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BACKGROUND: Evidence remains limited about the association of maternal exposure to ambient fine particulate matter (airborne particles with an aerodynamic diameter ≤2.5 µm [PM2.5]) with fetal congenital heart defects (CHDs) in highly polluted regions, and few studies have focused on preconception exposure. METHODS: Using a nationwide surveillance-based case-control design in China, we examined the association between maternal exposure to PM2.5 during periconception (defined as 3 months before conception until 3 months into pregnancy) and risk of CHD in offspring. The study included 1 434 998 births involving 7335 CHDs from 2014 through 2017 on the basis of the National Population-Based Birth Defects Surveillance System, covering 30 provinces, municipalities, or municipal districts in China. We assigned maternal PM2.5 exposure during the periconception period to each participant using satellite-based PM2.5 concentrations at 1-km spatial resolution. Multilevel logistic regression models were used to calculate the multivariable-adjusted odds ratio and 95% CI for CHDs in offspring associated with maternal PM2.5 exposure, and the exposure–response association was investigated using restricted cubic spline analysis. Subgroup or sensitivity analyses were conducted to identify factors that may modify the association. RESULTS: The average maternal exposure to PM2.5 levels across all participants was 56.51 µg/m³ (range, 10.95 to 182.13 µg/m3). For each 10 µg/m³ increase in maternal PM2.5 exposure, the risk of CHDs in offspring was increased by 2% (odds ratio, 1.02 [95% CI, 1.00 to 1.05]), and septal defect was the most influenced subtype (odds ratio, 1.04 [95% CI, 1.01 to 1.08]). The effect of PM2.5 on CHD risk was more pronounced during the preconception period. Mothers <35 years of age, those living in northern China, and those living in low-income areas were more susceptible to PM2.5 exposure than their counterparts (all P<0.05). PM2.5 exposure showed a linear association with total CHDs or specific CHD types. CONCLUSIONS: High maternal PM2.5 exposure, especially during the preconception period, increases risk of certain types of CHD in offspring. These findings are useful for CHD prevention and highlight the public health benefits of improving air quality in China and other highly polluted regions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether manual rotation of fetuses in occiput posterior positions at full dilation increases the rate of spontaneous vaginal delivery.Methods: In an open, single-center, randomized controlled trial, patients with a term, singleton gestation, epidural analgesia, and ultrasonogram-confirmed occiput posterior position at the start of the second stage of labor were randomized to either manual rotation or expectant management. Our primary endpoint was the rate of spontaneous vaginal delivery. Secondary endpoints were operative vaginal delivery, cesarean delivery, and maternal and neonatal morbidity. Analyses were based on an intention-to-treat method. A sample size of 107 patients per group (n=214) was planned to detect a 20% increase in the percent of patients with a spontaneous vaginal delivery (assuming 60% without manual rotation vs 80% with manual rotation) with 90% power and alpha of 0.05.Results: Between February 2017 and January 2020, 236 patients were randomized to either manual rotation (n=117) or expectant management (n=119). The success rate of the manual rotation maneuver, defined by conversion to an anterior position as confirmed by ultrasonogram, was 68%. The rate of the primary endpoint did not differ between the groups (58.1% in manual rotation group vs 59.7% in expectant management group (risk difference -1.6; 95% CI -14.1 to 11.0). Manual rotation did not decrease the rate of operative vaginal delivery (29.9% in manual rotation group vs 33.6% in expectant management group (risk difference -3.7; 95% CI -16.6 to 8.2) nor the rate of cesarean delivery (12.0% in manual rotation group vs 6.7% in expectant management group (risk difference 5.3; 95% CI -2.2 to 12.6). Maternal and neonatal morbidity was also similar across the two groups.Conclusion: Manual rotation of occiput posterior positions at the start of second stage of labor does not increase the rate of vaginal delivery without instrumental assistance.Clinical Trial Registration: ClinicalTrials.gov, NCT03009435. [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]

Diabetes and obesity increase the risk of congenital anomalies, but the putative mechanisms of this increased risk are not fully elucidated. In this chapter, we delve into sonographic characteristics associated with diabetes and obesity, including fetal structural anomalies, functional cardiac alterations, and growth abnormalities. We will also discuss the technical challenges of imaging in the patient with diabesity and propose methodologies for optimizing imaging. Lastly, we will address the prevention of workplace-associated musculoskeletal disorders injury for sonographers. [ABSTRACT FROM AUTHOR]

