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Beat-by-beat maternal and fetal heart couplings were reported to be evident throughout the fetal development. However, it is still unknown whether maternal-fetal heartbeat coupling parameters are associated with fetal development, and the potential interrelationships. Therefore, this study aims to investigate the associations of coupling parameters with fetal gestational age by multivariate regression models. Ten min abdominal lead-based maternal and fetal ECG signals were collected from 16 healthy pregnant women with healthy singleton pregnancies (19-32 weeks). Maternal and Fetal Heart Rate Variability (MHRV and FHRV) values as well as maternal-fetal heart rate coupling (strength, measured by A) parameters at various coupling ratios (associated with different Maternal:Fetal heartbeat ratios of 1:2, 1:3, 2:3, 2:4, 3:4, and 3:5) were calculated. Based on those features stepwise multivariate regression models were constructed by validating against the gold standard gestational age identified by crown-rump length from doppler echocardiogram. Among all models, the best model (Root Mean Square Error, RMSE=1.92) was found to be significantly (p<0.05) associated with mean fetal heart rate, mean maternal heart rate, standard deviation of maternal heart rate, λ[1:3], λ[2:3], λ[2:4]. Correlation coefficients and Bland Altman plots were constructed to statistically validate the results. The model developed based on coupling parameters only, showed the second-best performance (RMSE=2.50). Therefore, combining maternal and fetal heart rate variability parameters with maternal-fetal heart rate coupling values (rather than considering FHRV or MHRV parameters only) is found to be better associated with fetal development.Clinical relevance- This is a brief additional statement on why this might be of interest to practicing clinicians. Example: This establishes the anesthetic efficacy of 10% intraosseous injections with epinephrine to positively influence cardiovascular function.

Introduction: Early detection and monitoring for malignant arrhythmias is fundamental to prenatal care in long QT syndrome (LQTS). Recently, we studied the feasibility of isolating the fetal electrocardiogram (fECG) and measuring electrocardiographic intervals with a noninvasive fECG device using blind source separation with reference signal. Our aim was to evaluate the ability of fECG to diagnose LQTS., Case Presentations: We identified 3 cases of clinically suspected LQTS based on fetal echocardiogram (2 had sinus bradycardia, 1 had second-degree atrioventricular block with negative maternal anti-SSA/SSB antibody titers). With institutional review board approval, these patients were prospectively enrolled for fECG acquisition. Offline post-processing generated fECG waveforms and calculated QT intervals. Case 1 and 3 had a maternal history of LQTS. Two of the three fetuses with suspected LQTS had confirmed LQTS by postnatal ECG and genetic testing. FECG was able to identify a prolonged corrected QT interval in both cases. One of these also had fetal magnetocardiography (fMCG), which yielded similar findings to the fECG. The third fetus had a normal fECG; fMCG and postnatal ECG were also normal., Conclusions: In 3 cases, fECG findings corroborated the diagnosis of LQTS. Noninvasive fECG may offer a novel method for fECG that is portable and more clinically accessible., (© 2020 S. Karger AG, Basel.)

Background: Clinicians rely on age- and size-specific measures of cardiac structures to diagnose cardiac disease. No universally accepted normative data exist for fetal cardiac structures, and most fetal cardiac centers do not use the same standards. The aim of this study was to derive predictive models for Z scores for 13 commonly evaluated fetal cardiac structures using a large heterogeneous population of fetuses without structural cardiac defects., Methods: The study used archived normal fetal echocardiograms in representative fetuses aged 12 to 39 weeks. Thirteen cardiac dimensions were remeasured by a blinded echocardiographer from digitally stored clips. Studies with inadequate imaging views were excluded. Regression models were developed to relate each dimension to estimated gestational age (EGA) by dates, biparietal diameter, femur length, and estimated fetal weight by the Hadlock formula. Dimension outcomes were transformed (e.g., using the logarithm or square root) as necessary to meet the normality assumption. Higher order terms, quadratic or cubic, were added as needed to improve model fit. Information criteria and adjusted R 2 values were used to guide final model selection., Results: Each Z-score equation is based on measurements derived from 296 to 414 unique fetuses. EGA yielded the best predictive model for the majority of dimensions; adjusted R 2 values ranged from 0.72 to 0.893. However, each of the other highly correlated (r > 0.94) biometric parameters was an acceptable surrogate for EGA. In most cases, the best fitting model included squared and cubic terms to introduce curvilinearity., Conclusions: For each dimension, models based on EGA provided the best fit for determining normal measurements of fetal cardiac structures. Nevertheless, other biometric parameters, including femur length, biparietal diameter, and estimated fetal weight provided results that were nearly as good. Comprehensive Z-score results are available on the basis of highly predictive models derived from gestational age or other biometrics as preferable for clinical reasons. These results supplant current equations and will provide a foundation for future multicenter collaborations., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: Alterations in myocardial strain can identify cardiac dysfunction and can be measured in the mid-gestation fetus. This study evaluates feasibility of strain measurements in early fetuses and establishes normal early fetal strain values., Methods: Normal fetal echocardiograms were reviewed for image adequacy for strain measurements in 12- to 14-week gestation fetuses. Two readers performed independent strain measurements. Values were compared with data from 40 normal second trimester fetuses., Results: Strain evaluation could be attempted in 36 of 53 (68%) of first trimester echocardiograms (mean gestation 13.4 weeks); excessive motion or inadequate imaging planes precluded tracking analysis in the remainder. Strain measurements were feasible in 19 of 53 fetuses (36%, or 53% of those in whom tracking was attempted). Peak systolic global longitudinal left ventricular (RV) and right ventricular (LV) strain were similar (LV = -13.9 ± 5.7%, RV = -14.4 ± 5.5%, p = 0.7). RV strain was higher in first trimester fetuses compared with second trimester normals (p = 0.003). Intraobserver and interobserver agreement were moderate to strong for peak global LV and RV strain but poor for regional basal and mid-septal segments., Conclusions: Strain measurements were feasible in one-third of retrospectively assessed early fetal echocardiograms. Global longitudinal strain may be higher in earlier than mid-gestation fetuses. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

