visible between the spine and overlying skin at the back of the fetal neck during first‐trimester sonography (Figures 5.1 and 5.2). The larger this space, the higher the risk for trisomy 21, while the smaller the space, the lower the risk for trisomy 21. Measurement of the NT between 11 weeks and 3 days and 14 weeks and 2 days of gestation (45–84 mm) has been shown to be a useful sonographic marker for trisomy 21. Table 5.1 describes the components of a standardized NT sonographic protocol.
Nuchal translucency sonography can be technically challenging to master and it requires considerable effort to maintain quality over time. Given the importance of maintaining such accuracy, sonographers and physicians who provide this form of screening should be credentialed and enrolled in an ongoing quality assurance program. Examples of such QA programs include the Nuchal Translucency Quality Review (NTQR) managed by the Perinatal Quality Foundation in the US (www.ntqr.org) and the Fetal Medicine Foundation in Europe (www.fetalmedicine.org).
Figure 5.1 Nuchal translucency (NT) ultrasound measurement at 13 weeks’ gestation in a chromosomally normal fetus, measuring 1.5 mm. Various features of good NT ultrasound technique are evident in this image: adequate image magnification, midsagittal plane, neutral neck position, inner to inner caliper placement perpendicular to the fetal body axis, and separate visualization of the overlying fetal skin and amnion.
Source: Mary E. Norton, MD.
Figure 5.2 Increased nuchal translucency measurement at 13 weeks’ gestation in a fetus with Down syndrome.
Source: Mary E. Norton, MD.
Table 5.1 Nuchal translucency (NT) measurement criteria of the Nuchal Translucency Quality Review (NTQR) Program
| 1 | Fetal head, neck, and upper thorax should fill the majority of the image (>50%) |
| 2 | Image should be optimized so the NT lines are thin and clear |
| 3 | Fetus should be examined in a midsagittal plane |
| 4 | Fetal neck should be in a neutral position |
| 5 | Fetus should be observed away from the amnion |
| 6 | The “+” calipers should be used |
| 7 | Calipers should be placed on the echogenic inner borders of the nuchal membranes with none of the horizontal crossbars protruding into the translucent NT space |
| 8 | Calipers should be placed perpendicular to the long axis of the fetal body |
| 9 | At least three nuchal translucency measurements should be obtained and the maximum acceptable measurement should be used |
| 10 | The ALARA (as low as reasonably achievable) criteria should be followed and the thermal index for bone (TIB) set with an output standardized display of ≤0.7 |
First‐trimester PAPP‐A and hCG
[fo]Maternal serum levels of PAPP‐A are approximately 50% lower, and hCG levels (either total hCG or fβhCG) approximately twice as high, in trisomy 21 pregnancies compared with euploid pregnancies at 10–14 weeks of gestation, and these analytes can be used for assessment of trisomy 21 risk in the first trimester. The combination of maternal age, NT sonography, PAPP‐A, and hCG is referred to as first‐trimester combined screening and will detect about 85% of cases of trisomy 21, at a 5% false‐positive rate, between 10 and 14 weeks of gestation.
Secondary sonographic markers
While measurement of the NT combined with serum markers has been the mainstay of general population screening for many years, other sonographic features of aneuploidy have also been reported in the first trimester. Cystic hygroma is reported in about 1 of every 300 first‐trimester pregnancies, and refers to a markedly enlarged NT, often extending along the entire length of the fetus, with septations clearly visible. While it is not clear that a cystic hygroma is distinct from a markedly enlarged NT, this finding is associated with a 50% risk for fetal aneuploidy and in the remaining euploid pregnancies, almost half will be found to have major structural fetal malformations, such as cardiac defects and skeletal anomalies. Less than 25% of all cases of first‐trimester septated cystic hygroma or markedly enlarged NT (e.g., ≥6.5 mm) will result in a normal liveborn infant. Therefore, this finding should prompt immediate referral for CVS, and pregnancies found to be euploid should be evaluated carefully for other malformations with a detailed fetal anomaly scan and fetal echocardiography at 18–22 weeks of gestation, or in the first trimester if such evaluation is available.
Figure 5.3 Nasal bone image of a euploid fetus at 13 weeks. Various features of good nasal bone technique are evident in this image: a good midsagittal plane, clear fetal profile, downward‐facing spine, slight neck flexion, and two echogenic lines, representing the overlying fetal skin and the nasal bone. The white arrow indicates the fetal nose bone, which loses its echogenicity distally.
Source: Mary E. Norton, MD.
Other sonographic features that have been reported to be useful in detection of trisomy 21 at 11–14 weeks include an absent nasal bone (Figure 5.3), an abnormal Doppler blood flow pattern in the ductus venosus, and abnormal blood flow across the tricuspid valve with evidence of tricuspid regurgitation. However, studies suggesting a role for aneuploidy