Background: Endothelial cells (ECs) display considerable functional heterogeneity depending on the vessel and tissue in which they are located. Whereas these functional differences are presumably imprinted in the transcriptome, the pathways and networks that sustain EC heterogeneity have not been fully delineated.Methods: To investigate the transcriptomic basis of EC specificity, we analyzed single-cell RNA sequencing data from tissue-specific mouse ECs generated by the Tabula Muris consortium. We used a number of bioinformatics tools to uncover markers and sources of EC heterogeneity from single-cell RNA sequencing data.Results: We found a strong correlation between tissue-specific EC transcriptomic measurements generated by either single-cell RNA sequencing or bulk RNA sequencing, thus validating the approach. Using a graph-based clustering algorithm, we found that certain tissue-specific ECs cluster strongly by tissue (eg, liver, brain), whereas others (ie, adipose, heart) have considerable transcriptomic overlap with ECs from other tissues. We identified novel markers of tissue-specific ECs and signaling pathways that may be involved in maintaining their identity. Sex was a considerable source of heterogeneity in the endothelial transcriptome and we discovered Lars2 to be a gene that is highly enriched in ECs from male mice. We found that markers of heart and lung ECs in mice were conserved in human fetal heart and lung ECs. We identified potential angiocrine interactions between tissue-specific ECs and other cell types by analyzing ligand and receptor expression patterns.Conclusions: We used single-cell RNA sequencing data generated by the Tabula Muris consortium to uncover transcriptional networks that maintain tissue-specific EC identity and to identify novel angiocrine and functional relationships between tissue-specific ECs. [ABSTRACT FROM AUTHOR]

Use of intrapartum fetal heart rate (FHR) monitoring has had limited success in preventing hypoxic injury to neonates. One of the most common limitations of FHR interpretation is the failure to consider chronic and acute clinical factors that may increase the risk of evolving acidemia. This manuscript reviews common clinical factors that may affect the FHR and should be considered when determining the need for early intervention based on changes in the FHR. [ABSTRACT FROM AUTHOR]

Keywords: blood pressure; fetal heart; hypoxia; pregnancy; proteinuria EN blood pressure fetal heart hypoxia pregnancy proteinuria e47 e49 3 04/16/21 20210501 NES 210501 Hypertensive disorders complicate >10% of all pregnancies being the most prevalent complications worldwide. In female offspring from preeclampsia pregnancy, LV chambers were dilated (Figure [E]), and the fraction of shortening significantly reduced in comparison to female offspring from control pregnancy (Figure [E]). Chronic hypertension is defined by blood pressure higher than 140/90 mm Hg before pregnancy or before 20 weeks' gestation. [Extracted from the article]

Supplemental Digital Content is available in the text. Background: The adult mammalian cardiomyocytes lose their proliferative capacity, which is responsible for cardiac dysfunction and heart failure following injury. The molecular mechanisms underlying the attenuation of adult cardiomyocyte proliferation remain largely unknown. Because long noncoding RNAs (lncRNAs) have a critical role in the development of cardiovascular problems, we investigated whether lncRNAs have any role in the regulation of cardiomyocyte proliferation and cardiac repair. Methods: Using bioinformatics and initial analysis, we identified an lncRNA, named CPR (cardiomyocyte proliferation regulator), that has a potential regulatory role in cardiomyocyte proliferation. For in vivo experiments, we generated CPR knockout and cardiac-specific CPR-overexpressing mice. In isolated cardiomyocytes, we used adenovirus for silencing (CPR–small interfering RNA) or overexpressing CPR. To investigate the mechanisms of CPR function in cardiomyocyte proliferation, we performed various analyses including quantitative reverse transcription–polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), transcriptome analyses (microarray assay), RNA pull-down assay, and chromatin immunoprecipitation assay. Results: CPR level is comparatively higher in the adult heart than in the fetal stage. The silencing of CPR significantly increased cardiomyocyte proliferation in postnatal and adult hearts. Moreover, CPR deletion restored the heart function after myocardial injury, which was evident from increased cardiomyocyte proliferation, improvement of myocardial function, and reduced scar formation. In contrast, the neonatal cardiomyocyte proliferation and cardiac regeneration were remarkably suppressed in CPR-overexpressing mice or adeno-associated virus serotype 9–CPR—overexpressing heart. These results indicate that CPR acts as a negative regulator of cardiomyocyte proliferation and regeneration. Next, we found that CPR targets minichromosome maintenance 3, an initiator of DNA replication and cell cycle progression, to suppress cardiomyocyte proliferation. CPR silenced minichromosome maintenance 3 expression through directly interacting and recruiting DNMT3A to its promoter cysteine-phosphate-guanine sites, as evident from decreased minichromosome maintenance 3 promoter methylation and increased minichromosome maintenance 3 expression in CPR knocked-down cardiomyocytes and CPR knockout mouse heart. These results were confirmed in CPR-overexpressing cardiomyocytes and CPR-overexpressing mouse heart. Conclusions: Together, our findings identified that CPR is a suppressor of cardiomyocyte proliferation and indicated that lncRNAs take part in the regulation of cardiomyocyte proliferation and cardiac repair. Our study provides an lncRNA-based therapeutic strategy for effective cardiac repair and regeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although stillbirth is a significant health problem worldwide, the definitive cause of death remains elusive in many cases, despite detailed autopsy. In this study of partly explained and unexplained stillbirths, we used next-generation sequencing to examine an extended panel of 35 candidate genes known to be associated with ion channel disorders and sudden cardiac death. METHODS AND RESULTS: We examined tissue from 242 stillbirths (=22 weeks), including those where no definite cause of death could be confirmed after a full autopsy. We obtained high-quality DNA from 70 cases, which were then sequenced for a custom panel of 35 genes, 12 for inherited long- and short-QT syndrome genes (LQT1-LQT12 and SQT1-3), and 23 additional candidate genes derived from genome-wide association studies. We examined the functional significance of a selected variant by patch-clamp electrophysiological recording. No predicted damaging variants were identified in KCNQ1 (LQT1) or KCNH2 (LQT2). A rare putative pathogenic variant was found in KCNJ2 (LQT7) in 1 case, and several novel variants of uncertain significance were observed. The KCNJ2 variant (p. R40Q), when assessed by whole-cell patch clamp, affected the function of the channel. There was no significant evidence of enrichment of rare predicted damaging variants within any of the candidate genes. CONCLUSIONS: Although a causative link is unclear, 1 putative pathogenic and variants of uncertain significance variant resulting in cardiac channelopathies was identified in some cases of otherwise unexplained stillbirth, and these variants may have a role in fetal demise. [ABSTRACT FROM AUTHOR]

