Midtrimester ultrasound performed at 18 to 24 weeks of gestation reveals some definite fetal structural abnormalities and ultrasound soft indicators. Soft ultrasound indicators are not specific, are often present transiently, and are seen in normal fetuses, but their incidence is increased in chromosomally abnormal fetuses. The most well-studied soft ultrasound indicators include: choroid plexus cyst, intracardiac strong echogenicity, thickening of the posterior neck skin, strong echogenicity of the intestinal canal, dilated renal pelvis, short long bones, nasal bone defect or hypoplasia, mild lateral ventricular widening and single umbilical artery. 1. Choroid plexus cysts Choroid plexus cysts are seen in the axial plane of the fetal skull, located in the lateral ventricles, either singly or multiply, unilaterally or bilaterally, and manifest as a restricted echogenic area within the choroid plexus. The presence of only 1 soft indicator of a choroid plexus cyst does not indicate an increased risk of chromosomal abnormalities. The risk of fetal trisomy 18 is increased when ultrasonography reveals a combination of other structural abnormalities, but not trisomy 21. Choroid plexus cysts can occur in 1-2.5% of normal pregnancies. When fetal choroid plexus cysts are identified, careful examination of other fetal structures, especially the hands, is needed to detect the presence of overlapping fingers and clenched fists to aid in the exclusion of trisomy 18. If the fetus is not combined with other structural abnormalities, the risk of 18-trisomy is not increased; if accompanied by other structural abnormalities, amniocentesis karyotyping is recommended. 2. Intracardiac strong echogenicity Intracardiac strong echogenicity refers to tiny foci of calcification with echogenicity similar to bone intensity in the papillary muscle or any ventricle, which can be present in a single ventricle or in both ventricles, and can be single or multiple. It is important to note that the strong intracardiac echoes must be seen from multiple angles before they can be determined to be intracardiac strong echoes, except for the specular reflections of the papillary muscles. 1.5% to 4% of fetuses have strong intracardiac echoes. Frequent locations of pseudo-intracardiac strong echoes include the regulatory bundle, endocardial cushions, and tricuspid annulus. To correctly identify strong intracardiac echoes, the following methods are recommended: (1) present within the ventricles of the papillary muscle; (2) visible from multiple planes of view; (3) independent of the papillary muscle specular reflex area; and (4) should not exhibit a human-exit reflex. Coco et al. summarized the ultrasound findings in 12,672 mid-pregnancy pregnancies and concluded that strong intracardiac echoes in fetuses do not increase their risk of chromosomal abnormalities. Therefore, fetal intracardiac strong echoes found on ultrasound in pregnant women less than 35 years of age are normal physiological manifestations, and amniocentesis is not recommended. After finding typical intracardiac strong echoes, careful ultrasound examination of the fetus is needed to clarify the presence of structural abnormalities, and if combined with other obvious structural abnormalities or soft indicators, amniocentesis is recommended. 3. Posterior nuchal skin thickening Fetal nuchal skin thickening detected by ultrasound at 15-23 weeks of gestation is one of the earliest ultrasound soft indicators detected in mid pregnancy and one of the most predictive indicators. Early studies suggested that a posterior nuchal skin thickness ≥6 mm indicates the risk of fetal chromosomal abnormalities. Another study, using statistical analysis of subjects’ working characteristic curves, suggested a cut-off value of posterior nuchal skin thickness >5 mm before 20 weeks of gestation. Recent studies have found that posterior nuchal skin thickness values increase with gestational weeks, so specific cut-off values need to be developed for different gestational weeks.Smith-Bindman et al. showed that posterior nuchal skin thickening increased the risk of trisomy 21 with a likelihood ratio of 17 (95% CI:8-38). If the fetal nuchal translucency thickness is normal in early gestation, the incidence of posterior nuchal skin thickening is lower. In addition, posterior nuchal skin thickening may also be an early manifestation of fetal edema or lymphoedema. In 1990, Nyberg et al. and Persutte first reported strong echogenicity of the fetal intestinal canal. The diagnosis of strong intestinal echo is made in the middle of pregnancy when the fetal intestinal echo is consistent with that of the adjacent bone. There are three types of strong intestinal echogenicity: focal, multifocal or diffuse strong echogenicity. When examining fetal intestinal strong echo, the probe frequency should not be higher than 5 MHz. Once the intestinal strong echo is suspected, the ultrasound gain should be gradually reduced until only the bone and intestinal canal are visible. The intensity of strong intestinal echogenicity has been graded by Slotnick and Abuhamad to reduce the variation between different examiners, and the intensity of strong intestinal echogenicity compared with that of the iliac crest has been classified into 3 grades: grade 1 refers to lower intestinal echogenicity than that of the iliac crest; grade 2 refers to the same intestinal echogenicity as that of the iliac crest; and grade 3 refers to higher intestinal echogenicity than that of the iliac crest. The association with chromosomal aneuploidy and adverse pregnancy outcomes is stronger. The incidence of strong echogenicity of the intestinal canal in mid-pregnancy is 0.2% to 1.4%. It may occur in normal fetuses, fetal chromosomal abnormalities, fetal growth restriction, early gestation out cf, cystic fibrosis, congenital viral infection or thalassemia.Bromley et al. found that strong intestinal echoes were seen in only 0.6% of fetuses in mid-gestation; however, strong intestinal echoes were present in about 15% of trisomy 21 fetuses.Sepulveda and Sebire study Sepulveda and Sebire found that pathological changes