*3.1.2. Second-trimester prenatal screening*

Second-trimester serum markers are represented by alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol and inhibin-A.

Screening for aneuploidies was initially focused on the second trimester of pregnancy and demonstrated a substantial improvement in detection rates of trisomy 21, compared with screening using only maternal age. At a false positive rate of 5%, the detection rate improves from 30% in screening by maternal age alone to 60–65% by combining maternal age with serum AFP and free ß-hCG (double test), 65–70% with the addition of μE (triple test) and 70–75% with the addition of inhibin A (quadruple test). In the case of hCG, it is better to search for free ß-hCG than total hCG [24–27].

### *3.1.2.1. Alpha-fetoprotein*

The first report concerning the association between low level of maternal serum alpha-fetoprotein and fetal trisomy 21 was made in 1984, by Merkatz et al. [9]. At a risk cut-off of 1:270 for trisomy 21 (equivalent to the maternal age of 35), using this parameter alone would allow the detection of 55% of cases with trisomy 21 [28, 29].

The aFP is produced by fetal liver, but its biological functions and the reason why the aFP level is lower in Down syndrome pregnancies remain unclear. Placentas of affected pregnancies show a high level of aFP suggesting a defect in the secretion of AFP into the maternal circulation [30].
