. Studies in any 53 54 setting and from any country will be included. 55 56 For the purposes of this review we are including studies pertaining to CYP who are 57 international migrants, i.e. living in a country other than that of their birth, irrespective of the 58 birth place of their parents. Therefore, only studies on first generation migrant children will 59 be included, i.e. we would not include studies on children born to parents who were originally 60

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7 | P a g e 1 2 3 migrants. In view of this, and in view of existing systematic review evidence, studies will be

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 excluded that pertain exclusively to maternal and/or perinatal outcomes as these will not 6 address the outcomes for CYP who have themselves migrated. The perinatal period in this 7 systematic review is defined as birth up until the child’s first birthday unless is it explicitly 8 stated that the child migrated during this period. If studies specifically pertain to infants 9 10 under 1 year who have migrated then this data will be included and analysed within the 1-4 11 age group. We will exclude studies that only include patients from intensive care or high 12 dependency settings and where health outcomes do not fall within defined areas (see below). 13 In view of existing systematic review evidence and the defined outcomes areas, we will not 14 include studies exclusively reporting hospital attendance or admission rates without other 15 16 health outcomes presented. We will also exclude research letters, studies where the abstract 17 or full text is not available, and studies where it is not possible to obtain an English 18 translation. RestrictingFor systematic peer reviews review to English language only publications is routine 19 practice and has been shown not to significantly affect results regarding empirical studies21. 20 21 Outcomes of interest 22 23 Following identification of studies, the outcomes will be grouped into the following eight 24 areas, chosen to represent key health outcomes across the childhood life course. Outcomes 25 are chosen with reference to the Global Burden of Disease Study 201722 and to reflect the 26 17 27 ‘survive and thrive’, strategy of the sustainable development goals . More emphasis has 28 been placed on health outcomes where quantitative data may be available, where definitions 29 are recognised internationally and where the outcomes are plausibly affected my migration 30 status. For each outcome a finite list of more common conditions has been chosen. 31 32 1. Mortality (By age group 1-4, 5-9, 10-17 years) 33 34 If data are available following identification of studies, mortality will be broken down by 35 age-group and compared to the host population. In view of perinatal studies being excluded

36 and focus being on children who have themselves migrated we are excluding infant mortality http://bmjopen.bmj.com/ 37 (deaths under the age of one year). 38 39 2. Communicable diseases (incidence/prevalence) 40 41 Systematic review evidence suggests that despite the ‘healthy migrant’ effect rates of 42 infectious diseases are higher among migrant populations3. The search strategy will focus on 43

44 HIV, Hepatitis B, Tuberculosis (active and latent), Sexually transmitted diseases (Chlamydia on September 27, 2021 by guest. Protected copyright. 45 and Gonorrhoea), Schistosomiasis and parasitic infections3. 46 47 3. Non-communicable diseases (NCDs) 48 49 With reference to the global data, the search strategy will focus on neoplasms, asthma and 50 other chronic respiratory conditions, epilepsy and Type 1 diabetes mellitus (T1DM). With 51 chronic conditions characterised by occasional exacerbations, such as asthma, the focus will 52 be on exacerbations of the condition as opposed to baseline prevalence. 53 54 4. Over and under nutrition 55 56 Forced migration of children may be associated with periods of food insecurity both before 57 23 58 and during migration, with associated morbidity . Following migration to middle and high 24 59 income countries migrant children are at risk of becoming overweight or obese . We are 60 therefore seeking to identify studies addressing both under and over nutrition in migrant

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8 | P a g e 1 2 3 children. The search strategy will focus on terms around malnutrition, under-nutrition,