were present in about 35% of fetuses with strong echogenic intestinal canal. In early gestation hemorrhage, strong intestinal echogenicity may also occur due to the swallowing of fluid by the fetus. If strong intestinal echogenicity is found, a careful examination of the fetus is required and amniocentesis is recommended to determine the karyotype and the presence of cytomegalovirus, toxoplasma and microvirus infections, and to check for recent maternal cytomegalovirus and toxoplasma infections. Ambulatory ultrasound monitoring is recommended because of the possible coexistence of fetal growth restriction. Renal pelvis dilatation is common in mid-pregnancy, with an incidence of 0.3% to 4.5% (average of about 1%). Mild renal pelvis dilatation means that the width of the renal pelvis is between 4 and 10 mm, and there is no dilatation of the renal pelvis. Fetuses with renal pelvis width ≥10 mm or hydronephrosis are at risk for structural abnormalities and require continued evaluation. In 1990, Benacerraf et al. first found an association between renal pelvis dilatation and chromosomal abnormalities, with mild pelvis dilatation occurring in 25% and 2.8% of trisomy 21 fetuses and normal fetuses, respectively.In a prospective multicenter study by Chudleigh et al. 101,600 pregnant women underwent ultrasonography and 737 fetuses were found to have mild pelvis dilatation, 12 of which ( The risk of chromosomal abnormalities in fetuses with only mild renal dilatation and no other abnormalities was considered to be 0.3% and 2.2% in the maternal age <36 and ≥36 years groups, respectively. In a retrospective study by Havutcu et al. of 25586 pregnant women, 320 fetuses (1.3%) had a dilated renal pelvis without chromosomal abnormalities, 19 had a combination of other ultrasound abnormalities, and 301 had a dilated pelvis only. Other studies have also demonstrated that the presence of only one soft indicator, renal pelvis dilatation, does not correlate significantly with fetal chromosomal abnormalities. This suggests that in the absence of other structural abnormalities or risk factors, dilated fetal renal pelvis should not be used as an indication for amniocentesis. However, about 1/4 to 1/3 of fetal pelvic dilatation progressively worsens, increasing the risk of hydronephrosis and neonatal urinary reflux; therefore, ultrasonography is recommended in late pregnancy to determine fetal pelvic dilatation and, if it persists or worsens, to require postnatal evaluation or monitoring. Fetal renal pelvis widths of 4 to 7 mm found in mid-pregnancy generally do not require surgical treatment. 6. Short long bones Short fetal long bones can be used as one of the indicators of chromosomal abnormalities. Fetuses with short femur and humerus are at risk of developing 21-i body. Short femur means measured/expected value ≤ 0.91 and short humerus means measured/expected value ≤ 0.89. Studies have shown that 24% to 45% of fetuses with trisomy 21 have short femur and 24% to 54% have short humerus; while only 5% of normal fetuses have short long bones. It was found that a short humerus has more predictive value than a short femur, and the presence of a short humerus alone is more meaningful than the presence of both a short humerus and a short femur, so measurement of humeral length should become a routine item in mid-pregnancy ultrasonography. 7.Nasal bone defect or dysplasia Mid-pregnancy ultrasonography can examine the nasal bone in the mid-sagittal plane of the fetal head. Bromley et al. found that the incidence of nasal bone defects in normal fetuses and trisomy 21 fetuses was 0.5% and 43%, respectively, and the likelihood ratio of nasal bone defects to predict the risk of trisomy 21 was 83, which is the most sensitive soft indicator. Sonek et al. found that the incidence of nasal bone defects in normal fetuses and fetuses with trisomy 21 was 1% and 37%, respectively, with a positive likelihood ratio of 41 and a negative likelihood ratio of 0.64. Therefore, it is considered that nasal bone defects are very important ultrasound indicators and have important predictive value for trisomy 21. 8. Mild lateral ventricular widening The normal value of lateral ventricular width is within 10 mm, and it is defined as mild lateral ventricular widening when it is between 10 and 15 mm. The incidence of mild lateral ventricular widening is 0.15% in chromosomally normal fetuses and 1.4% in trisomy 21 fetuses, with a likelihood ratio of 9. Lateral ventricular widening increases the risk of fetal chromosomal abnormalities and increases the likelihood of distant neurological developmental abnormalities by 10% to 30%. Chang Ching-Hsien et al. showed that fetal lateral ventricular dilatation with a width of 10.0 to 12.0 mm has a better prognosis. If fetal lateral ventricle widening is found, careful examination of fetal structures should be performed and amniocentesis is recommended, as well as screening for indicators of fetal infection and, if necessary, MRI of the fetal nervous system should be performed to detect the combination of other intracranial developmental abnormalities, such as agenesis of the corpus callosum or obstruction of the ventricular system. 9. Single umbilical artery Single umbilical artery refers to the presence of one umbilical artery and one umbilical vein in the umbilical cord. The current view is that single umbilical artery does not increase the risk of chromosomal abnormalities if the fetus is not associated with other structural abnormalities, but it should be monitored dynamically to be alert to the occurrence of fetal heart and kidney developmental abnormalities and fetal growth restriction. Shen Lin and Wu Lianfang showed that single umbilical artery is an important indicator of adverse fetal outcome if accompanied by severe fetal growth restriction. Prenatal consultation for ultrasound soft indicators Ultrasound soft indicators can help determine the need for further fetal chromosomal testing. If 2 or more ultrasound soft indicators are present, they need to be taken seriously and evaluated to consider an interventional prenatal diagnosis to exclude chromosomal abnormalities.