PROTOCOL: Association of Antenatal Cytokine Concentrations With Neurodevelopmental Disorders of the Offspring: A Scoping Review

ABSTRACT Objective This is a protocol for a Campbell review. The aim of this scoping review is to identify and map the available evidence on the association of antenatal cytokine concentrations with neurodevelopmental disorders (NDDs) of the offspring and to inform future research avenues. Introduction NDDs are a heterogeneous group of conditions with onset in childhood which affect functioning due to altered brain development. NDDs have a multifactorial aetiology with genetic, epigenetic, and environmental factors, including the foetal intrauterine environment. Maternal immune activation (MIA) alters the intrauterine milieu of the developing foetus, and, in animal studies, has been shown to affect the brain cytoarchitecture, neuronal circuitry and glial function of the offspring. One of the mechanisms of MIA is through cytokines that may play a crucial role in affecting foetal neurodevelopment by crossing the placenta and altering cellular programming. Antenatal cytokine concentrations have the potential to be biomarkers for children at risk of NDDs, and treating a maladaptive cytokine response may reduce the risk of NDDs in these children. Therefore, it is important to understand the scope of evidence available on the association of antenatal cytokine concentration with offspring NDDs and identify the research gaps in this field. Inclusion Criteria The review will consider all primary and grey literature which focuses on the review objective. The review will not be limited by any time period or any language of the sources of evidence. Method The review will be conducted following the Joanna Briggs Institute (JBI) methodological framework for scoping reviews. Review questions and inclusion criteria will follow the Population, Concept, Context framework. A comprehensive search will be performed in SCOPUS, MEDLINE (Ovid), PsycINFO (Ovid), Web of Science core collection, Embase (Ovid), CINAHL databases and trial registers. Grey literature will be searched in Google Scholar, ProQuest Dissertations & Theses Global, Open Access Theses and Dissertations and library catalogues with the assistance of the librarian. Two independent reviewers will perform title‐abstract screening and full‐text screening. Eligible studies will be critically appraised using JBI critical appraisal tools. Data from eligible studies will be extracted by two reviewers using pretested data extraction tools. Findings will be presented in a final scoping review with a narrative summary and diagrammatic forms. Significance The mapped findings and the identified research gaps will guide further research in evaluating antenatal cytokines as an early biomarker of NDDs and the potential for antenatal therapy to reduce the risk of NDDs. Registration The review protocol is registered in the Open Science Framework (Link: https://osf.io/twsuq).