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SUMMARY OBJECTIVE: This study aimed to assess the perinatal outcomes of pregnancies with a prenatal diagnosis of congenital cystic adenomatoid malformation. METHODS: We conducted a retrospective cohort study based on information contained in the medical records of pregnant women whose fetuses had been prenatally diagnosed with congenital cystic adenomatoid malformation by ultrasonography. RESULTS: Sample analysis was based on 21 singleton pregnancies with confirmed isolated fetal congenital cystic adenomatoid malformations. The mean maternal±standard deviation age was 28±7.7 years. Types I, II, and III congenital cystic adenomatoid malformation were detected in 19% (4/21), 52.4% (11/21), and 28.6% (6/21), respectively. All fetuses presented with unilateral congenital cystic adenomatoid malformation (21/21) without associated anomalies, and 52.3% (11/21) were in the right lung. In total, 33.3% (7/21) of fetuses presented a “congenital cystic adenomatoid malformation volume ratio” >1.6 and were managed with maternal betamethasone administration. The mean gestational age at the time of steroid administration was 28.5±0.9 weeks, with a reduction in the lesion dimensions of 9.5% (2/21) (Types I and III of congenital cystic adenomatoid malformation). The mean gestational age at delivery was 38.7±2.4 weeks, and a cesarean section was performed in 76.2% (16/21) cases. Postsurgical resection was necessary for 23.8% (5/21) of the patients, and 4.7% (1/21) of them died because of respiratory complications after surgery. Pulmonary hypoplasia occurred in 9.5% (2/21) of the patients, and 4.7% (1/21) of them died because of respiratory insufficiency. The survival rate was 90.5% (19/21), and 57.2% (12/21) remained asymptomatic. CONCLUSION: Despite the isolated prenatal diagnosis of congenital cystic adenomatoid malformation, which showed good survival, congenital cystic adenomatoid malformation is associated with significant perinatal morbidity. Maternal betamethasone administration did not significantly reduce fetal lung lesion dimensions.

INTRODUCTION Amniotic fluid "sludge" has been associated with an increased rate of spontaneous preterm delivery before 35 weeks, a higher frequency of clinical and histologic chorioamnionitis in a high-risk population. Only one study evaluating the use of antibiotics in the presence of amniotic fluid "sludge" showed reduced rates of spontaneous preterm birth at

Background: Apert syndrome is characterized by craniosynostosis, midface hypoplasia and symmetric syndactyly. Case report: A 36-year-old mother, G2P1 underwent an ultrasound scan at 19 week's gestation. There was craniosynostosis, brachi-turricephaly and bilateral hand syndactyly. Genomic DNA from amniocentesis revealed the mutation C758C>Gp. (Pro to Arg substitution) at 252 of the exon 8 of the FGFR2 encoding for Apert syndrome. The pregnancy was terminated. Femoral chondral plate histology showed an increased interstitial matrix between bony trabeculae. Compared with normal, the trabeculae were thinner, more irregular with numerous osteoclasts suggesting abnormal bone remodeling. Hands and feet had an abrupt transition between resting and proliferating cartilage. Conclusion: Apert syndrome has increased intertrabecular matrix, thin trabeculae, increased remodeling, and irregular transition between the maturing and mineralization zones in the femur, and abnormal abrupt transition between the resting and proliferating cartilage in the fingers and toes.

The objective of this study was to determine the reference values for fetal heart functional measurements at 24 and 34 weeks of gestation and to develop Z-score equations for all measurements. A single-center, prospective, cross-sectional study with normal fetuses between 24 and 34 weeks of gestation was performed. All pregnant women underwent a comprehensive fetal Doppler echocardiogram with anatomical and functional analysis. Measurements of left and right cardiac output, combined cardiac output, mitral and tricuspid valve flow, inferior vena cava flow, and pulmonary vein flow were performed. The Shapiro-Wilk test and histogram evaluation were performed on all variables. Linear regression was used to assess the relationships between measurements and gestational age. A total of 612 pregnant women with singleton and normal fetuses were included. We assessed the reference values and percentiles of cardiac function as a function of gestational age. The variables that were not normally distributed were subjected to logarithmic or square root transformation. Eleven Z-score equations were developed, with equations for left and right ventricle output and combined cardiac output that were dependent on gestational age and with other equations that were independent of gestational age. The present study produced a large database, allowing the demonstration of reference values and percentiles as well as the development of Z-score equations to facilitate the echocardiographic evaluation of fetal heart function.

OBJECTIVE To compare the quality of standard fetal echocardiographic views obtained by four-dimensional ultrasound with those obtained by the simple targeted arterial rendering (STAR) technique, four-chamber view swing technique (FAST), and fetal intelligent navigation echocardiography (FINE/5D Heart® ) technique. METHODS This was a cross-sectional prospective study that included pregnant women between 22 and 34 weeks of gestation, with normal fetuses. Fetal heart volumes were acquired using spatio-temporal image correlation (STIC) with the fetal spine between 2 and 9 o'clock. The FAST/STAR techniques consist of the manipulation of STIC volumes by drawing OmniView™ lines to obtain echocardiographic views. The FINE/5D Heart® technique uses intelligent navigation to automatically generate echocardiographic views. The quality of the images was classified as excellent, good, acceptable, and unacceptable. The analysis was performed using the Bonferroni multiple comparisons test. RESULTS The study included 101 pregnant women aged between 16 and 44 years. There was no mean difference in image quality between the techniques regarding fetal spine position in all echocardiographic views (P > .05). However, in the five-chamber, left ventricular outflow tract, right ventricular outflow tract, ductal arch, superior vena cava/inferior vena cava, and abdomen/stomach views, there was a statistically significant mean difference quality between the techniques, regardless of the spine position (P

