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Objective: Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation, with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth, but current evidence on dosing, candidacy and outcomes is limited. In this pilot study, we evaluated the safety and feasibility of continuous low-dose MSO in the setting of SVP., Methods: This single-center, open-label, pilot phase-1 safety and feasibility clinical trial included 25 pregnant individuals with a diagnosis of fetal SVP. Participants self-administered continuous MSO using medical-grade oxygen concentrators for up to 24 h per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation using echocardiography and late-gestation cardiovascular magnetic resonance imaging. Early outcomes were assessed, including perinatal growth and preoperative brain injury, and neurodevelopmental outcomes were assessed at 18 months using the Bayley Scales of Infant and Toddler Development 3 rd edition, and compared with those of a contemporary fetal SVP cohort (n = 217) that received the normal standard of care (SOC)., Results: Among the 25 participants, the median maternal age at conception was 35 years, and fetal SVP diagnoses included 16 with right ventricle dominant, eight with left ventricle dominant and one with indeterminate ventricular morphology. Participants started the trial at approximately 29 + 2 weeks' gestation and self-administered MSO for a median of 16.1 h per day for 63 days, accumulating a median of 1029 h of oxygen intake from enrolment until delivery. The only treatment-associated adverse events were nasal complications that were resolved typically by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio or head-circumference-to-abdominal-circumference ratio Z-scores over gestation compared with SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z-score over the study period compared with SOC (P = 0.02), this was probably due to initial baseline differences in placental resistance. At late-gestation cardiovascular magnetic resonance imaging, MSO was not associated with an increase in fetal cerebral oxygen delivery. Similarly, no differences were observed in neonatal outcomes, including preoperative brain weight Z-score and brain injury, mortality by 18 months of age and neurodevelopmental outcomes at 18 months of age., Conclusions: This pilot phase-1 clinical trial indicates that low-dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with an increase in fetal cerebral oxygen delivery or improvements in early neurological or neurodevelopmental outcomes. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Image quality of fetal echocardiography (FE) has improved in the recent era, but few recent studies have reported the accuracy of FE, specifically in single ventricle (SV) congenital heart disease (CHD). This study aimed to assess the ability of FE to correctly predict SV-CHD postnatal anatomy and physiology in a contemporary cohort., Methods: The contemporary clinical reports of patients with SV-CHD, in which FE was performed between July 2017 and July 2021, were compared with postnatal echocardiograms from a formal quality assurance program. SV fetuses were grouped by anatomical subtype. Diagnostic errors were designated as major if the error would have caused significant alteration in parental counseling or postnatal management. The remaining errors were classified as minor. Physiological discrepancies, including prostaglandin-E (PGE) dependency, atrioventricular valve regurgitation (AVVR), pulmonary venous obstruction and restrictive atrial septum (RAS), were assessed by chart review of the postnatal course., Results: A total of 119 subjects were analyzed. SV subtypes in the cohort included hypoplastic left heart syndrome (HLHS) (n = 68), tricuspid atresia (n = 16), double-inlet left ventricle (n = 12), unbalanced atrioventricular canal (UAVC) (n = 11), heterotaxy (n = 9) and other (n = 3). The rate of major anatomical and physiological errors was low (n = 6 (5.0%)). A higher proportion of minor errors was noted in HLHS and tricuspid atresia, but the differences were not statistically significant. Physiological discrepancies were uncommon, with three major discrepancies, including underestimation of the degree of venous obstruction in one non-HLHS fetus with total anomalous pulmonary venous return, overestimation of RAS in one HLHS fetus and incorrect prediction of PGE dependency in one case false-negative for pulmonary blood flow. No discrepancy in degree of AVVR or RAS affected postnatal care. Minor physiological discrepancies included two false-positive predictions of PGE dependency with one false-positive for ductal-dependent systemic flow and one false-positive for pulmonary blood flow., Conclusions: In this contemporary review of FE at our center, there was high accuracy in describing anatomical and physiological findings in SV-CHD. Major physiological discrepancies were uncommon but included important cases of false-negative prediction of PGE dependency and underestimation of obstruction of total anomalous pulmonary venous return. These data can inform more accurate counseling of families with SV-CHD fetuses and guide diagnostic improvement efforts. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: The primary aim of this study was to evaluate the feasibility of automated measurement of fetal atrioventricular (AV) plane displacement (AVPD) over several cardiac cycles using myocardial velocity traces obtained by color tissue Doppler imaging (cTDI). The secondary objectives were to establish reference ranges for AVPD during the second half of normal pregnancy, to assess fetal AVPD in prolonged pregnancy in relation to adverse perinatal outcome and to evaluate AVPD in fetuses with a suspicion of intrauterine growth restriction (IUGR)., Methods: The population used to develop the reference ranges consisted of women with an uncomplicated singleton pregnancy at 18-42 weeks of gestation (n = 201). The prolonged-pregnancy group comprised women with an uncomplicated singleton pregnancy at ≥ 41 + 0 weeks of gestation (n = 107). The third study cohort comprised women with a singleton pregnancy and suspicion of IUGR, defined as an estimated fetal weight < 2.5 th centile or an estimated fetal weight < 10 th centile and umbilical artery pulsatility index > 97.5 th centile (n = 35). Cineloops of the four-chamber view of the fetal heart were recorded using cTDI. Regions of interest were placed at the AV plane in the left and right ventricular walls and the interventricular septum, and myocardial velocity traces were integrated and analyzed using an automated algorithm developed in-house to obtain mitral (MAPSE), tricuspid (TAPSE) and septal (SAPSE) annular plane systolic excursion. Gestational-age specific reference ranges were constructed and normalized for cardiac size. The correlation between AVPD measurements obtained using cTDI and those obtained by anatomic M-mode were evaluated, and agreement between these two methods was assessed using Bland-Altman analysis. The mean Z-scores of fetal AVPD in the cohort of prolonged pregnancies were compared between cases with normal and those with adverse outcome using Mann-Whitney U-test. The mean Z-scores of fetal AVPD in IUGR fetuses were compared with those in the normal reference population using Mann-Whitney U-test. Inter- and intraobserver variability for acquisition of cTDI recordings and offline analysis was assessed by calculating coefficients of variation (CV) using the root mean square method., Results: Fetal MAPSE, SAPSE and TAPSE increased with gestational age but did not change significantly when normalized for cardiac size. The fitted mean was highest for TAPSE throughout the second half of gestation, followed by SAPSE and MAPSE. There was a significant correlation between MAPSE (r = 0.64; P < 0.001), SAPSE (r = 0.72; P < 0.001) and TAPSE (r = 0.84; P < 0.001) measurements obtained by M-mode and those obtained by cTDI. The geometric means of ratios between AVPD measured by cTDI and by M-mode were 1.38 (95% limits of agreement (LoA), 0.84-2.25) for MAPSE, 1.00 (95% LoA, 0.72-1.40) for SAPSE and 1.20 (95% LoA, 0.92-1.57) for TAPSE. In the prolonged-pregnancy group, the mean ± SD Z-scores for MAPSE (0.14 ± 0.97), SAPSE (0.09 ± 1.02) and TAPSE (0.15 ± 0.90) did not show any significant difference compared to the reference ranges. Twenty-one of the 107 (19.6%) prolonged pregnancies had adverse perinatal outcome. The AVPD Z-scores were not significantly different between pregnancies with normal and those with adverse outcome in the prolonged-pregnancy cohort. The mean ± SD Z-scores for SAPSE (-0.62 ± 1.07; P = 0.006) and TAPSE (-0.60 ± 0.89; P = 0.002) were significantly lower in the IUGR group compared to those in the normal reference population, but the differences were not significant when the values were corrected for cardiac size. The interobserver CVs for the automated measurement of MAPSE, SAPSE and TAPSE were 28.1%, 17.7% and 15.3%, respectively, and the respective intraobserver CVs were 33.5%, 15.0% and 17.9%., Conclusions: This study showed that fetal AVPD can be measured automatically by integrating cTDI velocities over several cardiac cycles. Automated analysis of AVPD could potentially help gather larger datasets to facilitate use of machine-learning models to study fetal cardiac function. The gestational-age associated increase in AVPD is most likely a result of increasing cardiac size, as the AVPD normalized for cardiac size did not change significantly between 18 and 42 weeks. A decrease was seen in TAPSE and SAPSE in IUGR fetuses, but not after correction for cardiac size. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To determine which echocardiographic features of hypoplastic left heart complex (HLHC) in the fetal period are predictive of biventricular (BV) circulation and to evaluate the long-term outcome of patients with HLHC, including rates of mortality, reintervention and development of further cardiac disease., Methods: Echocardiograms of fetuses with HLHC obtained at 18-26 weeks and 27-36 weeks' gestation between 2004 and 2017 were included in the analysis. The primary outcome was successful BV circulation (Group 1). Group 2 included patients with single-ventricle palliation, death or transplant. Univariate analysis was performed on data obtained at 18-26 and 27-36 weeks and multivariate logistic regression was performed on data obtained at 27-36 weeks only., Results: Of the 51 included cases, 44 achieved successful BV circulation (Group 1) and seven did not (Group 2). Right-to-left/bidirectional foramen ovale (FO) flow and a higher mitral valve (MV) annulus Z-score were associated with successful BV circulation on both univariate and multivariate analysis. Bidirectional or left-to-right FO flow, left ventricular length (LVL) Z-score of < -2.4 and a MV Z-score of < -4.5 correctly predicted 80% of Group 2 cases. Late follow-up was available for 41 patients. There were two late deaths in Group 2. Thirteen patients in Group 1 required reintervention, 12 developed mitral stenosis and five developed isolated subaortic stenosis., Conclusions: BV circulation is common in fetuses with HLHC. Higher MV annulus and LVL Z-scores and right to left direction of FO flow are important predictors of BV circulation. Long-term sequelae in those with BV circulation may include mitral and subaortic stenosis. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To construct nomograms for fetal cardiac, ventricular and atrial relative size and geometry parameters from 18 to 41 weeks' gestation using a low-risk population of singleton pregnancies., Methods: This was a prospective cohort study of 602 low-risk singleton pregnancies undergoing comprehensive fetal echocardiography, from 18 to 41 weeks of gestation, to assess fetal cardiac, atrial and ventricular relative size and sphericity, ventricular dominance, wall asymmetry and relative wall thickness. Intra- and interobserver measurement reproducibility was evaluated using intraclass correlation coefficients (ICC). In order to construct reference ranges across pregnancy, parametric regressions were tested to model each measurement against gestational age and estimated fetal weight. The measurements evaluated were: cardiothoracic ratio; atrial-to-heart area ratios; ventricular-to-heart area ratios; cardiac, ventricular and atrial sphericity indices; right-to-left basal and midventricular ratios; septal-to-free wall thickness ratios; and relative wall thickness., Results: Fetal cardiac, ventricular and atrial morphometry for assessing relative size and geometry could be successfully performed in > 95% of the population, with moderate-to-excellent interobserver reproducibility (ICC, 0.623-0.907) and good-to-excellent intraobserver reproducibility (ICC, 0.787-0.938). Cardiothoracic ratio and ventricular right-to-left ratio showed a modest increase throughout gestation. Atrial-to-heart and ventricular-to-heart area ratios, atrial sphericity indices and septal-to-free wall thickness ratios were constant with gestational age. Left and right ventricular basal sphericity indices showed a tendency to decrease at the end of gestation, while left and right midventricular sphericity indices tended to decrease in the second trimester. The cardiac sphericity index and left and right relative wall thickness showed a modest decrease with gestational age. Nomograms across gestation were constructed for all echocardiographic parameters described., Conclusions: The assessment of cardiac, ventricular and atrial relative size and geometry is feasible and reproducible in the fetus. We provide standardized reference ranges for these parameters throughout gestation, enabling the accurate assessment of cardiac remodeling patterns during fetal life. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: Fetal cardiac function can be evaluated using a variety of parameters. Among these, cardiac cycle time-related parameters, such as filling time fraction (FTF) and ejection time fraction (ETF), are promising but rarely studied. We aimed to report the feasibility and reproducibility of fetal FTF and ETF measurements using pulsed-wave Doppler, to provide reference ranges for fetal FTF and ETF, after evaluating their relationship with heart rate (HR), gestational age (GA) and estimated fetal weight (EFW), and to evaluate their potential clinical utility in selected fetal conditions., Methods: This study included a low-risk prospective cohort of singleton pregnancies and a high-risk population of fetuses with severe twin-twin transfusion syndrome (TTTS), aortic stenosis (AoS) or aortic coarctation (CoA), from 18 to 41 weeks' gestation. Left ventricular (LV) and right ventricular inflow and outflow pulsed-wave Doppler signals were analyzed, using valve clicks as landmarks. FTF was calculated as: (filling time/cycle time) × 100. ETF was calculated as: (ejection time/cycle time) × 100. Intraclass correlation coefficients (ICC) were used to evaluate the intra- and interobserver reproducibility of FTF and ETF measurements in low-risk fetuses. The relationships of FTF and ETF with HR, GA and EFW were evaluated using multivariate regression analysis. Reference ranges for FTF and ETF were then constructed using the low-risk population. Z-scores of FTF and ETF in the high-risk fetuses were calculated and analyzed., Results: In total, 602 low-risk singleton pregnancies and 54 high-risk fetuses (nine pairs of monochorionic twins with severe TTTS, 16 fetuses with AoS and 20 fetuses with CoA) were included. Adequate Doppler traces for FTF and ETF could be obtained in 95% of low-risk cases. Intraobserver reproducibility was good to excellent (ICC, 0.831-0.905) and interobserver reproducibility was good (ICC, 0.801-0.837) for measurements of all timing parameters analyzed. Multivariate analysis of FTF and ETF in relation to HR, GA and EFW in low-risk fetuses identified HR as the only variable predictive of FTF, while ETF was dependent on both HR and GA. FTF increased with decreasing HR in low-risk fetuses, while ETF showed the opposite behavior, decreasing with decreasing HR. Most recipient twins with severe TTTS showed reduced FTF and preserved ETF. AoS was associated with decreased FTF and increased ETF in the LV, with seemingly different patterns associated with univentricular vs biventricular postnatal outcome. The majority of fetuses with CoA had FTF and ETF within the normal range in both ventricles., Conclusions: Measurement of FTF and ETF using pulsed-wave Doppler is feasible and reproducible in the fetus. The presented reference ranges account for associations of FTF with HR and of ETF with HR and GA. These time fractions are potentially useful for clinical monitoring of cardiac function in severe TTTS, AoS and other fetal conditions overloading the heart. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To assess differences in cardiac morphology and function in fetuses of mothers with gestational diabetes mellitus (GDM) compared to controls, and to assess whether, in women with GDM, fetal cardiac changes are accentuated with advancing gestational age., Methods: We studied 112 women with GDM and 224 women with uncomplicated pregnancy at 24-40 weeks' gestation. In all fetuses, a standard four-chamber oblique view was obtained and offline speckle-tracking analysis was performed to measure right and left endocardial global longitudinal strain (GLS) and tricuspid and mitral annular plane systolic excursion. Global sphericity index was also calculated. Echocardiographic parameters were compared between GDM fetuses and controls at two gestational time periods of 24 + 0 to 32 + 0 weeks and 32 + 1 to 40 + 1 weeks., Results: At 24 + 0 to 32 + 0 weeks, we phenotyped 43 fetuses from mothers with GDM and 71 from uncomplicated pregnancies, and, at 32 + 1 to 40 + 1 weeks, we phenotyped 69 fetuses from mothers with GDM and 153 from women with uncomplicated pregnancy. In fetuses of mothers with GDM, compared to controls, right ventricular functional indices were consistently lower both at 24 + 0 to 32 + 0 weeks and at 32 + 1 to 40 + 1 weeks. Right ventricular GLS was reduced in the GDM group at 24 + 0 to 32 + 0 weeks (adjusted mean difference, 0.7%; 95% CI, 0.3-1.1%) and at 32 + 1 to 40 + 1 weeks (adjusted mean difference, 0.9%; 95% CI, 0.6-1.1%). Fetal left ventricular global longitudinal function was similar in GDM pregnancies compared with controls, with the exception of the contractility of the left ventricular basal segment, which was reduced. Global sphericity index was reduced in GDM pregnancies only at 32 + 1 to 40 + 1 weeks (adjusted mean difference, -0.4; 95% CI, -0.7 to 0.1)., Conclusions: The offspring of women with GDM are at high risk for development of cardiovascular disease in childhood and early adulthood. Our study demonstrates that GDM is associated with a reduction mainly in fetal right ventricular function, compared to controls, and this response is not exaggerated with increasing gestational age. Further studies are needed to determine whether fetuses with the observed alterations in cardiac function are those at highest risk for subsequent development of cardiovascular disease. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To assess the relationship between presence of a redundant foramen ovale flap (RFOF), in the absence of a clearly restrictive foramen ovale, and ventricular disproportion, in three groups of fetuses: (1) those with a final diagnosis of aortic coarctation (CoA); (2) those referred for suspicion of ventricular disproportion and/or CoA which did not develop CoA postnatally; and (3) normal fetuses., Methods: This was a retrospective study including 73 fetuses: 12 with a final diagnosis of isolated CoA; 30 referred for suspicion of ventricular disproportion and/or CoA, which did not develop CoA postnatally; and 31 normal fetuses. Four-dimensional volume datasets and clips were assessed offline. Maximum diameters of the FOF (FOFD), left atrium (LAD), right atrium, left and right ventricles and, when available, aortic isthmus, were measured, as were areas of the FOF (FOFA), left atrium (LAA) and right atrium. The left/right ratios for all segments of the heart, as well as the FOFD/LAD ratio and FOFA/LAA ratio, were calculated. Regression analysis was performed to assess the relationship between RFOF and ventricular disproportion and means were compared by ANOVA., Results: Repeatability was fair, with all variables having an intraclass correlation coefficient ≥ 83%. In the pooled group of fetuses with no CoA found at birth (normal fetuses plus those with ventricular disproportion (n = 61)), there was a significant linear correlation between redundancy of the FOF and degree of ventricular disproportion (P < 0.01 and P < 0.05 for diameter and area ratios, respectively). Categorizing the FOF redundancy, FOFD/LAD ratio ≥ 0.65 was significantly associated with ventricular disproportion (P = 0.006). Based on the degree of FOF prominence, we described four categories of redundancy, ranging from no redundancy/ventricular disproportion (Stage 0) to severe redundancy/ventricular disproportion with transient obstruction of the foramen ovale or mitral orifice (Stage III). Comparing cases without neonatal evidence of coarctation but FOFD/LAD ratio ≥ 0.65 vs those with neonatal evidence of coarctation, there was no statistically significant difference in the degree of ventricular disproportion or in the Z-score of the aortic isthmus maximum diameter., Conclusions: This study demonstrates that: (1) there is an association between RFOF and ventricular disproportion, independent of the association with a restrictive foramen ovale, and (2) the presence of a RFOF may mimic CoA. In fact, it causes both ventricular disproportion and a significant reduction in the diameter of the aortic isthmus, associated in some cases also with reversed isthmic flow. Future prospective studies are needed to evaluate whether focusing the sonologist's attention on the appearance of the foramen ovale may reduce the rate of false-positive diagnosis of CoA. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation., Methods: This was a prospective observational case-control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age-matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA-affected heart specimen, using synchrotron radiation-based X-ray phase-contrast microcomputed tomography and histology, respectively., Results: We included 30 fetuses with CoA and 60 gestational age-matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left-to-right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0-2.7) vs 1.8 (1.7-2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1-84.9) vs 47.0 (43.0-55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct., Conclusions: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume-loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Both excessive and restricted fetal growth are associated with changes in cardiac geometry and function at birth. There are significant issues when indexing cardiac parameters for body size in the neonatal period. The aims of this study were to determine to what extent cardiac geometry is dependent on body size in term and preterm neonates with restricted or excessive fetal growth and how this is affected by adiposity., Methods: This was a cross-sectional study of neonates born between 31 and 42 weeks of gestation, divided into three groups: (1) small-for-gestational age (SGA, birth weight > 2 SD below the mean); (2) large-for-gestational age (LGA, birth weight > 2 SD above the mean); and (3) appropriate-for-gestational-age controls (AGA, birth weight ≤ 2 SD from the mean). Cardiac geometry and function were compared between the study groups, adjusting for body size. The potential impact of infant adiposity and maternal disease was assessed., Results: In total, 174 neonates were included, of which 39 were SGA, 45 were LGA and 90 were AGA. Body size was reflected in cardiac dimensions, with differences in cardiac dimensions disappearing between the SGA and AGA groups when indexed for body surface area (BSA) or thoracic circumference. The same was true for the differences in atrial and ventricular areas between the LGA and AGA groups. However, left ventricular inflow and outflow tract dimensions did not follow this trend as, when indexed for BSA, they were associated negatively with adiposity, resulting in diminished dimensions in LGA compared with AGA and SGA neonates. Adiposity was associated positively with left ventricular mass, right ventricular length and area and right atrial area. The SGA group showed increased right ventricular fractional area change, possibly reflecting differences in the systolic function of the right ventricle. We found evidence of altered diastolic function between the groups, with the mitral valve inflow E- to lateral E'-wave peak velocity ratio being increased in the LGA group and decreased in the SGA group., Conclusions: Cardiac geometry is explained by body size in both term and preterm AGA and SGA infants. However, the nature of the relationship between body size and cardiac dimensions may be influenced by adiposity in LGA infants, leading to underestimation of left ventricular inflow and outflow tract dimensions when adjusted for BSA. Adjustments for thoracic circumference provide similar results to those for BSA. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Our primary aim was to confirm whether intertwin discordance in ventricular strain and ductus venosus (DV) time intervals predicts twin-twin transfusion syndrome (TTTS). Secondary aims were to create gestational-age ranges for ventricular strain in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies without selective intrauterine growth restriction (sIUGR) and to characterize the relationship of ventricular strain with gestational age in MCDA twin pregnancies with sIUGR that did not develop TTTS., Methods: In the period 2015-2018, we enrolled 150 MCDA twin pregnancies consecutively into this prospective, blinded study of global longitudinal left and right ventricular strain. With the observer blinded to twin pairing and pregnancy outcome, videoclips of the four-chamber view, which had been recorded during ultrasound surveillance in the usual window for development of TTTS (16-26 completed gestational weeks), underwent offline measurement of strain. Uncomplicated MCDA twin pregnancies, without sIUGR, were used to test the association between strain, gestational age and estimated fetal weight using mixed-effects multilevel regression. Inter-rater reliability was tested in 208 strain measurements in 31 fetuses from pregnancies which did not develop TTTS and within-fetus variation was assessed in 16 such fetuses, in which multiple four-chamber views were taken on the same day. The effect of sIUGR on strain in otherwise uncomplicated MCDA twin pregnancy was analyzed. MCDA twin pregnancies were defined as 'pre-TTTS' when, having been referred for TTTS evaluation, they did not satisfy Quintero staging criteria, but subsequently developed TTTS requiring laser treatment. MCDA pregnancies which did not develop TTTS comprised the 'non-TTTS' group. Cardiovascular parameters measured in these cases included tissue Doppler parameters and DV early filling time as a percentage of the cardiac cycle (DVeT%). Intertwin strain and DVeT% discordance was compared between non-TTTS and pre-TTTS cases, matched for gestational age., Results: Paired strain data were available for intertwin comparison in 127/150 MCDA twin pregnancies, comprising 14 pre-TTTS and 113 non-TTTS pregnancies, after exclusions. Scans were collected at a median frame rate of 97 (range, 28-220) Hz. Laser therapy was performed at a median gestational age of 20.6 (range, 17.2-26.6) weeks. There were no group differences in right (RV) or left (LV) ventricular strain discordance between 68/113 non-TTTS and 13/14 pre-TTTS MCDA twin pregnancies < 20 completed gestational weeks (RV, P = 0.338; LV, P = 0.932). DVeT% discordance > 3.6% was found in eight of 13 pre-TTTS pregnancies. In non-TTTS pregnancies, the estimated variability in ventricular strain within each twin during the day was high (RV, 19.7; LV, 12.9). However, within each pair (intertwin variation), variability was low (RV, 5.5; LV, 2.9). Interclass correlation reflecting the proportion of total variability represented by the variability between twin pairs was low (RV, 0.22; LV, 0.18). Both RV (P < 0.001) and LV (P = 0.025) strain showed a negative association with gestational age. Among non-TTTS MCDA twin pregnancies, LV strain was, on average, higher by 1.83 in sIUGR compared with normally grown fetuses (P = 0.023), with no statistically significant difference in RV strain (P = 0.271)., Conclusions: Although ventricular strain has been reported previously as a possible predictor of developing TTTS, in this blinded, prospective study, we found no significant intergroup differences in ventricular strain in pre-TTTS compared with age-matched non-TTTS MCDA twin pregnancies. We recommend using DVeT% discordance as a more practical screening tool in MCDA twin pregnancies. This study also provides new information on the changes with gestational age, and the biological and technical variation, of global longitudinal ventricular strain in uncomplicated MCDA twin pregnancies and those with isolated sIUGR. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To evaluate the effect of fetal growth restriction (FGR) at term on fetal and neonatal cardiac geometry and function., Methods: This was a prospective study of 87 pregnant women delivering at term, comprising 54 normally grown and 33 FGR pregnancies. Fetal and neonatal conventional and spectral tissue Doppler and two-dimensional speckle tracking echocardiography were performed a few days before and within hours after birth. Fetal cardiac geometry, global myocardial deformation and performance and systolic and diastolic function were compared between normal and FGR pregnancies before and after birth., Results: Compared with normally grown fetuses, FGR fetuses exhibited more globular ventricular geometry and poorer myocardial deformation and cardiac function (left ventricular (LV) sphericity index (SI), 0.54 vs 0.49; right ventricular (RV) SI, 0.60 vs 0.54; LV torsion, 1.2 °/cm vs 3.0 °/cm; LV isovolumetric contraction time normalized by cardiac cycle length, 121 ms vs 104 ms; interventricular septum early diastolic myocardial peak velocity/atrial contraction myocardial diastolic peak velocity ratio, 0.60 vs 0.71; P < 0.01 for all). The poorest perinatal outcomes occurred in FGR fetuses with the most impaired cardiac functional indices. When compared with normally grown neonates, FGR neonates showed persistent alteration in cardiac parameters (LV-SI, 0.53 vs 0.50; RV-SI, 0.54 vs 0.44; LV torsion, 1.1 °/cm vs 1.4 °/cm; LV myocardial performance index (MPI'), 0.52 vs 0.42; P < 0.01 for all). Paired comparison of fetal vs neonatal cardiac indices in FGR demonstrated that birth was associated with a significant improvement in some, but not all, cardiac indices (RV-SI, 0.60 vs 0.54; RV-MPI', 0.49 vs 0.39; P < 0.001 for all)., Conclusions: Compared with normal pregnancies, FGR fetuses and neonates at term exhibit altered cardiac indices indicative of myocardial impairment that reflect adaptation to placental hypoxemia and alterations in hemodynamic load around the time of birth. Elucidating potential mechanisms that contribute to the alterations in perinatal cardiac adaptation in FGR could improve management and aid the development of better therapeutic strategies to reduce the risk of adverse pregnancy outcome. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: In mothers with pregestational or gestational diabetes, abnormal arterial stiffness (stiffer arteries) has been reported. The impact of abnormal maternal arterial stiffness on placental and fetal cardiovascular physiology is unknown. The purpose of this study was to determine the impact of maternal diabetes on maternal arterial stiffness and the association with fetal cardiovascular physiology as measured by fetal echocardiography., Methods: Between December 2013 and January 2017 a prospective study was conducted on diabetic (but otherwise healthy) and non-diabetic, healthy pregnant mothers aged 18-40 years at 20-28 weeks' gestation who had a normal fetal cardiac echocardiogram and obstetric ultrasound. Clinical data were collected by means of a patient questionnaire and measurement of blood pressure, height, weight, arterial augmentation index (AIx) and placental and fetal cardiovascular parameters were collected by fetal echocardiography. Descriptive statistics were calculated. Comparisons were made using parametric and non-parametric tests between controls and diabetic mothers., Results: Twenty-three healthy pregnant controls and 43 diabetic pregnant women (22 with pregestational and 21 with gestational diabetes) were included in the study. Maternal AIx was higher in those with diabetes than in healthy controls (12.4 ± 10.6% vs 4.6 ± 7.9%; P = 0.003). Fetal aortic valve (AoV) velocity time integral (VTI) was higher in fetuses whose mothers had diabetes than in those with non-diabetic mothers (7.7 ± 1.9 cm vs 6.3 ± 3.0 cm; P = 0.022). Left ventricular (LV) myocardial performance index (MPI) was lower in diabetic pregnancies than in controls (0.40 ± 0.09 vs 0.46 ± 0.11; P = 0.021). Umbilical artery (UA) resistance index (RI) was lower in diabetic pregnancies with glycated hemoglobin (HbA1c) levels ≥ 6.5% than in those with HbA1c levels < 6.5% (0.69 ± 0.06, n = 15 vs 0.76 ± 0.08, n = 21; P = 0.009) but not at higher HbA1C cut-offs. No correlation between AIx and AoV-VTI, LV-MPI or UA-RI was found., Conclusions: Arterial stiffness is higher in pregnant women with diabetes than in controls. Fetuses of diabetic mothers show altered cardiovascular parameters, with higher AoV-VTI and lower LV-MPI, which are markers of myocardial function. Placental function assessed by UA-RI was normal despite differences between groups. Arterial stiffness did not correlate with placental or fetal cardiovascular variables. Instead, the findings are likely to represent a shared response to the environment of abnormal glucose metabolism. The clinical significance of these findings is yet to be determined. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Fetuses with growth restriction have been reported to have an abnormal sphericity index (SI), which is indicative of the shape of the ventricular chambers of the heart. Our aim was to evaluate the SI for 24 transverse segments distributed from base to apex of the right (RV) and left (LV) ventricles to determine whether, in small-for-gestational-age (SGA) fetuses, the SI is abnormal at locations other than the basal segment., Methods: We evaluated 30 SGA fetuses between 25 and 37 weeks of gestation. SI was computed for both ventricles by dividing the end-diastolic mid-basal-apical length by each of 24 end-diastolic transverse segmental widths, from base (Segment 1) to apex (Segment 24). For each ventricle, the Z-score and centile for the SI from each of the 24 segments were computed using the mean and SD from published equations. The 24-segment method, defining abnormal SI as values < 10 th centile or > 90 th centile, was compared with that of using only the basal segment by chi-square analysis to determine the number of fetuses identified with an abnormal SI., Results: In 23 of the 30 (77%) SGA fetuses, at least one of the 24 transverse segments in one or both ventricles had an abnormal SI; in 17% of cases, both ventricles were affected, in 23% of cases only the RV was involved and in 37% of cases only the LV was involved. Compared with the 24-segment model, significantly fewer fetuses with an abnormal SI were identified using only basal Segment 1, from the RV base (58%, 7/12; P < 0.01) or only Segment 12, in the mid portion of the RV (50%, 6/12; P < 0.005). Combining measurements of Segment 1 and Segment 12 from the RV identified 83% of fetuses with at least one abnormal SI and was not significantly different from using the 24-segment model. Similarly, significantly fewer fetuses with an abnormal SI were identified using only LV basal Segment 1 (63%, 10/16; P < 0.006) or only Segment 12, in the mid portion of the LV (75%, 12/16; P < 0.03), when compared with the 24-segment model. Combining measurements of both LV Segment 1 and Segment 12 identified 81% (13/16) of fetuses with an abnormal SI and was not significantly different from using the 24-segment model., Conclusion: The 24-segment SI of RV and LV provides a comprehensive method with which to examine the shape of the ventricular chambers and identifies more SGA fetuses with an abnormal SI than are identified using only the basal segment SI. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Because of parallel circulation in the fetus and the differential effect that various disease states may have on the shape of the right and left ventricles, this study was conducted to evaluate the sphericity index (SI) of 24 transverse segments distributed from the base to the apex of each of the ventricular chambers., Methods: Two hundred control fetuses were examined between 20 and 40 weeks of gestation. The displacement of the ventricular endocardium during the cardiac cycle was computed using offline speckle-tracking software. From the ASCII output of the analysis, we analyzed 24 end-diastolic transverse segments, distributed from the base to the apex of each ventricle, as well as the end-diastolic mid-basal-apical length. The SI was computed for each of the 24 segments by dividing the mid-basal-apical length by the transverse length for each segment. Regression analysis was performed against biometric measurements and gestational age according to last menstrual period and ultrasound. Eight fetuses, in which the four-chamber view appeared subjectively to demonstrate chamber disproportion, were evaluated as examples to demonstrate the utility of this technology., Results: The SI for each segment was independent of gestational age and fetal biometric measurements. The SI of the right ventricle was significantly (P < 0.001) lower than that of the left ventricle for segments 1-18, suggesting that the right ventricle was more globular in shape than was the left ventricle at the base, mid and a portion of the apical segments of the chamber. Fetuses with various cardiac structural abnormalities and abnormal fetal growth had abnormal SI values that reflected either a more globular or a more flattened ventricular chamber., Conclusion: Determination of SI for each of 24 segments of the fetal right and left ventricles provides a comprehensive method to examine the shape of the ventricular chambers. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To define the pattern of fetal echocardiographic changes associated with isolated pulmonary valve stenosis (PS) and to correlate the echocardiographic findings with neonatal outcome and the need for postnatal pulmonary valvuloplasty within the first 12 months postpartum., Methods: This was a prospective cohort study between January 2009 and October 2015 of 16 fetuses with isolated PS and 48 controls matched by gestational age at ultrasound examination (± 2 weeks) evaluated at the Fetal Cardiology Unit at BCNatal (Barcelona). Standard fetal ultrasound and comprehensive echocardiography, which included cardiovascular morphometric parameters, and systolic and diastolic functional and timing measurements, were performed in all cases. Baseline characteristics and perinatal outcome were retrieved from clinical records. Cases were followed up until 12 months of age, and admission to intensive care unit, days of hospitalization, need for prostaglandins and requirement for postnatal surgery were reviewed. Fetal PS cases were analyzed according to the need for postnatal pulmonary valvuloplasty., Results: The study groups were similar in terms of baseline, fetal ultrasound and perinatal characteristics. Median gestational age at diagnosis of PS was 33.4 (range, 20.0-36.5) weeks. Most cases corresponded to mild or moderate PS; only three fetuses had reversed flow in the ductus arteriosus before delivery. Six (37.5%) newborns, including all three with reversed flow in the ductus arteriosus prenatally, required postnatal pulmonary valvuloplasty. Fetuses with PS presented with larger and more globular hearts, with increased myocardial wall thickness in the third trimester. Despite preserved right ventricular (RV) ejection fraction and