Prospective prenatal cell-free DNA screening for genetic conditions of heterogenous etiologies.

Prenatal cell-free DNA (cfDNA) screening uses extracellular fetal DNA circulating in the peripheral blood of pregnant women to detect prevalent fetal chromosomal anomalies. However, numerous severe conditions with underlying single-gene defects are not included in current prenatal cfDNA screening. In this prospective, multicenter and observational study, pregnant women at elevated risk for fetal genetic conditions were enrolled for a cfDNA screening test based on coordinative allele-aware target enrichment sequencing. This test encompasses the following three of the most frequent pathogenic genetic variations: aneuploidies, microdeletions and monogenic variants. The cfDNA screening results were compared to invasive prenatal or postnatal diagnostic test results for 1,090 qualified participants. The comprehensive cfDNA screening detected a genetic alteration in 135 pregnancies with 98.5% sensitivity and 99.3% specificity relative to standard diagnostics. Of 876 fetuses with suspected structural anomalies on ultrasound examination, comprehensive cfDNA screening identified 55 (56.1%) aneuploidies, 6 (6.1%) microdeletions and 37 (37.8%) single-gene pathogenic variants. The inclusion of targeted monogenic conditions alongside chromosomal aberrations led to a 60.7% increase (from 61 to 98) in the detection rate. Overall, these data provide preliminary evidence that a comprehensive cfDNA screening test can accurately identify fetal pathogenic variants at both the chromosome and single-gene levels in high-risk pregnancies through a noninvasive approach, which has the potential to improve prenatal evaluation of fetal risks for severe genetic conditions arising from heterogenous molecular etiologies. ClinicalTrials.gov registration: ChiCTR2100045739 .

Association between abnormal uterine artery pulsatility index and the risk of fetal congenital heart defects: a hospital-based cohort study.

To explore the associations between high uterine artery pulsatility index (UtA-PI) values and congenital heart disease (CHD) risk and whether they differed between singleton and multiple pregnancies. This hospital-based cohort study involving 52,047 pregnant women who underwent prenatal examinations from 2012 to 2016. Infants born to the included pregnant women were followed until 42 days after birth to identify those with CHDs. Generalized estimating equations were used to estimate the associations of high right UtA-PI (> 95th percentile) values with maternal preeclampsia and fetal CHDs. Logistic regression analyses were conducted using path analysis models to quantify the effect of high right UtA-PI values on fetal CHD risk. A total of 42,552 women and 43,470 infants (147 with CHDs) were included. Preeclampsia risk was associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 3.01; 95% CI 2.57-3.52). CHD risk was marginally associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 2.26, 95% CI 1.03-4.95). Considering only two factors, 96.0% of the fetal CHD risk was mediated by preeclampsia in singleton-pregnant women, while 93.8% of the risk was related to a high right UtA-PI in multiple-pregnant women. A high right UtA-PI was marginally associated with an increased fetal CHD risk in singleton-pregnant women and might play an important role in multiple-pregnant women. Further studies are warranted to confirm these findings given the high loss to follow-up rate.

GMRLNet: A Graph-Based Manifold Regularization Learning Framework for Placental Insufficiency Diagnosis on Incomplete Multimodal Ultrasound Data.

Multimodal analysis of placental ultrasound (US) and microflow imaging (MFI) could greatly aid in the early diagnosis and interventional treatment of placental insufficiency (PI), ensuring a normal pregnancy. Existing multimodal analysis methods have weaknesses in multimodal feature representation and modal knowledge definitions and fail on incomplete datasets with unpaired multimodal samples. To address these challenges and efficiently leverage the incomplete multimodal dataset for accurate PI diagnosis, we propose a novel graph-based manifold regularization learning (MRL) framework named GMRLNet. It takes US and MFI images as input and exploits their modality-shared and modality-specific information for optimal multimodal feature representation. Specifically, a graph convolutional-based shared and specific transfer network (GSSTN) is designed to explore intra-modal feature associations, thus decoupling each modal input into interpretable shared and specific spaces. For unimodal knowledge definitions, graph-based manifold knowledge is introduced to describe the sample-level feature representation, local inter-sample relations, and global data distribution of each modality. Then, an MRL paradigm is designed for inter-modal manifold knowledge transfer to obtain effective cross-modal feature representations. Furthermore, MRL transfers the knowledge between both paired and unpaired data for robust learning on incomplete datasets. Experiments were conducted on two clinical datasets to validate the PI classification performance and generalization of GMRLNet. State-of-the-art comparisons show the higher accuracy of GMRLNet on incomplete datasets. Our method achieves 0.913 AUC and 0.904 balanced accuracy (bACC) for paired US and MFI images, as well as 0.906 AUC and 0.888 bACC for unimodal US images, illustrating its application potential in PI CAD systems.

