Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years

Abstract

Increases in aortic pulse wave velocity, a measure of arterial stiffness, can lead to elevated systolic blood pressure and increased cardiac afterload in adulthood. These changes are detectable in childhood and potentially originate in utero, where an adverse early life environment can alter DNA methylation patterns detectable at birth. Here, analysis of epigenome-wide methylation patterns using umbilical cord blood DNA from 470 participants in the Southampton’s Women’s Survey identified differential methylation patterns associated with systolic blood pressure, pulse pressure, arterial distensibility, and descending aorta pulse wave velocity measured by magnetic resonance imaging at 8 to 9 years. Perinatal methylation levels at 16 CpG loci were associated with descending aorta pulse wave velocity, with identified CpG sites enriched in pathways involved in DNA repair ( P =9.03×10 −11 ). The most significant association was with cg20793626 methylation (within protein phosphatase, Mg2+/Mn2+ dependent 1D; β=−0.05 m/s/1% methylation change, [95% CI, −0.09 to −0.02]). Genetic variation was also examined but had a minor influence on these observations. Eight pulse wave velocity-linked dmCpGs were associated with prenatal modifiable risk factors, with cg08509237 methylation (within palmitoyl-protein thioesterase-2) associated with maternal oily fish consumption in early and late pregnancy. Lower oily fish consumption in early pregnancy modified the relationship between methylation and pulse wave velocity, with lower consumption strengthening the association between cg08509237 methylation and increased pulse wave velocity. In conclusion, measurement of perinatal DNA methylation signatures has utility in identifying infants who might benefit from preventive interventions to reduce risk of later cardiovascular disease, and modifiable maternal factors can reduce this risk in the child.