Developmental learning disorders in children with prenatal/perinatal exposure to hypoxia: A systematic review protocol

Background Developmental learning disorder (DLD) belongs to neurodevelopmental disorders because it results from the developmental neurodiversity of the brain. The main causes of DLD are genetics, but environmental factors, like inadequate supply of oxygen during pregnancy or labor, are considered. Methods Our search strategy will consist of electronic databases (PubMed, PsycINFO, Web of Science, EMBASE, and Cochrane Library) and hand searching. The observational studies including cohort and case-control studies will be included. The primary outcome will be (DLD). Screening and eligibility will be done independently by two reviewers based on pre-specified eligibility criteria. Data extraction will be based on a pre-pilot data extraction form, and conducted by two authors independently. Study quality will be assessed by two authors independently. Any discrepancies identified at any stage of the review will be resolved by discussion or/and consultation with another reviewer. We plan a narrative and tabular summary of the findings. Discussion This systematic review of aetiology follows the traditional approach to evidence-based healthcare. This secondary research will assess the association between hypoxia and DLD by assessing the relationship of health-related event and outcome and examining the association between them. This review can provide information for healthcare professionals and policymakers indicating whether taking into account information about hypoxia should be permanently included in the diagnostic ontogenetic interview in the process of diagnosing neurodevelopmental disorders. Systematic review registration PROSPERO: CRD42022371387.


Rationale 6
To the best of our knowledge, there is no systematic review nor meta-analysis on the association between exposure to prenatal/perinatal hypoxia and the occurrence of DLD symptoms at school age.Therefore, our motivation is to conduct the first systematic review of previous published observational studies (i.e., cohort studies, and case-control studies) that consider, as an exposure, presence of hypoxia during pregnancy or delivery and consider, as an outcome, DLD in the school-age children, as defined by the DSM-5 classification of neurodevelopmental outcomes.The understanding of the association between health-related event -hypoxia during pregnancy or delivery and outcome -DLD in school-age children will provide evidence in aetiology of DLD and thus, improve our understanding of the state of knowledge.The aim of this paper is to present the protocol for the aforementioned systematic review.Objectives 7 This systematic review seeks to address the research question: Whether prenatal hypoxia is associated with developmental learning disorder in school age?

Eligibility criteria 8
Studies will be chosen based on the pre-specified below mentioned eligibility criteria.Population (types of participants).The participants in the included studies will have been of primary school age, with no restrictions on sex or nationality, and have been diagnosed with DLD.DLD should have been diagnosed according to the national standards.Due to the research question of aetiology, we aim to exclude prematurely born children (defined as delivery up to 36;9 weeks of gestation).
Exposure of interest (independent variable).The review will include studies that consider, as an exposure, presence of prenatal/perinatal hypoxia indicated in the child's medical records.
Comparator/Control.We will include studies with participants of primary-school age, with no restrictions on nationality and without history of prenatal/perinatal hypoxia.Outcome (dependent variable).The review will include studies that consider, as an outcome, presence of developmental learning disorder.Study Type.We will include observational studies including cohort and case-control studies.
Location.We will not impose any restrictions on the location of the conducting of the research.Information sources 9 We will search the National Medical Library, PsycINFO, Web of Science, EMBASE, DARE, and the Cochrane Library.Electronic database searching will be complemented by manual data searches.Reference lists of the included review articles will be checked to identify any additional studies.The search will be not restricted to any year of publication, sample size, or language (provided an English language translation of the abstract is available).We will exclude editorials and letters.Search strategy 10 Medical Subject Headings (19) or equivalent and text word terms and words related to the nosological unit will be used to develop literature search strategies.Boolean operators and proximity operators (parentheses and quotations) will also be used.Data management 11a One reviewer will search databases and handsearch the reference list of the included review articles.All potentially relevant records will be extracted to EndNote reference management software.At this stage, duplicates will be detected and deleted.After a year additional search will be done the same way.

