Sequential Pathways of Testing After First-Trimester Screening for Trisomy 21 Journal Articles uri icon

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  • OBJECTIVE: To evaluate the performance and use of second-trimester multiple-marker maternal serum screening for trisomy 21 by women who had previously undergone first-trimester combined screening (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG), with disclosure of risk estimates. METHODS: In a multicenter, first-trimester screening study sponsored by the National Institute of Child Health and Human Development, multiple-marker maternal serum screening with alpha-fetoprotein, unconjugated estriol, and total hCG was performed in 4,145 (7 with trisomy 21) of 7,392 (9 with trisomy 21) women who were first-trimester screen-negative and 180 (7 with trisomy 21) of 813 (52 with trisomy 21) who were first-trimester screen-positive. Second-trimester risks were calculated using multiples of the median and a standardized risk algorithm with a cutoff risk of 1:270. RESULTS: Among the first-trimester screen-negative cohort, 6 of 7 (86%) trisomy 21 cases were detected by second-trimester multiple-marker maternal serum screening with a false-positive rate of 8.9%. Among the first-trimester screen-positive cohort, all 7 trisomy 21 cases were also detected in the second trimester, albeit with a 38.7% false-positive rate. CONCLUSION: Our data demonstrate that a sequential screening program that provides patients with first-trimester results and offers the option for early invasive testing or additional serum screening in the second trimester can detect 98% of trisomy 21-affected pregnancies. However, such an approach will result in 17% of patients being considered at risk and, hence, potentially having an invasive test. LEVEL OF EVIDENCE: II-2


  • Platt, Lawrence D
  • Greene, Naomi
  • Johnson, Anthony
  • Zachary, Julia
  • Thom, Elizabeth
  • Krantz, David
  • Simpson, Joe Leigh
  • Silver, Richard K
  • Snijders, Rosalinde JM
  • Goetzl, Laura
  • Pergament, Eugene
  • Filkins, Karen
  • Mahoney, Maurice J
  • Hogge, W Allen
  • Wilson, R Douglas
  • Mohide, Patrick Thomas
  • Hershey, Douglas
  • MacGregor, Scott
  • Bahado-Singh, Ray
  • Jackson, Laird G
  • Wapner, Ronald

publication date

  • October 2004

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