Using “Degree of Extremeness” instead of “Multiples of Median” in first trimester risk assessment for Down syndrome—an improved method or just a gimmick in face of political motivations?
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The concept of first trimester Down syndrome screening based on (NT) nuchal translucency measurement was introduced by the Fetal Medicine Foundation (FMF), London, in the late 1990s. For Germany, the mandate of NT training and auditing was assigned to the newly established German branch of the FMF in 2002. In January 2007, following the organisational split between FMF London and FMF Germany, the FMF Germany released its own, novel calculation software (“Prenatal risk calculation”, PRC), for this field. It is the aim of this study to compare the modified biochemical calculation method based on “Degree of Extremeness” (DoE) with the well-proven concept of “Multiple of Median” (MoM).
Materials and methods
The fβ-hCG and PAPP-A values of 266 first trimester examinations were categorised by gestational age, nicotine consumption and body weight. For each, a scatter plot and Pearson correlation was derived. As a second step, only patients with no nicotine consumption and a body weight between 55 and 65 kg were considered. The remaining 84 cases were again classified by gestational age and a statistical analysis was performed.
The correlation of the DoEs with the respective MoM values was found to be quite good (r = 0.76, P < 0.01). After dividing the population by gestational age, the cohort of early pregnancies showed a steeper fß-hCG correlation curve than later stages. The examination regarding nicotine consumption showed no significant differences between smokers and non-smokers. In contrast, maternal body weight was found to have a marked influence. When only body weights between 55 and 65 kg were included and smokers were excluded, the Pearson correlations clearly converged.
In this study, the utilisation of DoEs instead of MoMs was not clearly superior but it also did not seem to be inappropriate. However, it is most problematic to ignore evidently meaningful factors like body weight and ethnicity. It must also be considered risky to introduce a new calculation software to the market, when it is not clear whether the test performance is in fact comparable to established software concepts, especially in view of the fact that not only a new (unproven) database, but also a new (again unproven) algorithm is used in the PRC software. As the new program has not been evaluated yet, the test performance parameters should be validated urgently.
- Krampl E, Wertaschnigg D, Husslein P (2002) Down-Syndrom-Screening im ersten Trimenon. Geburtshilfe Frauenheilk 62(9):843–848 CrossRef
- Schuchter K, Wald N, Hackshaw AK, Hafner E, Liebhart E (1998) The distribution of nuchal translucency at 10–13 weeks of pregnancy. Prenat Diagn 18:281–286 CrossRef
- Wapner R, Thom E, Simpson JL, Pergament E, Silver R, Filkins K, Platt L, Mahoney M, Johnson A, Hogge WA, Wilson RD, Mohide P, Hershey D, Krantz D, Zachary J, Snijders R, Greene N, Sabbagha R, MacGregor S, Hill L, Gagnon A, Hallahan T, Jackson L (2003) First-trimester screening for trisomy-21 and 18. N Engl J Med 349:1405–1413 CrossRef
- Snijders RJM, Noble P, Sebire N, Souka A, Nicolaides KH (1998) UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation: fetal medicine foundation first trimester screening group. Lancet 351:343–346 CrossRef
- Eiben B, Hackelöer J, Huesgen G, Kozlowski P, Merz E, Osmers R, Wagner H (2002) Zur pränatalen Risikopraezisierung im 1. Trimenon der Schwangerschaft über die fetale Nackentransparenzmessung und über die biochemische Analyse aus dem maternalen Serum. Ultraschall Med 23(3):154–159
- Merz E (2002) 11-14SSW Screening – Zertifizierte Ultraschalluntersuchung und zertifizierter biochemischer Test in der Frühgravidität. Ultraschall Med 23(3):161–162 CrossRef
