Combining β‐core fragment and total oestriol measurements to test for Down syndrome pregnancies

Abstract

Recent articles by Cuckle et al., Canick et al., and Isozaki et al. have evaluated urine beta-core fragment as a screening test for Down syndrome in second-trimester pregnancies. They found over four-fold elevation of beta-core fragment levels in Down syndrome pregnancies, and between 62 and 88 per cent detection of this trisomy at a 5 per cent false-positive rate. Urine beta-core fragment may be a superior screening test for Down syndrome pregnancies. In the present study, urinary total oestriol has been evaluated as a marker to use in combination with beta-core fragment in screening for Down syndrome pregnancies. The two markers were evaluated separately in relation to the urine creatinine concentration. To amplify screening performance, we evaluated the ratio of beta-core fragment to total oestriol levels (creatinine-independent). beta-core fragment and total oestriol levels were determined (normalized to creatinine, ng/mg creatinine) in urine samples from 480 unaffected and 12 Down syndrome pregnancies, collected consecutively at a single prenatal diagnosis centre. The median beta-core fragment level in Down syndrome cases was 4.5 MOM. Fifty-eight per cent of Down syndrome cases had beta-core fragment levels exceeding the 95th centile of unaffected pregnancies. The median total oestriol level in Down syndrome cases was 0.33 MOM. Forty-two per cent of Down syndrome cases had total oestriol levels exceeding the 95th centile of unaffected pregnancies. We investigated the ratio of the two determinants (beta-core fragment, ng/ml divided by total oestriol, ng/ml) in our sample set. The median beta-core fragment:total oestriol ratio in Down syndrome cases was 13 MOM. Seventy-five per cent of Down syndrome cases had a ratio exceeding the 95th and the 99.5th centile of unaffected pregnancies. Total oestriol complements beta-core fragment in urine screening for Down syndrome pregnancies. A test measuring the ratio of the two urine determinants may be a significant improvement over current serum methods for detecting Down syndrome.