Cardiac remodeling from the fetus to adulthood.

Prenatal cardiac remodeling refers to in utero changes in the fetal heart that occur as a response to an adverse intrauterine environment. In this article, we will review the main mechanisms leading to cardiac remodeling and dysfunction, summarizing and describing the major pathological conditions that have been reported to be related to this in utero plastic adaptive process. We will also recap the current evidence regarding the persistence of fetal cardiac remodeling and dysfunction, both in infancy and later in adult life. Moreover, we will discuss primary, secondary, and tertiary preventive measures and future clinical and research aspects.

Intra- and interobserver reproducibility of second trimester ultrasound cervical length measurement in a general population.

OBJECTIVES: To evaluate the reproducibility of ultrasound cervical length (CL) measurement at the second trimester. METHODS: A set of 565 cervical ultrasound images were collected at 19 + 0-24 + 6 weeks' gestation. Two senior maternal-fetal specialists measured CL in each image on three occasions 2 weeks apart. In the interval between the first and following two measures, the clinicians reviewed 20 images together to agree on the criteria for measurement. Measurements were analyzed for intra- and inter-observer disagreement. The robustness of patient classification when CL measure was used with different cutoff thresholds was analyzed. RESULTS: Average intra-observer deviation was 2.8 mm for clinician 1 and 3.7 mm for clinician 2. Inter-observer deviation among the two clinicians was 5.2 and 3.2 mm before and after reviewing measurement criteria together. When cutoffs were used to classify as "short" cervix, disagreement ranged from 22 to 70% depending on operator and threshold used. CONCLUSION: Ultrasound CL measurements by experts showed moderate intra- and inter-observer reproducibility. The use of specific cutoffs to classify patients as high or low risk resulted in wide disagreements. The results stress the importance of training and quality assessments on considering universal screening application of CL measurement.

Analysis of maturation features in fetal brain ultrasound via artificial intelligence for the estimation of gestational age.

BACKGROUND: Optimal prenatal care relies on accurate gestational age dating. After the first trimester, the accuracy of current gestational age estimation methods diminishes with increasing gestational age. Considering that, in many countries, access to first trimester crown rump length is still difficult owing to late booking, infrequent access to prenatal care, and unavailability of early ultrasound examination, the development of accurate methods for gestational age estimation in the second and third trimester of pregnancy remains an unsolved challenge in fetal medicine. OBJECTIVE: This study aimed to evaluate the performance of an artificial intelligence method based on automated analysis of fetal brain morphology on standard cranial ultrasound sections to estimate the gestational age in second and third trimester fetuses compared with the current formulas using standard fetal biometry. STUDY DESIGN: Standard transthalamic axial plane images from a total of 1394 patients undergoing routine fetal ultrasound were used to develop an artificial intelligence method to automatically estimate gestational age from the analysis of fetal brain information. We compared its performance-as stand alone or in combination with fetal biometric parameters-against 4 currently used fetal biometry formulas on a series of 3065 scans from 1992 patients undergoing second (n=1761) or third trimester (n=1298) routine ultrasound, with known gestational age estimated from crown rump length in the first trimester. RESULTS: Overall, 95% confidence interval of the error in gestational age estimation was 14.2 days for the artificial intelligence method alone and 11.0 when used in combination with fetal biometric parameters, compared with 12.9 days of the best method using standard biometrics alone. In the third trimester, the lower 95% confidence interval errors were 14.3 days for artificial intelligence in combination with biometric parameters and 17 days for fetal biometrics, whereas in the second trimester, the 95% confidence interval error was 6.7 and 7, respectively. The performance differences were even larger in the small-for-gestational-age fetuses group (14.8 and 18.5, respectively). CONCLUSION: An automated artificial intelligence method using standard sonographic fetal planes yielded similar or lower error in gestational age estimation compared with fetal biometric parameters, especially in the third trimester. These results support further research to improve the performance of these methods in larger studies.

Mid-trimester prediction of spontaneous preterm birth with automated cervical quantitative ultrasound texture analysis and cervical length: a prospective study.

