Analysis on echocardiographic data of fetal heart defects at high altitude in Yunnan province and surrounding high altitude areas / 中华心血管病杂志

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.

Cardiomyopathy and cardiac function in fetuses and newborns of diabetic mothers

Abstract Objective: To evaluate cardiac function and structural changes in children of diabetic mothers in the fetal and neonatal period using Doppler-echocardiographic data. Method: A prospective, descriptive observational study conducted in a private and tertiary care service for high-risk pregnant women. It included 48 children of mothers with gestational diabetes mellitus (GDM) considered clinically compensated during pregnancy, with a single fetus and absence of malformations. Myocardial thickness, shortening fraction, left ventricular (LVMPI) and right ventricular (RVMPI) myocardial performance index, and mitral and tricuspid valve E/A ratio were evaluated in 96 echocardiographic exams with Doppler. Results: The hypertrophic cardiomyopathy was 29% vs 6% p = 0.006 in the prenatal and postnatal periods respectively. The shortening fraction was 0% vs 6% p = 0.242 in the fetuses and newborns respectively. The myocardial performance index of the right ventricle was 12% vs 54% p ≤ 0.001, and on the left ventricle 27% vs 60% p = 0.001 in the prenatal and postnatal periods respectively. The ratio of mitral valve E/A waves was 6% vs 50% p ≤ 0.001 and the ratio of tricuspid valve E/A waves was 0% vs 27% p 0.001 in the fetuses and newborns respectively. Conclusion: A decrease in the rate of myocardial hypertrophy and changes in cardiac function parameters were observed in the fetal and neonatal periods.

Secuencia de perfusión arterial reversa en embarazo gemelar; coagulación de arteria nutricia. Reporte del primer caso en el país / Twin reversed arterial perfusion sequence; coagulation of the umbilical cord. A report on the first case in Uruguay / Seqüência reversa de perfusão arterial na gravidez gemelar; coagulação da artéria nutritiva. Relato do primeiro caso no país

Resumen: La secuencia de perfusión arterial reversa (TRAP) es una complicación muy poco frecuente y grave de los embarazos gemelares monocoriónicos. Generalmente ocurre cuando el corazón de un gemelo de apariencia normal sirve como bomba para uno o más gemelos dismórficos cuya cabeza, órganos torácicos y extremidades superiores no se desarrollan completamente o no se desarrollan en absoluto y, por lo tanto, carecen de actividad cardíaca. La arquitectura placentaria vascular anómala provoca un cambio en el flujo arterial hacia el gemelo acardíaco. Los mecanismos fisiopatológicos exactos que conducen a este fenómeno devastador no se conocen bien. Compartiremos el caso clínico de una paciente de 19 años, cursando un embarazo gemelar monocorial monoamniótico, en que realizamos diagnóstico de TRAPS, y realizamos la coagulación laser de la arteria nutricia del feto acárdico.

Abstract: Twin reversed arterial perfusion sequence (TRAPS) is rather an unusual and severe complication of monochorionic twin pregnancies. It usually occurs when the normal-appearance heart of a twin acts as a pump for one or more dysmorphic twins whose head, thoracic organs and upper limbs fail to totally develop or do not develop at all and thus, have no cardiac activity. The abnormal vascular architecture at the placenta changes the arterial flow towards the acardiac twin. The exact pathophysiological mechanisms that result in this devastating phenomenon are still unknown. The study presents the clinical case of a 19-year- old patient pregnant with monoamniotic, monochorionic twins and a diagnosis of TRAPS, treated by laser coagulation of the acardiac twin's umbilical cord.

Resumo: A seqüência reversa de perfusão arterial (TRAPS) é uma complicação muito rara e grave de gestações gemelares monocoriônicas. Geralmente ocorre quando o coração de um gêmeo de aparência normal serve como uma bomba para um ou mais gêmeos dismórficos cuja cabeça, órgãos torácicos e membros superiores não se desenvolvem totalmente ou não se desenvolvem e, portanto, não têm atividade cardíaca. A arquitetura vascular placentária anormal causa uma mudança no fluxo arterial para o gêmeo acardíaco. Os mecanismos fisiopatológicos exatos que levam a esse fenômeno devastador não são bem compreendidos. Descrevemos o caso clínico de uma paciente de 19 anos, portadora de gestação gemelar monocoriônica monoamniótica, na qual fizemos o diagnóstico de TRAPS e realizamos coagulação a laser da artéria nutritiva do feto acardíaco.

