Prenatal cardiac biometry and flow assessment in fetuses with bicuspid aortic valve at 20 weeks' gestation: multicenter cohort study.

OBJECTIVE: To investigate prenatal changes in cardiac biometric and flow parameters in fetuses with bicuspid aortic valve (BAV) diagnosed neonatally compared with controls with normal cardiac anatomy. METHODS: This analysis was conducted as part of the Copenhagen Baby Heart Study, a multicenter cohort study of 25 556 neonates that underwent second-trimester anomaly scan at 18 + 0 to 22 + 6 weeks' gestation and neonatal echocardiography within 4 weeks after birth, in Copenhagen University Hospital Herlev, Hvidovre Hospital and Rigshospitalet in greater Copenhagen, between April 2016 and October 2018. From February 2017 (Rigshospitalet) and September 2017 (Herlev and Hvidovre hospitals), the protocol for second-trimester screening of the heart was extended to include evaluation of the four-chamber view, with assessment of flow across the atrioventricular valves, sagittal view of the aortic arch and midumbilical artery and ductus venosus pulsatility indices. All images were evaluated by two investigators, and cardiac biometric and flow parameters were measured and compared between cases with BAV and controls. All cases with neonatal BAV were assessed by a specialist. Maternal characteristics and first- and second-trimester biomarkers were also compared between the two groups. RESULTS: Fifty-five infants with BAV and 8316 controls with normal cardiac anatomy were identified during the study period and assessed using the extended prenatal cardiac imaging protocol. There were three times as many mothers who smoked before pregnancy in the group with BAV as in the control group (9.1% vs 2.7%; P = 0.003). All other baseline characteristics were similar between the two groups. Fetuses with BAV, compared with controls, had a significantly larger diameter of the aorta at the level of the aortic valve (3.1 mm vs 3.0 mm (mean difference, 0.12 mm (95% CI, 0.03-0.21 mm))) and the pulmonary artery at the level of the pulmonary valve (4.1 mm vs 3.9 mm (mean difference, 0.15 mm (95% CI, 0.03-0.28 mm))). Following conversion of the diameter measurements of the aorta and pulmonary artery to Z-scores and Bonferroni correction, the differences between the two groups were no longer statistically significant. Pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) was significantly lower in the BAV group than in the control group (0.85 vs 1.03; P = 0.04). CONCLUSIONS: Our findings suggest that fetuses with BAV may have a larger aortic diameter at the level of the aortic valve, measured in the left-ventricular-outflow-tract view, and a larger pulmonary artery diameter at the level of the pulmonary valve, measured in the three-vessel view, at 20 weeks' gestation. Moreover, we found an association of maternal smoking and low PAPP-A MoM with BAV. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of prospective measurement of outflow tracts in prediction of coarctation of the aorta.

OBJECTIVES: Prenatal diagnosis of coarctation of the aorta (CoA) is associated with reduced mortality and morbidity, however, accurate prenatal prediction remains challenging. To date, studies have used retrospective measurements of the outflow tracts to evaluate their potential to predict CoA. Our primary objective was to evaluate prospectively acquired measurements of the outflow tracts in fetuses with prenatally suspected CoA. A secondary aim was to report the postnatal prevalence of bicuspid aortic valve in this cohort. METHODS: Pregnancies with suspicion of isolated CoA and with a minimum of 6 months' postnatal follow-up available were identified from the cardiac database of a tertiary fetal cardiology center in the UK, between January 2002 and December 2017. Measurement of the aortic valve, pulmonary valve, distal transverse aortic arch (DTAA) and arterial duct (AD) diameters were undertaken routinely in fetuses with suspected CoA during the study period. Z-scores were computed using published reference ranges based on > 7000 fetuses from our own unit. RESULTS: Of 149 pregnancies with prenatally suspected CoA included in the study, CoA was confirmed within 6 months after birth in 77/149 (51.7%) cases. DTAA diameter Z-score and the Z-score of second-trimester DTAA/AD diameter ratio were smaller in fetuses with postnatally confirmed CoA than those in false-positive cases (-2.8 vs -1.9; P = 0.039 and -3.13 vs -2.61; P = 0.005, respectively). Multiple regression analysis demonstrated that the Z-scores of DTAA and AD diameters were the only significant predictors of postnatal CoA (P = 0.001). Bicuspid aortic valve was identified in 30% of the false-positive cases. CONCLUSIONS: Measurement of DTAA and AD diameter Z-scores can be used to ascertain risk for postnatal CoA in a selected cohort. The high incidence of bicuspid aortic valve in false-positive cases merits further study with respect to both etiology and longer-term significance. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Tetralogy of Fallot with absent pulmonary valve-When the ductus is present: A case of isolated branch pulmonary artery and review of literature.

