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A systematic review protocol to explore the prevalence and impacts of neurodevelopmental disorders in the care experienced by looked after population


 Background: Looked after children (LAC) placed in either a foster care, kinship, residential or adoption care settings continue to develop debilitating disorders that significantly impact their future overall wellbeing. Prevalence of these disorders are often depicted under broad categories such as mental, behavioural or neurodevelopmental disorders (NDDs). Limited in research, is the prevalence of specific disorders that fall under these broad categories.NDDs such as autism or attention deficit hyperactivity disorder which cannot be medically tested for and fall under an umbrella group in the current, expert field of genetics and neuropsychiatry will be explored. Unsupported, these disorders can lead to suboptimal health and social outcomes for both the child and family. In the general population, prevalence of these NDDs and impacts on health and social wellbeing are relatively well documented but for minority groups such as LAC; research is extremely limited. This review will aim to estimate the prevalence of NDDs in LAC and compare to those children who are not looked after. Additionally, it will identify if NDDs have any impact on the health and social wellbeing of this vulnerable group.Methods: This review will report in accordance with the guidelines outlined in the Preferred Reporting items for Systematic Reviews and Meta-Analyses. PubMed, ASSIA, IBSS, Web of Science, PsychINFO, Scopus, Psych articles, Social Care Online, secondary, grey literature and government publications will be searched to identify any eligible studies. No restrictions will be placed on age or design of publication. Eligible studies must include participants, 25 years of age or under and have confirmed diagnoses using standardised international diagnostic codes or tools. Odds ratio and 95% confidence intervals using the random-effects model will be utilised to analyse the data. The Joanna Briggs Institute critical appraisal tools will be utilised to assess quality and bias.Discussion: Attaining an estimated prevalence of these NDDs in the LAC group and identifying any impacts on health and social wellbeing will contribute to the existing but limited LAC literature. From a preventative perspective, the results will inform key stakeholders in health, educational and social sectors with important information to aid in safeguarding and meeting the unique needs of these vulnerable children.Systematic review registration: PROSPERO Registration number: CRD4201913103