systolic longitudinal motion, PS cases showed increased right cardiac output and signs of diastolic dysfunction, with higher ductus venosus pulsatility index (0.72 ± 0.32 vs 0.53 ± 0.16, P = 0.004) and tricuspid E/E' ratio (7.52 ± 3.07 vs 5.76 ± 1.79, P = 0.022). In addition, fetuses with PS displayed a compensatory increase in left ventricular (LV) radial and longitudinal motion, as shown by a higher ejection fraction (79.3 ± 8.23% vs 67.6 ± 11.3%, P = 0.003) and mitral annular-plane systolic excursion (5.94 ± 1.38 vs 5.0 ± 1.22 mm, P = 0.035). Finally, fetuses requiring postnatal pulmonary valvuloplasty showed a different pattern of echocardiographic findings from those not requiring valvuloplasty, with a significantly smaller RV and pulmonary valve diameter, reduced tricuspid annular-plane systolic excursion (5.08 ± 1.59 vs 8.07 ± 1.93 mm, P = 0.028), increased LV cardiac output (340 ± 16 vs 176 ± 44 mL/min/kg, P = 0.003) and more pronounced signs of LV diastolic dysfunction (mitral E' velocity, 5.78 ± 0.90 vs 8.16 ± 1.58 cm/s, P = 0.008)., Conclusions: Fetuses with PS present with more hypertrophic, larger and more globular hearts in the third trimester of pregnancy, associated with a higher right cardiac output and impaired biventricular relaxation. In addition, signs of increased LV contraction were observed. Our data suggest that RV and LV functional parameters could be useful for predicting the need for postnatal pulmonary valvuloplasty. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Although the postnatal physiology of D-loop transposition of the great arteries with intact ventricular septum (D-TGA/IVS) is well established, little is known about fetal D-TGA/IVS. In the normal fetus, the pulmonary valve (PV) is larger than the aortic valve (AoV), there is exclusive right-to-left flow at the foramen ovale (FO) and ductus arteriosus (DA), and the left ventricle (LV) ejects 40% of combined ventricular output (CVO) through the aorta, primarily to the brain. In D-TGA/IVS, the LV ejects oxygen-rich blood to the pulmonary artery, theoretically leading to pulmonary vasodilation, increased branch pulmonary artery flow and reduced DA flow. In this study, we tested the hypothesis that D-TGA/IVS anatomy results in altered cardiac valve sizes, ventricular contribution to CVO, and FO and DA flow direction., Methods: Seventy-four fetuses with D-TGA/IVS that underwent fetal echocardiography at our institution between 2004 and 2015 were included in the study. AoV, PV, mitral valve and tricuspid valve sizes were measured and Z-scores indexed to gestational age were generated. Ventricular output was calculated using Doppler-derived velocity-time integral, and direction of flow at the FO and DA shunts was recorded in each fetus using both color Doppler and flap direction. Measurements in the D-TGA/IVS fetuses were compared with data of 222 controls, matched for gestational-age range, from our institutional normal fetal database., Results: The LV component of CVO was higher in D-TGA/IVS fetuses than in controls (50.7% vs 40.2%; P < 0.0001), with no difference in the total CVO. Flow was bidirectional at the FO in 56 (75.7%) and at the DA in 24 (32.4%) D-TGA/IVS fetuses. Only 21.6% fetuses had normal right-to-left flow at both shunts. Bidirectional shunting was more common in third-trimester fetuses than in second-trimester ones (P < 0.03). AoV and PV diameters were nearly identical in D-TGA/IVS in contrast to control fetuses, hence AoV Z-score was higher than PV Z-score (1.13 vs -0.65, P < 0.0001) in D-TGA/IVS., Conclusions: In fetuses with D-TGA/IVS there is loss of the normal right-sided dominance, as each ventricle provides half of the CVO, with a relatively large AoV diameter and a small PV diameter, and high incidence of bidirectional FO and DA flow. This may support the theory that high pulmonary artery oxygen content reduces pulmonary vascular resistance, thereby increasing branch pulmonary artery flow and venous return, which results in increased LV preload and output. Pulmonary sensitivity to oxygen is thought to increase later in gestation, which may explain the higher incidence of bidirectional shunting. Consequences of these flow alterations include increased aortic and, most likely, brain flow, perhaps in an attempt to compensate for the substrate deficiency observed in D-TGA/IVS. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Congenital left ventricular diverticulum (LVD) is a rare abnormality of the myocardium which has been detected previously in the fetus. Lesions have been reported from as early as 12 weeks' gestation but are more commonly detected in the mid-second trimester. Fetal presentation of LVD ranges from an abnormal four-chamber view of the heart, arrhythmia or isolated pericardial effusion to fetal hydrops with associated heart failure. Here, we describe the prenatal diagnosis of an infant with LVD originating from the left ventricular outflow tract associated with coarctation of the aorta. The diagnosis was confirmed postnatally by two-dimensional echocardiography and cardiac magnetic resonance imaging. We hypothesize that the lesion compromised antegrade flow into the transverse aortic arch, which may have contributed to underdevelopment of the aortic arch and subsequently the development of coarctation of the aorta. This is a unique case of LVD and coarctation of the aorta., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To assess whether severity of congenital diaphragmatic hernia (CDH) correlates with the degree of left heart hypoplasia and left ventricle (LV) output, and to determine if factors leading to abnormal fetal hemodynamics, such as compression and reduced LV preload, contribute to left heart hypoplasia., Methods: This was a retrospective cross-sectional study of fetuses at 16-37 weeks' gestation that were diagnosed with CDH between 2000 and 2010. Lung-to-head ratio (LHR), liver position and side of the hernia were determined from stored ultrasound images. CDH severity was dichotomized based on LHR and liver position. The dimensions of mitral (MV) and aortic (AV) valves and LV were measured, and right and left ventricular outputs were recorded., Results: In total, 188 fetuses with CDH were included in the study, 171 with left CDH and 17 with right CDH. Fetuses with severe left CDH had a smaller MV (Z = -2.24 ± 1.3 vs -1.33 ± 1.08), AV (Z = -1.39 ± 1.21 vs -0.51 ± 1.05) and LV volume (Z = -4.23 ± -2.71 vs -2.08 ± 3.15) and had lower LV output (26 ± 10% vs 32 ± 10%) than those with mild CDH. MV and AV in fetuses with right CDH (MV, Z = -0.83 ± 1.19 and AV, Z = -0.71 ± 1.07) were larger than those in fetuses with left CDH, but LV outputs were similarly diminished, regardless of hernia side. Severe dextroposition and abnormal liver position were associated independently with smaller left heart, while LHR was not., Conclusion: The severity of left heart hypoplasia correlates with the severity of CDH. Altered fetal hemodynamics, leading to decreased LV output, occurs in both right- and left-sided CDH, but the additional compressive effect on the left heart is seen only when the hernia is left-sided. Improved knowledge of the physiology of this disease may lead to advances in therapy and better risk assessment for use in counseling affected families., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To establish formulae for the calculation of fetal cardiovascular Z-scores based on femur length (FL), and to compare cardiovascular parameters between fetuses with tetralogy of Fallot (TOF) and normal fetuses in order to assess their value for the prenatal diagnosis of TOF., Methods: A total of 329 normal fetuses and 43 fetuses with TOF were included in this study. Eleven cardiovascular dimensions were measured offline after cardiac spatiotemporal image correlation volume acquisition. Normal cardiovascular Z-score formulae were constructed for these measurements based on FL by performing a standard regression analysis followed by weighted regression of absolute residual values. The following ratios were calculated: right ventricular internal diameter (RVID) to left ventricular