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Maternal Serum Screening for Fetal Trisomy 18: A Comparison of Fixed Cutoff and Patient-Specific Risk Protocols

From the Division of Human Genetics, Department of Pediatrics; Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology; and the Department of Pediatric Dentistry, University of Connecticut Health Center, Farmington, Connecticut.

Address reprint requests to: Peter Benn, PhD University of Connecticut Health Center Division of Human Genetics 263 Farmington Avenue Farmington, CT 06030-6140 E-mail: benn{at}nso1.uchc.edu.

Objective: To compare the effectiveness of two widely used protocols for second-trimester screening for fetal trisomy 18.

Methods: Second-trimester screening results for 41,565 women were reviewed to determine whether pregnancies could be considered to be at high risk for trisomy 18. The screening test was considered positive if either maternal serum concentrations of alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3) fell below defined levels, or the second-trimester patient-specific risk (based on maternal age and serum analytes) was greater than 1:100. Detection rates, false-positive rates, and pregnancy outcomes for the two protocols were compared.

Results: The fixed-cutoff method showed a 23% detection rate and a 0.19% false-positive rate for trisomy 18. These low rates were in close agreement with a theoretical expectation for fixed-cutoff trisomy 18 screening. The risk-based approach resulted in a 69% detection rate and a 0.45% false-positive rate. Both methods identified pregnancies with other fetal anomalies.

Conclusion: Overall, the risk-based method is more effective than the fixed-cutoff approach to trisomy 18 screening.

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