UNASSIGNED: Prognosis of twin-to-twin transfusion syndrome (TTTS) varies depending on the Quintero stage and fetal cardiac function. The purpose of our study was to evaluate fetal cardiac function before and after different intrauterine treatments of TTTS through myocardial performance index (MPI).
UNASSIGNED: In this retrospective study, data were collected from August 2016 to December 2022. Totals of 68 cases of TTTS and 68 monochorionic diamniotic (MCDA) twins without TTTS were included. MPI was collected and compared between TTTS and MCDA twins without TTTS before intrauterine treatments. TTTS cases were divided into 3 groups according to different intrauterine treatments: (I) amnioreduction (34 cases), (II) fetoscopic laser photocoagulation (FLPC; 20 cases), and (III) selective reduction (14 cases). The MPI of the left ventricle (LV) and right ventricle (RV) in each surviving fetus were measured 48 hours before and after treatments by pulse Doppler ultrasound. One-way analysis of variance (ANOVA) was employed to assess whether there were statistical differences in LV-MPI and RV-MPI among the donors, recipients, and the control group. Paired t-test analysis was used to compare whether there were differences in MPI before and after intrauterine treatments.
UNASSIGNED: The MPIs of the LV and RV in the recipients were significantly higher than those in the MCDA twins without TTTS (P<0.05). After the amnioreduction treatment of TTTS, no significant differences were observed in the MPI of either the LV or the RV before and after treatment. At 48 hours after FLPC treatment, the value of the LV-MPI in donors was 0.25±0.08, and the value of the RV-MPI in recipients was 0.58±0.17. Both of them were significantly lower than those before the treatment (P<0.05). In the selective reduction group, the value of the RV-MPI in surviving recipients significantly decreased compared to that before treatment (P<0.05).
UNASSIGNED: MPI is an effective indicator to evaluate fetal cardiac function of TTTS and assess the efficacy of intrauterine treatments of TTTS.

Our aim in this study was to investigate whether there is an association between large-for-gestational age (LGA) fetuses and myocardial performance index (MPI). This is a cross-sectional study conducted from July 2022 to July 2023. Prospectively gathered data from 65 LGA cases and 65 age and gestational-age (GA)-matched controls were analyzed. Presence of polyhydramnios and diabetes were recorded in the study group. Fetal left ventricular mod-MPI, peak systolic velocity (PSV) of E and A waves, umbilical and middle cerebral artery (MCA) pulsatility indexes (PI) were sonographically measured. Association between these sonographic measures and LGA fetuses were sought. The LGA group had 33 diabetic cases (22 GDM and 11 PGDM). The LGA group had greater mod-MPI (0.51 vs. 0.45, p = 0.0048). The LGA group also had prolonged isovolumetric contraction time (ICT), compared to controls (37 ms vs. 33 ms, p = 0.008). ICT was longer in LGA fetuses with non-diabetic mothers (38 ms vs. 33 ms, p = 0.009). LGA fetuses with polyhydramnios but without diabetic mothers had also longer ICT (39 ms vs. 33 ms, p = 0.002). Mod-MPI was similar in controls and LGA without diabetes/LGA with polyhydramnios but without diabetes subgroups. Our results indicate that fetal mod-MPI values are higher in LGA fetuses and ICT is prolonged among LGA fetuses irrespective of presence of maternal diabetes.

