Abstract
Objective
The individual risk assessment of fetal Down’s syndrome based on measurement of nuchal translucency (NT) according to Nicolaides, optionally complemented by the determination of PAPP-A and free beta HCG has progressively supplanted other search strategies for fetal aneuploidies. It could be shown that this diagnostic strategy equally detects other numeric aneuploidies at a comparable rate. A positive test result is also predictive for the presence of a fetal malformation. In this field, several computer programs are available for clinical use. The objective of our study was to re-evaluate the first consecutive 1463 NT-risk calculations determined by Nicolaides’ method and to compare the risk calculation to the JOY software (NT-risk calculation module, JOY Patient Database) introduced in 2002.
Material and methods
At the Department of Obstetrics and Gynecology, Hannover Medical School, 1463 consecutive complete data sets comprising first trimester screening performed between May 2, 2000 and June 26, 2003 and corresponding fetal outcome were analysed using risk assessment based on the Nicolaides method (PIA Fetal Database NT-Module) and compared with the risk evaluation as determined by the JOY software (JOY Patient Database NT module). A risk exceeding 1:300 was considered to indicate the need for further invasive testing. In a first step, only cytogenetically detectable chromosomal aberrations were analysed. Then, a second evaluation including fetal malformations was performed.
Results
Among the 1463 cases, 1445 (98.77%) fetuses revealed to be cytogenetically healthy. Both softwares showed identical detection rates at the genetic and somatic level:13 cases of Down-Syndrome (0.89%), 2 cases of trisomy 18 (0.14%), one case of triploidy, one Turner-Syndrome, one Klinefelter-Syndrome (0.07% each) were detected. A positive test result was found in 15 cases ending in a spontaneous abortion, intrauterine death or peripartum death (1.03%) and in 22 cases of fetal malformation (1.50%). At the level of genetic detection the test positive rate dropped from 92 (PIA) to 71 (JOY) (-22.8%). At the level of combined adverse outcome the test positive rate was reduced from 100 (PIA) to 76 (JOY) (-22.0%), thus yielding in a marked improvement of the characteristic test performance parameters.
Conclusion
The novel, recently developed JOY software package allowed reliable evaluation of the risk for aneuploidy with increased specificity whereas sensitivity was unchanged. Our data suggest an improvement of the screening for aneuploidy when using this novel software: With an identical detection rate, the number of unnecessary invasive measures may be reduced.
Similar content being viewed by others
References
Snijders RJ, 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 352:343–346
Pandya PP, Snijders RJ, Johnson SP, De Lourdes Brizot M, Nicolaides KH (1995) Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation. Br J Obstet Gynaecol 102:957–962
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
Krampl E, Wertaschnigg D, Husslein P (2002) First-trimester screening for Down’s syndrome. Geburtshilfe Frauenheilkd 62:843–848
Nicolaides KH, Azar G, Byrne D, Mansur C, Marks K (1992) Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy. BMJ 304:867–869
Snijders RJ, Holzgreve W, Cuckle H, Nicolaides KH (1994) Maternal age-specific risks for trisomies at 9-14 weeks’ gestation. Prenat Diagn 14:543–552
Braithwaite JM, Morris RW, Economides DL (1996) Nuchal translucency measurements: frequency distribution and changes with gestation in a general population. Br J Obstet Gynaecol 103:1201–1204
Wald N, Stone R, Cuckle HS, Grudzinskas JG, Barkai G, Brambati B, Teisner B, Fuhrmann W (1992) First trimester concentrations of pregnancy associated plasma protein A and placental protein 14 in Down’s syndrome. BMJ 305:28
Kowalcek I, Mühlhoff A, Bieniakiewizc I, Gembruch U (2001) Non-invasive and invasive prenatal diagnosis and psychological challenges for the pregnant patient. Geburtshilfe Frauenheilkd 61:593–598
Snijders RJM, Nicolaides KH (1996) Assessment of risks. In: Snijders RJM, Nicolaides KH (eds) Ultrasound markers for fetal chromosomal defects. Parthenon Publishing, Carnforth, UK, pp 109–113
Palomaki GE, Haddow JE (1987) Maternal serum alpha-fetoprotein, age, and Down syndrome risk. Am J Obstet Gynecol 156:460–463
Snijders RJ, Sundberg K, Holzgreve W, Henry G, Nicolaides KH (1999) Maternal age- and gestation-specific risk for trisomy 21. Ultrasound Obstet Gynecol 13:167–170
Nicolaides KH, Sebire N, Snijders RJM (1999) Nuchal translucency and chromosomal anomalies. In: Nicolaides KH, Sebire N, Snijders RJM (eds) The 11-14-week scan: the diagnosis of fetal abnormalities. Parthenon Publishing, Carnforth, UK, pp 3–72
Wald NJ, Hackshaw AK (1997) Combining ultrasound and biochemistry in first-trimester screening for Down’s syndrome. Prenat Diagn 17:821–829
Scharf A, Schmidt P, Seppelt M, Maul H, Wuestemann M, Sohn C (2003) Vergleich der Risikokalkulation für Trisomie 21 nach Nicolaides mit einer neu entwickelten Software: Retrospektive Analyse an 744 Fällen, Geburtsh Frauenheilk 63:148–152
Spencer K, Souter V, Tul N, Snijders R, Nicolaides KH (1999) Screening program for trisomy 21at 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
Scharf A, Bock N, Maul H, Sohn C (2006) Analyse des Nackentransparenz (NT-)Screeningkonzepts an der Frauenklinik der MHH: Eine prospektive Follow-up-Studie. Z Geburtshilfe Neonatol 210(3):99–106
Souka A, Heath V (1999) Increased nuchal translucency with normal karyotype. In: Nicolaides KH, Sebire N, Snijders RJM (eds) The 11-14-week scan: the diagnosis of fetal abnormalities. Parthenon Publishing, Carnforth, UK, pp 73–97
Hyett J, Perdu M, Sharland G, Snijders R, Nicolaides KH (1999) Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks of gestation: population based cohort study. BMJ 318(7176):81–85
Harlap S; Shiono PH (1980) Alcohol, smoking, and incidence of spontaneous abortions in the first and second trimester. Lancet 2(8187):173–176
Chitty LS, Hunt GH, Moore J, Lobb MO (1991) Effectiveness of routine ultrasonography in detecting fetal structural abnormalities in a low risk population. BMJ 303:1165–1169
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schmidt, P., Staboulidou, I., Soergel, P. et al. Comparison of Nicolaides’ risk evaluation for down’s syndrome with a novel software: an analysis of 1,463 cases. Arch Gynecol Obstet 275, 469–474 (2007). https://doi.org/10.1007/s00404-006-0288-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00404-006-0288-y