Elevated cord blood homocysteine levels in newborns prenatally exposed to particulate air pollution; results from the ENVIRONAGE birth cohort

Abstract

Introduction Particulate air pollution is thought to increase the risk of cardiovascular disease. Homocysteine is an established cardiovascular disease risk factor. Recent studies show that exposure to particulate air pollution is associated with plasma homocysteine levels in adults. For the first time, we studied in utero exposure to PM2.5 and newborns’ homocysteine levels and interaction by single nucleotide polymorphisms (SNPs) in oxidative stress-related genes. Methods In 689 newborns of the ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort, we investigated the association between prenatal PM2.5 exposure and cord plasma homocysteine levels, and interaction by 12 SNPs through multiple linear regression. PM2.5 levels were obtained using a spatial temporal interpolation method. Homocysteine levels were measured by immunoassay. SNPs were assessed on the TaqMan OpenArray SNP genotyping platform. Results In multivariable-adjusted models, cord plasma homocysteine levels increased with 4.9% (95% CI: -0.6% to 10.6%; p=0.08) for each 5 µg/m³ increment in average PM2.5 during the whole pregnancy, and 3.8% (95% CI: -0.3% to 8.0%; p=0.07) and 3.5% (95% CI: 0.8% to 6.3%; p=0.01) for the 1st and 2nd trimester, respectively. The associations between PM2.5 and homocysteine were stronger in newborns with 1 or 2 variant alleles of rs769217 in catalase (CAT) (p-interaction: 0.07 and 0.01 for whole pregnancy and 2nd trimester, respectively). With regard to 3rd trimester exposure, only neonates with 1 or 2 variant alleles of rs1800562 in the hemochromatosis gene (HFE) showed a positive association between PM2.5 and homocysteine (p-interaction: 0.004). Conclusions Exposure to particulate air pollution in pregnancy is associated with increases in cord blood homocysteine levels and the association differs by CAT and HFE genotypes. Increased air pollution-induced homocysteine levels in early life might be a risk factor for cardiovascular disease later in life.