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Data on the value of exome sequencing in fetuses with no structural anomalies are limited, especially in the early stages of pregnancy and in low risk pregnancies. We investigated the yield of targeted clinical prenatal trio exome sequencing (pES) in pregnancies with and without fetal structural anomalies.We performed pES in 353 pregnancies: Group 1 included 143 pregnancies with high clinical suspicion for a genetic disease: pregnancies with increased nuchal translucency, ultrasound structural defects, intrauterine growth restriction, polyhydramnios, or effusion/nuchal edema. Group 2 included 210 pregnancies with no notable abnormal fetal ultrasound findings. 2a. Low risk pregnancies with minor ultrasound findings, referred to the geneticist due to mildly increased risk for genetic disease (50); and 2b. Normal pregnancy surveillance (160).Overall, 26 (7.36%) fetal analyses had pathogenic (P)/likely pathogenic (LP) variants. In group 1, 20/143 (13.99%) cases had P/LP variants. In group 2, 6/210 (2.86%) cases were found to have P/LP variants [5/50 in (2a) and 1/160 in (2b)].These results show a high rate of abnormal findings on pES even in apparently normal pregnancies.

Objective The fetal liver circulation has an important role in fetal growth. The intra-hepatic Umbilical-Porto-Systemic Venous Shunt (IHUPSVS) causes a reduction of the umbilical blood flow to the liver and has been reported to have a restrictive effect on fetal growth. The aim of this study was to evaluate the effect of IHUPSVS on fetal growth. Methods We conducted a retrospective cohort study of IHUPSVS diagnosed between 2001 and 2019. IHUPSVS was defined as any abnormal communication between any branch of the portal vein and hepatic vein. Pre- and postnatal characteristics were collected from medical files and compared between cases with fetal growth restriction (FGR) and those appropriate for gestational age (AGA). Results Twenty-five fetuses were included in the study. Eighteen (72%) had last estimated fetal weight and birth weight below the 10th centile, four (16%) of them between the third and fifth centile, and 11 (44%) below the third centile. Median gestational age at delivery was lower for FGR than AGA fetuses (37 vs. 38 weeks, p = 0.034) and rate of preterm delivery was higher (38.9 vs. 14.3, P = 0.24). Four cases had associated structural anomalies (2 in each group), and two had minor genetic aberrations (1 in each group). Conclusions Growth restriction is prevalent in fetuses with IHUPSVS, suggesting that fetal growth should be monitored. In equal measure, in cases with growth restriction, especially without other apparent cause, an intrahepatic shunt should be looked for.

Introduction Fetal and placental tumors are associated with high prevalence of obstetrical complications and poor fetal outcome. The aim of our study was to assess the added value of serial fetal Tricuspid Annular Plane Systolic Excursion (f-TAPSE) measurements for monitoring cardiac function in cases of fetal and placental tumors. Methods Serial measurements of f-TAPSE were performed prospectively in fetuses referred for fetal and placental tumors. The patients were followed longitudinally every 2 weeks. In each visit, tumor measurements, Doppler flow indices, fetal cardiothoracic index and measurements of f-TAPSE were performed. Results During the study period, 11 fetuses were followed prospectively: 7 chorioangiomas and 4 fetal tumors. In eight cases the f-TAPSE was measured in the upper range for gestational age. In three cases of small or poorly vascularized tumors, the measurements were within the 50th percentile for gestational age. In two cases who presented with elevated f-TAPSE, a regression in the f-TAPSE percentile was observed: in the first case, the tumor regressed, however in the second case; the f-TAPSE pseudo normalized and was followed by cardiac decompensation. Conclusions f-TAPSE may serve as a complementary tool for assessing tumors associated hyper-dynamic state and early diagnosis of cardiac decompensation.

OBJECTIVE Data regarding the neurodevelopmental outcome of children diagnosed in utero with isolated ventriculomegaly (IVM) are limited and principally founded on ultrasound-based studies. Here, we endeavored to assess the outcome of such cases in a large-scale, magnetic resonance imaging (MRI)-based study. METHODS We conducted a study on 133 cases of IVM with a documented fetal brain MRI scan. Children were assessed at ages 18 to 36 months by using the Vineland Adaptive Behavior Scales (VABS). RESULTS Vineland Adaptive Behavior Scales scores were within normal range. There was no significant difference between VABS score in symmetric versus asymmetric IVM (101.7 vs. 101.6, respectively; p = 0.94), and the VABS score of mild IVM was comparable with that of moderate IVM (101.8 vs. 101; p = 0.8). Only five cases (3.8%) were found to have an abnormal score (

