Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study

Background Children generally have low cholesterol and no clinical manifest ations of atherosclerosis, but fatty-streak formation begins in fetuses and is greatly increased by maternal hypercholesterolaemia during pregnancy. I n the FELIC study we assessed the evolution of such lesions during childhoo d. Methods Computer-assisted imaging was used to measure the area of the large st individual lesion and the cumulative lesion area per section in serial c ross-sections through the entire aortic arch and abdominal aorta of 156 nor mocholesterolaemic children aged 1-13 years, who died of trauma and other c auses. Children were classified by whether their mother had been normochole sterolaemic (n=97) or hypercholesterolaemic (n=59) during pregnancy. Athero sclerosis was correlated with 13 established or potential risk factors. Findings The largest fatty streaks in the aortic arch of children younger t han 3 years of hypercholesterolaemic mothers were 64% smaller than those pr eviously found in corresponding fetuses (p<0.0001), which suggests that fet al fatty streaks may regress after birth. In the two groups, lesion size in the aortic arch and abdominal aorta increased linearly with age (r=0.87-0. 98). However, lesions progressed strikingly faster in children of hyperchol esterolaemic mothers than in those of normocholesterolaemic mothers (p<0.00 01). Conventional risk factors for atherosclerosis in children or mothers c orrelated with lesion size, but did not account for the faster progression of atherogenesis in normocholesterolaemic children of hypercholesterolaemic mothers. Interpretation Our results suggest that maternal hypercholesterolaemia duri ng pregnancy induces changes in the fetal aorta that determine the long-ter m susceptibility of children to fatty-streak formation and subsequent ather osclerosis. If so, cholesterol-lowering interventions in hypercholesterolae mic mothers during pregnancy may decrease atherogenesis in children.