The objective of this study was to evaluate a novel automated test based on ultrasound cervical texture analysis to predict spontaneous Preterm Birth (sPTB) alone and in combination with Cervical Length (CL). General population singleton pregnancies between 18 + 0 and 24 + 6 weeks' gestation were assessed prospectively at two centers. Cervical ultrasound images were evaluated and the occurrence of sPTB before weeks 37 + 0 and 34 + 0 were recorded. CL was measured on-site. The automated texture analysis test was applied offline to all images. Their performance to predict the occurrence of sPTB before 37 + 0 and 34 + 0 weeks was evaluated separately and in combination on 633 recruited patients. AUC for sPTB prediction before weeks 37 and 34 respectively were as follows: 55.5% and 65.3% for CL, 63.4% and 66.3% for texture analysis, 67.5% and 76.7% when combined. The new test improved detection rates of CL at similar low FPR. Combining the two increased detection rate compared to CL alone from 13.0 to 30.4% for sPTB < 37 and from 14.3 to 42.9% sPTB < 34. Texture analysis of cervical ultrasound improved sPTB detection rate compared to cervical length for similar FPR, and the two combined together increased significantly prediction performance. This results should be confirmed in larger cohorts.

Atrioventricular plane displacement versus mitral and tricuspid annular plane systolic excursion: A comparison between cardiac magnetic resonance and M-mode echocardiography.

INTRODUCTION: Both echocardiography and CMR imaging are used to quantify longitudinal function. Inter-method variability for mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursion, and variability between directly measured MAPSE and TAPSE and as based on atrioventricular plane displacement (AVPD) analysis by CMR, are, however, not known. This study, therefore, assessed inter-method variability and variability between annular plane systolic excursion and AVPD-based values in a healthy adult population. METHODS: Echocardiography and CMR were performed in 111 adults (35 [32-38] years). Method comparisons were assessed with Deming regression, Bland-Altman analysis and coefficient of variation. Observer reproducibility was assessed by the concordance correlation coefficient. RESULTS: Echocardiography and semi-automatic CMR agreed on MAPSE (17 ± 2 mm vs. 17 ± 2 mm, p = 0.1) and TAPSE (25 ± 3 mm vs. 25 ± 3 mm, p = 0.5), correlated highly between methods (fitted-slope 1.22 [95% CI 1.07-1.38] and 1.12 [95% CI 0.95-1.29]) and showed low bias (0.42 [95% CI - 2.05 to 2.88] and - 0.18 [95% CI - 4.78 to 4.43]). Intra-/inter-observer reproducibility was high for both methods for both MAPSE (echocardiography 0.96/0.86; CMR 0.87/0.85) and TAPSE (echocardiography 0.96/0.95; CMR 0.97/0.96). MAPSE (16 ± 2 mm vs. 17 ± 2 mm; p < 0.001) and TAPSE (24 ± 3 vs. 25 ± 3 mm; p < 0.001) based on AVPD were similar but statistically different compared with semi-automatic CMR. CONCLUSIONS: Echocardiography and semi-automatic CMR have low variability and provide similar values for MAPSE and TAPSE and are thus interchangeable for follow-up studies. Lateral values based on tracked data from AVPD analysis are not clinically significantly different and could be used as a representation of annular displacement.

Cardiac Remodeling and Hypertension in HIV-Uninfected Infants Exposed in utero to Antiretroviral Therapy.