OBJECTIVE The objective of this study is to investigate prenatal diagnosis and postnatal outcome of fetuses with crossed ectopic kidney. METHOD Cases referred for an empty renal fossa and diagnosed with crossed ectopic kidney confirmed postnatally were analyzed retrospectively over a period of 10 years. Prenatal diagnosis was established following the detection of one kidney in a normal position and a second ipsilateral kidney fed by abnormal blood vessels on Doppler flow RESULTS: Between 2005 and 2015, 185 fetuses were referred for an empty renal fossa. Crossed ectopic kidney was diagnosed in 10 of them. Associated congenital urological anomalies included two cases of double collecting system and bilateral hydronephrosis in one. Associated extra renal findings were single umbilical artery (4/10), ventricular septal defects (1/10), and persistent left superior vena cava (1/10). On postnatal follow-up, bilateral vesicoureteral reflux was diagnosed in a case who presented prenatally with bilateral hydronephrosis and two cases of mild hydronephrosis. All cases were managed conservatively. CONCLUSION Crossed ectopic kidney should be suspected in cases presenting with an empty renal fossa and a normal positioned kidney. Thorough anatomical scan should be performed as well as periodic follow-up throughout pregnancy. Postnatal nephrological follow-up is recommended. © 2017 John Wiley & Sons, Ltd.

Objective To create nomograms of fetal renal compensatory growth in cases of unilateral renal agenesis (URA). Methods A retrospective study of fetuses with isolated URA diagnosed prenatally, and confirmed postnatal was performed. Results Seventy-four fetuses with isolated solitary kidney were included in the study. A total of 134 measurements of the kidney's length were performed. Ninety five of them were studied longitudinally (2–6 measurements each). The raw values of the compensatory kidney demonstrated a significant correlation with gestational age (Pearson correlation coefficient 0.901, p

Objective The linkage between 17q12 microdeletions, renal anomalies, and higher risk for neurodevelopmental disorders is well described in the literature. The current study presents prenatal diagnosis of normal-sized fetal hyperechogenic kidneys leading to the diagnosis of 17q12 deletion syndrome and autism spectrum disorder. Methods Over a period of 9 years in a single referral center, seven fetuses were diagnosed with hyperechogenic renal parenchyma and were followed up prospectively. Amniocentesis for molecular diagnosis was performed in all cases, and subsequently, five fetuses were found to harbor a 17q12 deletion by chromosomal microarray analysis. Postnatal evaluation was carried out by a developmental neurologist. Results Five of the seven fetuses had molecular diagnosis of 17q12 deletion. One patient elected termination of pregnancy. On long-term follow-up, all of the four children showed symptoms consistent with neurodevelopmental disorders. The two fetuses with no deletion have a normal follow-up with regression of the renal hyperechogenicity. Conclusions We report a strikingly high correlation between prenatal hyperechogenic kidneys, 17q12 microdeletion, and autism spectrum disorder with the advantage of optimal prenatal counseling as well as early diagnosis and intervention. © 2016 John Wiley & Sons, Ltd.

Objective Data regarding the neurodevelopmental outcome of fetal short corpus callosum (CC) diagnosed according to standard reference charts is scarce. The purpose of this study was to assess whether the finding is related to neurodevelopmental delay, and to examine reclassification to normal fetal CC length using CC length/EFW ratio. Method Historical prospective cohort study including pregnant women who were referred for fetal neurosonogram due to abnormal CC. Short CC was defined below the 5th percentile according to reference charts. Twenty cases were included in the study group and compared with a control group of 59 normal cases. The patients in the study group were divided into two groups according to CC length/EFW ratio. Children's neurodevelopment was assessed using the Vineland Adaptive Behavior Scale (VABS). Results VABS scores were within normal range in 90% of the cases. There was no significant statistical difference between the study group and the control group. In addition, there was no statistically significant difference between fetuses reclassified as normal callosal length according to CC length/EFW ratio in comparison to the control group. Conclusion The neurodevelopmental outcome of fetuses with diagnosed short CC did not differ from the neurodevelopment of normal fetuses in the control group.

