Prenatal diagnosis of biliary atresia: A case series.

BACKGROUND: Biliary atresia is a progressive disease presenting with jaundice, and is the most common indication for liver transplantation in the pediatric population. Prenatal series have yielded conflicting results concerning a possible association between BA and prenatal nonvisualization of the gallbladder. AIMS: This retrospective case series was performed to assess the association between biliary atresia, prenatal nonvisualization of the gallbladder and other sonographic signs. STUDY DESIGN/SUBJECTS: We identified biliary atresia patients who underwent a Kasai procedure by a single pediatric surgeon and/or follow up by a single pediatric gastroenterologist. Axial plane images and/or video recordings were scrutinized for sonographic signs of biliary atresia on the second trimester anomaly scan. OUTCOME MEASURES: Proportion of biliary atresia cases with prenatal sonographic signs. RESULTS: Twenty five charts of children with biliary and high quality prenatal images were retrieved. 6/25 (24%) of cases analyzed had prenatal nonvisualization of the gallbladder or a small gallbladder on the prenatal scan. Two cases had biliary atresia splenic malformation syndrome. None of the cases had additional sonographic markers of biliary atresia. CONCLUSIONS: Our study suggests that in addition to the well-established embryonic and cystic forms, an additional type can be suspected prenatally, which is characterized by prenatal nonvisualization of the gallbladder in the second trimester. This provides additional evidence that some cases of BA are of fetal rather than perinatal onset and may have important implications for prenatal diagnosis, for counseling and for research of the disease's etiology and pathophysiology.

Early second trimester transvaginal ultrasound anomaly scan does not cause adverse perinatal outcome.

OBJECTIVE: During an early second-trimester transvaginal ultrasound anomaly scan, pressure is applied to the uterus, and the fetus is often rotated manually to allow scanning of its various organs. This study was designed to determine if performing a transvaginal ultrasound anomaly scan during the early second trimester of pregnancy is associated with adverse perinatal outcome or cord entanglement. METHODS: During the 4.5year study period we prospectively collected cases of routine ultrasound scans at 14-17weeks gestation performed as anomaly screening, together with perinatal outcome. The study population consisted of 164 women who underwent a transvaginal approach, and the control population consisted of 224 women in which a transabdominal approach was used. Data on perinatal parameters was collected from delivery charts from the four local hospitals. RESULTS: There were more operative deliveries (vaginal or Cesarean) in the transvaginal scan group (32% vs. 23%, p=0.05). However, on multiple logistic regression analysis vaginal scans were not associated with increased operative delivery rates with an adjusted odds ratio of 1.47 and a 95% confidence interval of 0.85-2.54. There were no other clinically significant differences in perinatal outcomes, or in cord entanglement. CONCLUSIONS: Transvaginal ultrasound anomaly scan conducted in the early second trimester of pregnancy is a safe procedure for the fetus.

Abnormal shape of the cavum septi pellucidi: an indirect sign of partial agenesis of the corpus callosum.

OBJECTIVE: To describe and assess the presence of a new indirect sign of partial agenesis of the corpus callosum (pACC): an abnormally shaped cavum septi pellucidi (CSP). METHODS: We analyzed retrospectively images from all 71 cases of pACC seen at two referral centers between September 2006 and April 2014. Abnormally shaped CSP was diagnosed when its lateral dimension was greater than its anteroposterior dimension in the axial transthalamic plane, and the incidence of this sign was assessed. We also examined the following variables: gestational age at referral, indication for referral, which (if any) of the four corpus callosal segments were abnormal, presence of other, previously established, indirect signs of callosal agenesis (ACC) and presence of additional cerebral or extracerebral anomalies. RESULTS: In 56 of the 71 (79%) cases, the CSP was measurable; it was abnormally shaped in 19 (34%) of these cases, 15 (79%) of which had no other indirect signs of pACC. Of 23 cases with isolated pACC and no other indirect signs, 12 (52%) had an abnormally shaped CSP. CONCLUSIONS: In a significant proportion of cases of pACC detected prenatally, the shape of the CSP is abnormal. This should be considered an additional indirect sign of pACC, and is frequently the only clue to the diagnosis. When observing this sign in a screening context, pACC should be considered, and an attempt to visualize the corpus callosum directly in the midsagittal plane is suggested.

