*3.1.1.3. Other biochemical markers*

applied during the first or the second trimester of pregnancy. The presence of a fetal aneuploidy is associated with changes of maternal serum concentrations of some fetoplacental products: aFP, free ß-hCG, inhibin A, μE3 and PAPP-A. In normal pregnancies, aFP concentration in maternal serum increases from 11.3 ng/ml in the 8th week of gestation to 250 ng/ml in the 32nd week of pregnancy. After that, it then declines slightly until term. In normal pregnancies, hCG in the maternal serum increases in first trimester of pregnancy and reaches a peak in weeks 7–9 (100.000 IU/ml). After that, it reduces continuously until around 20 weeks of pregnancies, when reduction is stopped and plasma levels remain constant until term. In normal pregnancies, inhibin A increases from the 6th week of pregnancy to the 9th week of pregnancy and reaches a peak (~550 pg/ml). After that, the values decline continuously to the 14th week of pregnancy. In normal pregnancies, μE3 is first detectable at 9 weeks of gestation (0.05 ng/ml) and after that it increases continuously to about 30 ng/ml at term. In normal pregnancies, PAPP-A is first detected in maternal serum after 4 weeks of pregnancies. PAPP-A concentration increases exponentially in the first trimester. After that, the rise occurs slowly,

In biochemical screening, the measured concentration of the markers is converted into a multiple of the median (MoM) of unaffected pregnancies at the same gestation. The Gaussian distributions of log10 (MoM) in trisomy 21 and unaffected pregnancies are then derived, and the ratio of the heights of the distributions at a particular MoM represents the likelihood ratio for a trisomy [7].

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

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

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 second-

but it continues until delivery [9–12].

372 Congenital Anomalies - From the Embryo to the Neonate

*3.1.1. First-trimester prenatal screening*

serological marker could be ADAM-12.

of 42–46% of cases with trisomy 21 [15, 16].

*3.1.1.2. Pregnancy-associated plasma protein-a*

trimester screening is without benefits [15, 16].

*3.1.1.1. Human chorionic gonadotropin*

The serum marker used in second-trimester screening (aFP, μE3 and inhibin-A [INH-A]) shows minimal differences in trisomy 21 pregnancies and thus could not be used in firsttrimester screening [14].

ADAM 12 is a glycoprotein synthesized by the placenta and secreted through pregnancy. ADAM 12 presents proteolytic functions and has a low level in first-trimester cases with trisomy 21 or trisomy 18. This reduction is more pronounced in earlier gestation, with best results at around 8–10 weeks. ADAM 12 in combination with PAPP-A (both measured at 8–9 weeks), nuchal translucency (NT) and free β-hCG measured at 12 weeks allow a detection rate of 97% at a 5% false positive rate and thus could be the best protocol for prenatal screening in the first trimester of pregnancy [18, 19].
