Urinary free beta hCG, beta core fragment and total oestriol as markers of Down syndrome in the second trimester of pregnancy

Abstract

In a study of 69 random urine samples from cases of Down syndrome and 405 samples from unaffected pregnancies, we have assessed the value of various candidate markers that have been proposed as tools for screening for Down syndrome. We found that the marker urine free beta hCG in Down syndrome had a median MoM of 3.53 (95 per cent confidence interval 2.48-4.68) and at a 5 per cent cut-off would have identified 49 per cent (34/69) of cases. Urine beta core had a median MoM of 4.95 (3.87-8.62) and at a 5 per cent cut-off would have identified 39 per cent (27/69) of cases. Total oestriol had a median MoM of 0.65 (0.55-0.80) and at a 5 per cent cut-off would have identified 35 per cent (24/69) of cases. In conjunction with maternal age, the modelled detection rate increased to 55.8 per cent for free beta hCG, 49.8 per cent for beta core and 48.8 per cent for total oestriol. In combination free beta hCG, total oestriol and maternal age would have detected 68 per cent of cases for a 5 per cent false-positive rate. Using analyte ratios to obviate the need to correct for urine dilution in our study (rather than correcting to a fixed creatinine concentration) was not shown to be as effective as correcting using urine creatinine. Urine markers on the whole are unlikely to be of practical screening value considering the 85 per cent to 90 per cent detection rates achievable in the first trimester using a combination of ultrasound and maternal serum biochemistry.