ABNORMAL MATERNAL SERUM LEVELS OF HUMAN CHORIONIC-GONADOTROPIN FREE SUBUNITS IN TRISOMY-18

We have measured maternal serum levels of free α and β subunits of human chorionic gonadotropin between 8 and 12 weeks of gestation in 704 women at increased risk for trisomy. This group was studied because of advanced maternal age or a previous birth with chromosomal abnormality. All sera had been collected prior to chorion villus biopsy for prenatal diagnosis. Serum levels of free α and βhCG were determined by specific monoclonal antibody-based immunoradiometric assays. Analysis of chorionic tissue showed that in 38 of 704 (5.4%) pregnancies the fetus had a chromosome abnormality. There were 8 fetuses with trisomy 18 (1.1%) and 9 (1.3%) with trisomy 21. In all pregnancies carrying a trisomy 18 fetus, we observed either high levels of free αhCG or low levels of free βhCG or both. More importantly, the calculated ratio of free βhCG/αhCG was less than 0.25 multiples of the median (MoM) in 6 of 8 (75%) trisomy 18 cases. Only 21 of 666 mothers (3.2%) carrying a normal fetus had a ratio less than 0.25 MoM (P < 0.0001). There was no difference between this ratio in trisomy 21 and normal pregnancy. Thus, when adjusted for gestational age, a low free βhCG/αhCG ratio in maternal serum indicates a pregnancy at high risk [RR = 72 (95% CI 32, 162)] for trisomy 18.