Principles of first trimester screening in the age of non-invasive prenatal diagnosis: screening for chromosomal abnormalities.

PURPOSE: First trimester risk assessment for chromosomal abnormalities plays a major role in the contemporary pregnancy care. It has evolved significantly since its introduction in the 1990s, when it essentially consisted of just the nuchal translucency measurement. Today, it involves the measurement of several biophysical and biochemical markers and it is often combined with a cell-free DNA (cfDNA) analysis as a secondary test.

METHODS: A search of the Medline and Embase databases was done looking for articles about first trimester aneuploidy screening. We performed a detailed review of the literature to evaluate the screening tests currently available and their respective test performance.

RESULTS: Combined screening for trisomy 21 based on maternal age, fetal NT, and the serum markers free beta-hCG and PAPP-A results in a detection rate of about 90% for a false positive of 3-5%. With the addition of further ultrasound markers, the false positive rate can be roughly halved. Screening based on cfDNA identifies about 99% of the affected fetuses for a false positive rate of 0.1%. However, there is a test failure rate of about 2%. The ideal combination between combined and cfDNA screening is still under discussion. Currently, a contingent screening policy seems most favorable where combined screening is offered for everyone and cfDNA analysis only for those with a borderline risk result after combined screening.

CONCLUSION: Significant advances in screening for trisomy 21 have been made over the past 2 decades. Contemporary screening policies can detect for more than 95% of affected fetuses for false positive rate of less than 3%.