Cadmium exposure and health outcomes:An umbrella review of meta-analyses

Objective: This umbrella review synthesizes evidence from meta-analyses to assess the health outcomes associated with cadmium (Cd) exposure. Methods: Literature search was conducted in four Databases: PubMed, Embase, APA PsycNe, and the Cochrane Databases. Evaluating evidence strength via Assess Systematic Reviews 2 (AMSTAR 2), umbrella review methodology and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: Our review encompassed 79 non-overlapping studies, investigating 48 unique health outcomes through 113 independent effect sizes. Using the AMSTAR 2 tool, we found that 2 (3 %) meta-analyses were rated as high quality, 6 (8 %) as moderate quality, 38 as low quality, and 33 as very low quality. Applying the GRADE criteria, we observed that 1 (1 %) effect size was rated A (male fertility), 8 (7 %) were rated B (breast cancer, prostate cancer, hypertension, stroke, urolithiasis), 30 were rated C, and 74 were rated D. According to the umbrella review methodology, 5 (4 %) outcomes provided highly suggestive evidence, 13 (12 %) provided suggestive evidence, 51 provided weak evidence (class IV), and 44 had insufficient evidence for statistically significant results (class V). Meta-analyses on circulatory diseases, pregnancy outcomes, perinatal outcomes, skeletal and connective tissue diseases, neurological disorders, urinary system diseases, and male fertility had >80 % statistically significant results, while endocrine system diseases and mental and behavioral disorders had <33 %. Conclusion: Cd exposure is significantly linked to various health outcomes, with implications for clinical practice and public health recommendations.