BACKGROUND: We aimed to assess the postnatal pattern of cardiovascular remodeling associated with intrauterine exposure to maternal HIV and antiretroviral treatment (ART). METHODS: Prospective cohort including 34 HIV-exposed uninfected (HEU) infants and 53 non-HIV-exposed infants were evaluated from fetal life up to 6 months postnatally. A cardiovascular evaluation was performed including echocardiography, blood pressure, and carotid intima media thickness (cIMT) measurement. RESULTS: ART regimens during pregnancy included 2 nucleoside reverse transcriptase inhibitors (Abacavir + Lamivudine (32.4%), Emtricitabine + Tenofovir (41.2%), and Zidovudine + Lamivudine (20.6%)). At 6 months of age, HIV-exposed uninfected infants showed thicker myocardial walls (septal wall thickness mean 5.02 mm (SD 0.85) vs 3.98 mm (0.86); P < .001), relative systolic dysfunction with decreased mitral ring displacement (8.57 mm (2.03) vs 10.34 mm (1.84); P = .002), and decreased tricuspid S' (9.71 cm/s (1.94) vs 11.54 cm/s (2.07); P = .003) together with relative diastolic dysfunction showed by prolonged left isovolumic relaxation time (58.57 ms (13.79) vs 47.94 (7.39); P < .001). Vascular assessment showed significantly higher systolic and diastolic blood pressure (102 mmHg (16.1) vs 80 mmHg (13.9); P < .001 and 64 mmHg (14.4) vs 55 mmHg (10.2); P = .045 respectively), with 50% of HIV-exposed children meeting criteria for hypertension vs 3.77% of the non-HIV-exposed group (P < .001) and thicker mean cIMT in the HIV-exposed group (0.62 µm (0.09) vs 0.51 µm (0.09); P = .015). CONCLUSIONS: Subclinical cardiac impairment together with higher blood pressure and thicker cIMT were observed in HIV-exposed infants at 6 months of age. Half of them presented hypertension. Our findings support a possible increased cardiovascular risk in HIV uninfected infants exposed in utero to ART.

Uncomplicated Monochorionic Twins: Two Normal Hearts Sharing One Placenta.

Cardiovascular dysfunction has been reported in complicated monochorionic diamniotic (MCDA) pregnancies; however, little is known whether hemodynamic changes occur in uncomplicated MCDA twins. A prospective observational study was conducted including 100 uncomplicated MCDA twins matched by gestational age to 200 low-risk singletons. Echocardiography was performed at 26-30 weeks gestation and cord blood B-type natriuretic peptide (BNP) was measured at delivery. In both groups, z-scores for echocardiographic parameters were within normal ranges; however the monochorionic group had larger atrial areas (mean (standard deviation) right atria-to-heart ratio: 17.0 (2) vs. 15.9 (1); p = 0.018; left atria-to-heart ratio: 17.0 (3) vs. 15.8 (2); p < 0.001) and signs of concentric hypertrophy (right relative wall thickness: 0.66 (0.12) vs. 0.56 (0.11); p < 0.001; left relative wall thickness: 0.69 (0.14) vs. 0.58 (0.12); p < 0.001). Longitudinal function was increased in twins, leading to higher tricuspid annular plane systolic excursion (6.9 mm (0.9) vs. 5.9 mm (0.7); p < 0.001) and mitral annular plane systolic excursion (4.9 mm (0.8) vs. 4.4 mm (1.1); p < 0.001. BNP levels at birth were also higher in MCDA twins (median [interquartile range]: 20.81 pg/mL [16.69-34.01] vs. 13.14 pg/mL [9.17-19.84]; p < 0.001). Thus, uncomplicated MCDA fetuses have normal cardiac shape and function, but signs of cardiac adaptation were identified by echocardiographic and biochemical parameters, when compared with singletons.

Segmentation of the placenta and its vascular tree in Doppler ultrasound for fetal surgery planning.

PURPOSE: Twin-to-twin transfusion syndrome (TTTS) is a serious condition that occurs in about 10-15% of monochorionic twin pregnancies. In most instances, the blood flow is unevenly distributed throughout the placenta anastomoses leading to the death of both fetuses if no surgical procedure is performed. Fetoscopic laser coagulation is the optimal therapy to considerably improve co-twin prognosis by clogging the abnormal anastomoses. Notwithstanding progress in recent years, TTTS surgery is highly risky. Computer-assisted planning of the intervention can thus improve the outcome. METHODS: In this work, we implement a GPU-accelerated random walker (RW) algorithm to detect the placenta, both umbilical cord insertions and the placental vasculature from Doppler ultrasound (US). Placenta and background seeds are manually initialized in 10-20 slices (out of 245). Vessels are automatically initialized in the same slices by means of Otsu thresholding. The RW finds the boundaries of the placenta and reconstructs the vasculature. RESULTS: We evaluate our semiautomatic method in 5 monochorionic and 24 singleton pregnancies. Although satisfactory performance is achieved on placenta segmentation (Dice ≥ 84.0%), some vascular connections are still neglected due to the presence of US reverberation artifacts (Dice ≥ 56.9%). We also compared inter-user variability and obtained Dice coefficients of ≥ 76.8% and ≥ 97.42% for placenta and vasculature, respectively. After a 3-min manual initialization, our GPU approach speeds the computation 10.6 times compared to the CPU. CONCLUSIONS: Our semiautomatic method provides a near real-time user experience and requires short training without compromising the segmentation accuracy. A powerful approach is thus presented to rapidly plan the fetoscope insertion point ahead of TTTS surgery.

