The impact of magnesium levels in pregnancy on adverse birth outcomes: a protocol for a systematic review and meta-analysis.

backgroundMagnesium plays a critical role in maternal and fetal physiology, influencing vascular tone, inflammation, and cellular metabolism. Despite its established biological importance, evidence linking maternal magnesium status to adverse pregnancy outcomes remains inconsistent, partly due to heterogeneity in measurement methods, reference ranges, and study populations. These uncertainties are of significant public health importance globally but are of particular relevance in low- and middle-income countries (LMICs), where comorbidities such as HIV infection, anaemia, and obesity are prevalent. This review will therefore include studies from all settings while prespecifying subgroup analyses relevant to LMIC contexts.

objectivesThis systematic review and meta-analysis aims to synthesise global evidence on the association between maternal magnesium levels and adverse pregnancy outcomes. Secondary objectives are to explore trimester-specific patterns of maternal magnesium status, assess whether common comorbidities modify these associations, including HIV infection, anaemia, and obesity, and examine evidence from magnesium supplementation trials in a separate interventional evidence stream. ELIGIBILITY CRITERIA: We will include observational studies (cross-sectional, case-control, and cohort) and randomised controlled trials reporting quantitative maternal magnesium measurements and at least one adverse maternal or neonatal outcome. Peer-reviewed journal articles and postgraduate theses will be eligible, with no restrictions on language, setting, or publication year. INFORMATION SOURCES: Electronic searches will be conducted in PubMed, Embase, Scopus, Cochrane Library, DOAJ, LILACS, and African Index Medicus, alongside grey literature sources including OpenGrey and ProQuest Dissertations and Theses. RISK OF BIAS: Risk of bias will be assessed independently by two reviewers using design-specific tools: Hoy's Risk of Bias Tool for prevalence studies, ROBINS-I for non-randomised observational studies, and the Cochrane Risk of Bias 2 tool for randomised controlled trials. SYNTHESIS OF

resultsObservational and interventional studies will be analysed in separate prespecified analytic streams. Meta-analyses will be conducted where sufficient clinical and methodological homogeneity exists, using random-effects or quality-effects models. Where quantitative synthesis is not appropriate, findings will be synthesised narratively. Subgroup analyses will explore trimester of pregnancy, geographic region, laboratory measurement method, and comorbidity status. Certainty of evidence will be assessed using the GRADE framework. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42024518427.