Tetralogy of Fallot/Absent Pulmonary Valve (TOF/APV) has been classically associated with the absence of a patent ductus arteriosus (PDA). We present a rare case of APV in TOF with a discontinuous left pulmonary artery (LPA) that was suspected during fetal echocardiogram. Postnatal echocardiogram confirmed the origin of a hypoplastic LPA from the PDA. Despite an aneurysmal (right pulmonary artery) (RPA), axial imaging demonstrated widely patent tracheobronchial system with no evidence of bronchial compression. Clinically, the child required only minimal respiratory support. Genetic testing was positive for 22 q11deletion, commonly associated with this lesion. Surgery consisted of unifocalization of the discontinuous LPA with placement of a valved pulmonary homograft during complete repair of this lesion. Our case highlights the importance of prenatal detection, to aid in the prompt initiation of prostaglandins so as to ensure early rehabilitation of the left lung. Inability to visualize one of the branch pulmonary arteries (PA's) and a PDA on fetal echocardiogram in TOF/APV must raise suspicion for an eccentric branch PA with ductal origin.

Developmental considerations with regard to so-called absence of the leaflets of the arterial valves.

BACKGROUND: Absent arterial valve leaflets are rare anomalies. On the basis of our understanding of the normal development of the arterial valves, we draw inferences that might offer clues to their morphogenesis. METHODS: We describe the findings from four human fetal autopsies with so-called "absent" arterial valvar leaflets. We then make inferences relative to these finding on the basis of our current understanding of normal development, the latter obtained by analysis of episcopic data sets from a large series of mouse embryos. RESULTS: The fetuses had died between 12 and 15 weeks of gestation. In two cases, we found absence of the leaflets of the pulmonary valve, with patency of the arterial duct, but otherwise normal hearts. In a third case, there was absence of the leaflets of both arterial valves, along with a perimembranous ventricular septal defect and a "window-type" arterial duct. This fetus had a completely muscular subaortic infundibulum. The last fetus had a pulmonary dominant common arterial trunk, with absence of the truncal valvar leaflets, but again with a muscular subtruncal infundibulum. Findings from the analysis of the mouse embryos reveal that the arterial valvar leaflets are formed from the distal outflow cushions, but that the cushions have a separate function in septating the arterial roots and the proximal outflow tracts. CONCLUSIONS: When interpreting the fetal findings in the light of development, we conclude that there had been normal fusion of the major outflow cushions, but failure in excavation of their peripheral margins in three of the cases. In the fourth case, however, the cushions had not only failed to excavate but had also failed to separate the arterial roots.

Main pulmonary artery cross-section ratio is low in fetuses with tetralogy of Fallot and ductus arteriosus-dependent pulmonary circulation.

