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

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Abstract

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.

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