Does the exclusion of maternal background risk in calculation software PRC, PIA and JOY improve First Trimester Screening (FTS)?

Aims: In FTS maternal age is integrated into the calculation algorithm as a background risk, which is then modified by nuchal translucency, free ß-hCG and PAPP-A.^{1 2} This might increase the false positive rate in older, and the false negative rate in younger mothers.^{3 4} This study analysed the impact in test performance of 3 FTS software programs if the maternal background was excluded.

Material and method: In a first step, 1.932 combined FTS with known fetal outcome, collected at the Medical University of Hanover, underwent risk calculation with the software programs Prenatal Risk Calculation (PRC) (Version 1.0.61, gmt/nexus), JOY (Version 2.1, PET-software), and Pia Fetal Database (PIA) (GE-ViewPoint, GE Medical Systems). In a second step, recalculation without maternal background risk was executed in the respectively modified programs PRC, PIA and JOY. McNemar-Tests and ROC curves were employed for statistical analysis (WinStat v2005.1, R Fitch Software, Staufen).

Results: 16 aneuploidy cases were present, half of them in women younger than 35. Both the original and the modified versions identified 12 to 14 aneuploidies. The modification did not affect the sensitivity in PRC and JOY. However, the modified PIA algorithm identified only 12 cases in comparison to the original PIA algorithm, which identified 13. In PRC, PIA und JOY the modification decreased the false positive rate by 40.7–46.6% (p<0.0001), leading to an increase of specificity by 2.2%.

Conclusion: The exclusion of the maternal background risk led to a highly significant improvement of test performance in all 3 software programs, in particular with regard to pregnancies in women older than 35.

Literatur: [1] Snijders RJM, Sundberg K, Holzgreve W, Henry G, Nicolaides KH: Maternal age and gestation-specific risk for trisomy 21. Ultrasound Obstet Gynecol 1999; 14: 167-170 [2] Nicolaides KH, Sebire N, Snijders RJM: Die Ultraschalluntersuchung der 11.-14. Schwangerschaftswoche. Birmingham, Pathenon Publishing, 1999 [3] Schmidt P, Pruggmayer M, Steinborn A, Schippert C, Staboulidou I, Hillemanns P, Scharf A: Are nuchal translucency, pregnancy associated plasma protein-A or free-ß-human chorionic gonadotropin depending on maternal age? A multicenter study of 8116 pregnancies. Arch Gynecol Obstet 2007; 276 (3): 259-262 [4] Schmidt P and Scharf A: Advanced Firsttrimester Screening - A critical review of the fundamental studies and suggestions for improvement. Geburtsh Frauenheilk 2006; 67: S1-183