To determine reference values for fetal heart biometric parameters using the spatiotemporal image correlation (STIC) M mode and their applicability in congenital heart diseases (CHDs). A cross-sectional prospective study was conducted with 300 singleton pregnancies between 20 and 33 + 6 weeks of gestation. Right ventricular wall thickness (RVWT), interventricular septum thickness (IVST), and left ventricular wall thickness (LVWT) were measured off-line using the STIC-M mode with the cursor perpendicular to the interventricular septum. Polynomial regressions adjusted with the coefficient of determination (R 2) were performed. The curves were applied to 14 fetuses with structural CHD. For the reproducibility calculations, the concordance correlation coefficient (CCC) was used. The mean RVWT, IVST, and LVWT were 0.34 ± 0.09 cm, 0.28 ± 0.09 cm, and 0.30 ± 0.07 cm, respectively. There was correlation between RVWT, IVST, and LVWT and gestational age (GA): RVWT = −0.002 + 0.013 × GA (R 2 = 0.33), IVST = −0.011 + 0.011 × GA (R 2 = 0.25), and LVWT = 0.056 + 0.009 × GA (R 2 = 0.26). RVWT, IVST, and LVWT were altered ( 95th percentile) in 5/14, 5/14, and 7/14 of the fetuses with CHD, respectively. For RVWT, IVST, and LVWT, intra-observer (CCC = 0.86, 0.85, and 0.87, respectively) and inter-observer (CCC = 0.86, 0.86, and 0.86, respectively) reproducibility were good/moderate. The reference ranges determined for fetal heart biometric parameters using STIC-M had good intra- and inter-observer reproducibility and were applicable to fetuses with CHD.

Objective: To establish reference ranges of the fetal adrenal gland (AG) and fetal zone (FZ) volumes using three-dimensional ultrasound (3DUS).Methods: We performed a prospective cross-sectional study with 204 normal singleton pregnancies between 24 and 37 + 6 weeks of gestation. The fetal AG and FZ volumes were obtained using the virtual organ computer-aided analysis method with a 30° rotation. To establish reference ranges as the function of gestational age (GA), quantile regression was performed with the adjusted coefficient of determination (R2). Intra- and inter-observer repeatability was performed using the intraclass correlation coefficient (ICC).Results: The mean results of fetal AG and FZ values were 0.42 cm3 (0.04–1.22) and 0.10 cm3 (0.02–0.47), respectively. The best-fit quantile regression models for fetal AG and FZ volumes as the function of GA were in first-degree models: AG = −0.937 + 0.041 × GA (R2 = 0.124) and FZ = −0.201 + 0.009 × GA (R2 = 0.127), respectively. We observed good i...

Assessing the biochemical markers levels and the uterine artery Doppler (UtA) parameters in fetuses with growth restriction (FGR). Prospective case–control study included 66 patients with diagnosis of FGR and 64 healthy pregnancies at 24–41 weeks of gestation. For both groups, maternal circulating concentrations of biochemical factors of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin(sEng), adiponectin, A disintegrin and metalloproteinases (ADAM-12), pregnancy-associated plasma protein-A (PAPP-A), angiopoietin-2 (ANGI-2), vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were assayed by ELISA and UtA by Doppler were performed. ANOVA, Mann–Whitney tests and Pearson correlation coefficient were applied to compare the biochemical factors, UtA Doppler and EFW Z-score between the groups. Concentrations of sFlt-1, sEng, PAPP-A were significantly higher in FGR than controls (p

OBJECTIVE To determine fetal heart geometry during pregnancy using three-dimensional (3D) ultrasound and the spatiotemporal image correlation (STIC) rendering mode. METHODS This prospective, cross-sectional study evaluated 250 normal singleton pregnancies from 20 to 33 weeks and 6 days of gestation. STIC rendering was used to calculate the eight angles of the fetal heart: apex, base, mitral valve, tricuspid valve, left ventricle, right ventricle, left atrium, and right atrium angles. The concordance correlation coefficient (CCC) was used for intra- and inter-observer tests. RESULTS The average ± SD maternal age was 31.7 ± 4.9 years, and the average gestational age was 26.3 ± 4.2 weeks. There was little variation in fetal heart angles using STIC rendering according to the gestational age, with determination coefficient (R2 ) values of 0.01 for the apex and mitral valve angles and

