The establishment and severity assessment of ultrasound-guided prenatal bronchopulmonary dysplasia model in rat.

To study a new method for establishing animal models of prenatal bronchopulmonary dysplasia (BPD), we used lung ultrasound score (LUS) to semi-quantitatively assess the severity of lung lesions in model rats. Lipopolysaccharide (LPS) was injected into the right lung of the fetus of the rat under ultrasound-guided, and the right lung of the neonates were scanning for LUS. Specimens were collected for pathological scoring and detection of pulmonary surfactant-associated glycoprotein (SP)-C and vascular endothelial growth factor (VEGF) expression quantity. The correlation between LUS and pathological scores was analyzed. (1) The animal models were consistent with the pathological manifestations of BPD. (2) It showed a strong positive correlation between LUS and pathological scores in animal models (r = 0.84, P < 0.005), and the expression quantity of SP-C and VEGF in lung tissue were decreased (both P < 0.05). Animal models established by ultrasound-guided puncture of the lung of rats and injection of LPS were consistent with the manifestation of BPD. This method could be used to establish animal models of BPD before birth, and the severity of BPD could be assessed by using LUS.

Evaluation of extravascular lung water and cardiac function in normal vaginal delivery by intrapartum bedside ultrasound.

BACKGROUND: Healthy parturients may experience pulmonary edema and disturbed cardiac function during labor. We aimed to evaluate the extravascular lung water (EVLW), intravascular volume, and cardiac function of normal parturients during spontaneous vaginal delivery by bedside ultrasound. And to explore the correlation between EVLW and intravascular volume, cardiac function. METHODS: This was a prospective observational study including 30 singleton-term pregnant women undergoing spontaneous vaginal delivery. Bedside ultrasound was performed at the early labor, the end of the second stage of labor, 2 and 24 h postpartum, and 120 scanning results were recorded. EVLW was evaluated by the echo comet score (ECS) obtained by the 28-rib interspaces technique. Inferior vena cava collapsibility index (IVC-CI), left ventricle ejection fraction, right ventricle fractional area change, left and right ventricular E/A ratio, and left and right ventricular index of myocardial performance (LIMP and RIMP) were measured. Measurements among different time points were compared, and the correlations between ECS and other measurements were analyzed. RESULTS: During the spontaneous vaginal delivery of healthy pregnant women, 2 had a mild EVLW increase at the early labor, 8 at the end of the second stage of labor, 13 at 2 h postpartum, and 4 at 24 h postpartum (P < 0.001). From the early labor to 24 h postpartum, ECS first increased and then decreased, reaching its peak at 2 h postpartum (P < 0.001). IVC-CI first decreased and then increased, reaching its minimum at the end of the second stage of labor (P < 0.001). RIMP exceeded the cut-off value of 0.43 at the end of the second stage of labor. ECS was weakly correlated with IVC-CI (r=-0.373, P < 0.001), LIMP (r = 0.298, P = 0.022) and RIMP (r = 0.211, P = 0.021). CONCLUSIONS: During spontaneous vaginal delivery, the most vital period of perinatal care is between the end of the second stage of labor and 2 h postpartum, because the risk of pulmonary edema is higher and the right ventricle function may decline. IVC-CI can be used to evaluate maternal intravascular volume. The increase in EVLW may be related to the increase in intravascular volume and the decrease in ventricular function.

The Right Ventricular Fetal Tricuspid Annular Plane Systolic Excursion Index Is a New Index for Evaluating Fetal Cardiac Function of Gestational Hypertension.

ABSTRACT: The right ventricular fetal tricuspid annular plane systolic excursion index (FTI) can be used to evaluate right ventricular systolic function. The purpose of this study was to establish the reference range of the FTI in normal fetuses and evaluate its diagnostic value in hypertensive disorders during pregnancy. In this prospective observational study, the right ventricular FTI was measured in 208 normal single-gestation fetuses between 20 and 40 weeks. With the increase in gestational age, the right ventricular FTI did not significantly fluctuate. With the increase in the severity of HDCP, the right ventricular FTI decreased gradually. Compared with the normal group, the low right ventricular FTI group had a higher incidence of premature delivery and emergency delivery due to continuous abnormal fetal heart monitoring, but there were no significant differences in low birth weight, new born Apgar score less than 7 in 5 minutes, or admission to the neonatal intensive care unit. The FTI of the right ventricle of normal fetuses is relatively constant at different gestational weeks. The right ventricular FTI can be used to evaluate fetal cardiac function changes in pregnant women with HDCP.

