Multiple screening for fetal Down's syndrome with the classic triple test, dimeric inhibin A and ultrasound

Abstract

The aim of the study was to determine whether inhibin combined with ultrasound improves the classic second trimester triple test. Eighteen Down's syndrome and 200 euploid pregnancies were included. Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and estriol (E3), measured between 15 and 20 weeks' gestation by radioimmunoassay, were retrieved. Inhibin A was tested with a specific two-monoclonal-antibody ELISA. Ultrasound was performed between 15 and 25 weeks' gestation: femur length, nuchal thickness and morphological abnormalities were assessed. Statistical analysis used a multivariate discriminant analysis. Except for the classic triple test parameters, only inhibin and the standard deviation score (SDS) for femur length allowed us to make a statistically significant distinction between euploid and Down's syndrome pregnancies. For a 5% false-positive rate, the classic triple test sensitivity was 61%. When E3 was replaced with inhibin A, the sensitivity increased to 77.8% and to 66.7% with SDS femur length. Combining hCG, AFP, SDS femur length and inhibin A gave a sensitivity of 66.7% for a false-positive rate of 2.5%. In conclusion, the classic triple test can be more significantly improved by replacing E3 with inhibin than by including ultrasound. However, a combination of ultrasound and inhibin enhances both the sensitivity and specificity of the test. In Down's syndrome screening, the biological parameters improve sensitivity while ultrasound is a better indication of specificity.