OBJECTIVES: This study aimed to determine fetal echocardiographic features of tetralogy of Fallot in association with postnatal outcomes. METHODS: The Z-scores of the main and bilateral pulmonary arteries and the aorta were measured, and the following variables were calculated in 13 fetuses with tetralogy of Fallot: pulmonary artery-to-aorta ratio and main pulmonary artery cross-section ratio - the main pulmonary artery diameter squared divided by the sum of the diameter squared of the left and right pulmonary arteries. Fetuses were classified as having ductus arteriosus-dependent or ductus arteriosus-independent pulmonary circulation. RESULTS: We included two infants with pulmonary atresia and six infants with ductus-dependent pulmonary circulation, who underwent systemic-to-pulmonary shunt surgeries at ⩽1 month of age. The Z-scores of the main pulmonary artery and the pulmonary artery-to-aorta ratio in fetuses with ductus-dependent pulmonary circulation were lesser than those in fetuses with ductus independence, but not significantly. The main pulmonary artery cross-section ratio in fetuses with ductus dependence was significantly lesser (0.65±0.44 versus 1.56±0.48, p<0.005). Besides, the flow of the ductus arteriosus was directed from the aorta to the pulmonary artery in the ductus arteriosus-dependent group during the fetal period. CONCLUSIONS: The main pulmonary artery cross-section ratio was the most significant variable for predicting postnatal outcomes in fetuses with tetralogy of Fallot.

Prenatal Visualization of the Pulmonary and Aortic Valves and Leaflets Is Feasible Using 4-Dimensional Sonography.

OBJECTIVES: The purpose of this study was to determine whether the morphologic characteristics and area of the semilunar valves in healthy fetuses and fetuses with cardiac defects can be visualized by using spatiotemporal image correlation (STIC). METHODS: Spatiotemporal image correlation volumes from 74 healthy fetuses were recorded in 5 examinations between the 15th and 36th weeks of pregnancy. Second, we recorded STIC volumes from 64 fetuses with various cardiac defects. The quality of the volumes was rated. The areas of the aortic and pulmonary valves were measured in systole by rendering the valves on 4-dimensional sonography. The number of leaflets was examined. Longitudinal data analysis using linear mixed models was performed. RESULTS: Two hundred ninety-three volumes from normal hearts were examined. In 82.5%, the quality of the normal volumes was sufficient. Visualization of the valve opening was feasible in 96.1% of the normal hearts and 97.4% of the abnormal hearts. The success rate of visualization of the pulmonary and aortic valve leaflets was dependent on the gestational age, with the highest percentage (72.1% in normal hearts) at 19 to 24 weeks. Longitudinal regression analysis showed a positive relationship of the aortic and pulmonary valve areas with gestational age (P < .0001) and fetal biometric measurements (P < .0001). Fifty-eight abnormal volumes were examined. Cardiac defects with abnormal valve areas due to aortic and pulmonary stenosis could be clearly visualized by using STIC. CONCLUSIONS: Examination of the morphologic characteristics of the semilunar valves using STIC is feasible, which is difficult when using 2-dimensional sonography. With increasing implementation of 4-dimensional sonography, the understanding of rendered images might be useful for anyone practicing fetal echocardiography.

Prenatal differentiation between truncus arteriosus (Types II and III) and pulmonary atresia with ventricular septal defect.

OBJECTIVE: To describe antenatal sonographic signs that help in the differentiation of truncus arteriosus Types II and III (TA-II/III) from pulmonary atresia with ventricular septal defect (PA-VSD). METHODS: From a database of fetal echocardiographic examinations, we identified fetuses with sonographic features of a single great artery with VSD and relatively normal four-chamber view. Records were reviewed, comparing fetuses with TA-II/III and those with PA-VSD, with particular focus on: 1) characteristics of the overriding vessel, 2) appearance of the semilunar valves, 3) competence of the semilunar valves, 4) presence of major aortopulmonary collateral arteries (MAPCA), 5) main pulmonary artery being without antegrade flow, 6) site of arterial branching from the great artery and 7) other minor features, such as cardiac axis or associated anomalies. RESULTS: Seventeen fetuses were identified, eight with TA-II/III and nine with PA-VSD. Among the eight fetuses with TA-II/III, seven had abnormal valves and six had valve regurgitation, compared with none of the nine PA-VSD fetuses. Five TA-II/III fetuses had early branching to supply the lungs, whereas most fetuses with PA-VSD had more distal branching. Notably, in six of the TA-II/III fetuses, the root of the single great artery originated predominantly from the right ventricle, while all but one of the PA-VSD fetuses had typical equal overriding of the VSD. The main pulmonary artery was without antegrade flow in two cases with PA-VSD. Finally, four cases with PA-VSD had MAPCA, in two of which this was identified prenatally. CONCLUSION: Identification of abnormal arterial valves or valve regurgitation, site of origin of branching, presence of overriding of the great artery, a main pulmonary artery without antegrade flow and MAPCA are helpful in differentiating between TA-II/III and PA-VSD.