The article presents the study on the fetal and maternal characteristics and pregnancy and neonatal outcome data for fetal cardiac intervention (FCI) for fetuses with hypoplastic left heart syndrome and an intact or highly restrictive atrial septum (HLHS-IAS). It states that the study reflects areas of promise and improvement for high-risk patient group. It recommends continuation of FCI at select institutions to concentrate and standardize inventional approach and postnatal care.

This review presents a detailed discussion on recent trends in fetal cardiac imaging. Ultrasound technique which are most useful for clinical practice today and will likely change the approach to cardiac evaluation in the future are presented. [ABSTRACT FROM AUTHOR]

Background--The molecular regulation of heart development is regulated by cis- and trans-factors acting on the genome and epigenome. As a class of important regulatory RNAs, the role of long noncoding RNAs (lncRNAs) in human heart development is still poorly understood. Furthermore, factors that interact with lncRNAs in this process are not well characterized. Methods and Results--Using RNA sequencing, we systematically define the contrasting lncRNA expression patterns between fetal and adult hearts. We report that lncRNAs upregulated in adult versus fetal heart have different sequence features and distributions. For example, the adult heart expresses more sense lncRNAs compared with fetal heart. We also report the coexpression of lncRNAs and neighboring coding genes that have important functions in heart development. Importantly, the regulation of lncRNA expression during fetal to adult heart development seems to be due, in part, to the coordination of specific developmental epigenetic modifications, such as H3K4me1 and H3k4me3. The expression of promoter-associated lncRNAs in adult and fetal hearts also seems to be related to these epigenetic states. Finally, transcription factor-binding analysis suggests that lncRNAs are directly regulating cardiac gene expression during development. Conclusions--We provide a systematic analysis of lncRNA control of heart development that gives clues to the roles that specific lncRNAs play in fetal and adult hearts. [ABSTRACT FROM AUTHOR]

Background: Intramural ventricular septal defects (VSDs) are interventricular communications through right ventricular free wall trabeculations that can occur after repair of conotruncal anomalies. We assessed the prevalence of residual intramural VSDs and their effect on postoperative course.Methods and Results: Children who underwent biventricular repair of a conotruncal anomaly from January 1, 2006, to June 30, 2013, and had a postoperative transthoracic echocardiogram were included. Images were reviewed for residual intramural or nonintramural VSDs. The primary outcome was a composite of mortality, extracorporeal membrane oxygenation use, and need for subsequent catheter or surgical VSD closure. The secondary outcome was postoperative hospital length of stay. A residual VSD was present in 256 of the 442 subjects (58%), of which 231 (90%) were <2 mm in size. Forty-nine patients (11%) had intramural VSDs, and 207 (47%) had nonintramural VSDs. Patients with intramural VSDs were more likely to reach the primary composite outcome compared with those with nonintramural VSDs or no residual VSD (14 of 49 [29%] versus 15 of 207 [7%] versus 6 of 186 [3%]; P<0.0001). In addition, those with intramural VSDs had longer postoperative hospital length of stay compared with those with nonintramural VSDs or no residual VSD (20 days [interquartile range, 11-42 days] versus 7 days [interquartile range, 5-14 days] versus 6 days [interquartile range, 4-11 days]; P=0.0001). These associations remained significant after adjustment for known risk factors for poor outcomes, including residual VSD size and operative complexity.Conclusions: Among residual VSDs after repair of conotruncal anomalies, intramural VSDs are uniquely associated with postoperative morbidity, mortality, and longer postoperative hospital length of stay. It is important to recognize intramural VSDs in the postoperative period. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the rates of neonatal morbidity and cerebral palsy among preterm neonates (less than 37 weeks of gestation) delivered by cesarean for a non-reassuring fetal heart rate (FHR) tracing compared with those who did not. METHODS: This was a secondary analysis of a multicen-ter randomized trial of MgSO4 for the prevention of cerebral palsy. Newborns of women delivered by cesarean delivery for nonreassuring FHR were compared with a control group composed of the offspring of women who labored for 2 hours or longer but did not undergo cesarean delivery for nonreassuring FHR regardless of the mode of delivery. Using multivariable analysis to adjust for potential confounders, our objective was to compare two outcomes: 1) composite neonatal morbidity (Apgar score 3 or less at 5 minutes, seizure, sepsis, necrotizing enterocolitis grade II or III, intraventricular hemorrhage grade III or IV, or death before discharge) and 2) neurologic injury (cerebral palsy) at 2 years or more of corrected age between the groups. RESULTS: Of the 1,291 preterm neonates who met the inclusion criteria, 177 (14%) were delivered by cesarean for nonreassuring FHR compared with 1,114 (86%) in the control group. Composite neonatal morbidity was similar between the groups (30.5 compared with 22.2%, adjusted odds ratio [OR] 1.4, 95% confidence interval [CI] 0.9-2.1). The rate of cerebral palsy of any severity (8.3 compared with 4.0%, adjusted OR 2.3, 95% CI 1.2-4.5) and moderate-to-severe cerebral palsy at 2 years of corrected age (6.0 compared with 2.2%, adjusted OR 3.2, 95% CI 1.4-7.1) was significantly higher in children born through cesarean delivery for nonreassuring FHR. CONCLUSION: Nonreassuring fetal tracing deemed so serious as to require cesarean delivery is associated with an increased risk of cerebral palsy in preterm neonates. [ABSTRACT FROM AUTHOR]