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 underweight, low BMI, high BMI, overweight and obesity. Micronutrient deficiencies, such 6 as vitamin deficiencies, requiring blood tests to identify, are considered outside the scope of 7 this review. 8 9 5. Mental health outcomes 10 11 Poor mental health is increasingly recognised as an unmet health need in childhood and 12 adolescence and being identified as prevalent among migrant populations10 25. The search 13 strategy will focus on Post-traumatic stress disorder (PTSD), psychosis, depression, self-harm 14 15 and suicide. 16 6. Disability 17 18 Disability may be higherFor among peer migrant reviewchildren from countries only with poor health 19 20 infrastructure and has been identified as a significant unmet health need among migrant 21 children23 26. The search strategy will focus on hearing impairment, deafness, visual 22 impairment, blindness, cerebral palsy, autism, learning difficulties and/or developmental 23 delay. 24 25 7. Vaccine coverage and uptake 26 27 Lack of access to preventative health care and disruption to healthcare access in migrant CYP 28 affects vaccination coverage. Following migration, catch-up immunisation programmes 29 30 depend upon timely and coordinated healthcare input. The search strategy will focus on 31 immunisation, vaccination and specific vaccine-preventable pathogen targets (polio, 32 diphtheria, pertussis, measles, mumps, rubella, hepatitis B) combined with vaccine-specific 33 terms (vaccination, immunisation, immunity). 34 35 8. Accidental and non-accidental injuries (e.g. assault and abuse)

36 http://bmjopen.bmj.com/ 37 Road traffic accidents and inter-personal violence are examples of accidental injuries that 38 may be associated with migration. It is also known that migrant CYP are at increased risk of 39 40 assault and abuse both historically (in their country of origin and during transit) and 41 following migration23 27. Rates of sexual assault and abuse are also high, particularly among 42 forced migrants, and will be included in this category. The search strategy will focus on road 43 traffic accidents or injuries, interpersonal or domestic violence, physical or sexual assault or

44 on September 27, 2021 by guest. Protected copyright. 45 abuse, sexual violence and rape. 46 47 Search Strategy 48 The electronic databases Pubmed/Medline, Embase and Cochrane will be searched with date 49 50 range from 01/01/2000 onwards. A grey literature search will also be undertaken including 51 the following websites: Organisation for Economic Co-operation and Development (OECD), 52 WHO Global Health Observatory (GHO), Health evidence network, Health for 53 Undocumented Migrants and Asylum seekers (HUMA) Network and the International 54 55 Organization of Migration (IOM). We will also undertake reference checking for selected 56 manuscripts and search conference proceedings from international conferences relevant to 57 migrant child health. 58 59 The search strategy will use key words and index terms around migrant status, children and 60 young people (CYP) and the eight areas of health outcomes as described above. A draft

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9 | P a g e 1 2 3 search strategy for Ovid Medline for Mortality is attached (Appendix 1). The finalised search

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 strategy for all outcomes will be published online and any amendments identified 6 (PROSPERO register). 7 8 Selection process 9 28 10 Search results will be exported to EPPI-4 software for screening and selection. Two 11 independent reviewers (AA and IL) will screen all titles and abstracts. Full manuscripts will 12 be screened when it is not clear from the title or abstract whether the study meet the inclusion 13 criteria. Where there is disagreement between the two reviewers the study will be escalated 14 15 to a third reviewer (MH or PH) to resolve. Following the screening of full-text, articles will 16 be assessed for eligibility; a PRISMA flow diagram will be produced and the PRISMA 17 checklist followed29. 18 For peer review only 19 Data synthesis and analysis 20 21 Data will be extracted and entered into a Microsoft Excel spreadsheet by a single reviewer 22 (AJA or IL). We will extract the following data items: demographic features (age, sex and 23 country/countries of origin of CYP), study design, country/countries of arrival (study setting), 24 study period, study population, presence of control or comparator group, outcomes presented 25 26 (using pre-defined categories as listed above), outcome measures (rate ratio, hazard ratio or 27 odds ratio), follow-up period and funding source. 28 29 The Newcastle-Ottawa Scale(NOS)19 assessment tool will be used to assess the quality of 30 studies. The NOS scale assigns a ‘star system’ across three domains: the selection of the 31 study groups, the comparability of the groups; and the ascertainment of either the exposure or 32 33 outcome of interest for case-control or cohort studies respectively. The NOS score for each 34 study will be presented. A sensitivity analysis will be undertaken by rerunning the meta- 35 analyses excluding any low-quality outliers on the NOS scale.