Comparison of the left and right ventricular size and systolic function of low-risk fetuses in the third trimester: Which is more dominant?

Objective: To quantify fetal cardiovascular parameters utilizing fetal-specific 2D speckle tracking technique and to explore the differences in size and systolic function of the left and right ventricles in low-risk pregnancy. Methods: A prospective cohort study was performed in 453 low-risk single fetuses (28+0-39+6 weeks) to evaluate ventricular size [i.e., end-diastolic length (EDL), end-systolic length (ESL), end-diastolic diameter (ED), end-systolic diameter (ES), end-diastolic area, end-systolic area, end-diastolic volume (EDV), and end-systolic volume (ESV)] and systolic function [i.e., ejection fraction (EF), stroke volume (SV), cardiac output (CO), cardiac output per kilogram (CO/KG), and stroke volume per kilogram (SV/KG)]. Results: This study showed that (1) the reproducibility of the interobserver and intraobserver measurements was good to excellent (ICC 0.626-0.936); (2) with advancing gestation, fetal ventricular size and systolic function increased, whereas right ventricular (RV) EF decreased and left ventricular (LV) EF was not significantly changed; (3) LV length was longer than RV length in diastole (2.24 vs. 1.96 cm, P < 0.001) and systole (1.72 vs. 1.52 cm, P < 0.001); (4) LV ED-S1 and ES-S1 were shorter than the RV ED-S1 and ES-S1 (12.87 vs. 13.43 mm, P < 0.001; 5.09 vs. 5.61 mm, P < 0.001); (5) there were no differences between the LV and RV in EDA or EDV; (6) the mean EDV ratio of right-to-left ventricle was 1.076 (95% CI, 1.038-1.114), and the mean ESV ratio was 1.628 (95% CI, 1.555-1.701); (7) the EF, CO and SV of the LV were greater than the RV (EF: 62.69% vs. 46.09%, P < 0.001; CO: 167.85 vs. 128.69 ml, P < 0.001; SV: 1.18 vs. 0.88 ml, P < 0.001); (8) SV and CO increased with ED-S1 and EDL, but EF was not significantly changed. Conclusion: Low-risk fetal cardiovascular physiology is characterized by a larger RV volume (especially after 32 weeks) and greater LV outputs (EF, CO, SV, SV/KG and CO/KG).

Multimodal fusion model for classifying placenta ultrasound imaging in pregnancies with hypertension disorders.

BACKGROUND: A multimodal fusion model was proposed to assist the traditional visual diagnosis in evaluating the placental features of hypertension disorders of pregnancy (HDP). OBJECTIVE: The aim of this study was to analyse and compare the placental features between normal and HDP pregnancies and propose a multimodal fusion deep learning model for differentiating and characterizing the placental features from HDP to normal pregnancy. METHODS: This observational prospective study included 654 pregnant women, including 75 with HDPs. Grayscale ultrasound images (GSIs) and Microflow images (MFIs) of the placentas were collected from all patients during routine obstetric examinations. On the basis of intelligent extraction and features fusion, after quantities of training and optimization, the classification model named GMNet (the intelligent network based on GSIs and MFIs) was introduced for differentiating the placental features of normal and HDP pregnancies. The distributions of placental features extracted by the deep convolutional neural networks (DCNNs) were visualized by Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP). Metrics including sensitivity, specificity, accuracy, and the area under the curve (AUC) were used to score the model. Finally, placental tissue samples were randomly selected for microscopic analyses to prove the interpretability and effectiveness of the GMNet model. RESULTS: Compared with the Normal group in ultrasonic images, the light spots were rougher and the parts with focal cystic or hypoechogenic lesions were increased in the HDP groups. The overall diagnostic performance of the GMNet model depending on the region of interest (ROI) was excellent (AUC: 97%), with a sensitivity of 90.0%, a specificity of 93.5%, and an accuracy of 93.1%. The fusion features of GSIs and MFIs in the placenta showed a higher discriminative power than single-mode features (fusion features vs GSI features vs MFI features, 97.0% vs 91.2% vs 94.8%). Furthermore, according to the microscopic analysis, unevenly distributed villi, increased syncyte nodules and aggregated intervillous cellulose deposition were particularly frequent in the HDP cases. CONCLUSIONS: The GMNet model could sensitively identify abnormal changes in the placental microstructure in pregnancies with HDP.