This month we focus on current research in obstetric imaging. Dr. Dashe discusses five recent publications, which are concluded with a "bottom line" that is a take-home message. A complete reference for each can be found in on this page along with direct links to abstracts. [ABSTRACT FROM AUTHOR]

The article investigates the connection between preeclampsia and fetal congenital heart diseases. Information about the cohort study on fetuses with congenital heart defects, is highlighted. Also emphasized is the association of an angiogenic imbalance with the developmental defects of the human fetal heart diseases.

Fetal growth restriction (FGR) is associated with global adverse cardiac remodeling in utero and increased cardiovascular mortality in adulthood. Prenatal myocardial deformation has not been evaluated in FGR to date. We aimed to evaluate prenatal cardiac remodeling comprehensively in FGR including myocardial deformation imaging.Echocardiography was performed in 37 consecutive FGR (defined as birthweight <10th centile) and 37 normally grown fetuses. A comprehensive fetal echocardiography was performed including tissue Doppler and 2-dimensional-derived strain and strain rate. Postnatal blood pressure measurement at 6 months of age was also performed. FGR cases showed signs of more globular hearts with decreased longitudinal motion (left systolic annular peak velocity: controls mean 6 cm/s [SD 1.2] versus FGR 5.3 [1]) and diastolic dysfunction (isovolumic relaxation time: controls 44 ms [6] versus FGR 52 [9]). Peak strain and strain rate values of the left ventricle were not significantly different; however, a postsystolic shortening in the basal segment of the septal ventricular wall was observed in 57% of the FGR cases and in none of controls (P<0.001). FGR cases with postsystolic shortening had absence of a hypertrophic response, a poorer perinatal outcome (lower gestational age and birthweight, containing all cases of perinatal mortality [8%]), and higher values of blood pressure.Myocardial deformation imaging revealed a postsystolic shortening in 57% of FGR, which supports increased pressure overload as a mechanism for cardiovascular programming in FGR. Postsystolic shortening was associated with severity and with higher blood pressure postnatally. [ABSTRACT FROM AUTHOR]

Background--Fetal aortic valvuloplasty can be performed for severe midgestation aortic stenosis in an attempt to prevent progression to hypoplastic left heart syndrome (HLHS). A subset of patients has achieved a biventricular (BV) circulation after fetal aortic valvuloplasty. The postnatal outcomes and survival of the BV patients, in comparison with those managed as HLHS, have not been reported. Methods and Results--We included 100 patients who underwent fetal aortic valvuloplasty for severe midgestation aortic stenosis with evolving HLHS from March 2000 to January 2013. Patients were categorized based on postnatal management as BV or HLHS. Clinical records were reviewed. Eighty-eight fetuses were live-born, and 38 had a BV circulation (31 from birth, 7 converted after initial univentricular palliation). Left-sided structures, namely aortic and mitral valve sizes and left ventricular volume, were significantly larger in the BV group at the time of birth (P<0.01). After a median follow-up of 5.4 years, freedom from cardiac death among all BV patients was 96±4% at 5 years and 84±12% at 10 years, which was better than HLHS patients (log-rank P=0.04). There was no cardiac mortality in patients with a BV circulation from birth. All but 1 of the BV patients required postnatal intervention; 42% underwent aortic or mitral valve replacement. On the most recent echocardiogram, the median left ventricular end-diastolic volume z score was +1.7 (range, -1.3 to +8.2), and 80% had normal ejection fraction. Conclusions--Short- and intermediate-term survival among patients who underwent fetal aortic valvuloplasty and achieved a BV circulation postnatally is encouraging. However, morbidity still exists, and ongoing assessment is warranted. [ABSTRACT FROM AUTHOR]

