Integrated first and second trimester screening for Down syndrome

Abstract

Purposes: It is uncertain whether first trimester nuchal translucency is more effective than the well established second trimester serum screening for fetal Down syndrome or whether their combination works best. We report our data on a large multicenter non‐interventional trial in which all subjects underwent both first and second trimester screening to assess their relative efficacy.Methods: All women who attended the obstetric clinic before 15 weeks were recruited. An ultrasound examination was performed at 10–14 weeks to measure the nuchal translucency. The nuchal measurements were not acted upon unless the fetus showed gross features of hydrops fetalis. All women had serum alpha‐fetoprotein and human chorionic gonadotrophin assay at 15–20 weeks. The Down syndrome risk assigned by serum screening was disclosed and amniocentesis was offered if this assigned risk was at or >1:250 or if the women were 35 years and older. Efficacy of different combinations of screening were compared.Results: Between January 1997 and August 2000, 17590 women were recruited (19% was 35 years and older). After excluding subjects who miscarried, defaulted the serum test and other reasons, 16237 pregnancies were included in the final analysis. Of these, 35 pregnancies were affected by Down syndrome (2.2 cases per 1000 pregnancies). At a false‐positive rate of 5%, the detection rate of Down syndrome by nuchal translucency alone; nuchal translucency + age; serum human chorionic gonadotrophin, alpha‐fetoprotein + age and nuchal translucency + human chorionic gonadotrophin + alpha‐fetoprotein + age were 61, 69, 73 and 86%, respectively. Comparison of areas under the receiver‐operating characteristic curves showed statistically significant differences between these methods of screening.Conclusions: Integration of nuchal translucency and second trimester serum alpha‐fetoprotein and human chorionic gonadotrophin assay yielded the best screening efficacy for Down syndrome.