Quality assessment of transperineal ultrasound in Chinese tertiary medical centers: a multicenter study.

Background: Transperineal ultrasound (TPUS) is a vital examination method for diagnosing pelvic floor diseases. However, the quality of TPUS largely relies on the operator's experience, and there is a lack of studies on the evaluation of TPUS quality. Therefore, the objective of this study was to assess the quality of TPUS examinations in Chinese tertiary medical centers. Methods: This multicenter study conducted in 44 Chinese tertiary medical centers recruited postpartum women between September 2020 and September 2021. All participants underwent a standardized inquiry and TPUS examination. The participating centers were required to submit 5 parts of ultrasound data to the National Ultrasound Quality Control Center: 2-dimensional images at rest, 2-dimensional images at strain; 4-dimensional images of the levator ani hiatus; 4-dimensional images of the levator ani muscle; and 4-dimensional images of the anal sphincter. Quality assessment was performed by 2 experts with more than 5 years of experience in TPUS, and the reasons for nonqualification were stated. Results: In this study, 31 hospitals that were distributed across 20 provinces in China were included, submitting 2,251 cases in total. The overall qualified rate ranged from 12.00% to 86.92%. In each part, the qualified rate of 2-dimensional images at rest, 2-dimensional images at straining, levator ani hiatus, levator ani muscle, and anal sphincter was 94.27% (2,122/2,251), 78.54% (1,768/2,251), 85.52% (1,925/2,251), 93.03% (2,094/2,251), and 88.09% (1,983/2,251), respectively. Most of the nonqualified images belonged to 2-dimensional images at strain, and the errors in image acquisition (221/483, 45.76%) and measurement (262/483, 54.24%) were the main reasons for nonqualification. For levator ani hiatus images, error in image acquisition (275/326, 84.36%) was the main reason for nonqualification. Reconstruction error was the most common reason for nonqualification for levator ani muscle (133/157, 84.71%) and anal sphincter images (133/268, 49.63%). Conclusions: This multicenter study assessed the quality of TPUS in tertiary medical centers in China and identified the common reasons for nonqualification in each part. These findings can aid in forming the basis for quality control management and training for TPUS.

The dimethadione-exposed rat fetus: an animal model for the prenatal ultrasound characterization of ventricular septal defect.

BACKGROUND: Ventricular septal defect (VSD) is the most prevalent congenital heart disease (CHD) and is easily misdiagnosed or missed. An appropriate VSD animal model could be used to analyze the ultrasound characteristics and their related pathological bases, and provides the opportunity to further explore the pathogenesis of VSD. Currently, little is known about whether ultrahigh-frequency ultrasound biomicroscopy (UBM) is suitable to diagnose VSD of fetal rats. There is no research on whether a dimethadione (DMO)-induced fetal VSD model is suitable for the observation and analysis of imaging characteristics and the associated pathological basis. METHODS: We used DMO to induce VSD. UBM was used to perform the prenatal ultrasound characterization. With the pathological results used as the gold standard, the ultrasound characteristics and their related pathological bases were analyzed. RESULTS: The incidence of VSD in the DMO group was 42.05% and 39.71% (diagnosed by UBM and pathology, respectively, P > 0.05). The prenatal ultrasound findings and pathological basis of various diseases, including isolated VSD, complex CHD containing VSD, and extracardiac lesions, were detected and discussed. It was discovered that some fetuses showed features of noncompacted ventricular myocardium, and for the first time, clusters of red blood cell traversing the cardiomyocytes. CONCLUSIONS: The DMO-induced VSD model is a low-cost model with a high success rate and is suitable for the observation and analysis of VSD. UBM is suitable for evaluating VSD.

Maternal body fluid lncRNAs serve as biomarkers to diagnose ventricular septal defect: from amniotic fluid to plasma.