Systematic examination of the fetal abdominal precordial veins: a cohort study.

OBJECTIVES: Examination of the fetal venous system is a necessary part of complete fetal organ scanning to confirm landmark anatomy, such as the ductus venosus and course of the umbilical veins, and, whenever cardiovascular anomalies are identified, to exclude associated anomalous development of the fetal veins. We aimed to develop a protocol for systematic examination of the fetal venous system during midtrimester targeted organ scanning. METHODS: We included low-risk women with a singleton fetus presenting between January 2011 and June 2013 to our center for routine midtrimester (20-24 weeks) targeted organ scanning. Imaging of the venous system was added to the booked scan and comprised two-dimensional color Doppler scanning of the fetal abdomen in three discrete planes, two transverse and one longitudinal. The more caudal plane was obtained in a ventral or lateral transverse abdominal plane to image the umbilical vein, left portal vein, portal sinus, anterior right portal vein, posterior right portal vein, main portal vein and splenic vein and artery. Moving cephalad, a ventral or lateral transverse plane was obtained to image the right, middle and left hepatic veins and inferior vena cava (IVC). Finally, a longitudinal anteroposterior plane showed the umbilical vein, ductus venosus, IVC and left hepatic vein. In some cases the pulsed Doppler waveform of a given target vessel was also examined. Three-dimensional/4D ultrasound was applied as necessary, when anomalous cases were encountered. RESULTS: We examined 1810 women. Their body mass index ranged from 19 to 40 (mean, 24.7). In 38 (2.1%) women, the target anatomy was not visualized satisfactorily owing to maternal body habitus. A T-shaped configuration of the portal system vessels was observed in 63% of cases, an X-shaped configuration in 25% and an H-shaped configuration in 12%. During the study period, 24 congenital anomalies of the precordial venous system were diagnosed: nine cases of persistent right umbilical vein, seven of agenesis of the ductus venosus, five of anomalous portal venous drainage and three of interrupted IVC with azygos continuation. CONCLUSIONS: Examination of the fetal venous system is feasible with the application of three abdominal planes. While a venous system scan is not practicable as part of a screening-level examination, mastery of the normal anatomy is an essential part of the professional knowledge base, in order to provide ready and complete scanning of the system in cases of suspected anomalies or disordered cardiac function.

The fetal larynx and pharynx: structure and development on two- and three-dimensional ultrasound.

