Association between Cu/Zn/Iron/Ca/Mg levels and cerebral palsy: a pooled-analysis

It was well documented that macro/trace elements were associated with the neurodevelopment. We aimed to investigate the relationship between copper (Cu)/zinc (Zn)/iron/calcium (Ca)/magnesium (Mg) levels and cerebral palsy (CP) by performing a meta-analysis. We searched the PubMed, Embase, Cochrane and Chinese WanFang databases from January 1985 to June 2022 to yield studies that met our predefined criteria. Standard mean differences (SMDs) of Cu/Zn/Iron/Ca/Mg levels between CP cases and healthy controls were calculated using the fixed-effects model or the random-effects model, in the presence of heterogeneity. 95% confidence intervals (CI) were also computed. Sensitivity analysis was performed by omitting each study in turn. A total of 19 studies were involved in our investigation. CP cases showed markedly lower Cu, Zn, iron and Ca levels than those in controls among overall populations (SMD =  - 2.156, 95% CI - 3.013 to - 1.299, P < 10^-4; SMD =  - 2.223, 95% CI - 2.966 to - 1.480, P < 10^-4; SMD =  - 1.092, 95% CI - 1.513 to - 0.672, P < 10^-4; SMD =  - 0.757, 95% CI - 1.475 to - 0.040, P = 0.038) and Asians (SMD =  - 2.893, 95% CI - 3.977 to - 1.809, P < 10^-4; SMD =  - 2.559, 95% CI - 3.436 to - 1.683, P < 10^-4; SMD =  - 1.336, 95% CI - 1.807 to - 0.865, P < 10^-4; SMD =  - 1.000, 95% CI - 1.950 to - 0.051, P = 0.039). CP cases showed markedly lower Zn level than that in controls among Caucasians (SMD =  - 0.462, 95% CI - 0.650 to - 0.274, P < 10^-4). No significant differences of Cu, iron and Ca levels between CP cases and controls among Caucasians (SMD =  - 0.188, 95% CI - 0.412 to 0.037, P = 0.101; SMD =  - 0.004, 95% CI - 0.190 to 0.182, P = 0.968; SMD = 0.070, 95% CI - 0.116 to 0.257, P = 0.459) were observed. No marked difference of Mg level between CP cases and controls was noted among overall populations (SMD =  - 0.139, 95% CI - 0.504 to 0.226, P = 0.455), Asians (SMD =  - 0.131, 95% CI - 0.663 to 0.401, P = 0.629), and Caucasians (SMD =  - 0.074, 95% CI - 0.361 to 0.213, P = 0.614). Sensitivity analysis did not change the overall results significantly for Cu, Zn, iron and Mg. CP cases demonstrated significantly lower levels of Cu/Zn/iron/Ca than those in healthy controls, particularly in Asians. Decreasing trend of Cu/Zn/iron/Ca levels merit attention, particularly in the population with high susceptibility to CP. Frequent monitoring and early intervention may be needed.