Background: Maternal body fluids contain abundant cell-free fetal RNAs which have the potential to serve as indicators of fetal development and pathophysiological conditions. In this context, this study aimed to explore the potential diagnostic value of maternal circulating long non-coding RNAs (lncRNAs) in ventricular septal defect (VSD). Methods: The potential of lncRNAs as non-invasive prenatal biomarkers for VSD was evaluated using quantitative polymerase chain reaction (qPCR) and receiver operating characteristic (ROC) curve analysis. The biological processes and regulatory network of these lncRNAs were elucidated through bioinformatics analysis. Results: Three lncRNAs (LINC00598, LINC01551, and GATA3-AS1) were found to be consistent in both maternal plasma and amniotic fluid. These lncRNAs exhibited strong diagnostic performance for VSD, with AUC values of 0.852, 0.957, and 0.864, respectively. The bioinformatics analysis revealed the involvement of these lncRNAs in heart morphogenesis, actin cytoskeleton organization, cell cycle regulation, and protein binding through a competitive endogenous RNA (ceRNA) network at the post-transcriptional level. Conclusion: The cell-free lncRNAs present in the amniotic fluid have the potential to be released into the maternal circulation, making them promising candidates for investigating epigenetic regulation in VSD.

TUSPM-NET: A multi-task model for thyroid ultrasound standard plane recognition and detection of key anatomical structures of the thyroid.

The thyroid gland is a vital gland located in the anterior part of the neck. Ultrasound imaging of the thyroid gland is a non-invasive and widely used technique for diagnosing nodular growth, inflammation, and enlargement of the thyroid gland. In ultrasonography, the acquisition of ultrasound standard planes is crucial for disease diagnosis. However, the acquisition of standard planes in ultrasound examinations can be subjective, laborious and heavily reliant on the sonographer's clinical experience. To overcome these challenges, we design a multi-task model TUSP Multi-task Network (TUSPM-NET) that can recognize Thyroid Ultrasound Standard Plane (TUSP) and detect key anatomical structures in TUSPs in real-time. To improve TUSPM-NET's accuracy and learn prior knowledge in medical images, we proposed the plane target classes loss function and the plane targets position filter. Additionally, we collected 9778 TUSP images of 8 standard planes to train and validate the model. Experiments have shown that TUSPM-NET can accurately detect anatomical structures in TUSPs and recognize TUSP images. Compared to current models with better performance, TUSPM-NET's object detection map@0.5:0.95 improves by 9.3%; the precision and recall of plane recognition improve by 3.49% and 4.39%, respectively. Furthermore, TUSPM-NET recognizes and detects a TUSP image in just 19.9 ms, which means that the method is well suited to the needs of real-time clinical scanning.

Classification of normal and abnormal fetal heart ultrasound images and identification of ventricular septal defects based on deep learning.

OBJECTIVES: Congenital heart defects (CHDs) are the most common birth defects. Recently, artificial intelligence (AI) was used to assist in CHD diagnosis. No comparison has been made among the various types of algorithms that can assist in the prenatal diagnosis. METHODS: Normal and abnormal fetal ultrasound heart images, including five standard views, were collected according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Practice guidelines. You Only Look Once version 5 (YOLOv5) models were trained and tested. An excellent model was screened out after comparing YOLOv5 with other classic detection methods. RESULTS: On the training set, YOLOv5n performed slightly better than the others. On the validation set, YOLOv5n attained the highest overall accuracy (90.67 %). On the CHD test set, YOLOv5n, which only needed 0.007 s to recognize each image, had the highest overall accuracy (82.93 %), and YOLOv5l achieved the best accuracy on the abnormal dataset (71.93 %). On the VSD test set, YOLOv5l had the best performance, with a 92.79 % overall accuracy rate and 92.59 % accuracy on the abnormal dataset. The YOLOv5 models achieved better performance than the Fast region-based convolutional neural network (RCNN) & ResNet50 model and the Fast RCNN & MobileNetv2 model on the CHD test set (p<0.05) and VSD test set (p<0.01). CONCLUSIONS: YOLOv5 models are able to accurately distinguish normal and abnormal fetal heart ultrasound images, especially with respect to the identification of VSD, which have the potential to assist ultrasound in prenatal diagnosis.

Differential lncRNA/mRNA expression profiling and ceRNA network analyses in amniotic fluid from foetuses with ventricular septal defects.