Cardiac rhythm is an essential component of fetal cardiac evaluation. The Monica AN24 is a fetal heart rate monitor that may provide a quick, inexpensive modality for obtaining a noninvasive fetal electrocardiogram (fECG) in a clinical setting. The fECG device has the ability to acquire fECG signals and allow calculation of fetal cardiac time intervals between 16- and 42-week gestational age (GA). We aimed to demonstrate the feasibility of fECG acquisition in a busy fetal cardiology clinic using the Monica fetal heart rate monitor. This is a prospective observational pilot study of fECG acquired from fetuses referred for fetal echocardiography. Recordings were performed for 5-15 min. Maternal signals were attenuated and fECG averaged. fECG and fetal cardiac time intervals (PR, QRS, RR, and QT) were evaluated by two cardiologists independently and inter-observer reliability was assessed using intraclass coefficient (ICC). Sixty fECGs were collected from 50 mothers (mean GA 28.1 ± 6.1). Adequate signal-averaged waveforms were obtained in 20 studies with 259 cardiac cycles. Waveforms could not be obtained between 26 and 30 weeks. Fetal cardiac time intervals were measured and were reproducible for PR (ICC = 0.89; CI 0.77-0.94), QRS (ICC = 0.79; CI 0.51-0.91), and RR (ICC = 0.77; CI 0.53-0.88). QT ICC was poor due to suboptimal T-wave tracings. Acquisition of fECG and measurement of fetal cardiac time intervals is feasible in a clinical setting between 19- and 42-week GA, though tracings are difficult to obtain, especially between 26 and 30 weeks. There was high reliability in fetal cardiac time intervals measurements, except for QT. The device may be useful for assessing atrioventricular/intraventricular conduction in fetuses from 20 to 26 and >30 weeks. Techniques to improve signal acquisition, namely T-wave amplification, are ongoing.

Background: Mouse mutants are used to model human congenital cardiovascular disease. Few studies exist comparing normal cardiovascular development in mice vs. humans. We carried out a systematic comparative analysis of mouse and human fetal cardiovascular development., Methods: Episcopic fluorescence image capture (EFIC) was performed on 66 wild-type mouse embryos from embryonic day (E) 9.5 to birth; 2-dimensional and 3-dimensional datasets were compared with EFIC and magnetic resonance images from a study of 52 human fetuses (Carnegie stage 13-23)., Results: Time course of atrial, ventricular, and outflow septation were outlined and followed a similar sequence in both species. Bilateral venae cavae and prominent atrial appendages were seen in the mouse fetus; in human fetuses, atrial appendages were small, and a single right superior vena cava was present. In contrast to humans with separate pulmonary vein orifices, a pulmonary venous confluence with one orifice enters the left atrium in mice., Conclusion: The cardiac developmental sequences observed in mouse and human fetuses are comparable, with minor differences in atrial and venous morphology. These comparisons of mouse and human cardiac development strongly support that mouse morphogenesis is a good model for human development.

