Trace element with cytokine interactions reveal a magnesium interaction with inflammation-insulin-like growth factor...

Neural tube defects (NTDs) are severe congenital malformations with complex genetic, nutritional, and environmental causes. Beyond folate deficiency, the role of micronutrient imbalance, inflammation, and growth signaling remains unclear. This study aimed to evaluate demographic characteristics, maternal and child serum trace elements, inflammatory markers, and insulin-like growth factor 1 (IGF-1) in relation to NTD risk.

A case-control study was conducted on 342 participants, comprising children with NTDs and their mothers, along with matched healthy controls. Serum concentrations of selenium (Se), iron (Fe), chromium (Cr), and magnesium (Mg) were quantified using atomic absorption spectrophotometry, while tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), and IGF-1 were measured via enzyme-linked immunosorbent assay (ELISA). Non-parametric tests, correlations, regression, and canonical analyses assessed group differences and biomarker associations. Docking studies predicted metal-binding sites and explored Mg-IGF-1 interactions.

In children, Mg and Cr concentrations were significantly lower in NTD cases, while TNF-α and IL-6 were elevated; IGF-1 was markedly reduced (all p < .01). Among mothers, Mg deficiency strongly distinguished cases from controls (p < .001, r = 0.86), along with higher TNF-α and IL-6 and lower IGF-1. Mg showed negative correlations with TNF-α and IL-6 and a positive correlation with IGF-1. Regression analysis showed that both IGF-1 and IL-6 independently predicted Mg concentrations (R² = 0.217, p < .001). Canonical correlation identified Mg and Fe as major trace element contributors, with IGF-1 and IL-6 dominating the biomarker set. Docking analysis indicated specific residues in IGF-1 as potential Mg-binding sites.

Magnesium deficiency links inflammation with impaired IGF-1 signaling in NTD pathogenesis. It may serve as a modifiable biomarker, and Mg-targeted interventions could complement folic acid in NTD prevention.