First- and second-trimester screening: detection of aneuploidies other than Down syndrome.

Abstract

OBJECTIVE:

To evaluate the performance of first- and second-trimester screening methods for the detection of aneuploidies other than Down syndrome.

METHODS:

Patients with singleton pregnancies at 10 weeks 3 days through 13 weeks 6 days of gestation were recruited at 15 U.S. centers. All patients had a first-trimester nuchal translucency scan, and those without cystic hygroma had a combined test (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG) and returned at 15-18 weeks for a second-trimester quadruple screen (serum alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin-A). Risk cutoff levels of 1:300 for Down syndrome and 1:100 for trisomy 18 were selected.

RESULTS:

Thirty-six thousand one hundred seventy-one patients completed first-trimester screening, and 35,236 completed second-trimester screening. There were 77 cases of non-Down syndrome aneuploidies identified in this population; 41 were positive for a cystic hygroma in the first trimester, and a further 36 had a combined test, of whom 29 proceeded to quadruple screening. First-trimester screening, by cystic hygroma determination or combined screening had a 78% detection rate for all non-Down syndrome aneuploidies, with an overall false-positive rate of 6.0%. Sixty-nine percent of non-Down syndrome aneuploidies were identified as screen-positive by the second-trimester quadruple screen, at a false-positive rate of 8.9%. In the combined test, the use of trisomy 18 risks did not detect any additional non-Down syndrome aneuploidies compared with the Down syndrome risk alone. In second-trimester quadruple screening, a trisomy 18-specific algorithm detected an additional 41% non-Down syndrome aneuploidies not detected using the Down syndrome algorithm.

CONCLUSION:

First-trimester Down syndrome screening protocols can detect the majority of cases of non-Down aneuploidies. Addition of a trisomy 18-specific risk algorithm in the second trimester achieves high detection rates for aneuploidies other than Down syndrome.

LEVEL OF EVIDENCE:

II.

• Authors: Fionnuala M Breathnach, Fergal D Malone, Geralyn Lambert-Messerlian, Howard S Cuckle, T Flint Porter, David A Nyberg, Christine H Comstock, George R Saade, Richard L Berkowitz, Susan Klugman, Lorraine Dugoff, Sabrina D Craigo, Ilan E Timor-Tritsch, Stephen R Carr, Honor M Wolfe, Tara Tripp, Diana W Bianchi, Mary E D'Alton, First and Second Trimester Evaluation of Risk (FASTER) Research Consortium
• Journal: Obstetrics and gynecology (Obstet Gynecol) Vol. 110 Issue 3 Pg. 651-7 (Sep 2007) ISSN: 0029-7844 [Print] United States
• PMID: 17766613 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Chorionic Gonadotropin, beta Subunit, Human
• alpha-Fetoproteins
• inhibin A
• Inhibins
• Pregnancy-Associated Plasma Protein-A
• Estriol

Topics

• Adult
• Aneuploidy
• Chorionic Gonadotropin, beta Subunit, Human (analysis)
• Diagnosis, Differential
• Down Syndrome (diagnosis)
• Estriol (blood)
• Female
• Humans
• Inhibins (blood)
• Lymphangioma, Cystic (diagnosis)
• Maternal Age
• Nuchal Translucency Measurement
• Pregnancy
• Pregnancy Trimester, First (blood)
• Pregnancy Trimester, Second (blood)
• Pregnancy-Associated Plasma Protein-A (analysis)
• Prenatal Diagnosis (methods, standards)
• Reference Values
• Sensitivity and Specificity
• Ultrasonography, Prenatal (methods)
• alpha-Fetoproteins (analysis)