Characteristic differences and reference ranges for mitral, tricuspid, aortic, and pulmonary Doppler velocity waveforms during fetal life.

OBJECTIVES: We aimed to construct reference ranges for time intervals of each component of cardiac flow velocity waveforms in normal fetuses, comparing those variables between right and left ventricles. METHODS: In 359 fetuses at the gestational age of 17-38 weeks, the durations of atrioventricular (AV) valve opening (AVVO), AV valve closure (AVVC), total E- (total-E) and A- (total-A) waves, total ejection time (total-ET), acceleration time (acc-E for E-wave, acc-A for A-wave, and acc-ET for ejection time), and deceleration time (dec-E for E-wave, dec-A for A-wave, and dec-ET for ejection time) were studied cross sectionally. RESULTS: Both right and left acc-E showed the strongest correlations with gestational age (r = 0.478 and r = 0.519, respectively). Left AVVO showed a stronger correlation (r = 0.474) than right AVVO (r = 0.282) and, conversely, right AVVC showed a stronger correlation (r = 0.399) than left AVVC (r = 0.195) with gestational age. Significant differences (all P values <0.001) were observed for all right and left parameters other than total-A and acc-E. CONCLUSIONS: Characteristic differences between right and left ventricles were found in the reference ranges, suggesting the developmental properties of the fetal heart. © 2014 John Wiley & Sons, Ltd.

Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis.

Atrioventricular and semilunar valve abnormalities are common birth defects, but how cardiac valvulogenesis is directed remains largely unknown. During studies of genetic interaction between Egfr, encoding the epidermal growth factor receptor, and Ptpn11, encoding the protein-tyrosine-phosphatase Shp2, we discovered that Egfr is required for semilunar, but not atrioventricular, valve development. Although unnoticed in earlier studies, mice homozygous for the hypomorphic Egfr allele waved-2 (Egfrwa2/wa2) exhibit semilunar valve enlargement resulting from over-abundant mesenchymal cells. Egfr-/- mice (CD1 background) have similar defects. The penetrance and severity of the defects in Egfrwa2/wa2 mice are enhanced by heterozygosity for a targeted mutation of exon 2 of Ptpn11 (ref. 3). Compound (Egfrwa2/wa2:Ptpn11+/-) mutant mice also show premature lethality. Electrocardiography, echocardiography and haemodynamic analyses showed that affected mice develop aortic stenosis and regurgitation. Our results identify the Egfr and Shp2 as components of a growth-factor signalling pathway required specifically for semilunar valvulogenesis, support the hypothesis that Shp2 is required for Egfr signalling in vivo, and provide an animal model for aortic valve disease.

The secondary heart field is a new site of calcineurin/Nfatc1 signaling for semilunar valve development.