internal diameter (LVID) and pulmonary artery diameter (PA) to aorta diameter (Ao). Subsequently, all parameters were compared between the normal and TOF groups., Results: Formulae for calculating Z-scores for the 11 cardiovascular dimensions were constructed. FL was significantly correlated with all cardiovascular dimensions assessed (r = 0.816-0.944, P < 0.001 for all). RVID, Ao, PA, aortic arch isthmus, and ductus arteriosus mean Z-scores and PA/Ao ratio were statistically significantly different between normal fetuses and those with TOF. In the TOF group, all Ao Z-scores (43/43) were > + 2 and all PA/Ao ratios (43/43) were below the normal 95% range. However, only 48.8% (21/43) of the PA Z-scores were < -2., Conclusions: The cardiovascular Z-score formulae developed can provide a quantitative basis for the prenatal diagnosis of TOF. Aortic dilatation and abnormal PA/Ao ratio may be markers for the antenatal diagnosis of TOF., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To review the fetal echocardiograms of patients with total anomalous pulmonary venous connection (TAPVC) in order to determine whether the distance between the left atrium and the descending aorta would be useful in the prenatal diagnosis of fetal TAPVC., Methods: We reviewed the fetal echocardiograms of eight cases of TAPVC (five supracardiac type and three infracardiac type) with no other cardiac malformations. We evaluated the ratio of the left atrium-descending aorta distance to the diameter of the descending aorta ('post-LA space index') in 101 normal and eight TAPVC fetuses, and compared the values between groups. In addition, we examined the tricuspid valve/mitral valve diameter ratio (TVD/MVD) and the right ventricular end-diastolic diameter/left ventricular end-diastolic diameter ratio (RVDd/LVDd)., Results: The echocardiograms for fetuses with TAPVC and normal fetuses were performed at mean gestational ages of 27.5 weeks and 29.6 weeks, respectively. There were no significant differences in the TVD/MVD and RVDd/LVDd ratios between the groups. However, the post-LA space index was significantly higher in the TAPVC cases (mean, 1.51) than it was in the normal fetuses (mean, 0.71 ± 0.23) (P < 0.0001). On an analysis of the receiver-operating characteristics curve, a post-LA space index cut-off of 1.27 was found to be optimal for distinguishing between TAPVC and normal hearts, with a sensitivity of 100% and specificity of 99%., Conclusions: The novel post-LA space index could potentially be used for the prenatal diagnosis of TAPVC. A diagnosis of TAPVC is very likely in cases with a post-LA space index of > 1.27., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate cardiac anatomy and function in fetuses with right-sided congenital diaphragmatic hernia (RCDH), and to compare these values with those of normal controls., Methods: Fetal echocardiography was performed in 17 consecutive cases with isolated RCDH and 17 gestational age-matched controls. Two-dimensional measurements included ventricular and outflow tract diameters. Doppler ultrasound was used to measure the flow pattern in the ductus venosus and over the pulmonary and aortic valves, right and left ventricular myocardial performance index and the E/A wave ratio over the atrioventricular valves. Stroke volume, cardiac output and shortening fraction were calculated., Results: Median gestational age at evaluation was 27.4 (interquartile range, 24.4-28.9) weeks. RCDH cases had a significantly smaller right ventricle and pulmonary valve diameter. Furthermore, stroke volume and cardiac output from the right ventricle were lower than in controls. Myocardial contractility, however, appeared normal., Conclusions: Despite significantly reduced right ventricular dimensions and cardiac output, cardiac contractility was normal in a cohort of fetuses with RCDH., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To compare the ability of two different methods for longitudinal annular motion measurement, M-mode and tissue Doppler imaging (TDI), to demonstrate cardiac dysfunction in intrauterine-growth-restricted (IUGR) fetuses., Methods: Cardiac longitudinal annular motion in the basal free wall of the left ventricle (mitral annulus), interventricular septum and tricuspid annulus was assessed in 23 early-onset IUGR cases and 43 controls by TDI (annular peak velocities) and M-mode (displacement)., Results: All annular parameters were significantly decreased in the IUGR group with respect to controls using both methods. M-mode showed a trend towards equal performance as classifier between cases and controls, as compared to TDI, mainly in the tricuspid annulus., Conclusions: Both M-mode and TDI demonstrate annular motion changes and consequently cardiac dysfunction in IUGR fetuses. M-mode imaging is simpler to perform and could be as sensitive as TDI for detecting subtle changes., (Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.)

Isolated left ventricular non-compaction (LVNC) is a rare disorder, classified as a primary genetic cardiomyopathy by the American Heart Association or as an unclassified cardiomyopathy by the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. The key features are the prominent trabeculae and deep intratrabecular recesses resulting in thickened myocardium with the two layers consisting of compacted and non-compacted myocardium. These recesses are in continuity with the left ventricular cavity and are filled with blood without evidence of communication to the epicardial coronary artery system. We present a case of LVNC detected prenatally at 25 + 4 weeks of gestation., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

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., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: To determine the feasibility and reliability of using xPlane imaging to examine simultaneously the four-chamber and left ventricular outflow tract (LVOT) views in real time, to assess rotation angles from the four-chamber view to the LVOT view, and to investigate factors affecting the angles., Methods: In 145 fetuses at 11-37 weeks' gestation, we visualized the four-chamber view in one of three cardiac positions: a subcostal view with the apex at the 3 or 9 o'clock position; an apical view with the apex at the 12 or 6 o'clock position; or a view with the fetal heart apex midway between these two positions. We then used the rotation function of xPlane imaging, using the four-chamber view as the reference plane, to visualize the LVOT view simultaneously in real time on the secondary image plane, on the right side of the split screen, by rotating a reference line from 0° with a rotation step of 5°. The rotation angle necessary for the first appearance of LVOT was recorded as the first rotation angle. The reference line was then rotated until the LVOT was just out of view, and this last rotation angle was recorded as the second rotation angle. The difference between these two angles was recorded as the angle span of the LVOT display. Reliability was assessed by intraclass correlation coefficient (ICC)., Results: Of the 145 fetuses examined, 29 had cardiac defects. Using xPlane imaging, the LVOT was visualized successfully after 14 weeks in 95.1% of cases. The first and second rotation angles varied significantly with cardiac position (P < 0.001); when the fetal heart was examined using a subcostal approach with the apex at the 3 or 9 o'clock position, the first rotation angle was smaller than that at the apical view for normal hearts (20° vs. 50°, P < 0.001). There was also a significant difference for the second rotation angle and for the angle span, between fetuses with and without normal LVOT (P = 0.038 and 0.006, respectively). Regarding intra- and interobserver reliability for measurement of first and second rotation angles, the ICCs were high (range, 0.847-0.980)., Conclusion: Using xPlane imaging, it is feasible to examine simultaneously the four-chamber and LVOT views in real time, and measurement of the rotation angles between these two views is reproducible. The rotation angles depend on the position of the fetal heart, and