TRISOMY-21 IS ASSOCIATED WITH HYPERCHOLESTEROLEMIA DURING INTRAUTERINE LIFE

OBJECTIVE: Because individuals with Down syndrome appear to be protect ed from the development of atherosclerosis, we aimed to assess whether blood lipid and lipoprotein concentrations are different from control s in fetuses with trisomy 21. STUDY DESIGN: Eighteen fetuses with tris omy 21 and seven with trisomy 18 undergoing blood sampling at 18 to 36 weeks' gestation were matched by gestational age and size with an equ al number of controls. Cholesterol and triglycerides were assayed in a ll 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 a n equivalent number of controls. RESULTS: When compared with the refer ence range, fetuses with trisomy 21 had significantly increased choles terol levels (median Z score 2.31, 95% confidence interval 1.57 to 3.0 8, 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 lipopr oteins were similar. There were no differences between fetuses with tr isomy 18 and their matched controls. A value of fetal cholesterol grea ter than or equal to 85 mg/dl had a sensitivity of 72% and specificity of 95% in detecting fetuses with trisomy 21. CONCLUSIONS: Fetuses wit h trisomy 21 have abnormalities of lipid metabolism that are specific and may be genetically determined. The finding of high cholesterol lev els in fetuses undergoing blood sampling for indications other than ka ryotyping should prompt investigation of fetal chromosomes because of the increased risk of trisomy 21. The mechanism through which high lev els of cholesterol during prenatal life are not leading to increased r isk of atherosclerosis remains to be elucidated.