TTTS-STgan: Stacked Generative Adversarial Networks for TTTS Fetal Surgery Planning Based on 3D Ultrasound.

Twin-to-twin transfusion syndrome (TTTS) is characterized by an unbalanced blood transfer through placental abnormal vascular connections. Prenatal ultrasound (US) is the imaging technique to monitor monochorionic pregnancies and diagnose TTTS. Fetoscopic laser photocoagulation is an elective treatment to coagulate placental communications between both twins. To locate the anomalous connections ahead of surgery, preoperative planning is crucial. In this context, we propose a novel multi-task stacked generative adversarial framework to jointly learn synthetic fetal US generation, multi-class segmentation of the placenta, its inner acoustic shadows and peripheral vasculature, and placenta shadowing removal. Specifically, the designed architecture is able to learn anatomical relationships and global US image characteristics. In addition, we also extract for the first time the umbilical cord insertion on the placenta surface from 3D HD-flow US images. The database consisted of 70 US volumes including singleton, mono- and dichorionic twins at 17-37 gestational weeks. Our experiments show that 71.8% of the synthesized US slices were categorized as realistic by clinicians, and that the multi-class segmentation achieved Dice scores of 0.82 ± 0.13, 0.71 ± 0.09, and 0.72 ± 0.09, for placenta, acoustic shadows, and vasculature, respectively. Moreover, fetal surgeons classified 70.2% of our completed placenta shadows as satisfactory texture reconstructions. The umbilical cord was successfully detected on 85.45% of the volumes. The framework developed could be implemented in a TTTS fetal surgery planning software to improve the intrauterine scene understanding and facilitate the location of the optimum fetoscope entry point.

Evaluation of deep convolutional neural networks for automatic classification of common maternal fetal ultrasound planes.

The goal of this study was to evaluate the maturity of current Deep Learning classification techniques for their application in a real maternal-fetal clinical environment. A large dataset of routinely acquired maternal-fetal screening ultrasound images (which will be made publicly available) was collected from two different hospitals by several operators and ultrasound machines. All images were manually labeled by an expert maternal fetal clinician. Images were divided into 6 classes: four of the most widely used fetal anatomical planes (Abdomen, Brain, Femur and Thorax), the mother's cervix (widely used for prematurity screening) and a general category to include any other less common image plane. Fetal brain images were further categorized into the 3 most common fetal brain planes (Trans-thalamic, Trans-cerebellum, Trans-ventricular) to judge fine grain categorization performance. The final dataset is comprised of over 12,400 images from 1,792 patients, making it the largest ultrasound dataset to date. We then evaluated a wide variety of state-of-the-art deep Convolutional Neural Networks on this dataset and analyzed results in depth, comparing the computational models to research technicians, which are the ones currently performing the task daily. Results indicate for the first time that computational models have similar performance compared to humans when classifying common planes in human fetal examination. However, the dataset leaves the door open on future research to further improve results, especially on fine-grained plane categorization.

SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation.

Sirtuin 3 (SIRT3) is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress. Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances. In this study, we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells. SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1. Consistent with this, SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α. Notably, these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1. Finally, we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter. These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy, heart failure, and diabetic cardiomyopathy, our results point to SIRT3 as a potential target for treating these diseases.

Nomograms of Fetal Cardiac Dimensions at 18-41 Weeks of Gestation.