36 http://bmjopen.bmj.com/ 37 The decision to meta-analyse study results will depend on the availability of studies 38 pertaining to the various outcomes and heterogeneity of the data presented. The I2 statistic 39 will be used to explore heterogeneity of studies. A small number of studies (fewer than 40 2 41 three) or I of >75% will be adopted as the threshold for decision not to undertake meta- 42 analysis30. 43

44 Studies presenting original data on one or more of the eight defined health outcomes will be on September 27, 2021 by guest. Protected copyright. 45 considered for inclusion in meta-analyses. Summary parameters for most outcomes are likely 46 to be rate ratio, hazard ratio or odds ratio. If appropriate, other measures such as prevalence 47 48 or vaccine uptake rates, will be used. Study results will be pooled for meta-analysis using 31 49 STATA version 14 using a random effects model (Der-Simonian and Laird method) and 50 presented in forest plots. The likelihood of publication bias will be explored using funnel 51 plots if enough studies are identified. We acknowledge that if a small number of studies is 52 53 identified it may not be possible to assess publication bias. 54 If sufficient data are available, the following sub-group analyses will be undertaken: break- 55 56 down of health outcomes by age group (1-4, 5-9, 10-17 years), by migrant subgroup (refugee, 57 asylum seeker, child of economic migrants, student), by migrant destination (World Bank 58 income group18) and by study quality as assessed by the NOS scale tool19. 59 60

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10 | P a g e 1 2 3 A quantitative narrative synthesis will be undertaken of studies that are not included in the 4 meta-analysis, guided by the Systematic review Without Metaanalysis (SwIM) guidelines32. BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 We will clearly set out why studies are not included in a meta-analysis; the diversity of 7 studies will be addressed (including populations, methodology and outcomes) and the 8 completeness of outcome data. Studies will be grouped for synthesis according to the 8 pre- 9 defined outcomes (Table 1). Any quantitative effect sizes presented (that have not been 10 amenable to meta-analysis) will be presented in tables. Statistics will not be combined for 11 presentation outside of the meta-analysis. Where the heterogeneity cannot be explored using 12 the I² statistic, heterogeneity will be informally explored by ordering studies according to 13 14 characteristics including outcomes and population. Studies will be prioritised based on 15 assessed risk of bias, sample and effect size and relevance to the research question. For each 16 outcome a description of synthesised findings will be made including certainty of results 17 (with reference to p- values and confidence intervals where available), conclusions will take 18 account of quality ofFor included peer studies and review the assessed risk only of bias. 19 20 21 Bias due to confounding must be considered when addressing migration as a risk factor for 22 health outcomes: migration is inevitably correlated with race/ethnicity, poverty and 23 educational level. Bias due to missing data, selection bias and reporting bias will also be 24 considered. 25 26 Ethics and dissemination 27 28 Formal ethical approval will not be sought in line with systematic review guidelines: we will 29 only be accessing data already in the public domain. This review will make up part of an 30 MD(Res) thesis. We will submit results for publication in a high impact peer reviewed 31 journal. Results will be presented at international conferences in the areas of migrant health 32 33 and paediatrics and disseminated to policy makers via the Children and Families Policy 34 Research unit at UCL. The results of this review will be relevant for UK and international 35 stakeholders in the area of migrant child health. Funding has been secured for a separate

36 study involving unaccompanied asylum-seeking children in the UK, a particularly vulnerable http://bmjopen.bmj.com/ 37 group of migrant children. The results of this work will be shared with this group as part of 38 an ongoing engagement project. 39 40 This protocol has been submitted to the International Prospective Register for Systematic 41 Reviews (PROSPERO) and revised based on their recommendations, registration number: 42 CRD42020166305. 43

44 Author’s contributions on September 27, 2021 by guest. Protected copyright. 45 46 The protocol was conceived by all authors, written by AJA and reviewed by PH, MH and IL 47 prior to submission. PH is the guarantor of the review. 48 49 Funding sources/sponsors 50 51 This research received no specific grant from any funding agency in the public, commercial 52 or not-for-profit sectors. 53 54 Competing interest 55 We declare no known conflicts of interests. 56 57 References 58 59 60