Electronic fetal monitoring (EFM) is used for the majority of births that occur in the United States. While there are indications for use of EFM for women with high-risk pregnancies, its use in low-risk pregnancies is less evidence-based. In low-risk women, the use of EFM is associated with an increased risk for cesarean birth compared with the use of intermittent auscultation of the fetal heart rate. The purpose of this investigation was to evaluate the existence of evidence-based information on fetal heart rate monitoring in popular consumer-focused maternity books and Web sites. Content analysis of information in consumer-oriented Web sites and books was completed using the NVivo software (QRSinternational, Melbourne, Australia). Themes identified included lack of clear terminology when discussing fetal monitoring, use of broad categories such as low risk and high risk, limited presentation of information about intermittent auscultation, and presentation of EFM as the standard of care, particularly upon admission into the labor unit. More than one-third of the sources did not mention auscultation, and conflicting information about monitoring methods was presented. The availability of accurate, publically accessible information offers consumers the opportunity to translate knowledge into the power to seek evidence-based care practices during their maternity care experience. [ABSTRACT FROM AUTHOR]

New evidence regarding normal parameters of labor progress for healthy women has the potential to minimize risk of cesarean birth and thereby enhance current and future maternal well-being if clinicians apply the research findings to obstetric practice. The economic and reproductive health consequences of the increasing cesarean birth rate in the United States are considerable; therefore, action on this issue by all stakeholders is necessary. Review and integration of the recent recommendations for labor management from experts convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine are required to make maternity care in the United States as safe as possible. [ABSTRACT FROM AUTHOR]

Background--The electrophysiology of long QT syndrome (LQTS) in utero is virtually unstudied. Our goal here was to evaluate the efficacy of fetal magnetocardiography (fMCG) for diagnosis and prognosis of fetuses at risk of LQTS. Methods and Results--We reviewed the pre/postnatal medical records of 30 fetuses referred for fMCG because of a family history of LQTS (n=17); neonatal/childhood sudden cardiac death (n=3), or presentation of prenatal LQTS rhythms (n=12): 2° atrioventricular block, ventricular tachycardia, heart rate < 3rd percentile. We evaluated heart rate and reactivity, cardiac time intervals, T-wave characteristics, and initiation/termination of Torsade de Pointes, and compared these with neonatal ECG findings. After birth, subjects were tested for LQTS mutations. Based on accepted clinical criteria, 21 subjects (70%; 9 KCNQI, 5 KCNH2, 2 SCN5A, 2 other, 3 untested) had LQTS. Using a threshold of corrected QT= 490 ms, fMCG accurately identified LQTS fetuses with 89% (24/27) sensitivity and 89% (8/9) specificity in 36 sessions. Four fetuses (2 KCNH2 and 2 SCN5 A), all with corrected QT ≥ 620 ms, had frequent episodes of Torsade de Pointes, which were present 22-79% of the time. Although some episodes initiated with a long-short sequence, most initiations showed QRS aberrancy and a notable lack of pause dependency. T-wave alternans was strongly associated with severe LQTS phenotype. Conclusions--Corrected QT prolongation (≥490 ms) assessed by fMCG accurately identified LQTS in utero; extreme corrected QT prolongation (≥620 ms) predicted Torsade de Pointes. FMCG can play a critical role in the diagnosis and management of fetuses at risk of LQTS. [ABSTRACT FROM AUTHOR]

Background: Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells instruct myocardial growth by secreting essential factors including FGF (fibroblast growth factor) 9 and IGF (insulin-like growth factor) 2. However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. The current study is to investigate whether and how HDAC (histone deacetylase) 3 in the developing epicardium regulates myocardial growth., Methods: Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of HDAC3 in the developing epicardium., Results: We deleted Hdac3 in the developing murine epicardium, and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of epicardium-derived cells. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly downregulated in Hdac3 KO mouse epicardial cells. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO mouse epicardial cells and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO mouse epicardial cells., Conclusions: Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322 or miR-503, providing novel insights in elucidating the etiology of congenital heart defects and conceptual strategies to promote myocardial regeneration.

Received December 08, 2021 The following ACOG documents have been revised: ACOG Practice Bulletin No. 106: Intrapartum Fetal Heart Rate Monitoring: Nomenclature, Interpretation, and General Management Principles (Obstet Gynecol 2009;114:192-202) has been updated by ACOG Practice Advisory: Oxygen Supplementation in the Setting of Category II or III Fetal Heart Tracings (January 2022) For the most up-to-date documents on COVID-19, visit https://www.acog.org/covid-19. [Extracted from the article]

The article presents a study which investigated the incidence of atypical fetal heart rate deceleration characteristics in term labor and their link to acidemia. Within 5,388 participants, the atypical feature observed with the most frequency was shoulders followed by slow return, minimal deceleration variability, and nonexistent deceleration variability. There was no disparity observed in the incidence of atypical features between neonates with acidemia and without.

