The association in the first trimester fetus of increased nuchal fluid and aneuploidy was first described more than two decades ago,
2,
3,
4 and this finding has led to the establishment of first trimester aneuploidy screening with NT and biochemical markers. A thickened NT has been correlated with the presence of trisomy 21 (T21) and T21 fetuses have a mean NT thickness of 3.4 mm.
5 In a study involving 654 fetuses with T21, more than half were shown to have an NT ≥3.5 mm.
1 The NT in the normal fetus increases with increasing crown-rump length (CRL) measurement and NT screening has been successfully used to adjust the pregnancy’s aneuploidy a priori risk established by maternal age. This has been one of the most important elements of aneuploidy screening as it resulted in a significant reduction in unnecessary invasive testing on pregnant women with advanced maternal age.
In pregnancies with T21 fetuses, the maternal serum concentration of free β-human chorionic gonadotropin (β-hCG) is about twice as high and pregnancy-associated plasma protein A (PAPP-A) is reduced to half compared to euploid pregnancies
(Table 6.1). Although NT measurement alone identifies about 75% to 80% of T21 fetuses, the combination of NT with maternal biomarkers in the first trimester increases the T21 detection rate to 85% to 95%, while keeping the false-positive rate at 5%.
5,
6 Indeed, in a recent prospective validation study of screening for trisomies 21, 18 and 13 by a combination of maternal age, fetal NT, fetal heart rate and serum free β-hCG
and PAPP-A at 11+0 to 13+6 weeks of gestation in 108,982 singleton pregnancies, T21, 18, and 13 were detected in 90%, 97%, and 92% respectively with a false-positive rate of 4%.
6 Monosomy X was also detected in more than 90% of cases along with more than 85% of triploidies and more than 30% of other chromosomal abnormalities.
6 In addition to NT, other sensitive first trimester ultrasound markers of T21 include absence or hypoplasia of the nasal bone
(Fig. 6.1), cardiac malformations (atrioventricular septal defect) with or without generalized edema
(Figs. 6.2 and 6.3), tricuspid regurgitation
(Fig. 6.4A), aberrant right subclavian artery
(Fig. 6.4B), echogenic intracardiac focus
(Fig. 6.4C), and increased impedance
to flow in the ductus venosus
(Fig. 6.5). First trimester features of fetuses with T21 are listed in
Table 6.2. Additional first trimester findings in T21 fetuses are shown in images in various chapters of this book.