Exposure to Heavy Metals and Allergic Outcomes in Children: a Systematic Review and Meta-analysis

It has been reported that heavy metals have adverse effects on the immune system. However, the relationship between heavy metal exposure and allergic outcomes remains unclear. This systematic review was conducted to examine whether heavy metal exposure is associated with allergic outcomes during childhood. We performed a systematic search of all relevant articles in Web of Science, EMBASE, and PubMed, from inception through to November 2020. We used odds ratio (OR) and the standard mean differences (SMDs) with 95% confidence intervals (CIs) to present estimates from individual studies. In addition, random-effects meta-analysis was used to pool the data. We also conducted the meta-regression and subgroup analysis to explore potential sources of heterogeneity. After duplicate removal, we finally included 35 articles in the systematic review and meta-analysis from an initial 11,181 articles. The overall results showed that copper (Cu) was associated with asthma (pooled SMD = 1.50, 95% CI = 0.13-2.86); in the subgroup analysis, the results indicated that lead (Pb) was associated with asthma (pooled OR = 6.27, 95% CI = 2.24-17.56), and Cu and Pb were connected with atopic dermatitis (SMD =  - 1.05, 95% CI =  - 1.45 to - 0.65; SMD = 5.68, 95% CI = 5.05-6.32), respectively. Mercury (Hg) was associated with atopic dermatitis (pooled OR = 1.13, 95% CI = 1.04-1.22) and wheeze (OR = 1.20, 95% CI = 1.05-1.37). The meta-analysis results indicate that Cu might be connected with childhood asthma, but not with other allergic diseases; Hg and Pb may have no association with allergic diseases during childhood. Given some limits observed in the current studies, more prospective cohort studies are still needed to verify our findings. Review registration: PROSPERO CRD42020222167.