A Global Perspective of Correlation Between Maternal Copper Levels and Preeclampsia in the 21st Century: A Systematic Review and Meta-Analysis

BACKGROUND: Preeclampsia (PE) is a common multi-system disorder in pregnancy and a major cause of maternal and perinatal morbidity and mortality globally. Copper is a crucial micronutrient for human health. METHODS: A systematic review was performed according to Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) guidelines to synthesize the best available evidence regarding the correlation between maternal copper levels and PE from women with different geographical and economic backgrounds. RESULTS: A total of 34 studies containing 2,471 women with PE and 2,888 healthy pregnant controls across 16 countries were included for research. All studies were systematically reviewed and assessed with the Newcastle-Ottawa Scale (NOS), The Agency of Healthcare for Research and Quality (AHRQ) assessment tools according to the study types. Globally, there was no significant difference in maternal serum copper levels between women with PE and control (Mean difference 5.46, 95% CI −9.63, 20.54). Sub-group analysis from geographical and economic perspectives revealed contrasting results. In conclusion, copper is associated with PE, but the levels of copper leading to increased risk of PE varied across regions and economic development. CONCLUSIONS: The deranged maternal copper levels are correlated with risks of PE, but it presents variously across different geographical and economic contexts. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=306536. Identifier: CRD42022306536.