Meta-analysis of first trimester Down syndrome screening studies: free β-human chorionic gonadotropin significantly outperforms intact human chorionic gonadotropin in a multimarker protocol

Objective: The purpose of this study was to compare free β and intact human chorionic gonadotropin in first trimester screening with pregnancy-associated plasma protein-A and nuchal translucency. Study Design: A Monte Carlo simulation trial was conducted based on a literature review of the PUBMED database (1966 to November 2005). Results: In younger patients (<35 years), detection of Down syndrome increased by 4, 5, 6, and 7 percentage points when free β was added to pregnancy-associated plasma protein-A and nuchal translucency compared with 0, 0, 2, and 4 percentage points for intact human chorionic gonadotropin at 9-12 weeks' gestation, respectively. In advanced maternal age patients (≥35), inclusion of free β-human chorionic gonadotropin reduced the false-positive rate by 2.5, 3.1, 3.8, and 4.4 percentage points compared with 0.1, 0.3, 1.0, and 2.2 percentage points for intact human chorionic gonadotropin at 9-12 weeks, respectively. Conclusion: The results of our analysis suggest that in a first-trimester Down syndrome screening protocol free β-human chorionic gonadotropin achieves higher sensitivity and lower false-positive results than intact human chorionic gonadotropin . Moreover, intact human chorionic gonadotropin does not add substantially to screening performance until the end of the first trimester.