OBJECTIVE: There is a need for standardized reference values for cardiac dimensions in prenatal life. The objective of the present study was to construct nomograms for fetal cardiac dimensions using a well-defined echocardiographic methodology in a low-risk population. METHODS: This is a prospective cohort study including 602 low-risk singleton pregnancies undergoing a standardized fetal echocardiography to accurately assess fetal cardiac, ventricular, and atrial dimensions. Parametric regressions were tested to model each measurement against gestational age from 18 to 41 weeks of gestation. RESULTS: Nomograms were constructed for fetal cardiac dimensions (transverse and longitudinal diameters and areas) of the whole heart, atria, and ventricles, as well as myocardial wall thicknesses. All dimensions showed a progressive increase with gestational age. The best model for most parameters was a second-degree linear polynomial. Fetal cardiac, ventricular, and atrial diameters and areas were successfully obtained in 98.6% of the fetuses, while myocardial wall thicknesses could be obtained in 96.5% of the population. The results showed excellent interobserver and intraobserver reproducibility (intraclass correlation coefficient, ICC > 0.811 and ICC > 0.957, respectively). CONCLUSIONS: We provide standardized and comprehensively evaluated reference values for fetal cardiac morphometric parameters across gestation in a low-risk population. These no mograms would enable the early identification of different patterns of fetal cardiac remodeling.

Nomograms of Fetal Right Ventricular Fractional Area Change by 2D Echocardiography.

OBJECTIVES: Fetal right ventricular (RV) function assessment is challenging due to the RV geometry and limitations of in utero assessment. Postnatally, 2D echocardiographic RV fractional area change (FAC) is used to assess RV global systolic function by calculating the percentage of change in RV area from systole to diastole. Reports on FAC are scarce in prenatal life, and nomograms throughout pregnancy are not available. Our aims were (1) to study prenatal RV FAC feasibility and reproducibility and (2) to construct nomograms for RV FAC and end-diastolic (ED) and end-systolic (ES) RV areas from 18 to 41 weeks of gestation. METHODS: Prospective cohort study including 602 low-risk singleton pregnancies undergoing a fetal echocardiography from 18 to 41 weeks of gestation. RV ED and ES areas were measured following standard recommendations for ventricular dimensions and establishing strict landmarks to identify the different phases of the cardiac cycle. RV FAC was calculated as: ([ED area - ES area]/ED area) × 100. RV FAC intra- and inter-observer reproducibility was evaluated in 45 fetuses by calculating the intraclass correlation coefficient (ICC). Parametric regressions were tested to model each parameter against gestational age (GA) and estimated fetal weight (EFW). RESULTS: RV areas and FAC were successfully obtained in ∼99% of fetuses with acceptable reproducibility throughout gestation (RV ED area inter-observer ICC [95% CI] 0.96 [0.93-0.98], RV ES area 0.97 [0.94-0.98], and FAC 0.69 [0.44-0.83]). Nomograms were constructed for RV ED and ES areas and FAC. RV areas showed a quadratic and logarithmic increase with GA and EFW, respectively. In contrast, RV FAC showed a slight quadratic decrease throughout gestation (mean RV FAC ranged from 36% at 18 weeks of gestation [10-90th centiles: 25-47%, respectively] to 29% at 41 weeks [10-90th centiles: 18-40%, respectively]). The best models for RV areas and FAC were a second-degree polynomial. CONCLUSIONS: RV FAC is a feasible and reproducible parameter to assess RV global systolic function in fetal life. We provide reference ranges adjusted by GA and EFW that can be used as normal references for the assessment of RV function in prenatal conditions.

TTTS-GPS: Patient-specific preoperative planning and simulation platform for twin-to-twin transfusion syndrome fetal surgery.

