Fatty Streak Formation in Human Fetal Aortas Is Enhanced by Maternal Hypercholesterolemia

This study examined fetal aortas from 82 pregnancies to determine whether atherosclerotic fatty streaks form before birth — and whether maternal cholesterol levels influence the extent of these earliest lesions.

Fatty streaks were found in fetal aortas at birth, and their extent was significantly greater in the offspring of hypercholesterolemic mothers. In affected fetuses, oxidized LDL accumulated in the intima before monocyte recruitment — suggesting that LDL oxidation and intimal retention are the initiating events in atherogenesis, not monocyte infiltration.

The clinical and conceptual significance is substantial. Atherosclerosis is not a disease that begins with a modifiable adult risk exposure. The earliest lesions are established in utero, driven by maternal lipid metabolism, and the sequence of events (LDL oxidation first, inflammation second) supports the lipid-retention model of atherosclerosis over the inflammation-first model.

This finding also raises questions about the transgenerational cardiovascular impact of maternal lipid control during pregnancy — a dimension of prevention that has received less attention than adult risk management.

We rate the evidence moderate. A well-executed observational study establishing that atherosclerosis begins in utero under the influence of maternal lipids, with important implications for both the biology and the timeline of cardiovascular disease prevention.