Semilunar valve malformations are common human congenital heart defects. Bicuspid aortic valves occur in 2-3% of the population, and pulmonic valve stenosis constitutes 10% of all congenital heart disease in adults (Brickner et al., 2000) [1]. Semilunar valve defects cause valve regurgitation, stenosis, or calcification, leading to endocarditis or congestive heart failure. These complications often require prolonged medical treatment or surgical intervention. Despite the medical importance of valve disease, the regulatory pathways governing semilunar valve development are not entirely clear. In this report we investigated the spatiotemporal role of calcineurin/Nfatc1 signaling in semilunar valve development. We generated conditional knockout mice with calcineurin gene disrupted in various tissues during semilunar valve development. Our studies showed that calcineurin/Nfatc1 pathway signals in the secondary heart field (SHF) but not in the outflow tract myocardium or neural crest cells to regulate semilunar valve morphogenesis. Without SHF calcineurin/Nfatc1 signaling, the conal endocardial cushions-the site of prospective semilunar valve formation--first develop and then regress due to apoptosis, resulting in a striking phenotype with complete absence of the aortic and pulmonic valves, severe valve regurgitation, and perinatal lethality. This role of calcineurin/Nfatc1 signaling in the SHF is different from the requirement of calcineurin/Nfatc1 in the endocardium for semilunar valve formation (Chang et al., 2004) [2], indicating that calcineurin/Nfatc1 signals in multiple tissues to organize semilunar valve development. Also, our studies suggest distinct mechanisms of calcineurin/Nfat signaling for semilunar and atrioventricular valve morphogenesis. Therefore, we demonstrate a novel developmental mechanism in which calcineurin signals through Nfatc1 in the secondary heart field to promote semilunar valve morphogenesis, revealing a new supportive role of the secondary heart field for semilunar valve formation.

Effect of selective fetoscopic laser photocoagulation therapy for twin-twin transfusion syndrome on pulmonary valve pathology in recipient twins.

OBJECTIVE: To investigate the impact of selective fetoscopic laser photocoagulation (SFLP) on pre-existing pulmonary valve pathology in the recipient twin in twin-twin transfusion syndrome (TTTS). METHODS: We evaluated preoperative echocardiograms of all pregnancies with TTTS treated with SFLP at our institution from 2001 to 2009 (n = 76). Sixteen (21%) recipients had an abnormal pulmonary valve (stenosis/dysplasia, insufficiency or functional atresia) before SFLP. Postoperative echocardiograms and medical records from these 16 recipients were reviewed. Changes in pulmonary valve structure and function, and overall cardiac function, were noted after SFLP. RESULTS: The mean gestational age at SFLP was 21 (range, 18.7-24.3) weeks. Seven of sixteen (44%) recipients with abnormal pulmonary valve prior to SFLP survived. Six of the 16 (37.5%) recipient twins had documented absence of persistent pulmonary valve abnormalities at birth or at autopsy. Two (12.5%) of the 16 recipients (2.6% of the original cohort) had persistent pulmonary valve abnormalities at birth, requiring intervention. Systolic and diastolic function improved or normalized after SFLP in all patients undergoing longitudinal follow-up. There was a tendency for a better cardiovascular profile score (best = 10 points) at initial evaluation in pregnancies with survivors compared with those with no survivors (mean (SD): 5.6 (2.2) vs. 6.75 (1.28)), but this was not statistically significant. Severity of cardiac involvement did not predict persistence of valve pathology or survival. CONCLUSIONS: SFLP can improve flow through the pulmonary valve of the recipient twin in TTTS, probably as a consequence of improvements in right ventricular systolic and diastolic function. However, pulmonary valve pathology may persist and require postnatal intervention.

Reference ranges of fetal aortic and pulmonary valve diameter derived by STIC from 14 to 40 weeks of gestation.

