First-Trimester Down Syndrome Screening: Component Analytes and Timing for Optimal Performance

The most effective first-trimester Down syndrome screening protocol in current use employs three independent markers: maternal serum levels of PAPP-A and free βhCG, and measurement of fetal nuchal translucency (NT). Eleven weeks appears to be the optimum gestational age for performing first trimester DS risk assessment. Although the discrimination of free βhCG improves with increasing gestational age and is greatest at 13 weeks, PAPP-A and NT perform optimally at 10 and 11 weeks, respectively. In addition to accurate pregnancy dating, first trimester screening performance is improved by using a consistent NT measurement technique, NT cut-offs adjusted for gestational age or crown-rump length, and possibly center- or operator-specific NT medians. Whether or not absence or presence of the nasal bone adds to screening accuracy is a matter of some debate. Finally, because enlarged NT has been associated with cardiac defects and other structural anomalies, even in euploid fetuses, its presence should prompt a targeted second trimester ultrasound examination.