Twin-to-twin transfusion syndrome (TTTS) is a serious condition that may occur in pregnancies when two or more fetuses share the same placenta. It is characterized by abnormal vascular connections in the placenta that cause blood to flow unevenly between the babies. If left untreated, perinatal mortality occurs in 90% of cases, whilst neurological injuries are still present in TTTS survivors. Minimally invasive fetoscopic laser surgery is the standard and optimal treatment for this condition, but is technically challenging and can lead to complications. Acquiring and maintaining the required surgical skills need consistent practice, and a steep learning curve. An accurate preoperative planning is thus vital for complex TTTS cases. To this end, we propose the first TTTS fetal surgery planning and simulation platform. The soft tissue of the mother, the uterus, the umbilical cords, the placenta and its vascular tree are segmented and registered automatically from magnetic resonance imaging and 3D ultrasound using computer vision and deep learning techniques. The proposed state-of-the-art technology is integrated into a flexible C++ and MITK-based application to provide a full exploration of the intrauterine environment by simulating the fetoscope camera as well as the laser ablation, determining the correct entry point, training doctors' movements and trajectory ahead of operation, which allows improving upon current practice. A comprehensive usability study is reported. Experienced surgeons rated highly our TTTS planner and simulator, thus being a potential tool to be implemented in real and complex TTTS surgeries.

Comparison of 2D versus M-mode echocardiography for assessing fetal myocardial wall thickness.

OBJECTIVE: M-mode and 2D have been proposed for evaluating fetal myocardial thickness. However, studies comparing the performance of both modalities are lacking. We aimed to compare 2D versus M-mode reproducibility for assessing myocardial wall thicknesses. METHODS: A prospective study including 45 healthy fetuses from low-risk pregnancies evaluated between 18 and 41 weeks of gestation. Left and right ventricular free-wall and septal myocardial thicknesses were measured at end-diastole (ED) and end-systole (ES) in transverse 4-chamber view using 2D and M-mode. Intra- and interobserver reproducibility was evaluated by the concordance correlation coefficient (CCC). Both techniques were compared by t-test of the CCC. RESULTS: 2D and M-mode demonstrated excellent and similar intraobserver repeatability, with the best concordance in ES septal thickness (M-mode CCC 0.956 versus 2D-mode CCC 0.914). Interobserver reproducibility demonstrated also a high concordance, optimal in ES left ventricular free wall (M-mode 0.925 versus 2 D 0.855). Comparison of both techniques demonstrated a high concordance in all measurements, except for ED septal thickness with better reproducibility using M-mode (CCC 0.954 versus 0.847, p = .017). CONCLUSIONS: 2D and M-mode can be used in a reproducible manner for measuring fetal myocardial thickness, with a slightly better performance of M-mode for assessing ED septal wall thickness.

Characterizing cardiac dysfunction in fetuses with left congenital diaphragmatic hernia.

OBJECTIVE: To evaluate cardiac function by conventional echocardiography and tissue Doppler imaging in fetuses with left congenital diaphragmatic hernia (CDH). METHODS: Conventional echocardiography (myocardial performance index, ventricular filling velocities, and E/A ratios) and tissue Doppler imaging (annular myocardial peak velocities, E/E' and E'/A' ratios) in mitral, septal, and tricuspid annulus were evaluated in a cohort of 31 left-sided CDH fetuses and compared with 75 controls matched for gestational age 2:1. RESULTS: In comparison to controls, CDH fetuses had prolonged isovolumetric time periods (isovolumetric contraction time 35 ms vs 28 ms, P < .001), with higher myocardial performance index (0.49 vs 0.42, P < .001) and tricuspid E/A ratios (0.77 vs 0.72, P = .033). Longitudinal function assessed by tissue Doppler showed signs of impaired relaxation (mitral lateral A' 8.0 vs 10.1 cm/s, P < .001 and an increased mitral lateral E'/A' ratio 0.93 vs 0.78, P < .001) in the CDH fetuses as compared with controls, with preserved systolic function. CONCLUSION: Left CDH fetuses show echocardiographic signs of diastolic dysfunction, probably secondary to fetal heart compression, maintaining a preserved systolic function.

Remodeling of the cardiovascular circulation in fetuses of mothers with diabetes: A fetal computational model analysis.

