Clinical significance of ultrasound soft indices of fetus in the middle of pregnancy The incidence of chromosomal abnormalities in live births is 0.1% to 0.2%, the most common of which is trisomy 21 with an incidence of about 1/800 live births, others include trisomy 13, trisomy 18, X-chromosome haplogroup, triploidy, etc. Several tools are available to detect chromosomal abnormalities, including biochemical indicators, amniocentesis karyotyping, and ultrasonography. The results of amniocentesis karyotyping are more accurate, but the mediated procedure may result in a 0.5% to 1.0% risk of fetal death. Midtrimester ultrasonography 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 transient, 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 cysts, intracardiac strong echogenicity, thickening of the posterior neck skin, strong echogenicity of the intestinal canal, dilated renal pelvis, short long bones, nasal bone defects or hypoplasia, mild lateral ventricular widening and single umbilical artery. Ultrasound soft indicators are not pathognomonic, but can be used to assess the risk of chromosomal abnormalities. I. Presentation and clinical significance of ultrasound soft indicators 1. Choroid plexus cysts: Choroid plexus cysts are visible in the axial plane of the fetal skull, located in the lateral ventricles, and may be single or multiple, unilateral or bilateral, manifesting as a restricted anechoic 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. 2. Intracardiac strong echogenicity: Intracardiac strong echogenicity refers to tiny foci of calcification with echogenicity similar to bone intensity in the papillary muscle or in 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 during ultrasonography that strong intracardiac echoes must be seen from multiple angles before they can be identified as such, except for specular echoes 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. After detection of typical strong intracardiac echoes, amniocentesis is recommended if combined with other significant structural abnormalities or soft indicators. 3. Posterior cervical skin thickening: Fetal cervical skin thickening detected by ultrasound at 15 to 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. 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. The incidence of strong echogenicity of the intestinal canal in mid pregnancy is 0.2% to 1.4%. It may occur in normal fetus, fetal chromosomal abnormalities, fetal growth restriction, early gestation out of cf, cystic fibrosis, congenital viral infection or thalassemia, etc. Bromley et al. found that only 0.6% of fetuses with strong intestinal echogenicity were seen in mid-gestation; however, about 15% of fetuses with trisomy 21 had strong intestinal echogenicity. 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, the fetus may also have a strong echogenic intestinal canal due to swallowing of blood. If strong intestinal echogenicity is found, a careful examination of the fetus is required. Amniocentesis is recommended to determine the karyotype and the presence of cytomegalovirus, toxoplasma and microvirus infections, and the mother should be checked for recent cytomegalovirus and toxoplasma infections. Ambulatory ultrasound monitoring is recommended because of the possibility of coexisting fetal growth restriction. 5. Renal pelvis dilatation: Fetal pelvis dilatation is more common in the middle of pregnancy, with an incidence of 0.3% to 4.5% (average of about 1%). Mild renal pelvis dilatation refers to a renal pelvis width between 4 and 10 mm and the absence of dilated calyces. 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 mild pelvis dilatation was found in 737 fetuses, 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 25,586 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, and fetuses with short femur and humerus are at risk of developing 21-somes. Short femur refers to measured/expected value ≤ 0.91 and short humerus refers to measured/expected value ≤ 0.89. Studies have shown that 24% to 45% of fetuses with trisomy 21 have short femur and 24% N54% have short humerus; while in normal fetuses, only 5% 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 only 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. The nasal bone is <2.5 mm in length. 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. 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%. If fetal lateral ventricular 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, fetal neurological MRI should be performed to detect the combination of other intracranial developmental abnormalities, such as corpus callosum hypoplasia or ventricular system obstruction. 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 accompanied by other structural abnormalities, but it should be dynamically observed to be alert to the occurrence of fetal heart and kidney developmental abnormalities and fetal growth restriction. II. Prenatal counseling for ultrasound soft indicators Some studies have estimated the change in likelihood ratio by information assessment system , and concluded that the more types of ultrasound soft indicators present, the greater the risk of fetal chromosomal abnormalities and the higher the value of likelihood ratio, but this method has not been effectively applied in clinical practice. Currently, in the group with low risk of serological screening for trisomy 21, if there is a single ultrasound soft indicator or multiple ultrasound soft indicators, the concept of likelihood ratio can be introduced, and based on the likelihood ratio values, combined with the serological screening results, a comprehensive assessment is made, and if there is a risk of chromosomal abnormality, a prenatal diagnosis of mediated sex is recommended. It should also be noted that most soft ultrasound indices have a likelihood ratio for chromosomal abnormality risk only for trisomy 21, while some soft ultrasound indices may be associated with other chromosomal abnormalities, such as choroid plexus cysts associated with trisomy 18, which should be clearly explained to the pregnant woman and her family. Ultrasound soft indicators can help determine if further fetal chromosomal testing is needed. 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.