The article presents a study that estimated U.S. trends in perinatal outcomes among live births after assisted reproductive technology from 2000 to 2008. The study used retrospective cohort data from the National Assisted Reproducive Technology Surveillance System. It concludes that good perinatal outcomes increased among assisted reproductive technology live births and informs that odds for good outcome were greatest with the presence of a single fetal heart among singletons live births.

Background--Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. Methods and Results--We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000-2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1-21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age <20 weeks, ventricular rate ≤50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4±2.9 versus 24.9±4.9 weeks: P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age: 8 children developed cardiomyopathy. Conclusions--Risk factors associated with a poor outcome were gestation <20 weeks, ventricular rate ≤50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen. [ABSTRACT FROM AUTHOR]

The article discusses a study seeking to verify whether the characteristics of term neonates with acute intrapartum hypoxic ischemic encephalopathy and permanent central nervous system (CNS) impairment match the criteria developed by the Task Force on Neonatal Encephalopathy and Cerebral Palsy in the U.S. A reactive intrapartum fetal heart rate pattern and an umbilical artery cord pH were among the entry criteria. The study found that the entry criteria was met by 39 neonates.

The article discusses a study on the relationship of the time spent in fetal heart rate categories with short-term neonatal outcomes. The study reviewed fetal heart rate characteristics of women with a singleton fetus in term labor at 10 U.S. hospitals. Fetal heart rate categories were divided into three, namely, category I, II and III which were present 77.9%, 22.1% and 0.004% of the time, respectively. The authors conclude that increasing time in category II is linked with higher morbidity.

Objective: To evaluate the relation of different acceleration criteria to perinatal outcome for interpretation of nonstress test (NST) at 32 weeks of gestation or earlier.Methods: Nonstress tests within 1 week of delivery for women at 32 weeks of gestation or earlier were classified as reactive by 10-beat criteria, reactive by 15-beat criteria, or nonreactive. In women with three NSTs within 1 week of delivery, patterns were categorized into decreasing, increasing, irregular, or consistent reactivity. Perinatal outcomes included perinatal death, intensive delivery room resuscitation, 5-minute Apgar score less than 7, mechanical ventilation, necrotizing enterocolitis, intraventricular hemorrhage, and hypotension. Analysis included χ and logistic regression.Results: Seven hundred fifty-one NSTs from 488 women were assessed. Of the final NSTs before delivery, 105 (21.5%) were nonreactive, 151 (30.9%) were reactive by 10-beat criteria, 232 (47.5%) were reactive by 15-beat criteria, and 274 (56.1%) had decelerations. Unadjusted data consistently associated degree of reactivity with outcome and also associated gestational age with degree of reactivity. After adjustment for gestational age and birth weight, there was no association between NST criterion (or decelerations) and outcomes except between nonreactivity and perinatal death (odds ratio 6.1, 95% confidence interval 2.3-16.5). For 97 women who underwent three tests, all patterns were common (range 16.5-37.1%) and none was significantly associated with any outcome.Conclusion: In preterm pregnancies, the criterion used for NST interpretation is much less important than the gestational age at delivery. There was no appreciable difference between the 10-beat criteria and 15-beat criteria in predicting outcome. When tested repeatedly, fetuses frequently had varying degrees of reactivity without relation to outcome. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the long-term effects of anemia on the fetal heart. Study authors utilized echocardiography to examine the cardiac function of children who received intrauterine blood transfusions for red cell isoimmunization between 1992 and 2003. They found that fetal anemia due to red cell isoimmunization is associated with a reduction in left ventricular mass and left atrial area in childhood.

The article presents a study which examined the influence of chronic prenatal hypoxia on the epigenetic programming of protein kinase C epsilon gene repression. The researchers assumed that protein kinase C epsilon expression is essential to the repression of genes in the heart of the adult offsprings of rats. They found that hypoxia has a direct effect on epigenetic alteration of the methylation of the deoxyribonucleic acid (DNA).

The article compares fetal and neonatal growth curves in detecting intrauterine growth restriction (IUGR). The researchers examined 53 pregnancies with severe IUGR with abnormal pulsatility index and normal fetal heart rate. They found that neonatal outcome is similar in IUGR of the same clinical severity and that neonatal curves do not accurately detect low birth weight.

The article presents an analysis of fetal heart variability obtained by magnetocardiography. Its objective is to obtain fetal magnetocardiogram recordings in preterm fetuses in both shielded and unshielded clinical settings. The position of the superconducting quantum interference device biomagnetometer is over the gravid abdomen. A negative growth rate of 0.17 decibels per week was calculated from high-frequency/lower frequency ratio.