OBJECTIVE: To develop reference ranges of fetal aortic and pulmonary valve diameter derived from volume datasets of spatio-temporal image correlation (STIC). METHODS: A cross-sectional study was undertaken on low-risk pregnancies with well-established data from 14 to 40 weeks. Volume datasets of STIC were acquired for subsequent off-line analysis. Aortic and pulmonary valve diameters were measured in STIC multiplanar view using 4D-View version 9. Normal Z scores and centile reference ranges were constructed from these measurements against gestational age (GA) and biparietal diameter (BPD) as independent variables, using regression models for both mean and SD. RESULTS: A total of 606 volume datasets were successfully measured. Normal reference ranges for predicting mean values and SD of aortic and pulmonary valve diameter were constructed based on best-fit equations (linear function) as follows: mean aortic diameter (mm) was modeled as a function of GA (weeks) and BPD (mm) as - 2.4838 + 0.2702 × GA, (SD = 0.1482 + 0.0156 × GA) and - 1.5952 + 0.0989 × BPD (SD = 0.1672 + 0.00572 × BPD). Mean pulmonary diameter was modeled as - 2.5924 + 0.2935 × GA (SD = 0.2317 + 0.01524 × GA) and - 1.6830 + 0.1083 × BPD (SD = 0.1971 + 0.0059 × BPD). CONCLUSION: We have provided nomograms and Z scores of fetal aortic and pulmonary valve diameters. These reference ranges may be a useful tool in the assessment of fetal cardiac abnormalities.

Tricuspid atresia with absent pulmonary valve and intact ventricular septum: intrauterine course and outcome of an unusual congenital heart defect.

The extremely rare syndrome including absent pulmonary valve associated with membranous tricuspid atresia or severe tricuspid stenosis, intact ventricular septum and patent ductus arteriosus has been reported sporadically in the postnatal literature. This cardiac defect is characterized by right ventricular dysplasia with asymmetrical ventricular septal hypertrophy, ventricular septum bulging into the left ventricle, small right ventricular cavity, membranous tricuspid atresia or severe stenosis with abnormal papillary muscles and leaflets and absence of the pulmonary valve leaflets. The only prenatal case reported so far was diagnosed at 33 weeks of gestation and terminated shortly thereafter; the natural history of prenatally diagnosed cases is therefore unknown. We report on the intrauterine course of a case diagnosed at 17 weeks of gestation that had a favorable postnatal outcome after palliation.

Tetralogy of Fallot With Absent Pulmonary Valve and Nonconfluent Pulmonary Arteries: A Management Conundrum.

Tetralogy of Fallot with absent pulmonary valve syndrome is a rare form of congenital heart disease. Among the different variations with this rare anomaly is nonconfluent pulmonary artery branches with anomalous origin of the left pulmonary artery from the ductus arteriosus. The authors present one such case which was diagnosed prenatally to have tetralogy of Fallot with absent pulmonary valve and identified postnatally to have nonconfluent pulmonary artery branches in addition. We discuss the conundrum of respiratory management in this patient pre- and postoperatively due to a unique ventilation perfusion mismatch problem, which varies between the two lungs.

Measurements of the diameters of the great arteries and semi-lunar valves of chick and mouse embryos.

The great arteries of embryos are small channels of a complex three-dimensional arrangement. Measurements of their diameters, as required for understanding cardiovascular morphogenesis and the genesis of malformations, cannot be performed in two-dimensional histological sections. We present and evaluate a quick and simple method for performing highly significant and objective measurements of the diameters of blood vessels in vertebrate embryos and used this method for providing statistics of the diameter of the semi-lunar valves and the lumina of the great arteries of early chick and mouse foetus. We employed the high-resolution episcopic microscopy technique for generating volume data and three-dimensional computer models of the arterial trees of 30 chick embryos (Hamburger Hamilton stage 34), 30 mouse embryos of the OF1 strain harvested on 14.5 dpc, 30 embryos of the OF1 strain harvested on 15.5 dpc and 28 mouse embryos of the PARKES strain harvested on 14.5 dpc. The three-dimensional models (voxel size 2 mum x 2 mum x 2 mum and 3 mum x 3 mum x 3 mum) were used for defining virtual resection planes perpendicular to the longitudinal axis of the blood vessels at comparable positions. In these planes, we measured the lumen areas and the lumen perimeters. We also calculated the lumen diameter and the true lumen area from the perimeter and present statistical analysis. Finally, we evaluate and discuss the reliability and reproducibility of our method and present all measurements in a form that minimizes the influence of specimen size variation, specimen processing and data generation methods.

