T18 is the second most common aneuploidy after trisomy 21 syndrome (T21), epidemiological studies have shown that the disease has a high mortality, with abortion and prenatal mortality rates adding up to 80% , a live birth prevalence ranging from 1/10000 to 1/3000 , and a survival rate for 1 year less than 10% . There is a predominance of affected females, with a male to female ratio of 1:3 [1, 3], however, we report a 1:1 frequency of sexes, which may be a result of the small sample size.
It is generally believed that the embryological basis of T18 is the non-separation of chromosomes during egg meiosis, which is closely related to advanced-age pregnancy . In our study, the maternal ages were all under 35 years, with the oldest being 33 years. Most of the women were in their first pregnancy, suggesting that antenatal screening in pregnant women under 35 years-of-age should not be ignored.
Current prenatal fetal chromosomal abnormality screening tests include Down’s syndrome (DS), noninvasive prenatal testing (NIPT), and amniocentesis. Although DS screening and NIPT, which can predict chromosomal abnormalities, are more commonly performed because of their non-invasive nature, it is mandatory to confirm a positive DS screening or NIPT result with invasive procedures such as amniocentesis, which can provide diagnostic confirmation. Research has shown a detection rate for DS screening of 40% (2.00% false positive rate), with the addition of a T18 algorithm increasing the detection rate of T18 with an increase in the false positive rate . The diagnostic accuracy of a single NIPT for T18 is limited, and its price is relatively high. The positive predictive value of NIPT is lower for T18 than for T21 . Therefore, a combination of screening tests is recommended to increase the detection rate of aneuploidy, with ultrasonography forming a very important part. Although ultrasonography cannot directly detect the karyotype, fetuses with abnormal chromosomes tend to show congenital structural anomalies that can be detected on ultrasonography [12, 13]. Since the 1980s, many researchers have tried to summarize the performance and value of ultrasound in the diagnosis of T18 , but most research focused on the second or third trimester [15–17], with relatively few studies reporting on the detection of T18 before this stage of gestation. With improvement in the resolution of instruments and progress in ultrasonic technology, systematic fetal ultrasonography is gradually emerging, resulting in the detection of more fetal congenital anomalies before 16 weeks gestation [1, 13, 18].
Research shows that 95% of fetuses with T18 have at least one abnormal prenatal ultrasound finding . Lai et al.  stated that the detection rate of ultrasonography for T18 was 92.7% before 14 weeks and 100% at 18–21 weeks. In our study, more than 90% of cases showed NT thickening at 11–13+6 weeks gestation, and fetal structural abnormalities were detected in 100% of cases at 14–15+6 weeks gestation. Only one case showed no abnormal sonographic finding before 14 weeks of gestation, but a cardiac malformation was detected at 15 weeks gestation. These results show that structural abnormalities in T18 fetuses can be detected by systematic ultrasonography at 11–15+6 weeks.
Fetal NT measurement is an important method for screening for T18 in early pregnancy, and many studies on large samples of the general population have shown that the mean NT thickness in euploid fetuses is 1.7–1.8 mm [4, 13]. T18 fetuses usually show increased NT thickening [4, 13], and in our study, 9/12 fetuses (75.0%) showed NT thickening and two fetuses showed nuchal cystic hygroma. Tang et al.  stated that when abnormal NT and DV were observed concomitantly, the probability of any trisomy was higher than that with NT alone. In our study, five fetuses showed NT thickening and abnormal DV, and abnormal DV might be associated with serious cardiac malformations .
Cardiac malformations are the most common structural abnormalities in T18 fetuses [22, 23], at 11–13+6 weeks gestation, extracardiac and cardiac malformations were identified in 35.1% and 70.3% of T18 fetuses, respectively . In our study, cardiac malformations were detected in all fetuses (100%), with these being in combination with extracardiac malformations in 7 of the 12 cases (58.3%). Yang et al.  stated that the most sensitive ultrasonographic finding for T18 was increased NT under 16 weeks of gestation, but cardiac defect after 16 weeks gestation. The NT results in our study are consistent with previous reports, although cardiac malformations were detected in all 12 fetuses before 16 weeks gestation, indicating that an earlier detection time for fetal cardiac malformations may help to shorten the detection time window for T18 fetuses. Many studies have found that chromosome abnormalities are highly associated with congenital cardiac malformations [13, 22–24], with the most common malformation being VSD [13, 23]. However, although VSD is the most frequent cardiac malformation observed in T18 fetuses, there is a high risk of a false-positive result if it is used to predict T18 [13, 22]. Wiechec et al.  found that a right dominant heart (RDH) including DORV, COA, mitral atresia, and hypoplastic left heart syndrome (HLHS) was more predictive of T18 than VSD. In our subjects, five fetuses showed RDH, including two cases of DORV and three cases of COA, and we suggest taking particular care to rule out T18 when fetal RDH is detected.