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11 | P a g e 1 2 3 1. Abubakar I, Aldridge RW, Devakumar D, et al. The UCL–Lancet Commission on 4 Migration and Health: the health of a world on the move. The Lancet BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 2018;392(10164):2606-54. 7 2. Perruchoud R. Persons falling under the Mandate of the International Organization for 8 Migration (IOM) and to Whom the Organization may Provide Migration Services. 9 International Journal of Refugee Law 1992;4(2):205-15. 10 3. Aldridge RW, Nellums LB, Bartlett S, et al. Global patterns of mortality in international 11 migrants: a systematic review and meta-analysis. The Lancet 2018;392(10164):2553- 12 66. 13 14 4. Manhica H, Almquist Y, Rostila M, et al. The use of psychiatric services by young adults 15 who came to Sweden as teenage refugees: a national cohort study. Epidemiology and 16 psychiatric sciences 2017;26(5):526-34. 17 5. Buchanan A, Kallinikaki T. Meeting the needs of unaccompanied children in Greece. 18 InternationalFor Social Workpeer 2018:0020872818798007. review only 19 6. Chavez L, Menjívar C. Children without borders: A mapping of the literature on 20 21 unaccompanied migrant children to the United States. Migraciones internacionales 22 2017;5(18):71-111. 23 7. Kloning T, Nowotny T, Alberer M, et al. Morbidity profile and sociodemographic 24 characteristics of unaccompanied refugee minors seen by paediatric practices between 25 October 2014 and February 2016 in Bavaria, Germany. BMC public health 26 2018;18(1):983. 27 8. Stubbe Østergaard L, Norredam M, Mock-Munoz de Luna C, et al. Restricted health care 28 29 entitlements for child migrants in Europe and Australia. The European Journal of 30 Public Health 2017;27(5):869-73. 31 9. Hargreaves DS, Elliott MN, Viner RM, et al. Unmet health care need in US adolescents 32 and adult health outcomes. Pediatrics 2015;136(3):513-20. 33 10. Carrasco‐Sanz A, Leiva‐Gea I, Martin‐Alvarez L, et al. Migrant children's health 34 problems, care needs, and inequalities: European primary care paediatricians' 35 perspective. Child: care, health and development 2018;44(2):183-87. 36 http://bmjopen.bmj.com/ 37 11. Kerbl R, Grois N, Popow C, et al. Pediatric Healthcare for Refugee Minors in Europe: 38 Steps for Better Insight and Appropriate Treatment: Elsevier, 2018. 39 12. Carballo M, Hargreaves S, Gudumac I, et al. Evolving migrant crisis in Europe: 40 implications for health systems. The Lancet Global Health 2017;5(3):e252-e53. 41 13. Borraccino A, Charrier L, Berchialla P, et al. Perceived well-being in adolescent 42 immigrants: it matters where they come from. International Journal of Public Health 43 2018;63(9):1037-45. doi: 10.1007/s00038-018-1165-8 44 on September 27, 2021 by guest. Protected copyright. 45 14. Heslehurst N, Brown H, Pemu A, et al. Perinatal health outcomes and care among asylum 46 seekers and refugees: a systematic review of systematic reviews. BMC medicine 47 2018;16(1):89. 48 15. Markkula N, Cabieses B, Lehti V, et al. Use of health services among international 49 migrant children–a systematic review. Globalization and health 2018;14(1):52. 50 16. Jacob C, Baird J, Barker M, et al. The Importance of a Life Course Approach to Health: 51 52 Chronic disease risk from preconception through adolescence and adulthood. Geneva: 53 WHO 2017 54 17. Temmerman M, Khosla R, Bhutta ZA, et al. Towards a new global strategy for women’s, 55 children’s and adolescents’ health. bmj 2015;351:h4414. 56 18. Bank W. New Country Classifications by Income Level: 2018–2019. [TheDATABlog] 57 2018 58 59 60