Pregnancy is known to induce rapid, progressive, and substantial changes to the cardiovascular system, ultimately facilitating successful pregnancy outcomes. Women who develop hypertensive disorders during pregnancy are considered to have "failed" the cardiovascular stress test of pregnancy and likely represent a subpopulation with inadequate cardiovascular accommodation. Preeclampsia is a serious complication with a myriad of manifestations in both mother and offspring. This pregnancy syndrome is a polygenic disease and has now been linked to a greater incidence of cardiovascular disease. Moreover, offsprings born to preeclamptic mothers exhibit an elevated risk of cardiovascular disease, stroke, and mental disorders during adulthood. This suggests that preeclampsia not only exposes the mother and the fetus to complications during pregnancy but also programs chronic diseases during adulthood in the offspring. The etiology of preeclampsia remains unknown, with various theories being suggested to explain its origin. It is primarily thought to be associated with poor placentation and entails excessive maternal inflammation and endothelial dysfunction. It is well established now that the maternal immune system and the placenta are involved in a highly choreographed cross talk that underlies adequate spiral artery remodeling required for uteroplacental perfusion and free flow of nutrients to the fetus. Although it is not clear whether immunological alterations occur early during pregnancy, studies have proposed that dysregulated systemic and placental immunity contribute to impaired angiogenesis and the onset of preeclampsia. Recently emerged strong evidence suggests a potential link among epigenetics, microRNAs (miRNAs), and pregnancy complications. This chapter will focus on important aspects of epigenetics, immunological aspects, and cardiovascular and vascular remodeling of preeclampsia.

The aim of this study was to evaluate postnatal outcomes in fetuses with gastroschisis.This is a retrospective study (2009-2013) of patients with gastroschisis at the Hospital São Paulo (Federal University of São Paulo, Brazil).A total of 44 infants with gastroschisis were examined. The mean maternal age was 21.1 years and mean gestational age at delivery was 36.1 weeks. Delivery occurred before 34 weeks in 13.6%, between 34 and 36 weeks and 6 d in 40.9%, and after 37 weeks in 45.5%. The mean birth weight was 2349 g, with 37.2% small-for-gestational age infants. The mean umbilical cord blood pH was 7.32. Bowel resection and delayed fascial closure was performed in 14.6% and 19.5%, respectively. The mean hospitalization time in the neonatal intensive care unit was 52.7 d. Neonatal infection was detected in 52.4%, with a positive blood culture; 77.3% of those cases were coagulase negative staphylococci. The overall rate of mortality was 25%; 18.2% before birth, 45.4% during the neonatal period, and 36.4% in infants. The main cause of postnatal death was septicemia (55.5%).Despite advances in perinatal care and surgical techniques, infants with gastroschisis still present high rates of complications and death.

The aim of the study was to compare the expression of oestrogen receptor alpha (ERα) in neovaginal tissue of patients with vaginal agenesis following neovaginoplasty using regenerated, oxidised cellulose in premenopausal women. A prospective, observational case-control study was performed on eight patients with vaginal agenesis following modified Abbé-McIndoe neovaginoplasty and 10 control premenopausal women following benign gynaecologic surgery. 6F11 monoclonal antibody was used to determine ERα expression in the vaginal mucosa. Quantitative and qualitative evaluations were performed, respectively, in vaginal epithelium and stroma. The thickness of the vaginal epithelium was determined as the vertical distance between the basal layer cells and the apical surface of the superficial layer. The percentage of ERα-expressing cells was higher in the control group, except in the superficial zone of the epithelium. In the stromal tissue, ERα was detected in only one patient from the neovagina group compared with nine women in the control group. The neovagina group had a statistically thinner epithelium. Our study suggests that women with vaginal agenesis following modified Abbé-McIndoe neovaginoplasty using regenerated oxidised, cellulose experience relatively local hypo-oestrogenism in the first year after surgery, with repercussion in vaginal trophism.

To evaluate the agreement between ultrasonographers in classifying placental maturity grade using examination videos.A prospective, cross-sectional study was conducted using 25 videos of ultrasonographic examinations of single, healthy pregnancies ≥ 34 + 0 weeks. The Grannum (grades 0, I, II and III) and Julio (grades 0, 1, 2A, 2B and 3) classifications were used for placental maturity grade. The videos were evaluated on two occasions by 10 experienced ultrasonographers. Intra- and inter-observer agreements were evaluated using the Kappa (k) coefficient of agreement.According to the Grannum classification, the inter-observer agreement coefficients were good for grades III and 0 (k = 0.69 and 0.738, respectively) and moderate for grades I and II (k = 0.401 and 0.593, respectively) placentas. According to the Julio classification, the inter-observer agreement coefficients were good for grades 0 and 3 (k = 0.738 and 0.651, respectively), moderate for grades 1 and 2A (0.401 and 0.413, respectively) and poor for grade 2B (k = 0.161). Intra-observer coefficients for the Grannum and Julio classifications ranged from 0.567 to 0.890 and from 0.446 to 0.790, respectively.Placental maturity grading using the Grannum and Julio classifications demonstrated moderate/good intra- and inter-observer agreements on examination videos evaluation.