Systematic review registration: PROSPERO Registration number: CRD4201913103 Background Research continues to depict a bleak future for looked after children; predicting inauspicious health and social outcomes [1][2][3][4][5][6][7][8]. Although, research in LAC is still limited; poor outcomes associated with mental health, disability, suicide, criminal system involvement, teenage parenthood, substance misuse and educational attainment have become the predicted 'norm' for these children [1][2][3][4][5][6][7][8]. These discouraging findings have prompted governments to address these concerns; positioning this population at the forefront of policy and legislation [9,10]. Yet despite being classified as a high-risk group; factors such as multiple placements, residential moves, poor screening in development and education, delays in service provision, limited data collation, consent and segregated service sectors are still suggested to contribute to these outcomes [11][12][13].
Situated within these poor outcomes and currently, major priority objectives for government; are the areas of mental health and educational attainment [9]. Both factors are suggested to be intrinsically linked; forming and underpinning the fundamental building blocks to achieving subjective wellbeing and increasing social mobility [15][16]. Although major priorities for all children in the UK; research proposes that LAC are nine times more likely to have a special educational need due to social, emotional, behavioural, developmental and learning difficulties and four times more likely to have a mental health disorder compared to those not in the care setting and [14,[17][18][19].
The prevalence of psychiatric disorders is well documented in research as being higher in the LAC population; often suggested to be as a result of adverse childhood experiences or poor socioeconomic environments [20 -24]. However, these prevalence studies are often depicted and categorised under broad headings; such as mental, behavioural, emotional or developmental disorders [18, 21,25]. Although, significant findings; limited within secondary literature is a more indepth, individual analysis of what specific disorders represent these broad categories.
All psychiatric disorders can significantly impact on the individuals' mental health, emotions, memory, ability to learn and socialize at some point in their life [26,27]. Some may affect the individual on an intermittent basis or manifest during periods of immense stressful or challenging life events [26,27]. 4 However; there is emerging research in the psychiatric and neurological field that suggest that some disorders originate during or after birth and are classified as 'neurodevelopmental' disorders or are associated as such by leading experts in the field [28][29][30][31][32]. These disorders, like other psychiatric disorders significantly cause developmental deficits in emotional regulation, memory, and ability to learn and socialize.These disorders however remain for life [28][29][30][31][32].
There is a wide spectrum of neurodevelopmental disorders which can be diagnosed with a medical test; disorders such as Prader-Willi Syndrome or Fragile X Syndrome [33,34]. However, many neurodevelopmental disorders can only be diagnosed solely based on behaviour [35,36]. As a result, due to the often similar and complex behavioural symptomology associated with these neurodevelopmental disorders; many children do not attain a diagnosis until they reach adolescent or adult age [36 -38]. Furthermore, emerging research proposes that many of these neurodevelopmental disorders co-exist and therefore, make diagnosis even more challenging for the professional [39]. This lack of early diagnosis and intervention can leave the child struggling in the home, school and social setting with no support or understanding; attempting to navigate a world that makes no sense to them which frequently results in a detrimental impact on their health and social wellbeing [36][37][38]40]. This review will explore the prevalence and impact of neurodevelopmental disorders that are based on classifications defined in previous studies in the field of neurodevelopmental disorders but cannot be medically tested for [28][29][30][31][32]. The disorders of interest for this review will be Foetal Alcohol such as low sample numbers [1,3,20]. Nevertheless, with increased awareness of the diversity of how these disorders manifest in the child increasing in the psychiatric field and diagnostic accuracy 5 improving; research into these neurodevelopmental disorders has much improved [34][35][36]. Willis et al (2017) recently conducted a systematic review and found that the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) was suggested to be higher in in the LAC population compared to NoN-LAC [42]. Although, a significant finding, this review differs as the inclusion criteria includes two further 'looked after' groups; children who have been adopted or children who have been placed in a kinship care setting. Additionally, this review will screen both published and unpublished articles to alleviate anticipated publication bias due to the nature of the outcomes of interest [42,43].
Nevertheless, what is integral and of significant importance is that early identification and intervention of these neurodevelopmental disorders are key determinants for improving overall future health and social outcomes [44,45]. For the front-line professional who is primarily responsible for referring the LAC to appropriate services; research ascertains that many professionals still address this area as challenging, creating potentially significant barriers for early intervention [46]. Difficult to diagnose and often concealed from front line professionals, they are often inadvertently overlooked by the professional; as the urgency to treat or provide the child with support overrides further exploration of the underlying behavioural symptomology [47,48]. This can often lead to neurodevelopmental disorders being misdiagnosed or missed altogether in the general population and LAC population [47,48]. Unfortunately, as a result, these underlying neurodevelopmental disorders do not become apparent until the child reaches a mental health crisis point; particularly the adolescent era where services are then forced to intervene [47,48].
Furthermore, the results attained from this review might add some value to the existing body of literature that suggest that there might be familial risk, heritability and possible genetic factors associated with some of these disorders [28][29][30][31][32]49]. From an economic and policy perspective; with rising statistics of children entering the care system and an urgent need to meet their needs; this review proposes it is an appropriate time to add to the existing literature in this field. The review will aim to address the following research questions:

1.
How does the prevalence of these neurodevelopmental disorders in the Looked after population compare with those children who are NoN-LAC? 6 2.
What early impact do these disorders have on the health and social wellbeing of the Looked after child?

Methods
This protocol has been registered with the PROSPERO database for systematic reviews (Registration number: CRD4201913103) and will be reported in accordance with the guidelines outlined in the Preferred Reporting items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). The review will follow the PRISMA-P guidance and all processes will be clearly defined in the review [50].

Search Strategy
The PICO approach has been used to help define the primary research question and formulate the search strategy.
Does the child (P) who is in a looked after care setting (I) compared to those children that are not placed in the care setting (C) have a higher prevalence (O) of these neurodevelopmental disorders?
As observational and descriptive studies draw inference from a sample to a population; where there are limits in logistics and ethical considerations; it is anticipated that these studies will be the most prevalent in this review. However, all designs will be included providing they meet the inclusion and quality criteria [51].
The following databases will be searched to identify relevant primary literature for the review: PubMed, ASSIA, IBSS, Web of Science, PsychINFO, Scopus, Psych articles, Social Care Online. The proposed databases were selected based on those identified in other peer reviewed studies that explored similar outcomes of interest and were agreed and deemed appropriate by all authors [54,55].
The review will additionally systematically hand search published and unpublished secondary, grey and governmental literature as they can be a rich information source for exploring citations and reference lists to further identify any new primary articles. Furthermore, exploring unpublished literature will contribute to alleviating potential publication bias [43,53].
Due to the breadth of the research questions; there will be two stages to the search strategy. The first stage will explore the prevalence of these neurodevelopmental disorders in the LAC population and if 7 feasible compare to NoN-LAC. The second stage will explore any impacts on health and social wellbeing as a result of having these disorders.

