First-trimester combined test and integrated tests for screening for Down syndrome and trisomy 18
- Geralyn M Messerlian, PhD
Geralyn M Messerlian, PhD
- Professor of Pathology & Laboratory Medicine
- Alpert Medical School of Brown University
- Antonio Farina, MD
Antonio Farina, MD
- Associate Professor of Obstetrics & Gynecology
- University of Bologna, Italy
- Glenn E Palomaki, PhD
Glenn E Palomaki, PhD
- Associate Professor of Pathology and Laboratory Medicine
- Alpert Medical School of Brown University
First-trimester and integrated screening tests for Down syndrome and trisomy 18 will be reviewed here. Other aspects of Down syndrome screening are discussed separately:
A glossary of terms describing the various tests used in first- and second-trimester screening for Down syndrome is provided in the table (table 1).
- Reddy UM, Mennuti MT. Incorporating first-trimester Down syndrome studies into prenatal screening: executive summary of the National Institute of Child Health and Human Development workshop. Obstet Gynecol 2006; 107:167.
- Canick JA, Kellner LH. First trimester screening for aneuploidy: serum biochemical markers. Semin Perinatol 1999; 23:359.
- Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-trimester screening for Down's syndrome. Prenat Diagn 1997; 17:821.
- Spencer K, Macri JN, Aitken DA, Connor JM. Free beta-hCG as first-trimester marker for fetal trisomy. Lancet 1992; 339:1480.
- Haddow JE, Palomaki GE, Knight GJ, et al. Screening of maternal serum for fetal Down's syndrome in the first trimester. N Engl J Med 1998; 338:955.
- Wald NJ, George L, Smith D, et al. Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy. International Prenatal Screening Research Group. Br J Obstet Gynaecol 1996; 103:407.
- Canick JA, Lambert-Messerlian GM, Palomaki GE, et al. Comparison of serum markers in first-trimester down syndrome screening. Obstet Gynecol 2006; 108:1192.
- Palomaki GE, Lambert-Messerlian GM, Canick JA. A summary analysis of Down syndrome markers in the late first trimester. Adv Clin Chem 2007; 43:177.
- Nicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 2004; 191:45.
- Crossley JA, Aitken DA, Cameron AD, et al. Combined ultrasound and biochemical screening for Down's syndrome in the first trimester: a Scottish multicentre study. BJOG 2002; 109:667.
- Krantz DA, Hallahan TW, Orlandi F, et al. First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency. Obstet Gynecol 2000; 96:207.
- Wapner R, Thom E, Simpson JL, et al. First-trimester screening for trisomies 21 and 18. N Engl J Med 2003; 349:1405.
- Spencer K, Spencer CE, Power M, et al. One stop clinic for assessment of risk for fetal anomalies: a report of the first year of prospective screening for chromosomal anomalies in the first trimester. BJOG 2000; 107:1271.
- Muller F, Benattar C, Audibert F, et al. First-trimester screening for Down syndrome in France combining fetal nuchal translucency measurement and biochemical markers. Prenat Diagn 2003; 23:833.
- Bindra R, Heath V, Liao A, et al. One-stop clinic for assessment of risk for trisomy 21 at 11-14 weeks: a prospective study of 15 030 pregnancies. Ultrasound Obstet Gynecol 2002; 20:219.
- Avgidou K, Papageorghiou A, Bindra R, et al. Prospective first-trimester screening for trisomy 21 in 30,564 pregnancies. Am J Obstet Gynecol 2005; 192:1761.
- Wald NJ, Rodeck C, Hackshaw AK, et al. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). Health Technol Assess 2003; 7:1.
- Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med 2005; 353:2001.
- Cusick W, Buchanan P, Hallahan TW, et al. Combined first-trimester versus second-trimester serum screening for Down syndrome: a cost analysis. Am J Obstet Gynecol 2003; 188:745.
- Gekas J, Durand A, Bujold E, et al. Cost-effectiveness and accuracy of prenatal Down syndrome screening strategies: should the combined test continue to be widely used? Am J Obstet Gynecol 2011; 204:175.e1.
- Evans MI, Krantz DA, Hallahan TW, Galen RS. Meta-analysis of first trimester Down syndrome screening studies: free beta-human chorionic gonadotropin significantly outperforms intact human chorionic gonadotropin in a multimarker protocol. Am J Obstet Gynecol 2007; 196:198.
- Spencer K, Crossley JA, Aitken DA, et al. Temporal changes in maternal serum biochemical markers of trisomy 21 across the first and second trimester of pregnancy. Ann Clin Biochem 2002; 39:567.
- Szabó J, Gellén J. Nuchal fluid accumulation in trisomy-21 detected by vaginosonography in first trimester. Lancet 1990; 336:1133.
- Nicolaides KH, Azar G, Byrne D, et al. Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy. BMJ 1992; 304:867.
- Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A. SURUSS in perspective. BJOG 2004; 111:521.
- Spencer K, Bindra R, Nix AB, et al. Delta-NT or NT MoM: which is the most appropriate method for calculating accurate patient-specific risks for trisomy 21 in the first trimester? Ultrasound Obstet Gynecol 2003; 22:142.
