Trisomy 21 is associated with hypercholesterolemia during intrauterine life

Because individuals with Down syndrome appear to be protected from the development of atherosclerosis, we aimed to assess whether blood lipid and lipoprotein concentrations are different from controls in fetuses with trisomy 21.

Eighteen fetuses with trisomy 21 and seven with trisomy 18 undergoing blood sampling at 18 to 36 weeks' gestation were matched by gestational age and size with an equal number of controls. Cholesterol and triglycerides were assayed in all fetuses and compared with the reference range constructed from 157 normal fetuses. High-density lipoproteins and apoproteins A and B were assayed in eight fetuses with trisomy 21, four with trisomy 18, and an equivalent number of controls.

When compared with the reference range, fetuses with trisomy 21 had significantly increased cholesterol levels (median Z score 2.31, 95% confidence interval 1.57 to 3.08, p = 0.0001). Cholesterol and apoprotein A concentrations were also significantly higher than in fetuses with normal karyotypes matched by gestational age and size at sampling, whereas other lipids and lipoproteins were similar. There were no differences between fetuses with trisomy 18 and their matched controls. A value of fetal cholesterol > or = 85 mg/dl had a sensitivity of 72% and specificity of 95% in detecting fetuses with trisomy 21.

Fetuses with trisomy 21 have abnormalities of lipid metabolism that are specific and may be genetically determined. The finding of high cholesterol levels in fetuses undergoing blood sampling for indications other than karyotyping should prompt investigation of fetal chromosomes because of the increased risk of trisomy 21. The mechanism through which high levels of cholesterol during prenatal life are not leading to increased risk of atherosclerosis remains to be elucidated.