*3.1.2.6. Screening of other aneuploidies*

*3.1.2.2. Human chorionic gonadotropin*

374 Congenital Anomalies - From the Embryo to the Neonate

60% of pregnancies with trisomy 21 [31].

related to the increase of hCG [33–35].

fetus at the time of screening [27].

*3.1.2.4. Inhibin-A*

*3.1.2.3. Unconjugated estriol*

In 1987, Bogart et al. showed that human chorionic gonadotropin (hCG) levels are generally higher in the maternal serum of women with Down syndrome pregnancies. They noted that hCG appeared to be superior to aFP in detecting fetal chromosome abnormalities, and association of maternal age with hCG as the screening method allows the identification of about

hCG is a glycoprotein produced by the placenta, composed of two subunits: α and β. Maternal serum contains intact hCG but also free α, free β and degradation products. At 8–10 weeks of gestation, intact hCG and free β-hCG show peak concentrations. Similar high levels of these

The anomalies of the placenta, characterized by disturbance in fluid homeostasis, like fetal hydrops and/or a cystic placenta, are associated with high levels of hCG in maternal serum. Such anomalies are present in hydropic Down syndrome, triploidy, Turner syndrome or other causes of hydrops fetalis. Even in the absence of hydrops, in cases with trisomy 21, there is a fluid accumulation that causes enlarged nuchal translucency and thickening and this could be

The presence of a low level of estriol in maternal urine in the case of a pregnancy with trisomy 21 was first reported by Jørgansen and Trolle [36]. Other studies confirmed this particularity and μE3 could be used as a marker in the prenatal screening of Down syndrome [37, 38].

The placenta uses 16 alpha-hydroxydehydroepiandrosterone sulfate (DHEAS) as the precursor of μE3. In Down syndrome pregnancies, both μE3 and DHEAS present lower levels in different tissues, including placenta [39]. During the second trimester the concentration of μE3 rises quickly and this marker can identify pregnancies with a small or underdeveloped

The possible application of inhibin in Down syndrome prenatal screening was suggested by Van Lith et al. [10]. Inhibin is a glycoprotein synthesized by gonads and placenta. The functional protein is dimeric with two subunits, α and β. The subunit α could be coupled with two different β subunits (βA or βB) and forms inhibin-A or inhibin-B. Inhibin-A (INH-A) is increased in pregnancies with trisomy 21 and presents an interdependent secretion with hCG. INH-A allows a good distinction between affected and unaffected pregnancies, alone or in combination with hCG [40–42]. INH-A has not got variations in relation with gestational age and thus the accuracy of testing is better by comparison with other serological markers [43].

Second-trimester serum screening could be applied between 14 and 22 weeks of gestation, but usually it is carried out at 15–18 weeks of pregnancy. The serum markers could be combined in different ways but the most commonly used tests are double test (association between aFP

*3.1.2.5. Multiple marker screening in the second trimester of pregnancy*

compounds are found during the second trimester of pregnancy [32].

In case of a pregnancy with trisomy 18, all serum markers (aFP, μE3, hCG and INH-A) for the second trimester are characterized by low concentrations [57]. The risks are calculated using a multivariate normal model and the detection rates for this aneuploidy are similar to those of trisomy 21 screening [58]. For other autosomal trisomies (13, 16, 20) and for triploidy different protocols for the second-trimester biochemical screening were tried but without specific features [27].

Among the sex chromosome aneuploidies, only one presents a bad prognosis: monosomy X with fetal hydrops. In this case, the biochemical prenatal screening shows an association between low aFP and μE3 and elevated hCG and INH-A. In pregnancies with monosomy X without hydrops, all serological markers are lower than normal concentrations [59].