Ultrasound-based radiomics for the evaluation of fetal rat lung maturity: A noninvasive assessment method (Ultrasound-based radiomics in fetal rat lung).

OBJECTIVE: To establish a classification model for the evaluation of rat fetal lung maturity (FLM) using radiomics technology. METHOD: A total of 430 high-throughput features were extracted per fetal lung image from 134 fetal lung ultrasound images (four-cardiac-chamber views) of 67 Sprague-Dawley (SD) fetal rats with a gestational age of 16-21 days. The detection of fetal lung tissues included histopathological staining and the expression of surface proteins SP-A, SP-B, and SP-C. A machine learning classification model was established using a support vector machine based on histopathological results to analyze the relationship between fetal lung texture characteristics and FLM. RESULTS: The rat fetal lungs were divided into two groups: terminal sac period (SD1) and canalicular period (SD2). The mRNA transcription and protein expression level of SP-C protein were significantly higher in the SD1 group than in the SD2 group (p < 0.05). The diagnostic performance of the rat FLM classification model was measured as follows: area under the receiver operating characteristic curve (AUC), 0.93 (training set) and 0.89 (validation set); sensitivity, 89.26% (training set) and 87.10% (validation set); specificity, 85.87% (training set) and 79.17% (validation set); and accuracy, 87.79% (training set) and 83.64% (validation set). CONCLUSION: Ultrasound-based radiomics technology can be used to evaluate the FLM of rats, which lays a foundation for further research on this technology in human fetal lungs.

Model application to quantitatively evaluate placental features from ultrasound images with gestational diabetes.

PURPOSE: The goal of this study was to introduce PFCnet (placental features classification network), an multimodel model for evaluating and classifying placental features in gestational diabetes mellitus (GDM) and normal late pregnancy. Deep learning algorithms could be utilized to fully automate the examination of alterations in the placenta caused by hyperglycemia. METHODS: A total of 718 placental ultrasound images, including 139 cases of GDM, were collected, including gray-scale images (GSIs) and microflow images (MFIs). Ultrasonic assessment parameters and perinatal features were recorded. We divided gestational age into two categories for analysis (37 weeks and 37 weeks) based on the cut-off value level of placental maturity. The PFCnet model was introduced for identifying placental characteristics from normal and GDM pregnancies after extensive training and optimization. The model was scored using metrics such as sensitivity, specificity, accuracy, and the area under the curve (AUC). RESULTS: In view of multimodal fusion (GSIs and MFIs) and deep network optimization training, the overall diagnostic performance of the PFCnet model depending on the region of interest (ROI) was excellent (AUC: 93%), with a sensitivity of 89%, a specificity of 92%, and an accuracy of 92% in the independent test set. The fusion features of GSIs and MFIs in the placenta showed a higher discriminative power than single-mode features (accuracy: Fusion 92% vs. GSIs 84% vs. MFIs 82%). The independent test set at 37 weeks exhibited a better specificity (75% vs. 69%) but a lower sensitivity(95% vs. 100%). CONCLUSIONS: With its dual channel identification of placental parenchymal and vascular lesions in obstetric complications, the PFCnet classification model has the potential to be a useful tool for detecting placental tissue abnormalities caused by hyperglycemia.

Ultrasound-based radiomics technology in fetal lung texture analysis prediction of neonatal respiratory morbidity.

To develop a novel method for predicting neonatal respiratory morbidity (NRM) by ultrasound-based radiomics technology. In this retrospective study, 430 high-throughput features per fetal-lung image were extracted from 295 fetal lung ultrasound images (four-chamber view) in 295 single pregnancies. Images had been obtained between 28+3 and 37+6 weeks of gestation within 72 h before delivery. A machine-learning model built by RUSBoost (Random under-sampling with AdaBoost) architecture was created using 20 radiomics features extracted from the images and 2 clinical features (gestational age and pregnancy complications) to predict the possibility of NRM. Of the 295 standard fetal lung ultrasound images included, 210 in the training set and 85 in the testing set. The overall performance of the neonatal respiratory morbidity prediction model achieved AUC of 0.88 (95% CI 0.83-0.92) in the training set and 0.83 (95% CI 0.79-0.97) in the testing set, sensitivity of 84.31% (95% CI 79.06-89.44%) in the training set and 77.78% (95% CI 68.30-87.43%) in the testing set, specificity of 81.13% (95% CI 78.16-84.07%) in the training set and 82.09% (95% CI 77.65-86.62%) in the testing set, and accuracy of 81.90% (95% CI 79.34-84.41%) in the training set and 81.18% (95% CI 77.33-85.12%) in the testing set. Ultrasound-based radiomics technology can be used to predict NRM. The results of this study may provide a novel method for non-invasive approaches for the prenatal prediction of NRM.