Selection process 11b
Two authors independently will extract data from the studies based on a specifically designed data extraction form.Discrepancies will be resolved by discussion or/and consultation with third reviewer.Authors will be contacted in order to obtain any missing data or for clarification.Data collection process 11c Data will be extracted from the studies independently by two authors based on a purpose-designed pre-piloted data extraction form.This will be done by content area experts in the field of clinical psychology who are familiar with DLD and who will receive training in coding of entries.Any discrepancies will be resolved by consultation/discussion with another reviewer.If a discrepancy cannot be resolved, we will contact by e-mail the study authors; if we are unsuccessful in doing so, we will report the discrepancies in the review.We will attempt to obtain any missing data from corresponding authors by e-mail.For different reports describing the same study/project, data will be extracted from each report separately and combined across multiple data collection forms afterwards.

Data items 12
The following information will be extracted from the studies: Outcome will be expressed as associations identified in the studies between prenatal hypoxia is associated with developmental learning disorder.Odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to assess the relationship between prenatal hypoxia is associated with developmental learning disorder.The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias in each included study.Two independent versions of NOS will be used to evaluate cohort and case-control studies.The NOS judge eight items, categorized into three domains including selection, comparability, and in respect to the study type -outcome (cohort studies) or exposure (casecontrol studies).Each study could receive a maximum of nine stars (one star for each numbered item within the selection and outcome categories, and a maximum of two stars for comparability).Two review authors will independently assess potential biases while any discrepancies will be resolved by discussion between reviewers; if necessary, content area experts from clinical trial methodology will be included in the discussion.Risk of bias will be categorized as "good", "fair", and "poor" for converting NOS assessments following guidelines of the Agency for Healthcare Research and Quality (AHRQ).Studies scored for 3 or 4 stars in the selection domain, 1 or 2 stars in the comparability domain, and 2 or 3 stars in the outcome/exposure domain will be considered to represent good quality.Studies rated 2 stars in the selection domain, 1 or 2 stars in the comparability domain, and 2 or 3 stars in the outcome/exposure domain were considered to represent fair quality.Papers evaluated as being 0 or 1 stars in the selection domain, 0 stars in the comparability domain, and 0 or 1 stars in the outcome/exposure domain were considered to be poor quality.We don't plan to evaluate an overall quality of evidence since there are no plans for a meta-analysis.Data synthesis 15a NaN 15b NaN 15c NaN 15d Both narrative and tabular summary will be used to present evidence of the relationship of health-related event and outcome and examining the association between them.We do not plan to conduct a meta-analysis because we expect high heterogeneity of data measurement tools across country.Narrative synthesis will be done following domains: 1) Developing a preliminary synthesis of findings of included studies 2) Exploring relationships within and between studies a) Developing a theory explaining the role of hypoxia as a aetiological risk factor for neurodevelopmental disorders in the form of DLD depending on the DLD subtype (dyslexia, dysorthography, reading and math problems); b) Assessing The Narrative Synthesis (NS) guidelines will allow us to transparently report the data from the included studies.We will use the tools and techniques for assessing robustness of the synthesis described in the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews.This will allow you to assess the quality of the collected data.* It is strongly recommended that this checklist be read in conjunction with the PRISMA-P Explanation and Elaboration (cite when available) for important clarification on the items.Amendments to a review protocol should be tracked and dated.The copyright for PRISMA-P (including checklist) is held by the PRISMA-P Group and is distributed under a Creative Commons Attribution Licence 4.0.From: Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart L, PRISMA-P Group.Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.BMJ.2015 Jan 2;349(jan02 1):g7647.
The search strategy will include terms relating to outcome (Learning Development Disorders [MeSH] OR Learning Disabilities OR dyslex* OR legasthenia OR learning disorder OR learning difficult* OR learning disabilit* OR LD OR RD OR SLD OR LRD OR DLD OR reading difficult* OR reading disabilit* OR reading impairment OR reading disorder* OR impairment in reading) and exposure of interest (hypoxia OR asphyxia OR oxygen deficiency OR oxygen shortage OR asphyxiation OR suffocation).The initial search strategy (including searching terms and filters) has already been piloted on PubMed in June 2023 to investigate whether it can find potentially relevant reports.Study records: if the presence of hypoxia in a group of children with DLD increases the risk of comorbidity of other neurodevelopmental disorders.c)Assessingif the occurrence of perinatal hypoxia increases the risk of DLD and DLD with comorbid neurodevelopmental disorders depending on the sex of the child.