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12 | P a g e 1 2 3 19. Wells G. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non randomised 4 studies in meta-analyses. http://www ohri ca/programs/clinical_epidemiology/oxford BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 asp 2001 7 20. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review 8 and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic reviews 9 2015;4(1):1. 10 21. Morrison A, Polisena J, Husereau D, et al. The effect of English-language restriction on 11 systematic review-based meta-analyses: a systematic review of empirical studies. Int J 12 Technol Assess Health Care 2012;28(2):138-44. doi: 10.1017/s0266462312000086 13 14 [published Online First: 2012/05/09] 15 22. Roth GA, Abate D, Abate KH, et al. Global, regional, and national age-sex-specific 16 mortality for 282 causes of death in 195 countries and territories, 1980–2017: a 17 systematic analysis for the Global Burden of Disease Study 2017. The Lancet 18 2018;392(10159):1736-88.For peer review only 19 23. Hjern A. Health of refugee and migrant children: Technical guidance, 2018. 20 21 24. Labree L, Van De Mheen H, Rutten F, et al. Differences in overweight and obesity 22 among children from migrant and native origin: a systematic review of the European 23 literature. Obesity reviews 2011;12(5):e535-e47. 24 25. Fazel M, Reed RV, Panter-Brick C, et al. Mental health of displaced and refugee children 25 resettled in high-income countries: risk and protective factors. The Lancet 26 2012;379(9812):266-82. 27 26. Woodland L, Burgner D, Paxton G, et al. Health service delivery for newly arrived 28 29 refugee children: a framework for good practice. J Paediatr Child Health 30 2010;46(10):560-67. doi: 10.1111/j.1440-1754.2010.01796.x 31 27. Kadir A, Battersby A, Spencer N, et al. Children on the move in Europe: a narrative 32 review of the evidence on the health risks, health needs and health policy for asylum 33 seeking, refugee and undocumented children. BMJ paediatrics open 2019;3(1) 34 28. Thomas J, Brunton J, Graziosi S. EPPI-Reviewer 4: software for research synthesis. 35 EPPI-Centre Software. London: Social Science Research Unit, UCL Institute of 36 http://bmjopen.bmj.com/ 37 Education. 2010, 2018. 38 29. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews 39 and meta-analyses: the PRISMA statement. Int J Surg 2010;8(5):336-41. 40 30. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions: John 41 Wiley & Sons 2011. 42 31. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled clinical trials 43 1986;7(3):177-88. 44 on September 27, 2021 by guest. Protected copyright. 45 32. Campbell M, McKenzie JE, Sowden A, et al. Synthesis without meta-analysis (SWiM) in 46 systematic reviews: reporting guideline. BMJ 2020;368:l6890. doi: 47 10.1136/bmj.l6890 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 | Page 1

2 3 Appendix 1.

36 http://bmjopen.bmj.com/ 37 13 Epidemiologic studies/ 38 39 14 exp case control studies/ 40 41 42 15 exp cohort studies/ 43

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2 | Page 1

2 3 24 Cross-sectional studies/

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3 | Page 1

2 3 49 41 or 48

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 27, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 17 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 2 3 Reporting checklist for protocol of a systematic 4 5 review. 6 7 8 Based on the PRISMA-P guidelines. 9 10 11 Instructions to authors 12 13 Complete this checklist by entering the page numbers from your manuscript where readers will find 14 15 each of the items listed below. 16 For peer review only 17 Your article may not currently address all the items on the checklist. Please modify your text to 18 19 include the missing information. If you are certain that an item does not apply, please write "n/a" and 20 provide a short explanation. 21 22 23 Upload your completed checklist as an extra file when you submit to a journal. 24 25 In your methods section, say that you used the PRISMA-Preporting guidelines, and cite them as: 26 27 28 Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA. Preferred 29 Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. 30 31 Syst Rev. 2015;4(1):1.

32 http://bmjopen.bmj.com/ 33 Reporting Item Page Number 34 35 36 Title 37 38 Identification #1a Identify the report as a protocol of a systematic 1 39