Background: Long noncoding RNAs (lncRNAs) have been shown to be involved in the regulation of numerous biological processes in embryonic development. We aimed to explore lncRNA expression profiles in ventricular septal defects (VSDs) and reveal their potential roles in heart development. Methods: Microarray analyses were performed to screen differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) in the amniotic fluid between the VSD group and the control group. Bioinformatics analyses were further used to identify the functional enrichment and signaling pathways of important mRNAs. Then, a coding-noncoding gene coexpression (CNC) network and competitive endogenous RNAs (ceRNA) network were drawn. Finally, qRT‒PCR was performed to verify several hub lncRNAs and mRNAs in the network. Results: A total of 710 DE-lncRNAs and 397 DE-mRNAs were identified in the VSD group. GO and KEGG analyses revealed that the DE-mRNAs were enriched in cardiac development-related biological processes and pathways, including cell proliferation, cell apoptosis, and the Sonic Hedgehog signaling pathway. Four VSD related mRNAs was used to construct the CNC network, which included 149 pairs of coexpressing lncRNAs and mRNAs. In addition, a ceRNA network, including 15 lncRNAs, 194 miRNAs, and four mRNAs, was constructed to reveal the potential regulatory relationship between lncRNAs and protein-coding genes. Finally, seven RNAs in the ceRNA network were validated, including IDS, NR2F2, GPC3, LINC00598, GATA3-AS1, PWRN1, and LINC01551. Conclusion: Our study identified some lncRNAs and mRNAs may be potential biomarkers and therapeutic targets for foetuses with VSD, and described the lncRNA-associated ceRNA network in the progression of VSD.

Application of Artificial Intelligence in Anatomical Structure Recognition of Standard Section of Fetal Heart.

Congenital heart defect (CHD) refers to the overall structural abnormality of the heart or large blood vessels in the chest cavity. It is the most common type of fetal congenital defects. Prenatal diagnosis of congenital heart disease can improve the prognosis of the fetus to a certain extent. At present, prenatal diagnosis of CHD mainly uses 2D ultrasound to directly evaluate the development and function of fetal heart and main structures in the second trimester of pregnancy. Artificial recognition of fetal heart 2D ultrasound is a highly complex and tedious task, which requires a long period of prenatal training and practical experience. Compared with manual scanning, computer automatic identification and classification can significantly save time, ensure efficiency, and improve the accuracy of diagnosis. In this paper, an effective artificial intelligence recognition model is established by combining ultrasound images with artificial intelligence technology to assist ultrasound doctors in prenatal ultrasound fetal heart standard section recognition. The method data in this paper were obtained from the Second Affiliated Hospital of Fujian Medical University. The fetal apical four-chamber heart section, three vessel catheter section, three vessel trachea section, right ventricular outflow tract section, and left ventricular outflow tract section were collected at 20-24 weeks of gestation. 2687 image data were used for model establishment, and 673 image data were used for model validation. The experiment shows that the map value of this method in identifying different anatomical structures reaches 94.30%, the average accuracy rate reaches 94.60%, the average recall rate reaches 91.0%, and the average F1 coefficient reaches 93.40%. The experimental results show that this method can effectively identify the anatomical structures of different fetal heart sections and judge the standard sections according to these anatomical structures, which can provide an auxiliary diagnostic basis for ultrasound doctors to scan and lay a solid foundation for the diagnosis of congenital heart disease.

Chromosomal abnormalities in fetuses with congenital heart disease: a meta-analysis.

PURPOSE: The aim of this meta-analysis was to evaluate the risk of chromosomal abnormalities in fetuses with congenital heart disease (CHD). METHODS: Four literature databases were searched until 17th January 2022 using the relevant medical subject heading terms, word variants, and keywords for "congenital heart defect, fetal, and chromosomal abnormalities". The prevalence of overall chromosomal abnormality, aneuploidy, 22q11 deletion, other copy number variants (CNVs), and variants of unknown significance (VOUS) was analyzed. RESULTS: 45 studies met the inclusion criteria for the analysis. The pooled proportion of overall chromosomal abnormalities, aneuploidy, 22q11 deletion, and other CNVs in fetuses with CHD was 23% (95% CI: 20-26%), 19% (95% CI, 16-22%), 2% (95% CI, 2-3%), and 4% (95% CI, 3-5%), respectively. The incidence of overall chromosomal abnormalities, aneuploidy, and other CNVs in non-isolated CHD was higher than in isolated CHD, with odds ratios of 3.08, 3.45, and 4.02, respectively. The incidence of overall chromosomal abnormalities in septal defects was higher than in conotruncal defects and other defects, with odds ratios of 1.60 and 3.61, respectively. In addition, the pooled proportion of VOUS in CHD was 4%. CONCLUSION: CHD is commonly associated with chromosomal abnormalities. If karyotyping or fluorescence in situ hybridization is normal, chromosomal microarray should be performed to look for submicroscopic abnormalities, especially in fetuses with non-isolated CHD and septal defects.