Sepulveda et al.  found that omphalocele was the most common detected abnormality before 14 weeks of gestation. The incidence of omphalocele on the first trimester was only second to that of cardiac malformation in our study, with three cases (3/12, 25.0%) detected before 14 weeks gestation and four cases (4/12, 33.3%) detected before 16 weeks gestation. This shows that omphalocele is an important diagnostic clue, especially in combination with cardiac abnormalities, where the risk of T18 is increased.
While overlapping fingers and clenched or closed hands are characteristic manifestations of skeletal dysplasia in T18, other deformities such as abnormal foot posture, short limb deformity, and absence or dysplasia of the radius can also be detected in fetuses with T18 . In our study, five cases (5/12, 41.7%) of limb abnormalities were detected, with the incidence of limb abnormalities being only second to that of cardiac malformation, and the incidence being higher than that reported by Wiechec et al. . This higher incidence might be related to the gestational age of our subjects, which was a little later than the first trimester, and which is more conducive to the detection of fetal limb abnormalities. In our study, the limb abnormalities of T18 fetuses were mainly upper limb skeletal abnormalities, similar to those reported by Rice et al. .
Facial anomalies are also common noticeable ultrasound markers for T18 fetuses, with an incidence of 14.3–41.5% [23, 27]. The most common facial deformities are micrognathia, followed by cleft lip and palate, and ear abnormalities, with the incidence of eye and nose deformities being low . In our study, the main facial deformities were micrognathia, including one case accompanied by bilateral cleft lip, complete cleft palate, and unilateral accessory ear, indicating that relevant chromosome examinations should be carried out when such facial deformities are detected.
Nervous system anomalies are common ultrasonography-detectable malformations of T18 in the second and third trimester23, with an incidence of 12.9–21.6% [23, 27] for abnormal cranial bone configuration (including brachycephaly, strawberry-shaped skull, and microcephaly). However, no nervous system abnormalities were found in our study, which might be a result of the young observational gestational age, at which nervous system development was incomplete, with some abnormalities not being obvious at this early stage.
Soft markers are fetal prenatal sonographic findings of microstructural abnormalities that are nonspecific, often transient, and differ from fetal malformations. In themselves they do not affect fetal development, although they may be detected in normal fetuses, but they may also be associated with fetal chromosomal abnormalities and are considered as risk factors for underlying fetal aneuploidy . The most widely examined soft markers are thickened nuchal fold, mild ventriculomegaly, choroid plexus cysts, enlarged cisterna magna, absent or hypoplastic nasal bone, echogenic intracardiac focus, aberrant right subclavian artery, echogenic bowel, mild hydronephrosis, single umbilical artery, and short femur length . Some of these findings can be used as additional ultrasonic indicators to evaluate the possibility of T18 . Soft markers were identified in three (3/12, 25.0%) fetuses in our study, including one case of choroid plexus cysts and two cases of single umbilical artery. These results suggest that soft makers should not be ignored, that they have a certain value for screening for T18, and that pregnant women should be advised to have prenatal eugenic counseling when a fetal soft marker is identified.
Previous studies found a variety of structural abnormalities in T18 fetuses [13, 18, 23, 27], the non-disjunction of the chromosomes in the process of cell division in T18 fetuses may result in impacts on multiple systems . Among the 12 fetuses in our study, seven (7/12, 58.3%) showed multiple structural malformations, including three cases of two and three structural malformations, respectively, and one case of four structural malformations. Thus, when one structural malformation is detected in a fetus, attention should be paid to the exclusion of combined malformations. When multiple structural malformations are identified, the possibility of T18 should be carefully considered. In this study, the majority of multisite structural malformations were heart abnormalities combined with omphalocele, or heart abnormalities combined with limb abnormalities. We suggest that when these two types of combined malformations are found, the possibility of T18 should be carefully considered.