Correlation between cerebroplacental doppler ratio and neonatal respiratory disorders: A reference marker of fetal lung maturation.

AIM: The aim of this study was to investigate the role of cerebroplacental ratio (CPR) in the final prenatal care for neonatal respiratory diseases and to analyze the risk of relevant factors associated with neonatal respiratory disorders. METHODS: A prospective cohort study of 795 singleton pregnancies was conducted. The pulsatility indices (PI) of the umbilical artery (UA) and the middle cerebral artery (MCA) were measured, and the MCA to UA ratio (CPR) was determined. The severity of the case is determined by whether or not the newborn has respiratory problems. Compare the CPR correlation between the two groups and examine the illness prediction factors through a binary logistic regression method. RESULTS: Of the 801 participants, 114 had neonatal respiratory disorders. The mean values of CPR between neonatal respiratory diseases group and control group were 1.78±0.6, 1.97±0.9, respectively (P <  0.001). Maternal age, abortion history, cesarean section history, placental thickness, placental maturity, and amniotic fluid index (AFI) were determined to have no significant link between the two groups after comparison analysis (P >  0.05). It could be found that compared with the control group, CPR MoM indicators of neonatal respiratory distress syndrome, neonatal pneumonia and wet lung disease all show significant decreases. In binary logistic regression analysis, among the variables included in the model, CPR (OR:2.90, P = 0.015), fetal heart monitoring (OR:5.26, P <  0.001), delivery mode (OR:2.86, P <  0.001) and gestational age of delivery (OR:0.92, P <  0.001) were statistically significant in both groups. CONCLUSION: The findings of this study showed that infant respiratory problems were substantially related to CPR value. The correlation indicates that CPR was a powerful reference marker for respiratory disorders.

Identification of Pathogenic Variants in RPGRIP1L with Meckel Syndrome and Preimplantation Genetic Testing in a Chinese Family.

Meckel syndrome (MKS, OMIM:249000) is a severe multiorgan dysplastic lethal ciliopathy with extreme genetic heterogeneity. Defects in RPGRIP1L are the cause of MKS type 5 (MKS5, OMIM:611561). However, only six different variants have been reported in eight MKS5 cases with biallelic variants. Here, we describe the case of a Chinese family with recurrent fetal malformations. The proband was a 14-week gestation fetus with occipital encephalocele, polycystic kidneys, polydactyly, and single ventricular heart. Trio whole-exome sequencing was performed, and two novel compound heterozygous variants of RPGRIP1L (c.427C > T, p.Gln143Ter and c.1351-11A > G) were identified. cDNA studies of the splicing variant demonstrated a reading-frame shift with a subsequent premature stop codon (p.Glu451Serfs*6). After the proband was diagnosed with MKS5, the couple chose preimplantation genetic testing for monogenic disorders (PGT-M) and prenatal genetic diagnosis (PND) to prevent the transmission of pathogenic variants, which led to a successful pregnancy recently. In summary, we have identified two novel variants of RPGRIP1L in a Chinese family, which expand the variant spectrum of MKS5. Furthermore, we have described the successful application of PGT-M and PND in this family. These techniques could assist couples with a genetic predisposition in avoiding the transmission of genetic diseases to their offspring.

Prenatal prediction of neonatal respiratory morbidity: a radiomics method based on imbalanced few-shot fetal lung ultrasound images.

