Results
A total of 7,547 singleton pregnant women were enrolled in this study. Of these, 52 (0.7%) were miscarriage before 12 weeks of gestation, 51 (0.7%) were withdraw consent after recruitment in the study and 727 (9.6%) were lost to follow-up. The remaining 6,717 cases were included for analysis. Among these, 89 (1.3%) cases had NT between 95th and 99th percentile. The clinical characteristics of the study population are summarized in Table 1. The mean maternal age, gestational age at NT measurement, and NT value were 34±4.0 years, 12.1±0.7 weeks, and 3.0±0.3 mm, respectively. Among the study populations, 47 (52.8%) pregnancies selected the cfDNA screening, 33 (37.1%) pregnancies preferred IT, and 9 (10.1%) pregnancies underwent MSS as the first tier test after NT measurement. The clinical characteristics of the three groups were compared according to the first tier test (Table 1). The mean maternal age was 31.8±3.8 years in the MSS group, 33.8±3.8 years in the cfDNA screening group, and 34.9±4.1 years in the IT group. The mean value of NT measurement was 3.0± 0.2 mm in the MSS group, 2.9± 0.3 mm in cfDNA screening group, and 3.1± 0.3 mm in the IT group. There were no differences in maternal age and NT value between the three groups (p =0.096, 0.084), respectively. Comparing the patient’s choice based on NT value, the cfDNA screening was selected the most (28, 66.7%) in patients with NT between 95th percentile and 3 mm. IT was selected the most (24, 51.1%) in patients with NT between 3.0 and 3.5 mm (Table 2).
Chromosomal abnormalities were diagnosed in five cases (5.6%) including four cases with trisomy 21 and one case with balanced translocation. NT value was 3.0 mm or more in all cases. Three cases showed a high risk for trisomy 21 in cfDNA screening (one fetus with hypoplastic nasal bone on first-trimester ultrasound), and IT confirmed the concordant results in all cases. Two cases selected IT as the first tier test, and the results showed trisomy 21 and balanced translocation. One case with balanced translocation showed normal ultrasound findings and was delivered at term and phenotypically normal (Figure 1). No significant chromosomal abnormalities undetected by cfDNA screening were noted in pregnancies with NT between 95th and 99th percentile. Abnormal ultrasound findings at the NT measurement were detected in five cases (5.6%) (Table 3). The abnormalities consisted of three cases of cystic hygroma, one case of multiple structural anomalies including cystic hygroma, and another case of hypoplastic nasal bone. Two cases showing multiple structural anomalies and hypoplastic nasal bone were miscarriages before 20weeks of gestation. The one case with cystic hygroma showed hydronephrosis in the second trimester ultrasound, and a normal baby was delivered at term. The remaining two cases with cystic hygroma showed normal ultrasound finding at second trimester, and were normal babies. Detailed, high-resolution ultrasound examination during the second trimester was performed in 79 pregnancies, except when pregnancy was terminated or ended in miscarriage. Abnormal ultrasound findings were noted in eight cases (Table 3). The major structural anomalies included two cases with congenital heart disease. In two cases, IT was followed by detailed, high-resolution ultrasound examination, and the karyotyping result was normal. Soft markers were identified in the remaining six cases including three cases of increased nuchal fold thickness (NFT), two cases of pyelectasis, and one case of echogenic bowel. Five cases showed a low risk with cfDNA screening, and all of them were healthy babies. In one case with increased NFT, IT performed in the first trimester showed normal results.