OBJECTIVES: To present a systematic approach for evaluating the fetal pharynx and larynx based on two- and three-dimensional ultrasound (2D-US and 3D-US) modalities, describing the sonographic appearance and function of the fetal upper respiratory tract and measuring the anatomical components of the pharynx and larynx. METHODS: Gravidae presenting from the late first trimester to mid-gestation for routine booked examinations with structurally normal singleton fetuses of confirmed gestational age were enrolled. Transabdominal 2D-US was performed for anatomical and functional evaluation of the pharynx and larynx. Color Doppler was used to show fluid motion in the target area. 3D-US (Voluson® E6 with RAB-4-8-D transducer) scans of the fetal neck were acquired during fetal quiescence and in the absence of movements of the pharynx and larynx. Multiplanar reconstruction (MPR) in post-processing allowed adjustment of the volume to obtain the coronal plane. After a learning period to understand the sonographic anatomy of the target area, we measured the pharynx width and height, the upper, middle and lower larynx width and the larynx height. Render mode was applied for spatial evaluation of the target area. We developed a new methodological approach for structured evaluation of the fetal pharynx and larynx based on five spatial planes: posterior and anterior coronal planes and high, mid and low axial planes. RESULTS: We examined 582 fetuses during the second trimester of pregnancy; target anatomy was imaged successfully in 218 patients at 11-24 gestational weeks. Acquisition added approximately 1 min to examination time. Rates of successful visualization and measurements increased significantly as pregnancy progressed, being 23% (46/194) at 11-13 weeks, 29% (69/240) at 14-16 weeks, 35% (18/51) at 17-19 weeks and 88% (85/97) at 20-24 weeks (P < 0.01). Pharynx components identified were: the sphenoid bone, pterygoid processes, constrictor muscles, piriform recesses and uvula. Larynx components identified were: the epiglottis, aryepiglottic folds, corniculate cartilages, arytenoid cartilages, cricoid cartilage, thyroid cartilage and vocal cords. MPR showed the biconcave shape of the uvula, which may explain the 'equals sign' observed on 2D-US. We observed the bilateral mode of movements of the constrictor muscles, aryepiglottic folds and vocal cords, and the bidirectional fluid jet flows through the larynx. Scatterplots of measured structures vs gestational age were created. Pharynx width ranged from 0.11 to 0.93 (mean ± SD, 0.48 ± 0.17) cm; pharynx height ranged from 0.23 to 2.01 (mean ± SD, 0.94 ± 0.34) cm; upper larynx width ranged from 0.04 to 0.37 (mean ± SD, 0.15 ± 0.07) cm; middle larynx width ranged from 0.08 to 0.77 (mean ± SD, 0.34 ± 0.16) cm; lower larynx width ranged from 0.05 to 0.64 (mean ± SD, 0.24 ± 0.11) cm; and larynx height ranged from 0.20 to 1.83 (mean ± SD, 0.71 ± 0.31) cm. All measurements were positively correlated with gestational age. CONCLUSIONS: The fetal larynx and pharynx can be evaluated thoroughly using 2D- and 3D-US modalities. Knowledge of normal anatomy, function and biometry may prove useful in the evaluation of anatomical or functional pathology involving the fetal upper respiratory tract. Recognition of anatomical anomalies may enhance fetal intervention such as balloon placement in cases of diaphragmatic hernia.

Methylenetetrahydrofolate reductase C677T polymorphism and the risk of male infertility: a meta-analysis.

Several molecular epidemiological studies have been conducted to examine the association between MTHFR C677T polymorphism and male infertility susceptibility, but the results remain inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 10 case-control studies, including 2275 cases and 1958 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals were used to assess the strength of association in the additive model, dominant model and recessive model. In the overall analysis, no significant association between the polymorphism and risk of male infertility was observed. Stratified analysis showed that significantly strong association between MTHFR C677T polymorphism and male infertility were present only in Asians (OR = 1.79 for TT vs. CC genotype; OR = 1.42 for CT/TT vs. CC genotype; OR = 1.50 for TT vs. CC/CT genotype; OR = 1.36 for T vs. C allele), but not in Caucasians. Additionally, MTHFR 677T was associated with a significant increase in the risk of azoospermia in all genetic models. No significantly increased risks of oligoasthenoteratozoospermia were found in any of the genetic models. In conclusion, this meta-analysis supports that MTHFR C677T polymorphism is capable of causing male infertility susceptibility in Asians, but not in Caucasians.

Fetal heart ventricular mass obtained by STIC acquisition combined with inversion mode and VOCAL.

OBJECTIVE: Estimation of fetal heart ventricular mass is important for fetal cardiac evaluation in cases of structural or functional cardiac disorders or extracardiac factors. It may be used with other cardiac parameters to ascertain the severity and prognosis of such disorders, or the nature and timing of intervention. We applied a novel technique combining spatiotemporal image correlation (STIC) with three-dimensional inversion mode and Virtual Organ Computer-aided AnaLysis (VOCAL™) for fetal cardiac mass assessment in healthy fetuses in the second and third trimesters. METHODS: STIC acquisition was performed during fetal quiescence with the abdomen uppermost, at an angle of 30-50°, without color Doppler mapping. Myocardial volume measurements were performed in postprocessing using VOCAL mode, set to 15°. Beginning with the heart in four-chamber view at end diastole, a trace was drawn manually including the myocardium and interventricular septum. Inversion mode colors the intraventricular (anechoic, fluid-filled) voxels; this intraventricular volume was subtracted automatically from the total. Mass was determined by multiplying the result by the estimated fetal myocardial density (1.050 g/cm(3) ). The process was repeated for right and left ventricles. RESULTS: Data from 106 fetuses at 21-38 weeks' gestation were obtained and scatterplots of fetal cardiac ventricular mass distribution were created. Several cases of fetuses with disordered cardiac ventricle (supraventricular tachycardia, hypoplastic left heart syndrome, dilated cardiomyopathy, twin-to-twin transfusion syndrome, Ebstein anomaly, non-immune hydrops fetalis, septate right atrium and diaphragmatic hernia) were examined. Ventricular mass parameters were markedly affected as compared with normal cases of similar gestational age. CONCLUSIONS: STIC acquisition combined with inversion mode and VOCAL is a feasible method of cardiac ventricular mass quantification. This methodology may have added value in fetal cardiac evaluation in cases of anatomic malformation or cardiac dysfunction, or in cases of maternal diabetes.