The effect of ultrasound-guided intraperitoneal injection of ulinastatin on lung development in intrauterine growth-restricted fetal rabbits.

OBJECTIVES: To investigate the effect and mechanism of ulinastatin (UTI) on development of lungs in fetal rabbits with intrauterine growth retardation (IUGR). METHODS: Twenty pregnant rabbits were equally divided into normal, IUGR, UTI, and LY groups. The normal group was only injected with saline and marked with tattoo ink. IUGR models were established by injecting N-nitro-L-arginine methyl ester in the rabbits of IUGR, UTI, and LY groups. The three groups were injected with saline, UTI, or UTI + LY294002 (PI3K inhibitor) respectively, and then marked with tattoo ink. After cesarean section, neonatal weights, and levels of dipalmitoyl phosphatidylcholine (DPPC), nitric oxide (NO), P-Akt, P-eNOS, and pulmonary surfactant-associated protein A (SP-A) were determined in tissues of the lungs. Radial alveoli count (RAC), pulmonary interstitial ratio, and ultrastructural changes in type II alveolar epithelial cells (AEC II) were also determined through light and electron microscopy. RESULTS: Compared with control, the IUGR group showed significantly decreased weight, RAC, lamellar bodies in AEC II, and levels of P-Akt, P-eNOS, DPPC, NO, and SP-A, and increased pulmonary interstitial ratio (p < .05). The UTI treatment did not affect the weight; however, all other parameters were opposite to those observed in the IUGR group (p < .05). Furthermore, these UTI-mediated changes were inhibited by LY294002. CONCLUSIONS: Intraperitoneal UTI injection can promote the development of lungs and increase pulmonary surfactant production in IUGR fetal rabbits, potentially by activating PI3K/Akt/eNOS/NO signaling.

Prenatal diagnosis of triphalangeal thumb-polysyndactyly syndrome by ultrasonography combined with genetic testing: A case report.

BACKGROUND: Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a rare type of congenital limb deformity, and most studies focus on the genetics. Case reports of the sonographic characteristics of TPT-PS during pregnancy are rare. CASE SUMMARY: A 30-year-old woman (G3P1) who had pregnancies with TPT-PS fetuses is presented. The possibility of TPT-PS was shown by ultrasound performed at the 19th wk of pregnancy, featuring hands with six metacarpals, an extra digit at the 5th finger side, and an abnormally widened thumb. Whole-exome sequencing was subsequently conducted. The results showed that exons 1-17 of the LMBR1 gene had a heterozygous duplication, with a length of approximately 253 kb. CONCLUSION: We suggest prenatal ultrasound examination combined with genetic testing to diagnose TPT-PS accurately and to help clinicians and patients make decisions.

Reference range of fetal thorax using two-dimensional and three-dimensional ultrasound VOCAL technique and application in fetal thoracic malformations.

BACKGROUND: To establish the normal reference range of fetal thorax by two-dimensional (2D) and three-dimensional (3D) ultrasound VOCAL technique and evaluate the application in diagnosing fetal thoracic malformations. METHODS: A prospective cross-sectional study was undertaken involving 1077 women who have a normal singleton pregnancy at 13-40 weeks gestational age (GA). 2D ultrasound and 3D ultrasound VOCAL technique were utilized to assess fetal thoracic transverse diameter, thoracic anteroposterior diameter, thoracic circumference, thoracic area, lung volume, thoracic volume and lung-to-thoracic volume ratio. The nomograms of 2D and 3D fetal thoracic measurements were created to GA. 50 cases were randomly selected to calculate intra- and inter-observer reliability and agreement. In addition, the case groups including congenital skeletal dysplasia (SD) (15), congenital diaphragmatic hernia (CDH) (30), pulmonary sequestration (PS) (25) and congenital cystic adenomatoid malformation (CCAM) (36) were assessed by the nomograms and followed up subsequently. RESULTS: Both 2D and 3D fetal thoracic parameters increased with GA using a quadratic regression equation. The intra- and inter-observer reliability and agreement of each thoracic parameter were excellent. 2D fetal thoracic parameters could initially evaluate the fetal thoracic development and diagnose the skeletal thoracic deformity, and lung volume, thoracic volume and lung-to-thorax volume ratio were practical to diagnose and differentiate CDH, PS and CCAM. CONCLUSION: We have established the normal fetal thoracic reference range at 13-40 weeks, which has a high value in diagnosing congenital thoracic malformations.

