Exposure to metal mixtures and adverse pregnancy and birth outcomes: A systematic review

Background: Prenatal exposure to metal mixtures is associated with adverse pregnancy and birth outcomes like low birth weight, preterm birth, and small for gestational age. However, prior studies have used individual metal analysis, lacking real-life exposure scenarios. Objectives: This systematic review aims to evaluate the strength and consistency of the association between metal mixtures and pregnancy and birth outcomes, identify research gaps, and inform future studies and policies in this area. Methods: The review adhered to the updated Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) checklist, along with the guidelines for conducting systematic reviews and meta-analyses of observational studies of etiology (COSMOS-E). Our data collection involved searching the PubMed, MEDLINE, and SCOPUS databases. We utilized inclusion criteria to identify relevant studies. These chosen studies underwent thorough screening and data extraction procedures. Methodological quality evaluations were conducted using the NOS framework for cohort and case-control studies, and the AXIS tool for cross-sectional studies. Results: The review included 34 epidemiological studies, half of which focused on birth weight, and the others investigated neonate size, preterm birth, small for gestational age, miscarriage, and placental characteristics. The findings revealed significant associations between metal mixtures (including mercury (Hg), nickel (Ni), arsenic (As), cadmium (Cd), manganese (Mn), cobalt (Co), lead (Pb), zinc (Zn), barium (Ba), cesium (Cs), copper (Cu), selenium (Se), and chromium (Cr)) and adverse pregnancy and birth outcomes, demonstrating diverse effects and potential interactions. Conclusion: In conclusion, this review consistently establishes connections between metal exposure during pregnancy and adverse consequences for birth weight, gestational age, and other vital birth-related metrics. This review further demonstrates the need to apply mixture methods with caution but also shows that they can be superior to traditional approaches. Further research is warranted to deeper understand the underlying mechanisms and to develop effective strategies for mitigating the potential risks associated with metal mixture exposure during pregnancy.