This review will consider designs including before and after studies, prospective and retrospective cohort studies, case-control studies and analytical cross-sectional studies for inclusion. Furthermore, we will also consider descriptive epidemiological study designs including case series, individual case reports and descriptive cross-sectional studies for inclusion. In the absence of research studies, other text such as opinion papers and reports will be considered. The reviewed studies will be summarized based on their typology.

This study will primarily consider studies include migrant subjects between the ages of 2 to 18 years old from typically-developing populations regardless of gender, ethnicity/race, and country of origin/migration, with no known medical, neurobehavioral or psychological history. In this paper, a child will be considered an individual under the age of 18 years old [30]. The lower bound limit was set at age 2 years old to differentiate these groups specifically from infants [31]. In cases, where a clinical group is presented with or without a comparison normative group, the data from these studies will likewise be reported in the final documentation.

The exposure of interest shall be “migration.” Several definitions suggest that migration can be classified as either internal or external migration; while migrants can be further categorized as native-born or foreign-born. Due to the exploratory nature of this review, we will consider all of these types of migration exposures and consequently report these data, as well as the operational definitions used in the reviewed studies. However, excluded in the migration category are those results that have experienced forced migration (ie, refugees, victims of famine, disasters, etc). Previous research suggests that adverse life events in childhood may have an influence on a child’s neurobehavioral, psychophysiological or physiological development [32,33,34]. Thus, only types of voluntary migration are considered.

Part of the aim of this study is to summarize the common outcome measures to conceptualize allostatic load parameters. Based on the concept of allostasis, we will classify the outcome measures into two categories: 1) behavioral measures (ie, temperament, personality, resilience, health-seeking behaviors, etc); and 2) physiological measures (ie, heart rate, body mass index [BMI], height, weight, etc). Physiological measures may also be in the form of neurobiological or neurophysiological indices (ie, cortisol, hormones, heart rate variability, etc). Data from other outcomes not included in this protocol but emerges from this review shall be succinctly discussed in the final report.

Our search strategy aims to find peer-reviewed published studies. A three-step search strategy will be utilized in this review. An initial limited search of the included databases will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe an article by the primary author. A second search using all identified keywords and index terms will then be undertaken across all included databases. Lastly, a reference-searching strategy will be entailed among the primary studies that have gone through the second search level.

For this review, we expanded the search strategy to capture all possible studies using the following databases: Medline, CINAHL, ProQuest, PubMed, Science Direct and BioMed Central. This will be followed by an analysis of the text words contained in the title and abstract and of the index terms used to describe the article. The following databases were chosen based on the recommendation of an experienced librarian in the field of health sciences who likewise helped in validating the search terms of this review paper. The chosen databases include other databases within its system of resources, thus increasing the platform where the search strategy is employed. Studies published in English or which have an English version will be considered for inclusion in this review. The search data will range from January 2007 to December 2017. Initial keywords to be used will be: allostasis OR allostatic OR allostatic load OR allosta*; 2) migration OR migrant OR immigration OR immigrant OR migra* OR *migra*; and 3) children OR child* OR adolescen*. The use of “*” represents truncated terms implemented to increase the scope of the search for articles. This review will likewise consider dissertation papers that meet the previously mentioned inclusion criteria, provided these are appropriately indexed within the abovementioned databases and retrieved during the search. An example of search strategy and results conducted in MEDLINE is shown in Multimedia Appendix 2.

Furthermore, this review will entail contacting authors of the initially identified articles, reference list hand-searching and considering grey literature (ie, existing data sets, unpublished data, theses and dissertations, technical reports) to widen the scope of the search.

Full-text articles retrieved from the three-step search strategy and hand-searched additional articles will be screened and reviewed by two independent review authors for quality appraisal, levels of evidence and risk of bias for potential inclusion in this review. In the event of a disagreement between the two independent review authors, a meeting will be held to reach a consensus; but if a consensus cannot be reached, an independent third reviewer will be consulted. An example of the sample flow diagram of study selection procedures is shown in Multimedia Appendix 3.

Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI- MAStARI) [35]. The JBI-MAStARI is a comprehensive set of tools that guides researchers in the conduct and preparation of high-quality systematic reviews [35]. The JBI MAStARI appraisal tools are shown in Multimedia Appendix 4.We will use the NHMRC Evidence Hierarchy [36] to assign designations of “levels of evidence” according to the type of research question of the studies appraised. The NHMRC Evidence Hierarchy is shown in Multimedia Appendix 5. Any disagreements that arise between the two assigned independent reviewers will be resolved through discussion or with a third reviewer.

Quantitative data will be extracted from papers included in the review using the relevant standardized data extraction tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument [35]. The data extraction tool to be used in this research is shown in Multimedia Appendix 6. The same review authors that screened and reviewed the primary articles for review shall extract the following data:

When disagreements arise related to data extraction, a discussion will be conducted to reach a consensus on a decision. However, if a consensus cannot be reached, a third review author will be consulted. In the case of missing, incomplete or incomprehensive data, the authors of the reviewed papers will be contacted by email for clarifications and supplement of needed information whenever possible.

For assessing the risk of bias within studies, this review will adopt the Cochrane “Risk of bias” [37] tool which included the following criteria:

The risk of bias tool to be used in this research is shown in Multimedia Appendix 7. Furthermore, the risk of bias across studies shall be reported using the abovementioned criteria from the Cochrane [37] group, with additional criteria added in response to other authors’ recommendations [38,39]. On this basis we added two criteria, “Outcome Measure Processes” and “Age Inclusions” using the thresholds for across studies judgment as suggested [39]:

Assessment of risk of bias shall be undertaken by two review authors where discrepancies are identified and resolved through discussion to reach a consensus on results, while a third author will be consulted in case a consensus cannot be met.

Quantitative papers, when possible, will be pooled in a statistical meta-analysis using JBI-MAStARI [35]. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% CI will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different quantitative study designs included in this review.

Where statistical pooling is not possible, the findings will be presented in a narrative form including tables and figures to aid in data presentation where appropriate. This will involve the aggregation or synthesis of conclusions to generate a set of statements that thematically represents such aggregation through accumulating and categorizing these conclusions on the basis of congruency in meaning. The following themes will be narratively reported in the report: