First trimester combined screening – focus on early biochemistry

Abstract

First trimester combined screening (cFTS) for foetal trisomy 21 has become an established method in many countries. The screening is based on a combination of maternal-age-related risk, ultrasound (nuchal translucency) and two maternal serum biochemical markers, free beta human chorionic gonadotropin (FbhCG) and pregnancy associated plasma protein A (PAPP-A). The concentrations of these biochemical markers are affected by several maternal and pregnancy factors, which are discussed herein. Improvements in the algorithm have extended the screening to include trisomy 21 in mono- and dichorionic twin pregnancies, trisomy 18, trisomy 13 and triploidy. The results from large databases have shown that the screening algorithms are efficient for a range of rare autosomal trisomies and marker chromosomes and for a broad range of other chromosomal aberrations. Recent data show that the strength of the individual markers is highly dependent on the gestational age of sampling and indicate a general increase in the performance of the screening for trisomy 21 when using blood samples from early in the first trimester at gestational age 8-10 weeks.

The role of ultrasound in women who undergo cell-free DNA screening

“…Weak recommendation, moderate-quality evidence 5 We recommend that all women in whom a structural abnormality is identified by ultrasound be offered diagnostic testing with chromosomal microarray.…”

“…While an enlarged NT has been associated with other aneuploidies, it has limited utility in the detection of chromosomal abnormalities other than trisomies 21, 18, and 13 because of their overall lower prevalence as well as lower sensitivity for these other conditions. 5 An increased NT has been associated with structural anomalies, neuromuscular disorders, and a variety of other genetic conditions. It has been noted that imaging the fetus at 11e14 weeks of gestation (first-trimester ultrasound [Current Procedural Terminology] [CPT] code 76801) provides an early opportunity to evaluate the pregnancy and to potentially identify a fetus at risk for additional genetic or structural abnormalities.…”