- Cuckle H, Platt LD, Thornburg LL, et al. Nuchal Translucency Quality Review (NTQR) program: first one and half million results. Ultrasound Obstet Gynecol 2015; 45:199.
- Hermann M, Fries N, Mangione R, et al. Nuchal translucency measurement: are qualitative and quantitative quality control processes related? Prenat Diagn 2013; 33:770.
- Palomaki GE, Eklund EE, Neveux LM, Lambert Messerlian GM. Evaluating first trimester maternal serum screening combinations for Down syndrome suitable for use with reflexive secondary screening via sequencing of cell free DNA: high detection with low rates of invasive procedures. Prenat Diagn 2015; 35:789.
- Huang T, Dennis A, Meschino WS, et al. First trimester screening for Down syndrome using nuchal translucency, maternal serum pregnancy-associated plasma protein A, free-β human chorionic gonadotrophin, placental growth factor, and α-fetoprotein. Prenat Diagn 2015; 35:709.
- Johnson J, Pastuck M, Metcalfe A, et al. First-trimester Down syndrome screening using additional serum markers with and without nuchal translucency and cell-free DNA. Prenat Diagn 2013; 33:1044.
- Huang T, Boucher K, Aul R, et al. First and second trimester maternal serum markers in pregnancies with a vanishing twin. Prenat Diagn 2015; 35:90.
- Lambert-Messerlian, GM, Palomaki, GE, Knight, et al. Dimeric inhibin-A as a marker for Down syndrome in the first trimester. Am Coll Med Genet, 2004 Ann Clin Genet Mtg, Mar 4-7, Orlando, FL, Abstr No 63.
- Abele H, Wagner P, Sonek J, et al. First trimester ultrasound screening for Down syndrome based on maternal age, fetal nuchal translucency and different combinations of the additional markers nasal bone, tricuspid and ductus venosus flow. Prenat Diagn 2015; 35:1182.
- Ghaffari SR, Tahmasebpour AR, Jamal A, et al. First-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency, nasal bone, tricuspid regurgitation and ductus venosus flow combined with maternal serum free β-hCG and PAPP-A: a 5-year prospective study. Ultrasound Obstet Gynecol 2012; 39:528.
- Hsiao CH, Cheng PJ, Shaw SW, et al. Extended first-trimester screening using multiple sonographic markers and maternal serum biochemistry: a five-year prospective study. Fetal Diagn Ther 2014; 35:296.
- Wald NJ, Watt HC, Hackshaw AK. Integrated screening for Down's syndrome on the basis of tests performed during the first and second trimesters. N Engl J Med 1999; 341:461.
- Rausch DN, Lambert-Messerlian GM, Canick JA. Participation in maternal serum screening following screen positive results in a previous pregnancy. J Med Screen 2000; 7:4.
- Palomaki GE, Steinort K, Knight GJ, Haddow JE. Comparing three screening strategies for combining first- and second-trimester Down syndrome markers. Obstet Gynecol 2006; 107:367.
- Platt LD, Greene N, Johnson A, et al. Sequential pathways of testing after first-trimester screening for trisomy 21. Obstet Gynecol 2004; 104:661.
- ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol 2007; 109:217.
- Tul N, Spencer K, Noble P, et al. Screening for trisomy 18 by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation. Prenat Diagn 1999; 19:1035.
- Lambert-Messerlian, G, Canick, J, Malone, F, Porter, F, et al. First trimester levels of maternal serum hCG and inhibin A in pregnancies affected by fetal trisomy 18: A FASTER Trial study. Annual Meeting of the American College of Medical Genetics, Orlando, FL, March 4-7, 2004.
- Breathnach FM, Malone FD, Lambert-Messerlian G, et al. First- and second-trimester screening: detection of aneuploidies other than Down syndrome. Obstet Gynecol 2007; 110:651.
- Palomaki GE, Neveux LM, Knight GJ, Haddow JE. Maternal serum-integrated screening for trisomy 18 using both first- and second-trimester markers. Prenat Diagn 2003; 23:243.
- Kagan KO, Wright D, Valencia C, et al. Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free beta-hCG and pregnancy-associated plasma protein-A. Hum Reprod 2008; 23:1968.
- Kagan KO, Avgidou K, Molina FS, et al. Relation between increased fetal nuchal translucency thickness and chromosomal defects. Obstet Gynecol 2006; 107:6.
- FIRST-TRIMESTER COMBINED TEST
- Timing of blood sample and ultrasound
- - Beta-HCG
- - PAPP-A
- - Nuchal translucency
- OTHER FIRST-TRIMESTER SCREENING TESTS
- INTEGRATED TESTS
- Timing of blood samples and ultrasound
- Serum integrated test
- Step-wise sequential screening
- TEST PERFORMANCE
- The SURUSS trial
- The FASTER trial
- Screen-positive first-trimester combined test results
- Screen-positive integrated test results
- Screen-negative first-trimester or integrated test results
- Detection of structural anomalies
- DETECTION OF TRISOMY 18
- First-trimester combined test
- Integrated test
- Screen-positive trisomy 18 results
- DETECTION OF OTHER ANEUPLOIDIES
- PREDICTION OF ADVERSE PREGNANCY OUTCOME
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS