Association of Maternal Prepregnancy Dyslipidemia With Adult Offspring Dyslipidemia in Excess of Anthropometric, Lifestyle, and Genetic Factors in the Framingham Heart Study

Abstract

Adult offspring dyslipidemia is associated with maternal prepregnancy dyslipidemia in excess of measured lifestyle, anthropometric, and inherited genetic factors. The findings support the possibility of a maternal epigenetic contribution to cardiovascular disease risk in the general population. Further research is warranted to determine whether ongoing public health efforts to identify and reduce dyslipidemia in young adults prior to their childbearing years may have additional potential health benefits for the subsequent generation.

Maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature

“…Despite that, determination of early markers of endothelial dysfunction or metabolic changes in the neonates from MSPH would be necessary to associate this maternal condition with changes in the neonatal outcome. In addition, increased maternal TC has also been associated with higher atherosclerotic lesions in the childhood 9 and elevated lipid levels in the adulthood 32 of the offspring. Thus, it has been proposed that MSPH may be a maternal condition required for proper placental function with consequences on foetal vascular health during pregnancy and later in life 1 , 16 , 32 , 33 .…”

Epigenetics of Lipid Phenotypes

“…Nevertheless, these epigenetic markers—three of which overlap with known methylation correlates of fasting lipids— merit follow-up studies on the basis of their functional plausibility. Other prospective evidence comes from transgenerational studies that highlight the importance of the intrauterine environment for the risk of impaired metabolism in the offspring [27, 28]. These studies, however, are few and limited by the lack of mechanistic insights [28], repeated methylation measurements throughout the life course [22], or both.…”

Malprogramming of Hepatic Lipid Metabolism due to Excessive Early Cholesterol Exposure in Adult Progeny

“…Furthermore, although there is a normal physiological increase in maternal cholesterol (+25–50%) during pregnancy which is vital for embryogenesis and early organ development, an excessive increase in maternal serum cholesterol can manifest during pregnancy, particularly in women with elevated cholesterol prior to conception . Such an exaggerated rise in early cholesterol exposure has been associated with pre‐term delivery and low birth weight, increased childhood body mass index and adiposity, increased blood lipids in the neonatal, adolescent, and adult periods, and fetal fatty streaks that develop faster in childhood . It has been estimated that 10–25% of US women of childbearing years are hypercholesterolemic, having blood total cholesterol (TC) concentrations >240 mg dL −1 .…”

“…It has been estimated that 10%−25% of US women of childbearing years are hypercholesterolemic, having blood total cholesterol (TC) concentrations >240 mg/dL [21, 22]. This is concerning as maternal pre-pregnancy cholesterol concentration has been shown to influence the absolute increase in serum cholesterol during gestation [19] and is correlated to offspring lipid status [17].…”