*3.1.1. First-trimester prenatal screening*

During the first trimester of pregnancy, different serological components present variations, but only free β-hCG and PAPP-A were associated with the presence of a trisomy 21. Other serological marker could be ADAM-12.

#### *3.1.1.1. Human chorionic gonadotropin*

The first attempts of using the hCG in detection of trisomy 21 in the first trimester of pregnancy gave controversial results. Use of total hCG in the first-trimester screening is inadequate because this marker becomes elevated only after 11 weeks of gestation [13]. In opposition, β-hCG is substantially elevated at 8–14 weeks of gestation in trisomy 21 pregnancies [14]. At a 5% false positive rate, the association between β-hCG and maternal age allows the detection of 42–46% of cases with trisomy 21 [15, 16].

#### *3.1.1.2. Pregnancy-associated plasma protein-a*

Pregnancy-associated plasma protein-A (PAPP-A) is produced by placental trophoblasts, but its function still unclear. The level of maternal serum PAPP-A is low during the first trimester in pregnancies with trisomy 21 and thus this marker could be used in prenatal screening of first trimester [17]. By using a protocol that associates PAPP-A in combination with maternal age, at a 5% false positive rate, the detection rate of cases with trisomy 21 ranges from 48 to 52%. After 15 weeks of gestation, the efficacy of this marker is low and its use in secondtrimester screening is without benefits [15, 16].