OBJECTIVE: Hemoglobin (Hb) Bart\'s disease is a severe manifestation of alpha thalassemia, resulting in fetal tissue hypoxia and severe anemia. There is limited research available on assessing fetal speckle tracking analysis as a response to fetal anemia caused by Hb Bart\'s disease and its utility as a sonographic predictor for Hb Bart\'s disease. This study aimed to assess the diagnostic performance of fetal cardiac parameters derived from speckle tracking echocardiography for distinguishing between affected and unaffected fetuses in pregnancies at risk of Hb Bart\'s disease during the 17-24 gestational weeks.
METHODS: A total of 115 pregnant women at risk for fetal Hb Bart\'s disease, who underwent either amniocentesis or cordocentesis at Siriraj Hospital, Bangkok Thailand, were included. Speckle tracking analysis was performed on the 4-chamber view (4CV) of the fetal heart, assessing heart size, shape, ventricular contractility, and left ventricular function prior to invasive prenatal testing. Logistic regression analysis determined significant cardiac predictors and calculated the probability of a fetus having Hb Bart\'s disease.
RESULTS: Among the cohort, 38 fetuses (33%) were diagnosed with Hb Bart\'s disease, and 9 cases (7.8%) exhibited frank hydropic signs. In comparison to the control group, affected fetuses displayed a notable enlargement of the 4CV and a more globular shape specifically in the right ventricular chamber. Additionally, there were significant differences in the left global and longitudinal contractility between affected and unaffected fetuses. However, at mid-gestation, no significant distinctions were observed in terms of transverse contractility and left ventricular function between the two groups. Based on logistic regression analysis, combined cardiac parameters derived from speckle tracking analysis as a function of head circumference, could differentiate non-hydropic fetuses with Hb Bart\'s disease from unaffected fetuses, achieving a maximum sensitivity of 100%, specificity of 98.7%, and overall accuracy of 99.06%.
CONCLUSIONS: Speckle tracking echocardiography has the potential to accurately identify early fetal heart changes in individuals at risk of developing Bart\'s anemia during the second trimester. This not only offers a novel predictive marker for Hb Bart\'s disease but also helps address the question of the underlying mechanisms of heart failure associated with anemia. This article is protected by copyright. All rights reserved.

BACKGROUND: Fetal cardiology has shown a rapid development in the past decades. Fetal echocardiography is not only used for the detection of structural anomalies but also to assess fetal cardiac function. Assessment of the fetal cardiac function is performed mostly in the second and third trimesters. The study of fetal cardiac function at the end of first trimester has not been investigated properly, and there is a lack of reference values at early gestational weeks.
OBJECTIVE: This study aimed to assess if the measurement of time-related parameters of cardiac function in the left ventricle of the fetal heart is feasible and reproducible at the end of the first trimester. If possible, we provide nomograms of these parameters from 11 to 13+6 gestational weeks.
METHODS: We conducted a prospective observational study from March to September 2022. The study was carried out in 2 hospitals (Hospital Universitari Dexeus, Barcelona, and Hospital VITAHS 9 Octubre, Valencia, Spain). The scans were performed by 3 specialists in fetal medicine. The exclusion criteria were fetal cardiac rhythm abnormalities, abnormal nuchal translucency, abnormal ductus venosus, fetal malformations, stillbirth, estimated fetal weight <10 percentile, diabetes, and gestational hypertensive disorders. The cardiac function parameters studied in the left ventricle were isovolumetric contraction time, isovolumetric relaxation time, ejection time, filling time, cycle time, myocardial performance index, ejection time fraction, and filling time fraction. We study the feasibility and intra- and interobserver reproducibility of these parameters using the interclass correlation coefficient. Nomograms were created and the percentiles of the values of the different parameters were calculated.
RESULTS: A total of 409 cases were recruited but only 296 could be included in the statistical analysis once the exclusion criteria were applied. The intraobserver reproducibility study was excellent (interclass correlation coefficient >0.900), and the interobserver reproducibility study was good (interclass correlation coefficient >0.700). The data regression analysis showed that cycle time, filling time, isovolumetric contraction time, and filling time fraction increased with gestational age, whereas ejection time fraction decreased with gestational age and myocardial performance index (mean, 0.43±0.08), isovolumetric relaxation time (mean, 0.04±0.01), and ejection time (mean, 0.16±0.01) remained constant from 11 to 13 weeks.
CONCLUSIONS: The study of fetal cardiac function is feasible and reproducible at 11 to 13+6 gestational weeks. Nomograms of the studied parameters are provided.