OBJECTIVE The objective of this study is to evaluate the fetal cerebral vasculature by three-dimensional (3D) ultrasonography and Doppler technologies in normal fetuses and to describe a systematic method for analysis of volume data sets. METHODS 3D volumes of the fetal brain were acquired prospectively in 25 patients between 12.3 and 36.3 weeks' gestation. Volumes were acquired with high-definition Doppler flow. The feasibility of identifying the fetal cerebral blood vessels and venous sinuses was analyzed. RESULTS A step-by-step systematic approach to identify the cerebral vasculature from ultrasonographic volume data sets was developed. The volumes were rotated into a standard anatomic orientation in the multiplanar display, and then, by systematic navigation, the vessels were demonstrated. Arteries of the circle of Willis, basilar artery, pericallosal artery, and internal carotid arteries were demonstrated in more than half of the fetuses. Tiny vessels such as those that supply the cerebellum and those that branch from the pericallosal artery were demonstrated in less than 50% of the volumes. CONCLUSIONS The essential fetal cerebral vessels can be visualized by 3D volume analysis. Systematic analysis enables identification of the fetal brain arteries, veins, and sinuses and provides knowledge about anatomical variations and the diversity of human anatomy. © 2016 John Wiley & Sons, Ltd.

Objectives The purpose of this study was to demonstrate the normal perimeter and area of the three orthogonal planes (axial, sagittal and coronal) of the fetal Sylvian fissure along pregnancy using 3-dimensional (3D) ultrasound. Methods Ultrasound volumes of fetal head were acquired prospectively in 55 fetuses between 12 and 33 gestational weeks. All volumes were analyzed offline by two examiners separately. The largest axial, sagittal and coronal planes of the Sylvian fissure were identified, and the area and perimeter were measured. Results Measurements of the Sylvian fissure were demonstrated in 54 out of 55 volumes (98%). In all three planes, a linear growth was demonstrated along gestation. All measurements significantly correlated to gestational age and head circumference (p

Objective Hirschsprung disease (HD) is a rare gastrointestinal disorder. Our aim was to study the prenatal ultrasound findings of children who were diagnosed with HD after birth. Methods The study population included children who suffered from HD between 1990 and 2008. Data of anomaly scan findings in prenatal ultrasound, demographic and post-natal physical abnormalities and treatment were retrieved from medical files and interviews with the parents. Results Twenty-two patients confirmed histopathological diagnosis of HD at age of 1 day to 15 months. Nineteen fetuses had anomaly scan during pregnancy, which revealed minor sonographic abnormalities in three fetuses; two of them had hyperechogenic bowel. One fetus with hyperechogenic bowel had polyhydramnion, and another had a family history of three brothers with HD. A third fetus had dilated pelvic kidney. None of them had sonographic evidence of bowel dilatation. After birth, six patients (31%) were found to have other structural anomalies: ventriculoseptal defect, atriseptal defect, atrio-ventricular septal defect, and pyloric stenosis. Conclusions Abnormal sonographic findings of fetal bowel are absent in the vast majority of fetuses who are diagnosed with HD after birth. In women with a family history of HD, a third trimester anomaly scan may be warranted. © 2015 John Wiley & Sons, Ltd.

Objectives Blood vessel resistance is assessed by flow velocity indexes. However, the actual resistance should be more strongly correlated with vessel diameter rather than variations in flow velocity. We aimed to determine the utility of middle cerebral artery (MCA) diameter measurement as a tool for evaluating brain sparing effect in intrauterine growth-restricted (IUGR) discordant twins. Methods Ten dichorionic–diamniotic twin pairs with weight discordance were included in the study. Fetal assessment included estimated fetal weight, umbilical artery flow, MCA flow and MCA diameter. Paired statistical analysis was used to compare MCA diameter and MCA pulsatility index (PI) between the discordant twins. Results MCA diameter was significantly larger in the smaller twin (mean diameter 3.55 ± 0.26 vs 2.71 ± 0.22, P = 0.018, mean ratio 1.39 ± 0.14). There was no significant difference in MCA PI values within the twin pairs (mean PI 1.51 ± 0.13 vs 1.57 ± 0.07, P = 0.878, mean ratio 0.99 ± 0.11). Conclusions Measurement of MCA diameter can potentially be used as a tool for assessing vessel resistance. Further studies are needed to assess the feasibility and sensitivity of this method as well as the clinical significance of MCA dilatation in the presence of normal Doppler flow indexes. © 2014 John Wiley & Sons, Ltd.