Eligibility Criteria
No restriction will be placed on the age of publication. Publications in the English language and international literature will be included; however, it is recognised that there are limitations to this approach.
The legal definition for a 'Looked After Child' varies on an international level, however the review will be guided by the legal definitions underpinning the United Kingdom (UK), derived from both the Children Act 1989 and the Children Act 1995, Scotland (RCPCH, 2015). There will be a broad restriction on the terminology used to identify a child in care (adopted, residential, LAC, adopted, out of home care, foster child, kinship care) to ensure the review encapsulates the majority of children who are or have been in care; which coincides with governmental legislation, policy and third sector terminology for the definition of this population (RCPCH, 2015).
There will be no restriction on the care setting or time placed in a care as many of these children transition into different care settings such as adoption; residential or group care; reside with close family members or re-enter the care system [56]. The only restriction is that the child will have been placed in a care setting for over 24 hours which coincides with UK legislation. NoN-LAC will be defined as children or young adults that are not in a care setting or have never been in the care setting. There are limitations to this, as a child may have re-entered the care setting pre or prior to when the study collated the data [56]. However, this will be acknowledged as a limitation in the review.
As there is a duty of care to support some of these children up to the age of 25 in the UK; this will be the upper limit to the restriction. This will enable the review to capture those individuals who might have been diagnosed later in their life with these neurodevelopmental disorders. Additionally, this time period will enable the review to explore the earlier impacts on the health and social wellbeing of these children, as a result of having these neurodevelopmental disorders; for earlier intervention purposes. Additional adverse life experiences after leaving the care setting are often associated with this population; therefore, going any higher in age although a significant knowledge gap in research; 8 could confound the results of the review [56].
Synonyms associated with the neurodevelopmental disorders being explored as detailed in Table 1 will be included in the search strategy. As these neurodevelopmental disorders are life-long; this review aims to attain a life-time prevalence and compare prevalence between the LAC population and their NoN-LAC peers [31]. Only comparative studies that explore prevalence of these neurodevelopmental disorders between these two groups will be used to conduct a meta-analysis.
With the introduction of the new International Classification of Diseases 11th Revision (ICD-11) guidelines which acknowledge that many of these neurodevelopmental disorders now co-exist; this review will include studies that have prevalence rates for children who have more than one diagnosis [57].
Only studies that have confirmed diagnoses, or have used diagnostic codes defined by the diagnostic statistical manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD) or standardised diagnostic assessment tools which are guided by the DSM and ICD will be included in the review. It is accepted that there are limitations to this approach as coding of disorders can be often be applied without clinician interviews [58]. It is also important to note that there will be limitations to what diagnostic manual was used at the time of diagnosis as the diagnostic criteria would have changed over time for some of these disorders [58].
Furthermore, there are standardised diagnostic assessment tools which have been suggested to be male biased or thresholds of criteria too low to attain a diagnosis for varying reasons [59]. The review will follow other studies of similar methodology and include in the characteristics the description of the tools, codes and diagnostic manual used for transparency purposes. The review will acknowledge any limitations and address them in the review. There will be no predefined health and social impacts or outcomes; due to the anticipated, limited studies in this area with regards to these vulnerable children and the specific associated disorders being explored. Predefining these might prohibit or exclude any important impacts or outcomes that might be affecting these children as a result of having these disorders.

Study Selection
The review will be undertaken by three reviewers. Two reviewers will critically analyse, code and appraise the selected studies. The third reviewer will be assigned as mediator; should the review need to reach consensus on any final selected studies.
Initially, all studies will be screened by review of title, followed by review of abstract as demonstrated by the search strategy already conducted (see Appendix 1).
The next stage will be to apply the exclusion and inclusion criteria and remove studies that do not fit the specified criterion. Following this, all remaining papers will be fully screened. As the study is exploring two areas of interest; the study selection will be divided into two stages. The first stage will select and appraise the selected studies that meet the inclusion criteria for the prevalence of these disorders and the second stage will appraise the selected studies that meet the inclusion criteria for impacts on health and social wellbeing.
The review will also ensure that the studies captured by the systematic reviews are not duplicated and that no significant or new literature has been missed during, preceding or proceeding when the systematic reviews were conducted. Intermittent searches will also be conducted while the review is being undertaken to ensure that new literature is not missed [60].
After the searches are conducted; a reviewer's meeting will be scheduled to seek consensus and to agree if any more primary studies should be included in the review; to aid in addressing the research questions.