BACKGROUND: To develop a non-invasive method for the prenatal prediction of neonatal respiratory morbidity (NRM) by a novel radiomics method based on imbalanced few-shot fetal lung ultrasound images. METHODS: A total of 210 fetal lung ultrasound images were enrolled in this study, including 159 normal newborns and 51 NRM newborns. Fetal lungs were delineated as the region of interest (ROI), where radiomics features were designed and extracted. Integrating radiomics features selected and two clinical features, including gestational age and gestational diabetes mellitus, the prediction model was developed and evaluated. The modelling methods used were data augmentation, cost-sensitive learning, and ensemble learning. Furthermore, two methods, which embed data balancing into ensemble learning, were employed to address the problems of imbalance and few-shot simultaneously. RESULTS: Our model achieved sensitivity values of 0.82, specificity values of 0.84, balanced accuracy values of 0.83 and area under the curve values of 0.87 in the test set. The radiomics features extracted from the ROIs at different locations within the lung region achieved similar classification performance outcomes. CONCLUSION: The feature set we designed can efficiently and robustly describe fetal lungs for NRM prediction. RUSBoost shows excellent performance compared to state-of-the-art classifiers on the imbalanced few-shot dataset. The diagnostic efficacy of the model we developed is similar to that of several previous reports of amniocentesis and can serve as a non-invasive, precise evaluation tool for NRM prediction.

High maternal blood lipid levels during early pregnancy are associated with increased risk of congenital heart disease in offspring.

INTRODUCTION: This study aimed to investigate whether maternal blood lipid levels during early pregnancy are associated with the occurrence of congenital heart disease (CHD) in their offspring. MATERIAL AND METHODS: In this single-center case-control study, mothers of offspring with CHD (n = 230) and without CHD (n = 381) were included. Maternal lipid levels were determined on fasting blood samples taken in the first trimester. Relevant demographic and clinical data were extracted from the medical records. Maternal lipid profile was compared between the two groups, and regression analysis was performed to evaluate the association between lipid profile and CHD risk in offspring. RESULTS: Compared with the control group, levels of triglyceride, apolipoprotein-A1, and apolipoprotein-B in early pregnancy were significantly higher in the CHD group. Multivariate analyses showed that triglyceride (odds ratio [OR] 2.46, 95% CI 1.62-3.73, p < 0.01), total/high-density lipoprotein cholesterol (OR 2.10, 95% CI 1.07-4.13, p = 0.03), and apolipoprotein-A1 (OR 2.73, 95% CI 1.16-6.40, p = 0.02) were positively associated with CHD risk in offspring. CONCLUSIONS: Elevated maternal lipid profile was associated with increased risk of CHD in offspring.

Ambient fine particulate matter air pollution and the risk of preterm birth: A multicenter birth cohort study in China.

Preterm birth (PTB), defined as live birth before the 37th week of gestation, is believed to have profound impacts on the infant's health in later life. Air pollution has been suggested to be a potential risk factor of PTB, but the evidence was inconsistent. In this multicenter birth cohort study, we aimed to examine the association between fine particulate matter (PM2.5) exposure during pregnancy and PTB in China. A total of 5976 live births were identified between Jan. 2009 and Feb. 2011 from 8 provinces in China. Residential exposures to PM2.5 were assigned based on satellite remote sensing estimates. Cox proportional hazards regressions were employed to explore the correlation for each trimester as well as the entire pregnancy. A total of 443 (7.4%) preterm births were observed. The average PM2.5 during pregnancy was 57.2 ± 8.8 µg/m3. We found exposure to PM2.5 during the whole pregnancy (hazard ratio, HR = 1.262; 95% CI: 1.087-1.465) and in the first trimester (HR = 1.114; 95% CI: 1.007-1.232) was associated with higher risk of PTB. The associations of PM2.5 were stronger for subjects with older maternal or paternal age, lower maternal pre-pregnancy BMI, and lower family income. This study adds supports to the cumulating evidence linking PM2.5 exposure and elevated PTB risk. Measures of air pollution reduction are needed during pregnancy, especially at early stage of pregnancy to prevent adverse birth outcomes.

Abnormal placental perfusion and the risk of stillbirth: a hospital-based retrospective cohort study.