Pregnancy is known to induce rapid, progressive, and substantial changes to the cardiovascular system, ultimately facilitating successful pregnancy outcomes. Women who develop hypertensive disorders during pregnancy are considered to have "failed" the cardiovascular stress test of pregnancy and likely represent a subpopulation with inadequate cardiovascular accommodation. Preeclampsia is a serious complication with a myriad of manifestations in both mother and offspring. This pregnancy syndrome is a polygenic disease and has now been linked to a greater incidence of cardiovascular disease. Moreover, offsprings born to preeclamptic mothers exhibit an elevated risk of cardiovascular disease, stroke, and mental disorders during adulthood. This suggests that preeclampsia not only exposes the mother and the fetus to complications during pregnancy but also programs chronic diseases during adulthood in the offspring. The etiology of preeclampsia remains unknown, with various theories being suggested to explain its origin. It is primarily thought to be associated with poor placentation and entails excessive maternal inflammation and endothelial dysfunction. It is well established now that the maternal immune system and the placenta are involved in a highly choreographed cross talk that underlies adequate spiral artery remodeling required for uteroplacental perfusion and free flow of nutrients to the fetus. Although it is not clear whether immunological alterations occur early during pregnancy, studies have proposed that dysregulated systemic and placental immunity contribute to impaired angiogenesis and the onset of preeclampsia. Recently emerged strong evidence suggests a potential link among epigenetics, microRNAs (miRNAs), and pregnancy complications. This chapter will focus on important aspects of epigenetics, immunological aspects, and cardiovascular and vascular remodeling of preeclampsia.

Objective To determine the reference values for fetal tricuspid annular plane systolic excursion (f-TAPSE) and fetal ventricular shortening fraction (f-VSF) using spatiotemporal image correlation (STIC) with M-mode, and validate these curves in fetuses of pregnant women with preexisting diabetes mellitus (DM) and with intrauterine growth restriction (IUGR). Study Design Crosssectional study assessed 300 fetal cardiac volumes of normal pregnancies between 20 and 33 + 6 weeks of gestation. For the construction of the reference curves, we used a polynomial regression model adjusted with the coefficient of determination (R2). For the calculation of reproducibility, the concordance correlation coefficient (CCC) was used. Results f-TAPSE value correlated with gestational age (GA, R2 = 0.46), whereas fetal right ventricular shortening fraction (f-RVSF, R2 = 0.02) and fetal left ventricular shortening fraction (f-LVSF, R2 = 0.005) did not vary with GA. Fetuses of pregnant women with preexisting DM (30) had lower values of f-RVSF (p = 0.028), f-LVSF (p = 0.001), and f-TAPSE (p = 0.009) than normal fetuses. The f-TAPSE values were lower (p = 0.005) in IUGR group (17). The f-TASPSE values showed adequate reliability as well as good intra and interobserver concordance (CCC = 0.95 and 0.79, respectively). Conclusion The reference ranges for f-TAPSE, f-RVSF, and f-LVSF using the STIC M-mode were established and had good reproducibility for f-TAPSE measurements.

Objective To assess the quality of fetal heart views by three-dimensional/four-dimensional (3D/4D) ultrasonography using spatio-temporal image correlation (STIC) in the second and third trimester of pregnancy. Methods This prospective and cross-sectional study was conducted at a single referral service for the screening of congenital heart diseases (CHDs), with pregnant women at 20–30 weeks' gestation with a normal fetal heart. 3D/4D STIC were obtained from the fetal heart screening in the following views: four-chamber (4C), left and right ventricular outflow tracts (LVOT and RVOT), 3 vessels and trachea (3VT), aortic arch (AA), and ductal arch (DA). We categorized the images as satisfactory or unsatisfactory and performed McNemar's test to evaluate the differences between the two-dimensional (2D) echocardiography and 3D/4D STIC techniques. The inter-observer concordance was obtained by kappa coefficient. Results The rate of satisfactory fetal heart views using 3D/4D STIC was 54% by using 4 planes (4C, RVOT, LVOT, and 3VT) and 14% by using 6 planes (4C, RVOT, LVOT, 3VT, AA, and DA). In contrast, 100% of the 2D echocardiography images were satisfactory (McNemar's test, P

To determine reference values for fetal interventricular septum (IVS) volume by 3D/4D ultrasound using spatio-temporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL).A prospective cross-sectional study was conducted on 200 consecutive normal low-risk pregnant women at a gestational age ranging from 18w0d to 33w6d. The volume data sets of the fetal heart were acquired by applying STIC to a four-chamber plane. IVS volume was calculated offline using VOCAL with rotation of 30° (six planes). To assess the correlation of fetal IVS volume as a function of gestational age (GA), Pearson's correlation coefficient (r) and polynomial regression models with adjustments through the coefficient of determination (R(2)) were calculated. The intra-class coefficient (ICC) was used to evaluate intra- and inter-observer reproducibility.A good correlation between GA and fetal IVS volume (r = 0.827) was observed. The mean fetal IVS volume ranged from 0.13 ± 0.03 cm(3) (0.08-0.18 cm(3)) at 18wd0 of gestation to 1.33 ± 0.37 cm(3) (0.41-1.98 cm(3)) at 33w6d. The best correlation between fetal IVS volume and GA was exponential: fetal IVS volume = 0.11e(0.139×GA) (R(2 )= 0.785). A good intra- and inter-observer reliability were observed, with ICC = 0.999 and 0.991, respectively.Reference values for fetal IVS volume using STIC and VOCAL by 3D/4D ultrasound between 18w0d and 33w6d of gestation were determined and showed to be reliable and concordant.