40 review on September 27, 2021 by guest. Protected copyright. 41 42 Update #1b If the protocol is for an update of a previous N/A 43 systematic review, identify as such 44 45 46 Registration 47 48 #2 If registered, provide the name of the registry (such 10 49 50 as PROSPERO) and registration number 51 52 Authors 53 54 55 Contact #3a Provide name, institutional affiliation, e-mail 1 56 address of all protocol authors; provide physical 57 58 mailing address of corresponding author 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 18 of 19 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 Contribution #3b Describe contributions of protocol authors and 10, 1 2 3 identify the guarantor of the review 4 5 Amendments 6 7 8 #4 If the protocol represents an amendment of a N/A 9 previously completed or published protocol, 10 11 identify as such and list changes; otherwise, state 12 plan for documenting important protocol 13 14 amendments 15 16 Support For peer review only 17 18 19 Sources #5a Indicate sources of financial or other support for 10 20 the review 21 22 23 Sponsor #5b Provide name for the review funder and / or 10 24 sponsor 25 26 Role of sponsor #5c Describe roles of funder(s), sponsor(s), and / or N/A 27 28 or funder institution(s), if any, in developing the protocol 29 30 Introduction 31

32 http://bmjopen.bmj.com/ 33 Rationale #6 Describe the rationale for the review in the context 4,5 34 of what is already known 35 36 37 Objectives #7 Provide an explicit statement of the question(s) the 5,6 38 review will address with reference to participants, 39

40 interventions, comparators, and outcomes (PICO) on September 27, 2021 by guest. Protected copyright. 41 42 Methods 43 44 45 Eligibility criteria #8 Specify the study characteristics (such as PICO, 5-8 46 study design, setting, time frame) and report 47 48 characteristics (such as years considered, 49 language, publication status) to be used as criteria 50 51 for eligibility for the review 52 53 Information #9 Describe all intended information sources (such as 8 54 55 sources electronic databases, contact with study authors, 56 trial registers or other grey literature sources) with 57 58 planned dates of coverage 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 19 of 19 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 Search strategy #10 Present draft of search strategy to be used for at Supplementary 2 3 least one electronic database, including planned material (appendix 4 limits, such that it could be repeated 1) 5 6 7 Study records - #11a Describe the mechanism(s) that will be used to 8,9 8 data management manage records and data throughout the review 9 10 11 Study records - #11b State the process that will be used for selecting 8,9 12 selection process studies (such as two independent reviewers) 13 14 through each phase of the review (that is, 15 screening, eligibility and inclusion in meta-analysis) 16 For peer review only 17 18 Study records - #11c Describe planned method of extracting data from 8 19 data collection reports (such as piloting forms, done 20 21 process independently, in duplicate), any processes for 22 obtaining and confirming data from investigators 23 24 25 Data items #12 List and define all variables for which data will be 5-9 26 sought (such as PICO items, funding sources), any 27 28 pre-planned data assumptions and simplifications 29 30 Outcomes and #13 List and define all outcomes for which data will be 5-9 31

32 prioritization sought, including prioritization of main and http://bmjopen.bmj.com/ 33 additional outcomes, with rationale 34 35 36 Risk of bias in #14 Describe anticipated methods for assessing risk of 8,9 37 individual studies bias of individual studies, including whether this 38 39 will be done at the outcome or study level, or both;

40 on September 27, 2021 by guest. Protected copyright. 41 state how this information will be used in data 42 synthesis 43 44 Data synthesis #15a Describe criteria under which study data will be 9 45 46 quantitatively synthesised 47 48 Data synthesis #15b If data are appropriate for quantitative synthesis, 9 49 50 describe planned summary measures, methods of 51 52 handling data and methods of combining data from 53 studies, including any planned exploration of 54 55 consistency (such as I2, Kendall’s τ) 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 20 of 19 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 1 Data synthesis #15c Describe any proposed additional analyses (such 8,9 2 3 as sensitivity or subgroup analyses, meta- 4 regression) 5 6 7 Data synthesis #15d If quantitative synthesis is not appropriate, 9 8 describe the type of summary planned 9 10 11 Meta-bias(es) #16 Specify any planned assessment of meta-bias(es) 9 12 (such as publication bias across studies, selective 13 14 reporting within studies) 15 16 Confidence in #17For Describe peer how the review strength of the bodyonly of evidence 9 17 18 cumulative will be assessed (such as GRADE) 19 evidence 20 21 22 None The PRISMA-P checklist is distributed under the terms of the Creative Commons Attribution 23 License CC-BY 4.0. This checklist can be completed online using https://www.goodreports.org/, a tool 24 25 made by the EQUATOR Network in collaboration with Penelope.ai 26 27 28 29 30 31

