A PROSPECTIVE EVALUATION OF A 2ND-TRIMESTER SCREENING-TEST FOR FETAL DOWN-SYNDROME USING MATERNAL SERUM ALPHA-FETOPROTEIN, HCG, AND UNCONJUGATED ESTRIOL

Objective: To test the efficacy of a screening protocol using a combination of maternal age plus three biochemical markers-maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3)-for the antenatal detection of fetal Down syndrome. Methods: We conducted a prospective cohort study of 7718 women who underwent the triple-marker analysis between weeks 15-18 of pregnancy. A second-trimester risk for Down syndrome of 1:195 or greater was considered positive. Sensitivity, specificity, positive predictive value, and their 95% confidence intervals (Cls) were calculated. We evaluated test performance for various maternal age groups and screen-positive cutoffs, as well as the relative screening efficacies of maternal age and MSAFP, MSAFP plus hCG, and MSAFP, hCG, and unconjugated E3. Results: Four hundred sixty-one of the 7718 women screened (6%) were identified as positive; 319 women chose amniocentesis, for an overall amniocentesis rate of 4.1%. Twenty of 22 pregnancies affected with Down syndrome were correctly identified, as were 7255 of 7696 unaffected pregnancies, yielding a sensitivity and specificity of 91% (95% CI 79-100%) and 94% (95% CI 93.8-94.8%), respectively. The use of maternal age plus all three analytes improved test performance compared with maternal age plus MSAFP and hCG, but either had a significantly improved detection rate compared with that for maternal age and MSAFP alone. Conclusion: The triple-marker screen appears to be an effective method of detecting Down syndrome pregnancies while maintaining an acceptable amniocentesis rate.