The article discusses an approach to caring for a pregnant woman in the intensive care unit (ICU) and presents an overview of fetal assessment for ICU care providers. Clinical interventions have an impact on fetal status when a pregnant woman is critically ill. The article also offers information on the clinical implications of non-reassuring fetal heart rate patterns.

In 2002, approximately 3.4 million fetuses (85% of approximately 4 million live births) in the United States were assessed with electronic fetal monitoring (EFM), making it the most common obstetric procedure (1). Despite its widespread use, there is controversy about the efficacy, of EFM, interpretation of fetal heart rate (FHR) patterns, reproducibility of its interpretation, and management algorithms for abnormal or nonreassuring patterns. Moreover; there is evidence that the use of EFM increases the rate of cesarean and operative vaginal deliveries. The purpose of this document is to review nomenclature for FHR assessment, review the data on the efficacy of EFM, delineate the strengths and shortcomings of EFM, and describe the management of nonreassuring FHR patterns. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Adverse fetal heart rate (FHR) changes occur frequently during the first 30 minutes after epidural analgesia. The aim of this study was to estimate whether intravenous administration of ephedrine during induction of epidural analgesia can reduce the frequency of adverse FHR changes. METHODS: We prospectively studied 145 term singleton deliveries where epidural analgesia was administered. The patients were randomly allocated before the administration of epidural analgesia to receive an intravenous infusion of 10 mg ephedrine, after epidural induction, followed by a continuous infusion for 60 minutes of 20 mg ephedrine (study group) or to receive no ephedrine (control group). The FHR tracing was evaluated for 20 minutes before and 40 minutes after initiating epidural analgesia. Demographic data and clinical and delivery outcome were assessed and compared between the 2 groups. RESULTS: Injection of ephedrine significantly reduced the rate of major FHR changes appearing 15-25 minutes after induction of epidural analgesia in the study group compared with the control group (2/72 compared with 11/73, respectively; P = .009). To avoid I case of adverse FHR changes, 6.8 women should be treated with ephedrine. Maternal and fetal characteristics and outcome and mode of delivery were similar in the 2 groups. Mean arterial pressure was significantly higher in the study group from the time of analgesia induction and during the subsequent 25 minutes. Maternal heart rate was transiently reduced in the study group only. CONCLUSION: Ephedrine administration during the time of epidural analgesia initiation can reduce the frequency of adverse FHR changes commonly observed immediately afterward. [ABSTRACT FROM AUTHOR]

OBJECTIVE:To correlate the presence of baseline variability and the duration of a prolonged deceleration/bradycardia in intrapartum fetal heart rate (FHR) tracings with the development of neonatal acidemia.METHODS:We identified 186 patients with term gestations who had continuous electronic fetal monitoring for at least 2 hours before delivery, with an identified bradycardia during that period. Each patient had umbilical artery cord analysis done and delivery within 30 minutes of that bradycardia. One investigator blinded to the cord gas outcome reviewed the last 2 hours of the tracing using the National Institute of Child Health and Human Development guidelines for FHR monitoring. We assessed the presence or absence of variability before the bradycardia and recovery or no recovery of the bradycardia and placed the patients into four groups. Group 1 (128 patients) with normal variability and recovery, group 2 (40 patients) with normal variability and no recovery, group 3 (nine patients) with decreased variability and recovery, and group 4 (nine patients) with decreased variability and no recovery. We compared the incidence of neonatal acidosis defined as a pH of less than 7.0 at birth among the four groups. The relationship between the various groups was assessed using analysis of variance and the χ2 test. In addition, a multiple logistic regression model was developed with the parameters of amplitude and recovery used to predict pH at birth.RESULTS:The presence of decreased variability and no recovery of the FHR of a bradycardia was associated with the lowest pH 6.83 ± 0.16 and a 78% incidence of significant acidosis. Decreased variability before FHR bradycardia was the FHR parameter significantly correlated with low pH.CONCLUSION:The most significant factor predicting the development of pathologic neonatal acidemia and indicating the need for urgent delivery in the presence of a bradycardia is decreased variability before the bradycardia. [Copyright &y& Elsevier]

Focuses on a study which investigated fetal response to decreased oxygenation, the physiology of subsequent fetal heart rate (FHR) patterns during labor. Physiology of the utero-placental unit; Physiology of the FHR; Details of the FHR response to hypoxia; Mechanisms of periodic FHR patterns; Relationship between FHR patterns and perinatal asphyxia.

The article discusses the Boston Circulatory Arrest Study which examines the cognitive outcomes of survivors of infants following congenital heart surgery. The study revealed the failure of surgical strategy to identify increased risk for the outcome measures in infants. Other findings of the report are also discussed.