The objective of this review was to demonstrate the main tools of three- and four-dimensional ultrasonography, using the spatiotemporal image correlation software and its respective applications for assessing the fetal heart and its vascular connections, along with its potential contribution towards screening for congenital heart diseases. Today, conventional, two-dimensional, echocardiography continues to be the gold standard for diagnosing congenital heart diseases. However, recent studies have demonstrated that spatiotemporal image correlation offers some advantages that boost two-dimensional accuracy in detecting congenital heart diseases, given that the fetal heart assessment can be completed in the absence of the patient (offline) and be discussed by different examiners. Additionally, data volumes can be sent for analysis in reference centers via internet links. Spatiotemporal image correlation also enables direct measurement of heart structures in rendering mode, such as the interventricular septum and the annulus of the atrioventricular valves. Furthermore, it enables assessment of cardiac function when used in association with the virtual organ computer-aided analysis software, thus making it possible to calculate the total systolic function, ejection fraction, and cardiac output.

Technological innovations accompanying advances in medicine have given rise to the possibility of obtaining better-defined fetal images that assist in medical diagnosis and contribute toward genetic counseling offered to parents during the prenatal period. In this article, we show our innovative experience of diagnosing fetal malformations through correlating 3-dimensional ultrasonography, magnetic resonance imaging, and computed tomography, which are accurate techniques for fetal assessment, with a fetal image reconstruction technique to create physical fetal models.

Two-dimensional (2D) echocardiogram with the aid of color Doppler and pulsed Doppler allows one to record blood flow waveforms in several structures of the heart. The determination of normal values of these flows in the fetus can help understand cardiac hemodynamics. Given this importance, numerous surveys have been conducted with various existing echocardiographic techniques in order to improve the functional evaluation and consequently, planning of delivery. The aim of this review was to discuss the findings of the reference values of blood flows obtained by 2D echocardiography with Doppler, the current trend of the determination of Z-scores in the functional measurements, and their future prospects.

Objective This study aims to determine reference curves for fetal atrioventricular valve areas by means of three-dimensional ultrasound using the spatiotemporal image correlation (STIC) software. Methods This was a cross-sectional prospective study on 328 normal fetuses between the 18th and the 33rd weeks of pregnancy. In order to obtain valve areas, the four heart chambers plane was used with the fetus in a dorsal posterior position. To construct reference ranges, a linear regression model was used, adjusted according to the coefficient of determination (R2). To calculate the reproducibility of the tricuspid valve area, the intraclass coefficient correlation (ICC) was used. Results The mean areas of the tricuspid and mitral valves ranged from 0.19 ± 0.08 and 0.20 ± 0.10 cm2 in the 18th week to 0.93 ± 0.31 and 1.06 ± 0.39 cm2 in the 33rd week, respectively. The intra-observer and interobserver reproducibility was excellent with ICC = 0.997 and 0.933, respectively. Conclusions Reference curves for fetal atrioventricular valve areas were determined and presented good reproducibility. © 2012 John Wiley & Sons, Ltd.

Objective: To compare the agreement of multiplanar and rendering modes in the assessment fetal atrioventricular valves (mitral and tricuspid) areas by three-dimensi onal (3D) ultrasonography using the software spatio-temporal image correlation (STIC). Methods: We conducted a prospective cross-sectional study with normal pregnant women, with single fetuses, between 18-33 weeks. To measure the areas, we used the plan of fourchamber view. In the case of multiplanar, the plane was rotated on the axis “Z” form the heart to position at 9h. For rendering, the green line (region of interest - ROI) was placed from the atria of the heart perpendicular to the crux. The agreement was assessed by a Bland-Altman (limits of agreement) using the relative difference between the measures: ((rendering mode) - (multiplanar mode)) / (average). Results: 328 fetuses were evaluated. We have not identified the occurrence of systematic error between methods: the average relative difference was 1.62% (-2.07% to 5.32%, confidence interval 95%) in the mitral and 1.77% (- 1.08% to 4.62%) in the tricuspid valve. The limits of agreement between methods were -65.26% to 68.51% for the mitral and -49.91% to 53.45% for the tricuspid. Conclusions: There was no systematic error between modes and thus the observed values for the area of fetal atrioventricular valves can be used for comparisons needs to be corrected. However, relatively large variations may be observed when repeating the measurement area by different modes.

Objective To provide reference values for fetal thigh volume using three-dimensional (3D) ultrasound and the eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL) method. Methods This is a cross-sectional study that enrolled 425 healthy pregnant women between the 20th and 40th weeks of gestation. The XI VOCAL was performed along the axial cross-section in ten sequential areas for the volumetric calculations, having the proximal and distal echogenic diaphysis as references. Second-degree polynomial regression models, with the determination of percentiles, were created to evaluate the relation between the fetal thigh volume and gestational age (GA). Intraoperator and interoperator reproducibility was evaluated using intraclass correlation coefficient. Results The mean fetal thigh volume varied from 8.00 (3.90–11.90 cm3) to 122.14 cm3 (105.0–153.50 cm3) at 20 and 40 weeks of gestation, respectively. Fetal thigh volume was strongly correlated with gestational age, and the reference values can be obtained by the following mathematical equation: fetal thigh volume (cm3) = 68.70–7.63 × GA + 0.23 × GA2 (R2 = 0.946). The intraoperator and interoperator reproducibility were excellent, with an intraclass correlation coefficient = 1.000 and 0.999, respectively. Conclusions The reference range of fetal thigh volume was determined by 3D-ultrasound using the XI VOCAL method. Copyright © 2011 John Wiley & Sons, Ltd.

