Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece

Abstract

Background: Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures.

Objective: To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood.

Methods: This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log₂-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated.

Results: BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood.

Impact statement: Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.

Keywords: Children’s cardiometabolic health; Cholesterol; Environmental mixtures; Essential elements; Low-density lipoprotein; Toxic metals.

Fig. 1. Joint associations of the metals with low-density lipoprotein at 4 years of age, estimated by BKMR (n = 291).

Mn manganese, Co cobalt, Se selenium, Mo molybdenum, Cd cadmium, Hg mercury, Pb lead. All models were adjusted for maternal education, child sex, child secondhand smoke exposure at 4 years of age, and child fish/seafood intake at 4 years of age. A Difference in the outcome when setting all metals in the mixture to different percentiles compared with the reference (50th percentile) with corresponding 95% credible intervals. B Exposure-response functions and corresponding 95% credible intervals for each metal while holding the other exposures at their 50th percentiles. C Exposure-response function for each metal exposure (column) with the second exposure (row) fixed at its 10th, 50th, and 90th percentiles while holding the other exposures at their 50th percentiles.