Fetal and placental tumors are associated with high prevalence of obstetrical complications and poor fetal outcome. The aim of our study was to assess the added value of serial fetal Tricuspid Annular Plane Systolic Excursion (f-TAPSE) measurements for monitoring cardiac function in cases of fetal and placental tumors.Serial measurements of f-TAPSE were performed prospectively in fetuses referred for fetal and placental tumors. The patients were followed longitudinally every 2 weeks. In each visit, tumor measurements, Doppler flow indices, fetal cardiothoracic index and measurements of f-TAPSE were performed.During the study period, 11 fetuses were followed prospectively: seven chorioangiomas and four fetal tumors. In eight cases, the f-TAPSE was measured in the upper range for gestational age. In three cases of small or poorly vascularized tumors, the measurements were within the 50th percentile for gestational age. In two cases who presented with elevated f-TAPSE, a regression in the f-TAPSE percentile was observed: in the first case, the tumor regressed; however, in the second case, the f-TAPSE pseudo normalized and was followed by cardiac decompensation.f-TAPSE may serve as a complementary tool for assessing tumors associated hyper-dynamic state and early diagnosis of cardiac decompensation. © 2017 John WileySons, Ltd.

Objectives The objective of this article is to investigate whether sonographic identification of the fetal anal mucosa (AM) can assist in the diagnosis of anal atresia (AA) in fetuses referred for congenital anomalies of kidney and urinary tract (CAKUT) malformation. Methods During a 3-year study period, 245 fetuses referred for CAKUT were prospectively examined for the presence of the AM on an axial trans-perineal view. The prenatal findings were confirmed clinically. Results The AM was identified in all but two fetuses. The diagnosis of AA was confirmed clinically. In two additional cases, the babies were born with imperforated anus. In the first case, the AM was identified prenatally. The baby was born with a thin membrane covering the anal pit, which was easily penetrated revealing a patent anal canal. The second case was a false–negative, in which the echogenic ischial tuberosity was falsely mistaken for the AM. None of the cases earlier had bowel dilatation or enterolithiasis. Overall, the incidence of AA in our group was 30-fold relative to the general population (1.2% vs 0.04%). Conclusions In a CAKUT population, absence of the AM in the posterior perineal triangle in the axial trans-perineal view emerges as an important sonographic marker for prenatal diagnosis of AA. © 2014 John Wiley & Sons, Ltd.

Objectives In pediatrics, anogenital distance (AGD) serves as a bioassay of normal phenotypic androgen action on the external genitalia. Recently, hypospadias and cryptorchidism were reported to be associated with reduced AGD. No normal reference ranges exist for fetuses throughout gestation. This study defines the normal centile chart of the AGD, in male and female fetuses, between 20 and 35 weeks of gestation. Methods Participants were low-risk pregnant women, 20 to 35 weeks of gestation. All fetuses were singleton, with normal anatomic scan and appropriate fetal biometry for gestational age. Fetal AGD was measured by transabdominal ultrasound. The perineum was assessed in the axial plane. The distance was measured from the center of the anus to the posterior convergence of the fourchette in female fetuses and to the posterior base of the scrotum in male fetuses. Statistical analysis included the construction of the normal, modeled, centile, and standard deviation range, for each gestational age. Intraobserver and interobserver variability was assessed by the interclass correlation and Bland–Altman plot. Results Adequate measurements were obtained for 218 female and 206 male fetuses. For 17 cases, measurements were not possible because of fetal lie. AGD increased linearly throughout gestational age (GA) (r2 = 0.808) for both sexes and was expressed by the following regression equation: for male fetuses, −12.348 + 1.075*GA, and for female fetuses, −3.179 + 0.513*GA, where GA is gestational age. The normal centiles, means, and standard deviations, per week, are presented. Conclusion AGD measurement in utero is feasible. These measurements assess the normality of the perineal region and may assist in the detection of genital anomalies. © 2014 John Wiley & Sons, Ltd.

Objective This study aimed to compare measurement of the lateral cerebral ventricular diameter using either the traditional axial view or the coronal plane. Materials and methods We performed a prospective study on 144 fetuses, 77 evaluated as part of a routine fetal scan and 67 referred for a neurosonogram. Distal lateral ventricles were measured both in axial and coronal plane. Results Good visualization of the ventricles was achieved in 91% of the cases using the coronal plane (both ventricles) and in 95% of the cases using the axial plane (only the distal ventricle) (p > 0.001). The mean width of the distal lateral ventricle in the axial plane was 7.9 ± 1.9 mm versus 8.2 ± 1.9 mm on the coronal plane (p