Congenital semilunar valvulogenesis defect in mice deficient in phospholipase C epsilon.

Phospholipase Cepsilon is a novel class of phosphoinositide-specific phospholipase C, identified as a downstream effector of Ras and Rap small GTPases. We report here the first genetic analysis of its physiological function with mice whose phospholipase Cepsilon is catalytically inactivated by gene targeting. The hearts of mice homozygous for the targeted allele develop congenital malformations of both the aortic and pulmonary valves, which cause a moderate to severe degree of regurgitation with mild stenosis and result in ventricular dilation. The malformation involves marked thickening of the valve leaflets, which seems to be caused by a defect in valve remodeling at the late stages of semilunar valvulogenesis. This phenotype has a remarkable resemblance to that of mice carrying an attenuated epidermal growth factor receptor or deficient in heparin-binding epidermal growth factor-like growth factor. Smad1/5/8, which is implicated in proliferation of the valve cells downstream of bone morphogenetic protein, shows aberrant activation at the margin of the developing semilunar valve tissues in embryos deficient in phospholipase Cepsilon. These results suggest a crucial role of phospholipase Cepsilon downstream of the epidermal growth factor receptor in controlling semilunar valvulogenesis through inhibition of bone morphogenetic protein signaling.

Reference Ranges for the Size of the Fetal Cardiac Outflow Tracts From 13 to 36 Weeks Gestation: A Single-Center Study of Over 7000 Cases.

BACKGROUND: Assessment of the outflow tract views is an integral part of routine fetal cardiac scanning. For some congenital heart defects, notably coarctation of the aorta, pulmonary valve stenosis, and aortic valve stenosis, the size of vessels is important both for diagnosis and prognosis. Existing reference ranges of fetal outflow tracts are derived from a small number of cases. METHODS AND RESULTS: The study population comprised 7945 fetuses at 13 to 36 weeks' gestation with no detectable abnormalities from pregnancies resulting in normal live births. Prospective measurements were taken of (1) the aortic and pulmonary valves in diastole at the largest diameter with the valve closed, (2) the distal transverse aortic arch on the 3 vessel and trachea view beyond the trachea at the distal point at its widest systolic diameter, and (3) the arterial duct on the 3 vessel and trachea view at its widest systolic diameter. Regression analysis, with polynomial terms to assess for linear and nonlinear contributors, was used to establish the relationship between each measurement and gestational age. The measurement for each cardiac diameter was expressed as a z score (difference between observed and expected value divided by the fitted SD corrected for gestational age) and percentile. Analysis included calculation of gestation-specific SDs. Regression equations are provided for the cardiac outflow tracts and for the distal transverse aortic arch:arterial duct ratio. CONCLUSIONS: The study established reference ranges for fetal outflow tract measurements at 13 to 36 weeks' gestation that are useful in clinical practice.

Variations in structure of the outflow tract of the human embryonic heart: A new hypothesis for generating bicuspid aortic semilunar valves.

Outflow tract development of the heart is complex. The presence, differential growth and interactions of the various tissues through space and time contribute to the final development of the tract. This paper presents a novel interpretation of observations of outflow tract development, in particular of the aortic and pulmonary semilunar valves in embryos from the Shaner Collection at the University of Alberta. Three-dimensional reconstructions assist in the visualization of the spatial relationships of the developing valve tissues. In some embryos the aortic intercalated valve swelling is displaced proximally, giving rise to a bicuspid aortic semilunar valve more distally. In addition, the developing valve tissue first appears external to the myocardial cuff. The pulmonary semilunar valve regions appear to be more normal. This paper thus proposes a novel mechanism for generating a bicuspid aortic valve and also supports the idea that there is some independence of the aortic and pulmonary regions from each other during development.