the normality of the LVOT. Proposed algorithms for examination of the fetal heart with three-/four-dimensional ultrasonography may need to be adapted to optimize visualization of the standard planes., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To evaluate echocardiographic characteristics and clinical relevance of color Doppler twinkling artifacts in fetuses with isolated echogenic intracardiac foci (EIF)., Methods: This study included 50 fetuses with EIF, at 18-38 weeks of gestation. Echocardiographic examination, which was performed using a 1.0-5.0-MHz phased array probe, included gray-scale, color and spectral Doppler imaging. Twinkling artifacts were assessed using fetal color Doppler echocardiography on isolated EIF situated in the left and/or right ventricles. The prevalence, appearance and clinical relevance of the color Doppler twinkling artifacts were analyzed., Results: Eight of 50 fetuses with EIF (16%) showed color Doppler twinkling artifacts, which appeared as a rapidly changing color complex seen persistently behind the EIF. The spectra obtained in all eight with color Doppler artifacts were composed of straight vertical bands occurring in mid to late systole and early diastole. After birth, none of 50 fetuses with EIF had structural heart diseases or showed clinical signs of cardiac failure., Conclusions: Color Doppler twinkling artifacts from isolated EIF occur in some fetuses and may be considered as an additional echocardiographic feature of EIF. Attention should be paid to the identification and interpretation of these artifacts so that they may be accurately distinguished from true color flow generated by atrioventricular valvular regurgitation jets., (Copyright 2010 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: Quantification of fetal heart ventricle volume can aid in the evaluation of functional and anatomical aspects of congenital heart disease. The aim of this study was to establish nomograms for ventricular volume using three-dimensional (3D) inversion mode ultrasonography with the spatio-temporal image correlation (STIC) modality and to calculate ejection fraction and stroke volume., Methods: The fetal heart was scanned using the STIC modality, during fetal quiescence with abdomen uppermost, at an angle of 30-50 degrees , without color Doppler flow mapping. In post-processing, starting with the classic four-chamber view plane in the A-frame, the reference point was moved to the center of the ventricle. The operator used the edit volume followed by Virtual Organ Computer-aided AnaLysis (VOCAL) mode options; in manual trace the VOCAL settings were set to 15 degrees . The trace was drawn and included the myocardium; inversion mode thresholding provided the volume of the intraventricular (anechoic) voxels within the region of interest. The total volume and the intraventricular volume were displayed. The process was repeated for right (R) and left (L) ventricles at end diastole (EDV) and end systole (ESV). The stroke volume (SV = EDV - ESV) and ejection fraction (EF = SV/EDV) were calculated from these measurements. Intraclass correlation was used to evaluate intra- and interobserver agreement., Results: One hundred fetuses ranging from 20 + 5 to 40 + 0 gestational weeks were included in the study. In addition, six fetuses diagnosed during the study period with a cardiac anomaly were examined and their ventricular volumes compared with those of the main study group. LEDV ranged from a mean of 0.53 cm(3) at midgestation to a mean of 3.96 cm(3) at term. LESV ranged from a mean of 0.17 cm(3) at midgestation to 1.56 cm(3) at term. REDV ranged from a mean of 0.68 cm(3) at midgestation to a mean of 5.44 cm(3) at term. RESV ranged from a mean of 0.26 cm(3) at midgestation to 2.29 cm(3) at term. Total stroke volume ranged from a mean of 0.78 cm(3) at midgestation to a mean of 5.5 cm(3) at term. The mean right : left ventricle ratio was 1.4, and left ejection fraction ranged from 42.5 to 86% in these fetuses. Nomograms were created for RESV, LESV, REDV, LEDV and total stroke volumes vs. estimated fetal weight and gestational age. Intra- and interobserver agreement reached 96%., Conclusions: 3D inversion mode sonography combined with STIC represents a simple and reproducible method for estimating fetal cardiac ventricle volume. This innovative methodology may add to overall evaluation of cardiac volume and function, and improve our understanding of normal and abnormal cardiac structure, as well as the severity and prognosis of cardiac lesions., (Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To evaluate the effect of fetal anemia and intrauterine transfusion on ventricular shortening fraction., Methods: The end-diastolic and end-systolic transverse dimensions of the left and right ventricles were obtained using M-mode ultrasonography. The shortening fractions of both ventricles were calculated at three time points: before, immediately after and one day after intrauterine transfusion. The blood volume given at intrauterine transfusion was expressed as a percentage of estimated fetoplacental blood volume., Results: Complete measurements were obtained from 49 transfusions in 23 fetuses. Intrauterine transfusion was performed at a median gestational age of 31 (range, 19-35) weeks. Median hemoglobin concentration before and after intrauterine transfusion was 7.9 (range, 2.7-13.7) g/dL and 14.3 (range, 12.7-16.1) g/dL, respectively. Both left and right ventricular shortening fractions differed significantly between the three time points. Left ventricular shortening fraction decreased immediately after transfusion in 43 (88%) of the 49 procedures. Right ventricular shortening fraction decreased immediately after transfusion in 42 (86%) of the 49 procedures. At the first intrauterine transfusion, there was only a weak correlation between the decrease in shortening fraction of both ventricles and the transfused volume (left: R(2) = 0.15; P = 0.20/right: R(2) = 0.005; P = 0.81)., Conclusion: Transfusion significantly decreases the shortening fraction of both ventricles of the fetal heart. There is, however, little correlation between the decrease in shortening fraction and the volume of red cells given at intrauterine transfusion. Published by John Wiley & Sons, Ltd., (Copyright (c) 2005 ISUOG.)

Objective: To evaluate cardiac dimensions and function in euploid fetuses with intracardiac echogenic foci., Study Design: Forty-eight fetuses with a single cardiac echogenic focus situated in the left ventricle had echocardiography performed at 22-24 weeks of gestation. Fifty normal fetuses at 22-24 weeks' gestation served as controls. Two-dimensional and M-mode directed fetal echocardiography were used to exclude cardiac anomalies and measure right and left ventricular free walls and interventricular septal thickness and ventricular systolic and diastolic dimensions. Cardiac size was expressed as a ratio of ventricular wall thickness/biparietal diameter, and cardiac function was expressed as ventricular shortening fraction. Doppler fetal echocardiography measurements included pulmonary and aortic maximum systolic velocities and time to peak velocities as indices of ventricular systolic function, and the ratio between early ventricular filling (E-wave) and active atrial filling (A-wave) peak velocities at the level of the atrioventricular valves as an index of ventricular diastolic function., Results: Early ventricular filling/active atrial filling peak velocity ratios were significantly lower in fetuses with intracardiac echogenic foci than in control fetuses. In the mitral valve the ratio was 0.37 +/- 0.14 (0.039) (mean +/- SD (95% confidence interval for difference between the means)) vs. 0.59 +/- 0.19 (0.052) and in the tricuspid valve it was 0.42 +/- 0.16 (0.045) vs. 0.62 +/- 0.21 (0.058). No significant differences were found in cardiac dimensions, ventricular shortening fraction and Doppler systolic indices., Conclusion: Euploid fetuses with intracardiac echogenic foci show low E/A ratio values in midtrimester echocardiography. This finding might indicate cardiac diastolic dysfunction.