Screening for Trisomy 21 with Maternal Age, Fetal Nuchal Translucency and Maternal Serum Biochemistry at 11–14 Weeks: A Regional Experience from Germany

Objective: To examine the efficacy of first trimester screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT), maternal serum free β-human chorionic gonadotropin (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in a regional setting [maternity unit of the Women’s University Hospital, Hannover Medical School (study center); two regional private centers for prenatal diagnosis and human genetics; laboratory for prenatal diagnosis and human genetics]. Methods: Fetal NT, crown-rump length, maternal serum free β-hCG and PAPP-A were measured at 11–14 weeks of gestation. Risk calculation was carried out using the FMF computer algorithm. The patients were informed and counseled about possible invasive test options if the risk was 1 in 300 or greater. Fetal outcome was obtained by questionnaires given to the patients or sent to their gynecologists. The detection and false-positive rates for the different screening strategies were calculated. Results: Pregnancy outcome was obtained in 2,497 cases, of which 2,196 cases had completed first trimester screening with NT and maternal serum biochemistry and 301 additional cases had NT measurement only. The median age was 32.5 years. In our population 11 affected fetuses were found. The estimated risk for trisomy 21 was 1 in 300 or greater in 64, 82, 88 and 88% of affected fetuses using maternal age alone, in combination with nuchal translucency, with maternal serum biochemical markers or with both NT and biochemical markers for a false-positive rate of 28.2, 5.1, 15.3 and 4.0%. Conclusions: First trimester screening using maternal age, NT, free β-hCG and PAPP-A is highly effective for the detection of trisomy 21 and is associated with a sensitivity of about 90% for 5% false-positive patients.