Objectives The purpose of this study was to establish reference intervals for fetal ear length using 3-dimensional sonography in the rendering mode. Methods A cross-sectional study was conducted on 114 women from 19 weeks to 23 weeks 6 days of normal pregnancy. Fetal ear length measurement was performed in the rendering mode, obtained from 2-dimensional mode reconstruction. To determine the correlation between ear length and gestational age, scatterplots were constructed, and the Pearson correlation coefficient was calculated. Mean, median, SD, maximum, and minimum values and percentiles for each gestational age were calculated. To calculate the intraobserver reproducibility, we used the intraclass correlation coefficient. Results The mean ear length ± SD increased from 14.43 ± 1.28 mm (range, 12.80-16.50 mm) in the 19th week of pregnancy to 19.72 ± 1.87 mm (range, 17.20-22.40 mm) in the 23rd week. Three-dimensional sonographic ear length measurements were correlated with gestational age, with the best adjustment represented by the following exponential equation: ear length = exp(1.215 × gestational age - 8.692) (R(2) = 0.423). The intraobserver reproducibility was excellent, resulting in an intraclass correlation coefficient of 0.967 (95% confidence interval, 0.939-0.982). Conclusions Reference intervals for fetal ear length using 3-dimensional sonography in the rendering mode from 19 weeks to 23 weeks 6 days of pregnancy were determined and proved reproducible.

Objective. To compare fetal upper arm and thigh volume measurements acquired by three-dimensional (3D) ultrasound using the multiplanar and the eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL) methods with different number of sectional planes.Methods. This study enrolled 40 healthy pregnant women between 20 and 40 weeks of gestation. The volume of fetal limbs was calculated using the multiplanar (with 5.0 mm intervals) and the XI VOCAL (with 5, 10, 15, and 20 slice planes) methods. Comparison between the techniques was made by analysis of variance and Bonferroni statistical tests.Results. Mean fetal upper arm volume measured by the 15 sectional planes XI VOCAL method was lower than the same method using 5 and 10 planes instead (p = 0.025 and 0.039, respectively). Fetal thigh volume showed no statistically significant differences among all studied methods.Conclusion. The XI VOCAL using 15 sectional planes method underestimated the fetal upper arm volume by 5 and 10 planes XI VOCAL ...

The aim of this study was to evaluate feasibility of fetal lateral ventricle (LV) volumetry in fetuses with ventriculomegaly and to compare measurements performed by 3D sonographic method virtual organ computer-aided analysis (VOCAL) with those obtained by magnetic resonance imaging (MRI).This cross-sectional study evaluated 30 fetuses with atrial width (AW) between 10 and 30 mm, from 20 to 36 gestational weeks. Fifty-nine ventricles were measured by two observers. Sonographic volumetric measurements using VOCAL 30° were performed with an ACCUVIX XQ machine (Medison, Korea) and MRI assessments with a Sonata system using ARGUS software (Siemens, Germany). Agreement between both techniques was assessed by intraclass correlation coefficient (ICC) calculation, and proportionate Bland-Altman plots were constructed.A high degree of reliability was observed between VOCAL and MRI measurements (ICC 0.928, 95%CI [0.876;0.958]). Bland-Altman plots confirmed the high correlation (mean of differences: 1.62 cm(3) and standard deviation: ± 8.41 cm(3)).Three-dimensional volumetry of fetal LVs by VOCAL method has good agreement with fetal MRI in fetuses with ventriculomegaly and may be used as an additional tool in patient counseling and prognosis prediction.

There is convincing evidence suggesting a potential benefit of chromosomal microarray analysis for fetal abnormalities beyond conventional fetal karyotyping. Microarray chromosomal genomic hybridization (a-CGH) may provide submicroscopic rearrangements especially duplicated or deleted portion of the DNA also known as copy number variants (CNVs). A limitation of chromosomal microarray analysis is the potential to identify variants of unknown clinical significance (VOUS). This occurred in 3.4% of cases in the NICHD trial. Such results were classified as “likely benign” in 1.8% of cases and “likely pathogenic” in 1.6%. The result may be uncertain because the CNVs may be rare, novel or characterized by variable penetrance. Furthermore, in such cases, a parental search is mandatory to detect a carrier state or a de novo mutation and to calculate recurrent risk in a genetic counseling. Is genetic counseling advice before testing with a-CGH? Should an informed consent be obtained? Pre as well as post-test genetic counseling is mandatory when karyotyping is performed with a-CGH. Patients must be counseled concerning the incidence of VOUS, identification of diseases with variable clinical presentation, identification of consanguinity and/or non-paternity as well as adult-onset diseases. It is mandatory that healthcare givers do not performed the testing before genetic counseling and signed informed consent. In addition, as the amount of information depends by the type of array technique used and laboratory policy, it is essential that doctors as well as patients be informed about this. Notwithstanding, the NICHD trial have demonstrated that women who received abnormal results reported a need for extensive support and counseling while referring a lack of good understanding of the potential for uncertain results. Is there evidence to indicate that a-CGH should be performed in all cases as integrated prenatal karyotyping testing when fetal malformations are detected on ultrasound? Array chromosomal genomic hybridization (a-CGH) studies performed in fetuses with sonographic anomalies and normal karyotype have demonstrated to detect clinically significant CNVs in 2% of cases. Moreover, when rapid fetal karyotyping is clinically indicated, oligonucleotide a-CGH for direct analysis of uncultured amniocytes has shown to be feasible. The use of oligonucleotide arrays increases the sensitivity and accuracy of detection over previous bacterial artificial chromosome (BAC)-based arrays and shorter reporting time. In a series of 162 fetuses with sonographic anomalies of whom 6.8% had abnormal karyotype and 23.7% had abnormal

