First- and Second-Trimester Evaluation of Risk for Down Syndrome

Ball, Robert H. MD^1,2; Caughey, Aaron B. MD, MPP²; Malone, Fergal D. MD^3,4; Nyberg, David A. MD⁵; Comstock, Christine H. MD⁶; Saade, George R. MD⁷; Berkowitz, Richard L. MD^3,8; Gross, Susan J. MD⁹; Dugoff, Lorraine MD¹⁰; Craigo, Sabrina D. MD¹¹; Timor-Tritsch, Ilan E. MD¹²; Carr, Stephen R. MD¹³; Wolfe, Honor M. MD¹⁴; Emig, Danielle MPH¹⁵; D'Alton, Mary E. MD³ for the First and Second Trimester Evaluation of Risk (FASTER) Research Consortium

Author Information

From the¹University of Utah and Intermountain HealthCare, Salt Lake City, Utah;²University of California, San Francisco, San Francisco, California;³Columbia University College of Physicians and Surgeons, New York, New York;⁴Royal College of Surgeons in Ireland, Dublin, Ireland;⁵Swedish Medical Center, Seattle, Washington;⁶William Beaumont Hospital, Royal Oak, Michigan;⁷University of Texas Medical Branch, Galveston, Texas;⁸Mount Sinai School of Medicine, New York, New York;⁹Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York;¹⁰University of Colorado Health Sciences Center, Denver, Colorado;¹¹Tufts University School of Medicine, Boston, Massachusetts;¹²New York University School of Medicine, New York, New York;¹³Brown University School of Medicine, Providence, Rhode Island;¹⁴University of North Carolina Medical Center, Chapel Hill, North Carolina; and¹⁵DM-STAT, Boston, Massachusetts.

See related editorial on page 2.

* For a listing of other members of the FASTER Research Consortium, see the Appendix.

Supported by Grant Number RO1 HD 38652 from the National Institutes of Health and the National Institute of Child Health and Human Development. Dr. Caughey is a Women's Reproductive Health Research Scholar, sponsored by the National Institute of Child Health and Human Development, Grant # HD01262.

Corresponding author: Robert H. Ball, MD, Department of Obstetrics, Gynecology, and Reproductive Sciences, Box 0132, UCSF, San Francisco, California 94143-0132; e-mail:[email protected].

Financial Disclosure The authors have no potential conflicts of interest to disclose.

Obstetrics & Gynecology110(1):p 10-17, July 2007. |DOI:10.1097/01.AOG.0000263470.89007.e3

OBJECTIVE:

To investigate the differences in costs and outcomes of Down syndrome screening using data from the First and Second Trimester Evaluation of Risk (FASTER) Trial.

METHODS:

Seven possible screening options for Down syndrome were compared: 1) Triple Screen—maternal serum alpha fetoprotein, estriol, and hCG; 2) Quad—maternal serum alpha fetoprotein, estriol, hCG, and Inhibin A; 3) Combined First—nuchal translucency, pregnancy-associated plasma protein A (PAPP-A), free β-hCG; 4) Integrated—nuchal translucency, PAPP-A, plus Quad; 5) Serum Integrated—PAPP-A, plus Quad; 6) Stepwise Sequential—Combined First plus Quad with results given after each test; and 7) Contingent Sequential—Combined First and only those with risk between 1:30 and 1:1,500 have Quad screen. The detection rates for each option were used given a 5% false-positive rate except for Contingent Sequential with a 4.3% false-positive rate. Outcomes included societal costs of each screening regimen (screening tests, amniocentesis, management of complications, and cost of care of Down syndrome live births), Down syndrome fetuses identified and born, the associated quality-adjusted life years, and the incremental cost-utility ratio.

RESULTS:

Based on the screening results derived from the 38,033 women evaluated in the FASTER trial, the Contingent Sequential screen dominated (lower costs with better outcomes) all other screens. For example, the Contingent Sequential cost 32.3 million dollars whereas the other screens ranged from 32.8 to 37.5 million dollars. The Sequential strategy led to the identification of the most Down syndrome fetuses of all of the screens, but at a higher cost per Down syndrome case diagnosed ($719,675 compared with $690,427) as compared with the Contingent Sequential. Because of the lower overall false-positive rate leading to fewer procedure-related miscarriages, the Contingent Sequential resulted in the highest quality-adjusted life years as well. The Contingent Sequential remained the most cost-effective option throughout sensitivity analysis of inputs, including amniocentesis rate after positive screen, rate of therapeutic abortion after Down syndrome diagnosis, and rate of procedure-related miscarriages.

CONCLUSION:

Analysis of this actual data from the FASTER Trial demonstrates that the Contingent Sequential test is the most cost-effective. This information can help shape future policy regarding Down syndrome screening.