BACKGROUND: A lack of information on specific and interventional factors for stillbirth has made designing preventive strategies difficult, and the stillbirth rate has declined more slowly than the neonatal death rate. We compared the prevalence of stillbirth among the offspring of women with or without abnormal placental perfusion (APP). METHODS: We conducted a hospital-based retrospective cohort study involving women with a singleton pregnancy between 2012 and 2016 (N = 41,632). Multivariate analysis was performed to compare the prevalence of stillbirth in infants exposed to APP (defined as any abnormality in right or left uterine artery pulsatility index or resistance index [UtA-PI, -RI] [e.g., > 95th percentile] or presence of early diastolic notching) with that in those not exposed to APP. RESULTS: Stillbirths were more common among women with APP than among those with normal placental perfusion (stillbirth rate, 4.3 ‰ vs 0.9 ‰; odds ratio (OR), 4.2; 95% confidence interval (CI), 2.2 to 8.0). The association strengths were consistent across groups of infants exposed to APP that separately defined by abnormality in right or left UtA-PI or -RI (OR ranged from 3.2 to 5.3; all P ≤ 0.008). The associations were slightly stronger for the unexplained stillbirths. Most of the unexplained stillbirth risk was attributed to APP (59.0%), while a foetal sex disparity existed (94.5% for males and 58.0% for females). Women with normal placental perfusion and a male foetus had higher credibility (e.g., higher specificities) in excluding stillbirths than those with APP and a female foetus at any given false negative rate from 1 to 10% (93.4% ~ 94.1% vs. 12.3% ~ 14.0%). CONCLUSIONS: APP is associated with and accounts for most of the unexplained stillbirth risk. Different mechanisms exist between the sexes. The performance of screening for stillbirth may be improved by stratification according to sex and placental perfusion.

Three-dimensional power Doppler ultrasonography indicates that increased placental blood perfusion during the third trimester is associated with the risk of macrosomia at birth.

PURPOSE: To investigate the association between placental blood perfusion and the occurrence of macrosomia at birth. METHODS: This was a prospective cohort study including women with singleton pregnancies that aimed to measure placental blood perfusion using three-dimensional (3D) power Doppler ultrasonography in the second and third trimester. We acquired three indices of placental blood flow, including vascularization index (VI), flow index (FI), vascularization flow index (VFI), along with routine two-dimensional (2D) biometric measurements, including abdominal circumference (AC) and estimated fetal weight (EFW). Pregnancy outcomes were divided into two groups: newborns with a normal birth weight and those with macrosomia. We then compared all of the recorded variables between these two groups. We also determined the predictive efficiency of each variable using receiver-operating characteristic (ROC) curves. RESULTS: The placental 3D power Doppler indices, including VI and FI, were significantly higher in the third trimester of pregnancies developing macrosomia, but not during the second trimester, as compared to those with a normal birth weight. ROC curves analysis for third-trimester VI and FI suggested a slight ability to predict macrosomia; this was also the case for AC and EFW. Interestingly, VI showed high sensitivity and low specificity, while FI showed low sensitivity and high specificity; this was also the case for AC and EFW. CONCLUSIONS: Three-dimensional power Doppler ultrasound indices were significantly higher during the third-trimester for pregnancies developing macrosomia. However, these indices had only moderate ability to predict macrosomia.

Association of abnormal placental perfusion with the risk of male hypospadias: a hospital-based retrospective cohort study.

BACKGROUND: The effect and extent of abnormal placental perfusion (APP) on the risk of male hypospadias are poorly understood. We compared the prevalence of male hypospadias in the offspring of women with APP and quantify the extent of the APP effect on the anomaly. METHODS: A hospital-based retrospective analysis of births from 2012 to 2016 was conducted in 2018. Women of singleton pregnancy and male infants born to them were included (N = 21,447). A multivariate analysis was performed to compare the prevalence of male hypospadias in infants exposed to APP with those that were not exposed to APP. RESULTS: Compared with the infants of women without APP, infants of women with APP showed an increased risk of male hypospadias (odds ratio, 2.40; 95% confidence interval, 1.09-5.29). The male hypospadias cumulative risk increased with the severity of APP. Infants exposed to severe APP had a significantly higher risk of male hypospadias than those without APP exposure (9.2 versus 1.7 per 1000 infants, P < 0.001). A path analysis indicated that 28.18-46.61% of the risk of hypospadias may be attributed to the effect of APP. CONCLUSIONS: Male hypospadias risk was associated with APP and increased with APP severity, as measured in the second trimester. APP had an important role in the development of the anomaly.

Levator ani evaluation at transperineal elastography in women with deep infiltrating endometriosis postoperatively.