Data collection and extraction
An extraction form will be designed to collate the information related to the areas of interest.
Characteristics such as study name, country, total sample size, age, gender (% male), type of placement, case ascertainment method, disorder, diagnostic system used, diagnostic instrument, number of cases of neurodevelopmental disorders and any impacts on health and social wellbeing.
The form will systematically provide clear and unambiguous results to enable further analysis to occur [60].

Quality and Bias assessment
To screen and assess the quality of the literature in this review; the Joanna Briggs Institute (JBI) critical appraisal tools will be utilised [61]. These are appropriate tools that have been used in other reviews and suggested to be applicable due to the diversity of the designs normally anticipated in a systematic review [61]. All appraisal tools will address the bias in design, conduct and analysis [61].
For consistency purposes, two reviewers will independently assess and appraise the studies [60]. If there is a divergence in assessment, a review meeting will be arranged and the third reviewer will become mediator to reach consensus. This will be documented within the review as a narrative summary, to provide clarity and transparency.

Data Synthesis and Analysis
Data synthesis and analysis will be guided by the studies that are selected for review. If feasible. a meta-analysis will be conducted. The first stage will aim to estimate a pooled prevalence of the specific disorders in the LAC population versus the NoN-LAC population [60]. If sample sizes are too small the review will also transform the data into number of cases per population to enable an effect size to be calculated. [60].
It is anticipated that there may be high heterogeneity between studies, therefore, the random effect model will be used to estimate a mean of a distribution of effects [60,62]. Using this model should provide a more balanced weight to smaller and larger studies to estimate a more standardised mean effect. [60,62]. Effect will be expressed as odds ratio with a proportion of 95% confidence intervals around the summary estimates. Forest plots will be used to provide a graphical representation of the results. To address publication bias, the funnel plot or trim and fill method will be used; although it is anticipated that the trim and fill method will be more appropriate due to the smaller studies associated with the care experienced population [60,[62][63].
Subsequently, where statistical analysis is not possible; a descriptive analysis will be provided detailing the prevalence ranges of the neurodevelopmental disorders (eg, ADHD ranged from 2% to 16% in six of the studies) and characteristics of the studies.
A thematic analysis will be used to enable a framework and narrative synthesis to occur. All information relating to the impacts on the health and social wellbeing of this population; as a result of having these neurodevelopmental disorders will be double coded by two reviewers. In the final stage, all analyses will be amalgamated to provide a discussion of the results attained.

Software considerations
The SUMARI software package, a comprehensive review management system that has been designed to assist researchers in the health and social sciences to conduct and support systematic reviews will be utilised to extract, critically appraise and part analyse the data [64]. To conduct the meta-analysis; the RevMan 5.0 software package will be used to meet the needs of the research design [65].

Dissemination and Research Integrity
The findings will be disseminated through various pathways, such as peer review journals, public and third sector organisations, Welsh government policy departments, the Children's Commissioner, appropriate paediatric National and International Conferences; using various methods such as posters, websites and presentations.

Limitations 12
The protocol anticipates that there will be several limitations to acknowledge, due to the complexities that surround this population. One limitation may be that there will be differences in the definition of a LAC or NoN-LAC; which will be noted and addressed in the review should it impact the results in anyway. It is also acknowledged that diagnostic criteria will have evolved and changed; in relation to the classification of these disorders outlined in the previous and current ICD and DSM. Although, the rationale for making the upper age limit 25 is detailed, a limitation to this could be that the review excludes older individuals with or without these disorders and possibly additional information regarding health and social wellbeing. Any limitations that arise during the review process will be documented and included within the final systematic review publication.

Discussion
Early identification and early intervention are key components to improving health and social wellbeing. Rates of children entering the care system are increasing on a global level; demands on services are placing immense pressures on government funding, third sectors, front line services, families and more importantly, on the children themselves [66,67]. With data collection and diagnostic accuracy progressing at a considerable rate; this review will contribute to the exploration and prevalence of these neurodevelopmental disorders, that are often and sometimes very difficult to diagnose. For this vulnerable, high-risk population who are embedded in services, early identification and intervention are still unattainable for many, due to the multi-faceted complexities that encompass their lives. Therefore, from an impact perspective, the results of this review could provide policy and services with key information that might further explain what dynamics may be driving demands into children service and aid in directing appropriate services to meet the needs of these children.

Ethics approval and consent to participate
Not applicable. Due to the nature of this review, no ethical approval is needed. However, ethical