Supplemental Digital Content is available in the text. Anatomic variants in the right atrium are under-recognized and under-reported phenomena in cardiac imaging. In the fetus, right atrium serves as a conduit for oxygenated blood to be delivered to the left heart bypassing the right ventricle and the nonfunctional lungs. The anatomy in the fetal right atrium is designed for such purposeful circulation. The right and left venous valves are prominent structures in the fetal heart that direct inferior vena caval flow towards the foramen ovale. These anatomic structures typically regress and the foramen ovale closes after birth. However, the venous valves can persist leading to a range of anatomic, physiological, and pathological consequences in the adult. We describe various presentations of persistent venous valves, focusing on the right venous valve in this illustrated multimodality imaging article. [ABSTRACT FROM AUTHOR]

Background: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy.Methods: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies.Results: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal.Conclusions: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573. [ABSTRACT FROM AUTHOR]

The article describes the case of a 24-year-old Honduran woman who developed a pruritic rash at 16 weeks gestation. A monochorionic, diamniotic twin gestation with two male fetuses was shown in ultrasonography. The delivery of two live male newborns was prompted by fetal heart rate decelerations noted at 32 4/7 weeks. Fetal risks such as preterm delivery and meconium staining are associated with intrahepatic cholestasis of pregnancy. The patient recovered with declining laboratory values during the postpartum period.

The article presents the authors' perspective on the three-tier system of interpretation of fetal heart rate monitoring proposed by the 2008 Eunice Kennedy Shiver National Institute of Child Health and Human Development in the U.S. They remark that the middle tier of the proposed system is vast and heterogeneous, which they proposed can be subcategorized based on evidence from previous studies. They contend that the subcategorization will allow guidelines for interventions of the FHR patterns.

Background: Long QT syndrome (LQTS) is a leading cause of sudden cardiac death in early life and has been implicated in ≈10% of sudden infant deaths and unexplained stillbirths. The purpose of our study was to use fetal magnetocardiography to characterize the electrophysiology and rhythm phenotypes of fetuses with de novo and inherited LQTS variants and identify risk factors for sudden death before birth.Methods: We reviewed the fetal magnetocardiography database from the University of Wisconsin Biomagnetism Laboratory for fetuses with confirmed LQTS. We assessed waveform intervals, heart rate, and rhythm, including the signature LQTS rhythms: functional 2° atrioventricular block, T-wave alternans, and torsade de pointes (TdP).Results: Thirty-nine fetuses had pathogenic variants in LQTS genes: 27 carried the family variant, 11 had de novo variants, and 1 was indeterminate. De novo variants, especially de novo SCN5A variants, were strongly associated with a severe rhythm phenotype and perinatal death: 9 (82%) showed signature LQTS rhythms, 6 (55%) showed TdP, 5 (45%) were stillborn, and 1 (9%) died in infancy. Those that died exhibited novel fetal rhythms, including atrioventricular block with 3:1 conduction ratio, QRS alternans in 2:1 atrioventricular block, long-cycle length TdP, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with TdP and perinatal death. Fetuses with familial variants showed a lower incidence of signature LQTS rhythm (6/27=22%), including TdP (3/27=11%). All were live born.Conclusions: The malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth. Their ability to manifest rhythms not known to be associated with LQTS increases the difficulty of echocardiographic diagnosis and decreases the likelihood that a resultant fetal loss is attributed to LQTS. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03047161. [ABSTRACT FROM AUTHOR]

Background: Fetal aortic valvuloplasty (FAV) may prevent progression of midgestation aortic stenosis to hypoplastic left heart syndrome. However, FAV has well-established risks, and its survival benefit remains unknown. Our primary aim was to determine whether FAV for midgestation aortic stenosis increases survival from fetal diagnosis to age 6 years.Methods and Results: We performed a retrospective analysis of 143 fetuses who underwent FAV from 2000 to 2017 and a secondary analysis of the Pediatric Heart Network Single Ventricle Reconstruction trial. Using these results, we developed a decision model to estimate probability of transplant-free survival from fetal diagnosis to age 6 years and postnatal restricted mean transplant-free survival time. FAV was technically successful in 84% of 143 fetuses with fetal demise in 8%. Biventricular circulation was achieved in 50% of 111 live-born infants with successful FAV but in only 16% of the 19 patients with unsuccessful FAV. The model projected overlapping probabilities of transplant-free survival to age 6 years at 75% (95% CI, 67%-82%) with FAV versus 72% (95% CI, 61%-82%) with expectant fetal management, resulting in a restricted mean transplant-free survival time benefit of 1.2 months. When limiting analyses to the improved FAV experience since 2009 to reflect current practice, (probability of technical success [94%], fetal demise [4%], and biventricular circulation [66%]), the model projected that FAV increased the probability of survival to age 6 years to 82% (95% CI, 73%-89%). Expectant management is favored if risk of fetal demise exceeded 12% or probability of biventricular circulation fell below 26%, but FAV remained favored over plausible recent range of technical success.Conclusions: Our model suggests that FAV provides a modest, medium-term survival benefit over expectant fetal management. Appropriate patient selection and low risk of fetal demise with FAV are critical factors for obtaining a survival benefit. [ABSTRACT FROM AUTHOR]