AIMS: Myocardial structural and functional abnormalities are known to occur in fetuses of mothers with diabetes mellitus (FMDM). The main aim of this investigation was to explore the cardiovascular circulatory patterns in FMDM using a validated lumped computational model of the cardiovascular system. METHODS: This was a multi-institutional study involving FMDM compared to fetuses of maternal controls (FC). Fetal echocardiographic Doppler data from left and right ventricular outflow tracts, aortic isthmus, middle cerebral and umbilical arteries were fitted into a validated fetal circulation computational model to estimate patient-specific placental and vascular properties. Non-parametric comparisons were made between resistances, compliances and flows in the brain and placenta in FMDM and FC. RESULTS: Data from 23 FMDM and 31 FC were fitted into the model. In FMDM, compared to FC, placental relative resistance was lower (0.59 ±â€¯0.50 versus 0.91 ±â€¯0.41; p < .05) with higher brain relative resistance (2.36 ±â€¯1.65 versus 1.60 ±â€¯0.85; p < .05). Middle cerebral artery flow was lower in FMDM than FC (0.12 ±â€¯0.14 vs. 0.27 ±â€¯0.21 ml/min; p 0.04) with a lower cerebral-placental flow ratio. Combined stroke volume was lower in FMDM (3.65 ±â€¯2.05 ml) than FC (4.97 ±â€¯2.45 ml) (p 0.04). CONCLUSIONS: Blood flow is redistributed in FMDM to the placenta, away from the brain. This alteration may play a role in the postnatal health of these fetuses.

Understanding the Aortic Isthmus Doppler Profile and Its Changes with Gestational Age Using a Lumped Model of the Fetal Circulation.

OBJECTIVE: The aortic isthmus (AoI) blood flow has a characteristic shape with a small end-systolic notch observed during the third trimester of pregnancy. However, what causes the appearance of this notch is not fully understood. We used a lumped model of the fetal circulation to study the possible factors causing the end-systolic notch and the changes of AoI flow through gestation. METHODS: A validation of the model was performed by fitting patient-specific data from two normal fetuses. Then, different parametric analyses were performed to evaluate the major determinants of the appearance of the end-systolic notch. The changes in the AoI flow profile through gestation were assessed. RESULTS: Our model allows to simulate the AoI waveform. The delay in the onset of ejection together with the longer ejection duration of the right ventricle are the most relevant factors in the origin of the notch. It appears around 25 weeks of gestation and becomes more pronounced with advancing gestation. DISCUSSION: We demonstrated that the end-systolic notch on the AoI flow occurs mainly as a result of a delayed and longer ejection of the right ventricle. Our findings improve the understanding of hemodynamic changes in the fetal circulation and the interpretation of clinical imaging.

Zidovudine treatment in HIV-infected pregnant women is associated with fetal cardiac remodelling.

OBJECTIVE: To evaluate the cardiac structure and function of the fetuses of pregnant women with HIV infection on combined antiretroviral treatment (cART) and the HIV-related and nonrelated determinants of abnormal findings. DESIGN: A prospective cohort study including 42-noninfected fetuses from HIV pregnant women on cART and 84 fetuses from non-HIV-infected women. METHODS: Fetal echocardiography was performed at 26-32 weeks of pregnancy to assess cardiac structure and function. The impact of maternal and perinatal factors on fetal cardiac remodelling was evaluated by multivariate regression analysis. RESULTS: Fetuses from HIV pregnant women on cART presented larger hearts and pericardial effusion together with thicker myocardial septal walls (mean 3.56 mm (SD 0.88) vs non-HIV mean 2.75 mm (SD 0.77); P = 0.002) and smaller left ventricular cavities (10.81 mm (SD 2.28) vs 12.3 mm (SD 2.54); P = 0.033). Fetuses from HIV women also presented signs of systolic (mitral systolic annular peak velocity 5.85 cm/s (SD 0.77) vs non-HIV 6.25 cm/s (SD 0.97); P = 0.007) and diastolic (isovolumic relaxation time 52 ms (SD 8.91) vs non-HIV 45 ms (SD 7.98); P < 0.001) dysfunction. In the multivariate analysis, maternal treatment with zidovudine was the only factor significantly associated with fetal cardiac changes (P = 0.014). CONCLUSION: Fetuses from HIV-infected mothers on cART have cardiac remodelling and dysfunction, which might explain the cardiovascular changes described in childhood. Fetal cardiac remodelling was essentially associated with maternal treatment with zidovudine which challenges its use during pregnancy.