Three-dimensional (3D) and four-dimensional (4D) ultrasound have been proposed to be valuable tools for the examination of fetal heart. Spatio-temporal image correlation (STIC) is a technique that adds a time component to 3D ultrasound imaging of the fetal heart, so we can evaluate cardiac structures as a 4D cine sequence containing information of one full cardiac cycle. STIC gives the investigator the opportunity to freeze the displayed cardiac loop in end-diastolic and end-systolic phases. By STIC, 3D measurements of both the left and right ventricle can be used to calculate fetal heart stroke volume, cardiac output and ejection fraction, and expressions of cardiac function. The ultimate goal of STIC technique is to improve fetal cardiac function analysis by decreasing the dependency on operator skills required by two-dimensional ultrasound. In this article, we describe literature practical approach for the examination of the fetal heart function using 4D ultrasound by STIC technique.

OBJECTIVE: To evaluate the intra- and interobserver reproducibility of three-dimensional power Doppler sonography (3D power Doppler) in the assessment of fetal brain blood flow in the middle cerebral artery territory. MATERIALS AND METHODS: A cross-sectional study was developed with 20 healthy pregnant women between 26 and 34 gestational weeks. The middle cerebral artery territory closest to the transducer was scanned and the blood flow volume was calculated with the method Virtual Organ Computer-aided AnaLysis. The following 3D power Doppler indices were later obtained: vascularization index (VI), flow index (FI) and vascularization-flow index (VFI). The intraclass correlation coefficient (ICC) and Bland-Altman plots were utilized for calculating the intra- and interobserver variability. RESULTS: A good intra- and interobserver agreement was observed, with ICC > 0.90 for all the 3D power Doppler indices: VI [ICC = 0.992 (CI 95%: 0.981-0.997)], FI [ICC = 0.999 (CI 95%: 0.998-0.999)], VFI [ICC = 0.995 (CI 95%: 0.987-0.998)]. Interobserver reproducibility: VI [ICC = 0.988 (CI 95%: 0.970-0.995)], FI [ICC = 0.999 (CI 95%: 0.997- 1.000)], VFI [ICC = 0.994 (CI 95%: 0.994-0.998)]. CONCLUSION: 3D power Doppler has shown to be a practical and easy method in the assessment of fetal brain blood flow, with good intra- and interobserver reproducibility. The FI presented the best intra- and interobserver agreement

Cerebral malformations may lead to permanent postnatal sequels. The antenatal detection of anomalous or absent fetal sulci and gyri may indicate abnormal brain development and future neurological and psychomotor problems in that infant. The prenatal diagnosis of these conditions allows genetic counseling, psychological support of the parents and optimization of obstetric management. Diagnosis is usually based on two-dimensional obstetric ultrasound (2DUS) and eventually fetal magnetic resonance imaging (MRI), to confirm findings. Fetal three-dimensional ultrasound (3DUS) using the rendering mode has been recently introduced but has not yet been extensively tested in clinical practice.This study reviewed and compared three imaging modalities, 2DUS, 3DUS, and MRI, in the analysis of the development of the main sulci and gyri of central nervous system of normal fetuses between 20 and 32 weeks' gestation.

To evaluate morphology of lateral ventricles of ventriculomegaly/hydrocephaly fetuses using 3D-sonography by virtual organ computer-aided analysis (VOCAL) technique and magnetic resonance imaging (MRI) and verify morphologic patterns related to etiology.Seventeen fetuses presenting with ventricular enlargement (atria10 mm) were evaluated. 3D datasets were acquired from a coronal reference plane and post-processed by the rotational imaging using VOCAL 30°. MRI study was analyzed in the three plans in all sequences. Morphologic aspects such as global shape, anterior, posterior and inferior horn characteristics, wall irregularities and deformities were analyzed and related to etiology factor.Twenty-nine percent of the cases were secondary to Arnold-Chiari syndrome and presented with global dilation of the three-horns. Cases related to aqueduct stenosis presented with ependymal rupture and wall irregularities in advanced cases. Corpus callosum agenesis cases presented with small ventricular volumes, thin shape, normal or slightly enlarged anterior and inferior horns with dilation restricted to posterior horn. Cases related to trisomy 18 and cytomegalovirus presented irregular ventricular walls associated with anomalous ventricular shapes, suggesting parenchymal destruction.Ventricular morphology evaluation gives important information on etiology of ventricular enlargement, supporting prognosis prediction and decision making process of the affected fetuses and their families.