Objective: To describe international surveillance and treatment strategies for managing anti-SSA/Ro autoantibody positive pregnancies. Study Design: An electronic REDCap questionnaire was distributed to Fetal Heart Society and North American Fetal Therapy Network members which queried institution-based risk stratification, surveillance methods/frequency, conduction abnormality treatments, and postnatal anti-SSA/Ro pregnancy assessment. Results: 101 responses from 59 centers (59% US, 17% international) were collected. Most (79%) do not risk stratify pregnancies by anti-SSA/Ro titer; those that do use varied cutoff values. Many pregnant rheumatology patients are monitored for cardiac abnormalities regardless of maternal anti-SSA/Ro status. Surveillance strategies were based on maternal factors (anti-SSA/Ro status 85%, titer 25%, prior affected child 79%) and monitoring durations varied. Most respondents treat 2° and 3° fetal atrioventricular block, commonly with dexamethasone and/or IVIG. Conclusions: Wide variation exists in current fetal cardiac surveillance and treatment for anti-SSA/Ro autoantibody positive pregnancies, highlighting the need for evidence-based protocols to optimize care. [ABSTRACT FROM AUTHOR]

Background: Prenatal detection (PND) has benefits for infants with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), but associations between sociodemographic and geographic factors with PND have not been sufficiently explored. This study evaluated whether socioeconomic quartile (SEQ), public insurance, race and ethnicity, rural residence, and distance of residence (distance and driving time from a cardiac surgical center) are associated with the PND or timing of PND, with a secondary aim to analyze differences between the United States and Canada.Methods: In this retrospective cohort study, fetuses and infants <2 months of age with HLHS or TGA admitted between 2012 and 2016 to participating Fetal Heart Society Research Collaborative institutions in the United States and Canada were included. SEQ, rural residence, and distance of residence were derived using maternal census tract from the maternal address at first visit. Subjects were assigned a SEQ z score using the neighborhood summary score or Canadian Chan index and separated into quartiles. Insurance type and self-reported race and ethnicity were obtained from medical charts. We evaluated associations among SEQ, insurance type, race and ethnicity, rural residence, and distance of residence with PND of HLHS and TGA (aggregate and individually) using bivariate analysis with adjusted associations for confounding variables and cluster analysis for centers.Results: Data on 1862 subjects (HLHS: n=1171, 92% PND; TGA: n=691, 58% PND) were submitted by 21 centers (19 in the United States). In the United States, lower SEQ was associated with lower PND in HLHS and TGA, with the strongest association in the lower SEQ of pregnancies with fetal TGA (quartile 1, 0.78 [95% CI, 0.64-0.85], quartile 2, 0.77 [95% CI, 0.64-0.93], quartile 3, 0.83 [95% CI, 0.69-1.00], quartile 4, reference). Hispanic ethnicity (relative risk, 0.85 [95% CI, 0.72-0.99]) and rural residence (relative risk, 0.78 [95% CI, 0.64-0.95]) were also associated with lower PND in TGA. Lower SEQ was associated with later PND overall; in the United States, rural residence and public insurance were also associated with later PND.Conclusions: We demonstrate that lower SEQ, Hispanic ethnicity, and rural residence are associated with decreased PND for TGA, with lower SEQ also being associated with decreased PND for HLHS. Future work to increase PND should be considered in these specific populations. [ABSTRACT FROM AUTHOR]

Objective. To assess the prevalence of cardiac abnormalities in fetuses of women with clinical or serologic evidence of systemic lupus erythematosus (SLE). Methods. A retrospective review of fetal echocardiograms performed secondary to maternal SLE or connective tissue antibodies with or without fetal complete heart block (CHB) was performed to evaluate the prevalence of fetal structural heart disease, valve regurgitation, abnormal ventricular function, pericardial effusion, endocardial fibroelastosis and rhythm abnormalities. Results. Forty-one fetuses were studied. One fetal demise occurred. Three fetuses had structural abnormalities, including d-transposition of the great arteries (n = 1) and pulmonic stenosis (n = 2). Seventeen fetuses had valve regurgitation. The prevalence of valve regurgitation was: tricuspid (n = 15), mitral (n = 6), pulmonic (n = 4) and aortic (n = 2). Two fetuses with pulmonic insufficiency had pulmonic stenosis. Four fetuses had CHB, one of which developed atrial flutter. Prolongation of the mechanical AV interval occurred in five fetuses; none developed CHB. Conclusions. In addition to CHB and myocardial dysfunction, structural heart defects occur in fetuses of women with serologic or clinical evidence of SLE. In our series, this occurred more frequently than reported for the general population. Valve regurgitation was present in all fetuses with CHB and many in sinus rhythm and may represent cardiac inflammation. Pulmonic insufficiency in utero may be a marker for a structural valve abnormality. [ABSTRACT FROM AUTHOR]