OBJECTIVE: To explore whether operation can change the elasticity of levator ani in deep infiltrating endometriosis (DIE) with operation and pharmacotherapy using transperineal elastography. METHODS: Total thirty-four patients who were diagnosed as DIE were included in the study. Transperineal elastography were performed in all cases preoperatively and postoperatively. The levator ani was evaluated by means of the scoring system and strain ratio (SR) values on maximal Valsalva and quiescent condition, respectively. RESULTS: On quiescent condition, the preoperative mean elastography scores and SR of the levator ani were statistically significantly higher than the postoperative ones in both shaving technique group and segmental colorectal resection group. And on maximal Valsalva, the preoperative mean elastography scores and SR of the levator ani were statistically significantly lower than the postoperative ones in both groups. After surgery and 6 cycles of GnRHa therapy, the mean elastography score and SR of the levator ani were statistically significantly lower than before GnRHa therapy in shaving technique group on quiescent condition. And on maximal Valsalva, the mean elastography score and SR were statistically higher than before GnRHa therapy. However, in segmental colorectal resection group, the differences were not observed before and following 6 cycles of GnRHa therapy. CONCLUSION: The elasticity of levator ani of DIE was changed by both shaving technique and segmental colorectal resection. And transperineal elastography could access the alterations.

Elasticity of adenomyosis is increased after GnRHa therapy and is associated with spontaneous pregnancy in infertile patents.

OBJECTIVE: To explore the effects of GnRHa on adenomyosis by transvaginal elastography. METHODS: A prospective observational study included patients who were diagnosed as adenomyosis by conventional transvaginal ultrasound and infertility. The sonographic characters of elastography, the degree of dysmenorrhea and the values of serum CA125 before and following GnRHa (Triptorelin 3.75 mg were administered every 28 days) plus add-back therapy were reviewed and analyzed. Each case had a 6 months follow up and the information of pregnancy were recorded. RESULTS: 45 patients who completed the 6 months follow-up were included in the analysis. Twelve cases (group 1) were pregnancy during the follow-up and the other thirty-three cases (group 2) failed their attempts. The numerical rating scale and CA125 of all the cases were both significantly reduced 6 months after therapy. All of enlarged uterus decreased to accessible normal size. In group 1, the mean elasticity score was significantly higher for the uterine after therapy than before (3.6 ± 0.3 vs 2.3 ± 0.5, p = 0.004). In group 2, the mean elasticity score did not change for the uterine after therapy than before (2.2 ± 0.5 vs 2.5 ± 0.6, p = 0.77). CONCLUSION: Elasticity of adenomyosis is increased after GnRHa therapy. And the higher elasticity of adenomyosis after GnRHa therapy is associated with spontaneous pregnancy in infertile patents.

A Comparison of Prediction of Adverse Perinatal Outcomes between Hadlock and INTERGROWTH-21st Standards at the Third Trimester.

Little is known about the clinical value of the Hadlock and INTERGROWTH-21st EFW standards for predicting adverse perinatal outcomes (APOs) in the third trimester. The purpose of this study was to study the association between low estimated fetal weight percentile (EFWc) in the third trimester and the risk of APOs and compare predictions of APOs between Hadlock and INTERGROWTH-21st EFW standards. A prospective cohort of 690 singleton pregnancies with ultrasonography performed in the third trimester between March 2015 and March 2016 in China was conducted. EFW and the corresponding EFWc were measured using the Hadlock and INTERGROWTH-21st standards, respectively. Cox proportional hazard models were used to assess the relationship between low EFWc (i.e., <5 percentile, P5) and the risk of APOs. Compared with fetuses with ≥P5 of the EFWc, fetuses with

Evaluation of pelvic floor muscle by transperineal elastography in patients with deep infiltrating endometriosis: preliminary observation.

PURPOSE: To assess the elasticity of the pelvic floor muscle (PFM) affected by deep infiltrating endometriosis (DIE) with transperineal elastography. METHODS: This prospective observational study included 88 patients who were diagnosed with DIE, ovarian endometrioid cyst, or ovarian teratoma. All the patients were assigned to one of the three groups and underwent transperineal elastography. The scoring system and strain ratio (SR) values were recorded and analyzed. Assessments were conducted at maximal Valsalva and under quiescent condition, respectively. RESULTS: The mean elastography score was statistically significantly higher for the levator ani of group I than groups II and III under quiescent condition. In addition, SR of the levator ani in group I was higher than that in groups II and III. However, at maximal Valsalva, the mean elastography score of group I was lower than that of groups II and III. In addition, SR of group I was lower than that of groups II and III. CONCLUSION: The elasticity of the PFM in DIE patients could be qualitatively evaluated by transperineal elastography. The coordination of the PFM was injured and decreased elasticity appeared in DIE patients.