OBJETIVO: Avaliar a reprodutibilidade do volume do braço e coxa fetais aferido pela ultrassonografia tridimensional utilizando o método eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL). MATERIAIS E MÉTODOS: Realizou-se estudo de reprodutibilidade com 43 fetos normais entre 20 e 37 semanas. Para o cálculo do volume do braço e coxa fetais utilizou-se o método XI VOCAL com delimitação de 10 planos consecutivos. Para o cálculo da variabilidade interobservador, um examinador realizou uma medida do volume do braço e coxa dos 43 fetos, enquanto um segundo examinador, sem o conhecimento prévio dos resultados do primeiro examinador, realizou uma segunda medida dos mesmos volumes. Utilizaram-se, para os cálculos estatísticos, o coeficiente de correlação intraclasse (ricc), gráficos de Bland-Altman e teste t-Student pareado (p). RESULTADOS: Observou-se alta reprodutibilidade interobservador. Para o volume do braço, obtiveram-se ricc = 0,996 (intervalo de confiança [IC] 95%: 0,992; 0,998) e média das diferenças = 0,13 ± 1,29% (95% limites de concordância: -2,54; +2,54%). Para o volume da coxa, obtiveram-se ricc = 0,997 (IC 95%: 0,995; 0,999) e média das diferenças = 0,24 ± 7,60% (95% limites de concordância: -7,6; +7,6%). CONCLUSÃO: O volume do braço e coxa fetais aferido pela ultrassonografia tridimensional utilizando o método XI VOCAL apresentou elevada reprodutibilidade interobservador.OBJECTIVE: To assess the reproducibility of fetal thigh and upper arm volumes measurement by threedimensional ultrasonography utilizing the eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL) method. MATERIALS AND METHODS: This reproducibility study enrolled 43 pregnant women with healthy singleton pregnancies between 20 and 37 gestational weeks. The XI VOCAL 10 planes was the method utilized for volumetric measurement of the fetal limbs. The calculation of the interobserver reproducibility was based on blind volumetric measurements of fetal thighs and upper-arms performed by two observers in 43 fetuses. Intraclass correlation coefficient (ICC), Bland-Altman plots and paired Student's t-test (p) were utilized in the statistical analysis. RESULTS: A high interobserver reproducibility was observed. For the upper arm volume ICC was 0.996 (confidence interval [CI] 95%: 0.992; 0.998) and mean difference = 0.13 ± 1.29% (95% limits of agreement: -2.54; +2.54%). For the thigh volume, ICC was 0.997 (CI 95%: 0.995; 0.999) and mean difference = 0.24 ± 7.60% (95% limits of agreement: -7.6; +7.6%). CONCLUSION: Fetal thigh and upper arm volumes measured by three-dimensional ultrasonography with the XI VOCAL method presented a high interobserver reproducibility.

OBJETIVO: Avaliar a reprodutibilidade interobservador dos índices de vascularização do Doppler de amplitude tridimensional (Doppler de amplitude 3D) no primeiro trimestre de gestação. MATERIAIS E MÉTODOS: Realizou-se estudo de reprodutibilidade com 32 gestantes normais entre 7 e 10 semanas e 6 dias. Para o cálculo do volume tridimensional dos embriões utilizou-se o método VOCAL (Virtual Organ Computer-aided AnaLysis) com ângulo de rotação de 12°. Em seguida obtiveram-se, automaticamente, os três índices vasculares do Doppler de amplitude 3D: índice de vascularização (VI), índice de fluxo (FI) e índice de vascularização e fluxo (VFI). Para o cálculo da variabilidade interobservador, um examinador realizou uma segunda medida dos 32 embriões e um segundo examinador realizou uma terceira medida dos mesmos volumes, ambos desconhecendo os resultados do outro. Utilizaram-se, para análise estatística, o coeficiente de correlação intraclasse (CCI) e gráficos de Bland-Altman. RESULTADOS: Observou-se boa reprodutibilidade interobservador dos três índices vasculares. O VI apresentou CCI = 0,9 e média da diferença = -1,1; o FI apresentou CCI = 0,9 e média da diferença = -0,5; e o VFI apresentou CCI = 0,9 e média da diferença = -1,1. CONCLUSÃO: Os índices vasculares do Doppler de amplitude 3D do embrião no primeiro trimestre de gestação foram altamente reprodutíveis, em especial o FI.OBJECTIVE: To evaluate the interobserver reproducibility of vascular indices obtained with three-dimensional power Doppler (3D power Doppler) ultrasonography at the first trimester of gestation. MATERIALS AND METHODS: The present reproducibility study involved 32 healthy pregnant women with 7 to 10 weeks and 6 days of gestation. The VOCAL (Virtual Organ Computer-aided AnaLysis) method was utilized to calculate embryos volume, with a 12° rotational angle. Subsequently, the software automatically displayed three 3D power Doppler vascular indices: vascularization index (VI), flow index (FI) and vascularization and flow index (VFI). In order to calculate the interobserver variability, an investigator performed a second blind measurement of the 32 embryos, and another investigator performed a third blind measurement of the same volumes. The interclass correlation coefficient (ICC) and Bland-Altman plots were utilized for statistical analysis. RESULTS: A good interobserver reproducibility was observed in relation to the three vascular indices. The VI presented ICC = 0.9 and mean difference between measurements = -1.1. For the FI, the ICC was 0.9 and mean difference = -0.5. The VFI presented ICC = 0.9 and mean difference = -1.1. CONCLUSION: The vascular indices, particularly the FI, obtained with 3D power Doppler ultrasonography at the first trimester of gestation demonstrated a high reproducibility.