32 http://bmjopen.bmj.com/ 33 34 35 36 37 38 39

Health outcomes in international migrant children: Protocol for a systematic review

Journal: BMJ Open ManuscriptFor ID peerbmjopen-2020-041173.R2 review only Article Type: Protocol

Date Submitted by the 02-Mar-2021 Author:

Complete List of Authors: Armitage, Alice; UCL, Institute of Child Health; University College London Heys, Michelle; University College London Institute of Child Health, University College London Institute of Child Health Lut, Irina; UCL, Institute of child health Hardelid, Pia; UCL Institute of Child Health, Centre for Paediatric Epidemiology and Biostatistics

Primary Subject Global health Heading:

Secondary Subject Heading: Paediatrics, Mental health, Infectious diseases, Health policy

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1 2 3

36 http://bmjopen.bmj.com/ 37 38 39 40 41 42 43

44 on September 27, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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1 | P a g e 1 2 3 DR ALICE JANE ARMITAGE (Orcid ID: 0000-0001-6972-3651)

4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 6 7 Article type: Protocol for systematic review 8 9 10 11 12 13 Health outcomes in international migrant children: 14 Protocol for a systematic review 15 16 17 18 For peer review only 19 20 21 22 Authors: Alice Jane Armitage1, Michelle Heys2, Irina Lut3, Pia Hardelid4 23 24 25 26 Email addresses: [email protected], [email protected], [email protected], 27 [email protected] 28 29 30 1 31 Guarantor: Pia Hardelid 32 33 1. UCL, Institute of Child Health, 30 Guilford St, London, UK WC1N 1EH 34 2. University College London Institute of Child Health, University College London Institute 35 of Child Health, London, UK 36 http://bmjopen.bmj.com/ 37 3. UCL, Institute of child health, London, UK 38 4. UCL Institute of Child Health, Centre for Paediatric Epidemiology and Biostatistics 39 30 Guilford Street, London, UK WC1N 1EH 40 41 42 Correspondence to: 43 Dr Alice Jane Armitage

44 UCL Great Ormond Street Institute of Child Health, 30 Guilford St, Holborn, London WC1N on September 27, 2021 by guest. Protected copyright. 45 1EH, Tel 020 7242 9789 46 47 [email protected] 48 49 Keywords: Transients and migrants, Global health, Paediatrics, Population Health, 50 Systematic Review 51 52 53 Tables: 1 54 Figures: 0 55 Appendices: 1 56 57 58 Word Count: 3139 59 60

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4 BMJ Open: first published as 10.1136/bmjopen-2020-041173 on 3 May 2021. Downloaded from 5 Abstract 6 Introduction 7 Migration status is a key determinant of health, but health outcomes among migrant children 8 and young people (CYP), i.e. those aged under 18 years, are poorly understood. A ‘healthy- 9 migrant’ effect has been demonstrated among adults, but evidence for the same effect in CYP 10 11 is lacking. No large studies or reviews exist reporting comprehensive or holistic health 12 outcomes among migrant CYP. We aim to identify and synthesise original quantitative 13 research on health of migrant CYP to explore the relations between migration status and 14 health outcomes. 15 16 17 Methods and analysis 18 A search of Pubmed/Medline,For peer Embase and review Cochrane and greyonly literatures sites will be 19 undertaken for any original quantitative research on health outcomes of migrant CYP from 20 01/01/2000 onwards. Outcomes addressed: mortality, communicable diseases, non- 21 22 communicable diseases, nutritional status, mental health, disability, vaccine coverage, and 23 accidental and non-accidental injuries (including assault and abuse). Search results will be 24 screened and presented in a PRISMA flow diagram. 25 26 27 The Newcastle-Ottawa Scale (NOS) assessment tool will be used to assess study quality. If 28 feasible, depending on study availability data heterogeneity (explored using I2 statistic), 29 results will be pooled for meta-analysis. If sufficient data are available, a priori defined sub- 30 group analyses will be undertaken. A narrative quantitative synthesis will be presented, 31 32 taking account of study quality and assessed risk of bias. 33 34 The anticipated search completion date is 01/06/2021with write-up completed by 01/04/2022. 35