Added value of three-/four-dimensional ultrasound in offline analysis and diagnosis of congenital heart disease.

OBJECTIVE: Many published studies have shown that application of three-dimensional (3D) and real-time 3D (4D) ultrasound modalities can improve certain aspects of fetal echocardiography, but have left open the question of whether these modalities improved the accuracy of prenatal detection of anatomical fetal cardiovascular malformations. We aimed to determine whether 3D/4D ultrasound improved diagnostic ability in cases of congenital heart disease (CHD). METHODS: Women who attended for early- or midtrimester targeted organ scans had complete fetal echocardiography according to our five-planes protocol, as well as examination of the ductus venosus and longitudinal aortic arch planes, performed with 2D ultrasound combined with 2D color Doppler, spatiotemporal image correlation (STIC), STIC with color Doppler, and STIC with B-flow. Ultrasound data of cases of CHD were stored in a dedicated archive. Stored cases were anonymized and the list order was randomized. Stored 2D ultrasound cineloops and 4D ultrasound volumes were reviewed separately according to a standardized table of 23 specified structures on five required planes of visualization: the upper abdomen, four-chamber view, five-chamber view, pulmonary artery bifurcation view, and three vessels and trachea plane. Separate diagnoses were recorded and finally compared. Diagnoses were confirmed by pathological examination or neonatal echocardiography. RESULTS: During the study period, 13 101 examinations were performed; 181 diagnoses of CHD were made. In 12 of these, 3D/4D ultrasound added to the accuracy of our diagnosis: one right aortic arch with anomalous branching; one transposition of the great arteries with pulmonary atresia diagnosed with tomographic ultrasound imaging (TUI); one segmental interrupted aortic arch diagnosed with TUI; one right ventricle aneurysm diagnosed with B-flow; two agenesis of ductus venosus to the coronary sinus diagnosed by multiplanar reconstruction (MPR) and B-flow; two total anomalous pulmonary venous connection diagnosed with MPR; and four ventricular septal defect (VSD) diagnosed with the aid of virtual planes. There were 12 missed diagnoses and no false-positive results. CONCLUSIONS: 3D/4D ultrasound modalities may have advantages in some aspects of fetal cardiovascular evaluation, however, overall 3D/4D ultrasound modalities had added value in only about 6% of cases of fetal anatomical cardiovascular anomalies.

Shunt diameter in agenesis of the ductus venosus with extrahepatic portosystemic shunt impacts on prognosis.

OBJECTIVES: Agenesis of the ductus venosus (ADV) is a rare condition in which there are two variants of umbilical vein drainage: intrahepatic shunt or extrahepatic (portosystemic) shunt. It has been posited that the extrahepatic variant carries a poorer prognosis. However, in the absence of associated anomalies there is still a wide variation in outcome. We evaluated the portal system in cases of ADV and aimed to identify parameters that might predict outcome. METHODS: We conducted a retrospective study of cases of ADV with extrahepatic shunt that had been examined in two centers, and collected new cases prospectively. The route of the shunt was depicted using two-dimensional (2D) and three-dimensional (3D) ultrasound imaging. In an attempt to characterize portal system and shunt developmental variations and their possible impact on outcome, the diameter of the shunt was compared with the diameter of the umbilical vein and the entire portal vasculature was assessed. Poor outcome was defined as persistent morbidity or fetal or neonatal death. RESULTS: Twenty-two cases of ADV were identified: nine retrospectively and 13 prospectively. Aberrant shunts from the umbilical vein were identified to the right atrium, coronary sinus, inferior vena cava (IVC) and iliac vein. In seven of 22 cases (32%) a wide connection was observed. In six of these seven cases (86%) the outcome was poor, including four with severe associated anomalies and two with hepatic dysfunction. In five of these cases, cardiomegaly with tricuspid regurgitation was observed, as well as underdevelopment of the portal system. In only five of 15 cases with a narrow shunt (33%) was the outcome poor, and in all five cases the poor outcome was related to associated anomalies. CONCLUSION: In cases of ADV with extrahepatic shunt, portal system development is impacted by the diameter of the shunt. If the shunt is narrow, the portal system will have developed normally. A wide shunt is associated with underdevelopment or absence of the portal system. In cases of ADV with extrahepatic shunt, prognosis is determined by the severity of associated anomalies, the diameter of the shunt and development of the portal system.

