The Early Life Exposome: Associations with Child Lipid Profile

摘要

Background: High cholesterol levels during childhood have been associated with increased risk of atherosclerosis later in life. Apart from traditional risk factors for dyslipidemia, such as high fat diet and obesity, the contribution of environmental exposures on variations in lipid levels in childhood, is unclear. Aim: To assess the impact of a wide array of environmental exposures during pregnancy and childhood on lipid profiles in children using an exposome-wide approach. Methods: Within the HELIX exposome project, we measured over 90 prenatal and 110 childhood environmental exposures in 1,301 mother-child pairs from 6 European countries. We also measured in 2-hour fasting plasma samples, total (TC), high-density (HDL), low-density (LDL) lipoprotein cholesterol, and triglyceride (TG) levels at the age of 6-11 years. Associations were assessed using agnostic exposome-wide analyses (ExWAS) correcting for multiple comparisons. Results: Childhood exposure to organochlorine compounds was associated with increased lipids. Exposure to hexachlorobenzene (HCB) was associated with higher TC, LDL and TG levels (mean change per IQR increase: 6.6 mg/dL, 95% CI: 4.4 to 8.8; 5.7 mg/dL, 95% CI: 3.6 to 7.8 and 6.0 mg/dl, 95% CI: 2.6 to 9.4 respectively) after multiple testing correction. Dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) childhood levels were also associated with increased TGs (6.9 mg/dl, 95% CI: 3.4 to 10.4 and 9.6 mg/dl, 95% CI: 5.4 to 13.9 respectively). Childhood exposure to polybrominated diphenyl ether (PBDE 153) was associated with a 5.2 mg/dL change in TC (95% CI: 2.6 to 7.8), while copper exposure was associated with a -1.7 mg/dL change in HDL (95% CI: -2.7 to -0.8) and a 3.3 mg/dL change in LDL (95% CI: 1.5 to 5.1). Conclusions: Children with higher exposure to organochlorine compounds and copper had higher levels of lipids. Further work is needed to examine the underlying mechanisms and to exclude the role of reverse causation.