- Eiben B, Thode C, Glaubitz R, Merz E (2007) Das neue Ersttrimesterscreening-Programm PRC der FMF-Deutschland—erste Erfahrungen zur Trisomie-21-Entdeckungsrate. Frauenarzt 48(5):468–470
- Merz E (2007) First trimester screening—a new algorithm for risk calculation of chromosomal anomalies developed by FMF Germany. Ultraschall Med 28:270–272 CrossRef
- Palomaki GE, Haddow JE (1987) Maternal serum alpha-fetoprotein, age, and Down syndrome risk. Am J Obstet Gynecol 156(2):460–463
- Schetinin V, Fieldsend JE, Partridge D, Coats TJ, Krzanowski WJ, Everson RM, Bailey TC, Hernandez A (2007) Confident interpretation of Bayesian decision tree ensembles for clinical applications. IEEE Trans Inf Technol Biomed 11(3):312–319 CrossRef
- Wald NJ, Hackshaw AK (1997) Combining ultrasound and biochemistry in first-trimester screening for Down’s syndrome. Prenat Diagn 17:821–829 CrossRef
- Spencer K, Souter V, Tul N, Snijders R, Nicolaides KH (1999) Screening program for trisomy 21 at 10/14 weeks using fetal nuchal translucency, maternal serum free β-human chorionic gonadotropin an prgnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 13:231–237 CrossRef
- Yigiter AB, Kavak ZN, Bakirci N, Gokaslan H (2006) Effect of smoking on pregnancy-associated plasma protein A, free beta-human chorionic gonadotropin, and nuchal translucency in the first trimester of pregnancy. Adv Ther 23(1):131–138 CrossRef
- Leung TY, Spencer K, Leung TN, Fung TY, Lau TK (2006) Higher median levels of free beta-hCG and PAPP-A in the first trimester of pregnancy in a Chinese ethnic group: implication for first trimester combined screening for Down’s syndrome in the Chinese population. Fetal Diagn Ther 21(1):140–143 CrossRef
- Krantz DA, Hallahan TW, Macri VJ, Macri JN (2005) Maternal weight and ethnic adjustment within a first-trimester Down syndrome and trisomy 18 screening program. Prenat Diagn 25(8):635–640 CrossRef
- Sorensen T, Larsen SO, Christiansen M (2005) Weight adjustment of serum markers in early first-trimester prenatal screening for Down syndrome. Prenat Diagn 25(6):484–488 CrossRef
- Spencer K, Heath V, El-Sheikhah A, Ong CY, Nicolaides KH (2005) Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations. Prenat Diagn 25(5):365–369 CrossRef
- Spencer K, Bindra R, Nicolaides KH (2003) Maternal weight correction of maternal serum PAPP-A and free beta-hCG MoM when screening for trisomy 21 in the first trimester of pregnancy. Prenat Diagn 23(10):851–855 CrossRef
- Nicolaides KH, Sebire N, Snijders RJM (1999) Die Ultraschalluntersuchung der 11.-14. Schwangerschaftswoche. Pathenon, Birmingham
- Scharf A, Schmidt P, Seppelt M, Maul H, Wüstemann M, Sohn C (2003) Vergleich der Risikokalkulation für Trisomie 21 nach Nicolaides mit einer neu entwickelten Software: Retrospektive Analyse an 744 Fällen. Geburtshilf Frauenheilk 63:148–152 CrossRef
- Schmidt P, Staboulidou I, Soergel P, Wüstemann M, Hillemanns P, Scharf A (2007) Comparison of Nicolaides’ risk evaluation for Down’s syndrome with a novel software: an analysis of 1463 cases. Arch Gynecol Obstet 275:469–474 CrossRef
- Soergel P, Pruggmayer M, Schwerdtfeger R, Muehlhaus K, Scharf A (2006) Screening for trisomy 21 with maternal age, fetal nuchal translucency and maternal serum biochemistry at 11–14 weeks: a regional experience from Germany. Fetal Diagn Ther 21(3):264–268 CrossRef
- Using “Degree of Extremeness” instead of “Multiples of Median” in first trimester risk assessment for Down syndrome—an improved method or just a gimmick in face of political motivations?
Archives of Gynecology and Obstetrics
Volume 278, Issue 2 , pp 119-124
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Trisomy 21
- First trimester screening
- Risk assessment
- Industry Sectors
- Author Affiliations
- 1. Department of Obstetrics and Gynaecology, Medical University of Hannover, Werner-Schrader-Str. 61, 38302, Wolfenbüttel, Germany
- 2. Department of Obstetrics and Gynaecology, University of Heidelberg Medical School, Heidelberg, Germany