International Expert Consensus and Recommendations for Neonatal Pneumothorax Ultrasound Diagnosis and Ultrasound-guided Thoracentesis Procedure.

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

Measurement of fetal conus distance with 3D ultrasonography as a reliable prenatal diagnosis method for tethered cord syndrome.

AIM: The aim of this study is to investigate if three-dimensional (3D) ultrasonography is a reliable diagnosis method for prenatal tethered cord syndrome (TCS) by measuring fetal conus distance (CD) in comparison to two-dimensional (2D) ultrasonography and magnetic resonance imaging (MRI). METHODS: This retrospective study included 468 normal fetuses as control group and 14 TCS fetuses as tethered group. CD were measured by 2D, 3D ultrasonography and MRI, and the reliability and repeatability of CD measurement was compared between two experienced ultrasound specialists or among the multiple measurements for each specialist. RESULTS: The results showed that 3D ultrasonography was superior to 2D ultrasonography in the repeatability of measuring CD. The CD were positively correlated to gestational ages in control group (P < 0.05). The CD of TCS group (-1.342 ± 0.124) was significantly shorter than that of normal control group (0.013 ± 0.965) (P < 0.01). There were no significant differences in the effectiveness of locating conus medullaris and measuring CD between 3D ultrasonography and MRI.Conclusion Measurement of fetal CD with 3D ultrasonography can serve as a reliable and cost-effective prenatal diagnosis method for TCS.

Prenatal Ultrasound Evaluation of the Position of Conus Medullaris for the Diagnosis of Tethered Cord Syndrome.

To determine the conus distance between the end of the conus medullaris and the distal end of the last vertebral body in healthy fetuses with various gestational ages using ultrasonography for its diagnostic value in tethered cord syndrome (TCS). This retrospective study included 540 healthy and 8 autopsy-confirmed TCS fetuses. Ultrasonographic measurement of the conus distance was performed when the fetus was in a prone position within the spine in the near field at 14 to 41 weeks of gestational age. Linear correlation analysis was performed to analyze the relationship between the conus distance and the gestational age, biparietal diameter, femur length, head circumference, and abdominal circumference. The normal results were compared with 8 cases of postnatally confirmed TCS. In 526 (95.9%) of 548 fetuses, the conus distance was successfully measured. The 95% limits of agreement in measurement of conus distance were -2.2 to 2.6 mm for the intraobserver variability and -3.7 to 3.1 mm for the interobserver variability. Significant correlations between the conus distance and the gestational age, biparietal diameter, femur length, head circumference, and abdominal circumference were observed. The most marked association was found to be between conus distance and femur length. The conus distance was significantly less in TCS fetuses than in healthy fetuses. Ultrasonographic measurement of conus distance is an easy and reliable method to evaluate the position of the conus medullaris and, therefore, can be helpful in the prenatal diagnosis of TCS.

Reference ranges of fetal spleen biometric parameters and volume assessed by three-dimensional ultrasound and their applicability in spleen malformations.

AIM: The aims of this article are to establish three-dimensional ultrasonographic nomograms of normal fetal spleen size and to evaluate the clinical application value. METHODS: An observational, cross-sectional study was performed on 455 women with a normal singleton pregnancy between 18 and 38 weeks' gestational age (GA). Fetal spleen volume was measured using three-dimensional ultrasound equipped with virtual organ computer-aided analysis, and biometric parameters were assessed in multiplanar mode to create reference ranges to GA. Thirty cases were randomly selected to conduct reliability analyses via intraobserver and interobserver ultrasonographic measurement. Moreover, 50 cases of suspected splenic malformations were evaluated by the newly established nomograms and followed up subsequently. RESULTS: Using regression formulas, we found that fetal spleen size increased with GA. We observed strong reliability in intraobserver and interobserver volume measurements with intraclass correlation coefficients of 0.994 and 0.962. Bland-Altman analyses showed narrow limits of agreement [intraobserver: (-3.2 to 3.5)%; interobserver: (-3.2 to 4.3)%]. Of the 50 cases with suspected splenic malformations, six cases of splenomegaly and one case of splenic cyst were diagnosed. CONCLUSION: Three-dimensional ultrasound nomograms of normal fetal spleen size across a range of GA have a strong diagnostic value. Volume measurements with good reliability were optimal in clinical practice.