*3.2.2. Second-trimester screening*

*3.2.1.1. Nuchal translucency*

376 Congenital Anomalies - From the Embryo to the Neonate

identified by this method [63].

*3.2.1.2. Nasal bone*

Nuchal translucency (NT) was introduced in medical practice in the 1990s and it is the sonographic appearance of a subcutaneous collection of fluid in the region of fetal neck [63]. Using a fixed cut-off for the NT measurement of 3 mm, it was possible to identify 64% of chromosomally abnormal cases, while only 4.1% of normal fetuses showed similar NT values [64]. It was proved that cut-off value was variable depending on gestational age, and it developed a Gaussian model for the NT variable that allowed this test to be readily combined with other markers [65].

The measurement of fetal NT thickness is done at the 11–14th week of gestation. This sonographic scan has been combined with maternal age to provide an effective method of screening for trisomy 21—at 5% false positive rate, about 75% of trisomic pregnancies can be

The explanations of NT are multiple but the most plausible are cardiovascular defects which cause over-perfusion of the head and neck and abnormal or delayed development of the lymphatic system. Thus, NT marker could be associated also with other chromosomal anomalies that produce fluid accumulation in the neck region. Also, NT can be a transient phenomenon that appears in a normal fetus and it spontaneously resolves in the second trimester [66].

Cicero et al. were the first who evaluated the absence of the nasal bone (NB) in pregnancies and showed that it was present in 73% of trisomy 21 fetuses versus 0.5% of unaffected fetuses. They concluded that in trisomy 21, the absence of the nasal bone is not related to the nuchal translucency thickness, and thus both sonographic markers could be combined to provide an effective method of early screening for trisomy 21 [67]. This combined screening allows an increase of sensitivity from about 57 to 86% at a fixed false positive rate of about 1%. If the biochemical screening in the first trimester is added, a sensitivity of more than 90% could probably be achieved at a false positive rate of 1% [5, 67]. The analysis of nasal bone in aneuploidy versus euploidy, made by Kagan et al., showed that the nasal bone was absent in 2.6% of the euploid fetuses, in 59.8% with trisomy 21, 52.8% with trisomy 18, 45.0% with trisomy 13 and in none of the fetuses with Turner syndrome [68]. In contrast, Cicero et al. indicated that trisomy 21 was associated with the absence of nasal bone in 68.8% of cases, trisomy 18 in 54.8% of cases, trisomy 13 in 34.2% of cases, monosomy X in 10.9% of cases, gonosomal aneuploidies (XXX, XXY, XYY) in 5% of cases and other types of autosomal aneuploidies in 16.7% of cases,

but none of the 19 cases with triploidy presented the absence of nasal bone [69].

Another potential marker for trisomy 21 in the first trimester of pregnancy is tricuspid regurgitation (TR) observed by pulsed wave Doppler ultra-sonography. Falcon et al. indicated a tricuspid regurgitation in 67.5% of fetuses with trisomy 21, 33.3% of fetuses with trisomy 18 and only 4.4% of euploid fetuses [70]. Kagan et al. reported this anomaly in 55.5% of fetuses with trisomy 21, 33.3% of fetuses with trisomy 18, 30% of fetuses with trisomy 13, 37.5% of fetuses with monosomy X and only 0.9% of euploid fetuses. The free β-hCG and PAPP-A present

*3.2.1.3. Other sonographic markers in the first trimester*

During the second trimester of pregnancy different sonographic markers could be identified, as well as major congenital anomalies. The most common markers in the second trimester are nuchal thickening, hyperechoic bowel, shortened extremities, renal pyelectasis, echogenic intracardiac foci (EIF) and choroid plexus cysts. The discovery of such a marker is important especially in cases with trisomy 21 because many cases with Down syndrome do not present major congenital anomalies. In other aneuploidies and also in triploidy, usually the visceral anomalies are common, and identification of a congenital defect imposes an invasive procedure, followed by a chromosomal diagnosis [62].