The objective of this study is to investigate prenatal diagnosis and postnatal outcome of fetuses with crossed ectopic kidney.Cases referred for an empty renal fossa and diagnosed with crossed ectopic kidney confirmed postnatally were analyzed retrospectively over a period of 10 years. Prenatal diagnosis was established following the detection of one kidney in a normal position and a second ipsilateral kidney fed by abnormal blood vessels on Doppler flow RESULTS: Between 2005 and 2015, 185 fetuses were referred for an empty renal fossa. Crossed ectopic kidney was diagnosed in 10 of them. Associated congenital urological anomalies included two cases of double collecting system and bilateral hydronephrosis in one. Associated extra renal findings were single umbilical artery (4/10), ventricular septal defects (1/10), and persistent left superior vena cava (1/10). On postnatal follow-up, bilateral vesicoureteral reflux was diagnosed in a case who presented prenatally with bilateral hydronephrosis and two cases of mild hydronephrosis. All cases were managed conservatively.Crossed ectopic kidney should be suspected in cases presenting with an empty renal fossa and a normal positioned kidney. Thorough anatomical scan should be performed as well as periodic follow-up throughout pregnancy. Postnatal nephrological follow-up is recommended. © 2017 John WileySons, Ltd.

Objective To evaluate fetal secondary palate in fetuses at 12 to 16 weeks' gestation by three-dimensional ultrasound. Methods Between June 2006 and July 2008, volumes of palate were prospectively acquired in fetuses at gestational age of 12 to 16 weeks. Acquisition was performed when the fetus was facing the transducer with head extended at an angle of 30° to 40° to the ultrasound beam. Secondary palate was assessed off-line. Results Secondary palate was assessed in 45 fetuses with normal face anatomy and 4 fetuses with malformations of the face (one with retrognathia, one with retrognathia and micrognathia, one with cleft lip and one with cleft lip and primary palate). The secondary palate was visualized in 19/49 (38.7%) fetuses: in 2/49, only hard palate was demonstrated; in 6/49, only soft palate and in 11/49, both hard and soft palate were fully demonstrated. Conclusion Information concerning evenness of secondary palate may be provided by three-dimensional ultrasound in 38.7% of examined fetuses at 12 to 16 weeks of gestation. This examination should be offered in pregnancies at high risk for cleft palate. © 2013 John Wiley & Sons, Ltd.

Objective The aim of this research was to evaluate the ability of three-dimensional (3D) ultrasound for demonstrating the palate of fetuses at high risk for cleft palate. Method Fifty-seven fetuses at high risk for cleft palate were referred for specialist ultrasound at 12–40 weeks' gestation. A detailed assessment of palate was made using both two-dimensional and 3D ultrasounds on the axial plane. Antenatal diagnoses were compared with postnatal findings. Results Cleft palate was suspected in 13 (22.8%); a normal palate was demonstrated in 38 (67%), and in six (10.2%), the palate view could not be obtained. Mean gestational age at the first visit was 27 weeks 6 days (range of 12–40 weeks 3 days). Examination after delivery revealed that one of the 38 fetuses with presumed normal palate had a cleft hard palate, and one had a cleft soft palate (false negative 5%). Among the 13 fetuses with suspected cleft palate, three had an intact palate (false-positive 23%). Sensitivity, specificity, positive predictive value, and negative predictive value of detection of palatal clefts were 71.4%, 91.9%, 62.5%, and 94.4%, respectively. Conclusion Using 3D technology, we diagnosed a cleft palate in 83% of high-risk cases, with 5% false negative. 3D technology might produce some technical artifacts resulting in a 23% false-positive rate. © 2013 John Wiley & Sons, Ltd.

The linkage between 17q12 microdeletions, renal anomalies, and higher risk for neurodevelopmental disorders is well described in the literature. The current study presents prenatal diagnosis of normal-sized fetal hyperechogenic kidneys leading to the diagnosis of 17q12 deletion syndrome and autism spectrum disorder.Over a period of 9 years in a single referral center, seven fetuses were diagnosed with hyperechogenic renal parenchyma and were followed up prospectively. Amniocentesis for molecular diagnosis was performed in all cases, and subsequently, five fetuses were found to harbor a 17q12 deletion by chromosomal microarray analysis. Postnatal evaluation was carried out by a developmental neurologist.Five of the seven fetuses had molecular diagnosis of 17q12 deletion. One patient elected termination of pregnancy. On long-term follow-up, all of the four children showed symptoms consistent with neurodevelopmental disorders. The two fetuses with no deletion have a normal follow-up with regression of the renal hyperechogenicity.We report a strikingly high correlation between prenatal hyperechogenic kidneys, 17q12 microdeletion, and autism spectrum disorder with the advantage of optimal prenatal counseling as well as early diagnosis and intervention. © 2016 John WileySons, Ltd.