Elemental metabolomics in human cord blood: Method validation and trace element quantification

Background: Trace elements are an essential requirement for human health and development and changes in trace element status have been associated with pregnancy complications such as gestational diabetes mellitus (GDM), pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth. Elemental metabolomics, which involves the simultaneous quantification and characterisation of multiple elements, could provide important insights into these gestational disorders. Methods: This study used an Agilent 7900 inductively coupled plasma mass spectrometer (ICP-MS) to simultaneously measure 68 elements, in 166 placental cord blood samples collected from women with various pregnancy complications (control, hypertensive, PE, GDM, FGR, pre-term, and post-term birth). Results: There were single element differences across gestational outcomes for elements Mg, P, Cr, Ni, Sr, Mo, I, Au, Pb, and U. Hypertensive and post-term pregnancies were significantly higher in Ni concentrations when compared to controls (control = 2.74 mu g/L, hypertensive = 6.72 mu g/L, post-term = 7.93 mu g/L, p < 0.05), iodine concentration was significantly higher in post-term pregnancies (p < 0.05), and Pb concentrations were the lowest in pre-term pregnancies (pre-term = 2.79 mu g/L, control = 4.68 mu g/L, PE = 5.32 mu g/L, GDM = 8.27 mu g/L, p < 0.01). Further analysis was conducted using receiver operating characteristic (ROC) curves for differentiating pregnancy groups. The ratio of Sn/Pb showed the best diagnostic power in discriminating between control and pre-term birth with area under the curve (AUC) 0.86. When comparing control and post-term birth, Mg/Cr (AUC = 0.84), and Cr (AUC = 0.83) had the best diagnostic powers. In pre-term and post-term comparisons Ba was the best single element (81.5%), and P/Cu provided the best ratio (91.7%). Conclusions: This study has shown that analysis of multiple elements can enable differentiation between fetal cord blood samples from control, hypertensive, PE, GDM, FGR, pre and post-term pregnancies. This data highlights the power of elemental metabolomics and provides a basis for future gestational studies.