Absent gallbladder on fetal ultrasound: prenatal findings and postnatal outcome.

OBJECTIVES: Fetal gallbladder non-visualization on prenatal ultrasound in the second trimester is uncommon and in most cases the gallbladder is detected eventually. Associations of gallbladder non-visualization with cystic fibrosis, aneuploidy, agenesis of the gallbladder and biliary atresia have been reported. We present our experience and review the literature. METHODS: During the study period from January 2004 to June 2009 we collected prospectively cases of non-visualization of the fetal gallbladder in the second trimester. In each case the fetus was evaluated by two examiners on at least two occasions, at least a week apart. Cases with no additional sonographic malformations were designated as isolated. Further evaluation included follow-up scans and a meticulous search for fetal anomalies. All patients were offered genetic consultation. Cystic fibrosis testing, amniocentesis for karyotyping and analysis of fetal digestive enzymes in the amniotic fluid were offered. RESULTS: We collected 21 cases of non-visualization of the fetal gallbladder, 16 of which were isolated and five of which had additional malformations. In four of these five, the associated anomalies were severe and the pregnancies were terminated for aneuploidy (two cases of trisomy 18 and one triploidy) or for the severity of the associated anomalies. Associated anomalies included left isomerism with complex cardiac anomaly and intrauterine growth restriction with multisystem anomalies. The fifth fetus had interrupted inferior vena cava with azygos continuation without other anomalies and the child was alive and well at the age of 4 years. In 15 of the 16 isolated cases, antenatal and postnatal development were normal at the last follow-up, ranging from 4 months to 2.5 years. One case of cystic fibrosis was diagnosed prenatally and this pregnancy was terminated. There were no diagnoses of abnormal karyotype or biliary atresia among cases of isolated non-visualization of the gallbladder. CONCLUSIONS: When prenatal non-visualization of the fetal gallbladder is associated with other severe malformation, aneuploidy should be suspected. When it is isolated, if cystic fibrosis is ruled out, the outcome is good.

The fetal venous system, part I: normal embryology, anatomy, hemodynamics, ultrasound evaluation and Doppler investigation.

Since its introduction in the mid-1980s sonographic evaluation of the human fetal venous system has advanced dramatically. The venous system is well-recognized as a target for investigation in cases of circulatory compromise, and a broad spectrum of malformations affecting this system has been described. Appreciation of the normal embryology, anatomy and physiology of this system is essential to an understanding of structural anomalies and the sequential changes encountered in intrauterine growth restriction or other developmental disorders. We review the normal embryology, anatomy, and hemodynamics of the human fetal venous system, and provide an overview of Doppler investigation, as well as three- and four-dimensional ultrasound modalities and their application to this system.

The fetal venous system, Part II: ultrasound evaluation of the fetus with congenital venous system malformation or developing circulatory compromise.

The human fetal venous system is well-recognized as a target for investigation in cases of circulatory compromise, and a broad spectrum of malformations affecting this system has been described. In Part I of this review, we described the normal embryology, anatomy and physiology of this system, essential to the understanding of structural anomalies and the sequential changes encountered in intrauterine growth restriction and other developmental disorders. In Part II we review the etiology and sonographic appearance of malformations of the human fetal venous system, discuss the pathophysiology of the system and describe venous Doppler investigation in the fetus with circulatory compromise.