OBJECTIVE: The aim of the study was to compare left ventricle stroke volume in healthy, eutrophic fetuses in the 2nd and 3rd trimesters evaluated using the velocity time integral and aortic annulus area with left ventricular stroke volume measured using Simpson\'s single-plane rule and to determine the discrepancy equation.
METHODS: The study included 354 fetuses. In each fetus, during the same examination, simultaneous assessment of stroke volume was performed by pulsed-wave Doppler using the product of the velocity time integral and aortic annulus area and by the fetalHQ® software using Simpson\'s single-plane rule. The Mann-Whitney U test was used to compare the \"product-derived\" stroke volume and stroke volume using fetalHQ® software values in the 2nd and 3rd trimesters separately. The agreement between the two methods were verified using Bland-Altman analysis. A linear regression model was used to obtain the discrepancy equation.
RESULTS: In the 2nd trimester, the mean percentage difference between both the techniques showed that the stroke volume values determined using pulsed-wave Doppler were, on average, 88% higher than the stroke volume values determined using fetalHQ®. The upper limit of agreement between the compared techniques was approximately 146% and the lower limit of agreement was equal to 29.6%. In the 3rd trimester, the results indicated that the stroke volume values determined using pulsed-wave Doppler were, on average, 76% higher than the stroke volume values determined using fetalHQ®. The upper limit of agreement between the compared techniques was approximately 129% and the lower limit of agreement was 23%. Based on the results of the linear regression models, discrepancy formulas of the stroke volume values were obtained. The equations to calculate the predicted mean and standard deviations were used to compute the reference intervals for the mean, 5th and 95th centiles.
CONCLUSIONS: The calculation of left ventricular stroke volume using pulsed Doppler has higher result in relation to stroke volume determined using Simpson\'s rule significantly. The aortic annulus area showed a higher correlation regarding stroke volume than the velocity time integral in both the 2nd and 3rd trimesters. Stroke volume increased with the increase in aortic annulus area, whereas the velocity time integral remained relatively constant. The retrospective analysis of the collected material enabled the determination of the discrepancy equation.

Fetal growth restriction (FGR) can result in adverse perinatal outcomes due to cardiac dysfunction. This study used 2D speckle-tracking echocardiography to assess left ventricle (LV) longitudinal strain across FGR severity stages. A prospective longitudinal cohort study measured global (GLS) and segmental LV longitudinal strain in FGR fetuses, with evaluations conducted at various time points. FGR was classified into subtypes based on published criteria using fetal weight centile and Doppler parameters. A linear mixed model was employed to analyze repeated measures and compare Z-score measurements between groups throughout gestational age. The study included 40 FGR fetuses and a total of 107 evaluations were performed: 21 from small for gestational age (SGA), 74 from the FGR stage I, and 12 from the FGR stage ≥ II. The results indicate that SGA and stage I FGR fetuses exhibit higher LV GLS than stages ≥ II. Throughout gestation, SGA and FGR stage I fetuses showed similar behavior with consistently better LV GLS values when compared to FGR stages ≥ II. No significant differences were observed in LV GLS strain behavior between SGA and FGR stage I. In conclusion, all FGRs show signs of early cardiac dysfunction, with severe cases demonstrating significantly a lower LV GLS when compared to mild cases, suggesting deterioration of cardiac dysfunction with progression of fetal compromise.

A thoracoamniotic shunt was placed in a fetus affected by a right congenital diaphragmatic hernia (RCDH) complicated by voluminous nonimmune hydrops (NIH) at 30 weeks of gestation. The fetus showed congestive cardiac failure with a combined cardiac output (CCO) of 460.7 ml/min (Z-score: -1.2). After seven days, no edema, ascites, or pleural effusion was present. CCO increased significantly, reaching a Z-score of -0.2, as well as right and left cardiac output (Z-scores: -0.3 and -0.8, respectively). Two weeks later, the cardiac function and the ascites got worse despite the correct shunt placement, suggesting a possible occlusion. At 33 weeks, a C-section was performed due to labor in breech presentation. Despite the intensive care provided, the newborn died due to pulmonary hypertension and respiratory insufficiency. The thoracoamniotic shunt\'s effect on fetal circulation and the mechanisms of NIH in the event of RCDH are still unclear. Due to the high mortality rate of this condition and its poorer outcomes compared to left-sided defects, shunting cannot be considered an efficient attempt to improve fetal and neonatal survival rates to date. A close relationship between the amount of lymphatic effacement and cardiac function is clear, but further studies are needed to provide more information about this severe condition and its treatment.

Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero.
We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation.
In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks\' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared.
From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group.
Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.

BACKGROUND: The modified myocardial performance index (mod-MPI) is a noninvasive Doppler-derived metric used to evaluate fetal cardiac function. However, the reference ranges for mod-MPI in normal fetuses are not clearly defined, which limits the use of this technology in fetuses with potential cardiac compromise. Thus, we aimed to perform a systematic review and meta-analysis of published mod-MPI reference ranges across gestation.
METHODS: The published literature was systematically searched, and all published articles in any language that provided values for the left ventricular mod-MPI obtained in low-risk, singleton fetuses were considered eligible for further review. All retrieved titles and abstracts were independently reviewed by two researchers. Mean and standard deviation by gestational week was extracted or calculated from published data. DerSimonian-Laird random-effects models were used to estimate pooled means and 95% confidence intervals (CIs).
RESULTS: The search resulted in 618 unique citations, of which 583 did not meet inclusion criteria, leaving 35 abstracts selected for full-text review. Review of the references of these 35 articles identified another 5 studies of interest. Of the 40 articles reviewed, six met inclusion criteria. There was significant heterogeneity seen in the mod-MPI results reported. Mod-MPI increased as pregnancy progressed in all studies. The pooled mean mod-MPI at 11 weeks\' gestation was 0.400 (95% CI 0.374-0.426) and increased to 0.585 (95% CI 0.533-0.637) at 41 weeks\' gestation. The increase was linear in 5 of 6 studies, while in 1 study, the mod-MPI was stable until 27 weeks\' gestation, and then increased throughout the third trimester. Despite all having trends increasing over pregnancy, there was no study in which all the weekly means fell within the pooled 95% CI.
CONCLUSIONS: While mod-MPI does increase over gestation, the true \"reference ranges\" for fetuses remain elusive. Future efforts to further optimize calculation of time intervals possibly via automation are desperately needed to allow for reproducibility of this potentially very useful tool to assess fetal cardiac function.

BACKGROUND: Maternal red blood cell alloimmunization during pregnancy can lead to hemolysis and various degrees of fetal anemia, which can be treated with intrauterine blood transfusion (IUT) to prevent adverse outcomes. Knowledge about fetal myocardial function and adaptation is limited. The aim of the present study was to measure fetal atrioventricular plane displacement before and after IUT and compare these measurements with previously established reference ranges.
METHODS: An observational study was conducted on pregnant women affected by red blood cell alloimmunization. Fetal echocardiography was performed before and after IUT. The atrioventricular plane displacement of the left and right ventricular walls and interventricular septum, described as mitral, septal, and tricuspid annular plane systolic excursion (MAPSE, SAPSE, and TAPSE, respectively), was assessed using color tissue Doppler imaging with automated analysis software. A Mann-Whitney U test was used to compare the z scores to the normal mean before and after IUT.
RESULTS: Twenty-seven fetuses were included. The mean z score for pre-IUT MAPSE was significantly increased compared with the reference ranges, +0.46 (95% confidence interval [CI] +0.17 to +0.75; p = 0.039), while the mean z scores for post-IUT SAPSE and TAPSE were significantly decreased, -0.65 (95% CI -1.11 to -0.19; p < 0.001) and -0.60 (95% CI -1.04 to -0.17; p = 0.003), respectively. The difference in atrioventricular plane displacement z scores before and after IUT was statistically significant in all three locations. The median difference between the pre-IUT and post-IUT z scores was -0.66 (95% CI -1.03 to -0.33, p < 0.001) for MAPSE, -1.05 (95% CI -1.43 to -0.61, p < 0.001) for SAPSE, and -0.60 (95% CI -1.19 to -0.01, p = 0.046) for TAPSE.
CONCLUSIONS: This study suggests that atrioventricular plane displacement, when determined using automated analysis software, may represent a quantitative parameter, describing fetal myocardial function and adaptation before and after IUT.