Gran feto acardio: diagnóstico tardío de gestacion gemelar monocorial biamniótica complicada por secuencia TRAP: reporte de un caso y revisión de la literatura / Great acardiac fetus: late diagnosis of monochorionic diamniotic twin pregnancy complicated by sequence TRAP: case report and review of the literature

OBJETIVOS: reportar el caso de una paciente con gestación gemelar monocorial-biamniótica complicada por secuencia TRAP que dio lugar al nacimiento de un feto bomba de 1932 gramos sin malformaciones anatómicas y de un feto acardio anceps de 1800 gramos, y realizar una revisión sobre esta patología y la importancia de su diagnóstico y tratamiento precoces. MATERIALES Y MÉTODOS: se presenta el caso de un feto acardio en una gestante con embarazo sin control estricto en el Hospital San Pedro de Logroño en el año 2019, de interés por su diagnóstico tardío y elevado peso al nacimiento del feto acardio. Se realizó una búsqueda de la literatura en las bases de datos Medline vía PubMed, OVID, Embase y SciE-LO con las palabras clave DeCS y términos MeSH. Como criterios de inclusión se consideraron artículos tipo series y reportes de casos y artículos de revisión desde enero de 1950 hasta enero de 2020. RESULTADOS: la búsqueda incluyó 39 referencias bibliográficas sobre las que se repasaron las principales cuestiones teóricas a exponer. El peso del feto acardio de nuestro caso fue muy elevado sin provocar repercusión en el feto sano, en comparación con la bibliografía, lo que aporta singularidad al caso, siendo sólo equiparable la serie de casos de Brassard et al (1999), con pesos de los fetos acardio por encima de 1700 gramos y diferenciándose en 100 gramos del feto bomba. CONCLUSIONES: el feto acardio es una complicación infrecuente de embarazos gemelares monocoriales. Se requiere la presencia de anastomosis vasculares placentarias entre ambas circulaciones. El diagnóstico precoz es importante para disminuir la morbilidad y usar, en la medida de lo posible, técnicas terapéuticas no invasivas.

OBJECTIVES: to report the case of a patient with a monochorionic-biamniotic twin gestation complicated by TRAP sequence that gave rise to the birth of a pump fetus without anatomical malformations (1932 g) and an acardiac anceps fetus (1800 g), and to review this pathology and the importance of its early diagnosis and management. MATERIAL AND METHODS: the case of an acardiac fetus is presented in a pregnant woman without strict control at the Hospital San Pedro de Logroño in 2019, worthwhile because of its late diagnosis and high birth weight. A search of the literature was carried out in the Medline databases via PubMed, OVID, Embase and SciELO with the MeSH terms. As inclusion criteria, we considered series-type articles and case reports, cohorts and review articles from January 1950 to January 2020. RESULTS: 39 bibliographic references were included with the main theoretical questions to be reviewed. Our acardiac fetus weight was very high comparing with the bibiography and without causing repercussion in the healthy fetus, which contributes to the uniqueness of the case, only the series report by Brassard et al (1999) is comparable, with weights of the acardiac fetus above 1700 grams and differing by 100 grams from the pump fetus. CONCLUSIONS: the acardiac fetus is an infrequent complication of monochorionic twin pregnancies. The presence of placental vascular anastomoses between both circulations is required. Early diagnosis is important to decrease morbidity and to use, as far as possible, non-invasive therapeutic techniques.

Cardiopatías congénitas, diagnóstico y manejo prenatal / Congenital heart disease, prenatal diagnosis and management

Dentro de las malformaciones congénitas, las cardiopatías son las anomalías más frecuentes y se asocian a una elevada morbimortalidad perinatal y a largo plazo. El objetivo de esta actualización es revisar la tasa de detección prenatal, las características del tamizaje a lo largo del embarazo, tanto en el primero como en el segundo trimestre, las indicaciones de ecocardiografía avanzada, y establecer un algoritmo de manejo ante el diagnóstico prenatal de una cardiopatía congénita. Se discutirán los estudios invasivos y no invasivos que pueden realizarse y el seguimiento obstétrico. Finalmente, se revisarán las características principales de la terapia fetal en anomalías cardíacas, tanto intervencionismo cardíaco como el tratamiento intrauterino de las arritmias.

Among congenital malformations, heart defects are the most common type of anomaly, and these are associated with a high perinatal, long-term morbidity and mortality. The objective of this update was to review the rate of prenatal detection, screening characteristics throughout the pregnancy, in both the first and second trimesters, indications for advanced echocardiography, and to establish a management algorithm in case of prenatal diagnosis of a congenital heart disease. Potential invasive and non-invasive tests and obstetric follow-up will be discussed here. Finally, the main characteristics of fetal therapy in heart anomalies will be reviewed, both cardiac interventions and intrauterine treatment of arrhythmias.

Coração fetal: por que e quando investigar? / Fetal ultrasound: why explore the heart?

O incremento do arsenal diagnóstico do pré-natal, por meio de exames de ultrassom, com tecnologias de imagens cada vez mais perfeitas, proporciona o estudo detalhado da anatomia fetal. A mortalidade infantil está diretamente relacionada com as malformações congênitas fetais, especialmente com as alterações anatômicas do coração. Aproximadamente 90% das gestantes não apresentam nenhum fator de risco para malformações cardíacas congênitas (MCCs), portanto o rastreamento pré-natal deve ser realizado em todas as gestações, conforme sugestão da primeira Diretriz Brasileira de Cardiologia Fetal. A revisão bibliográfica da literatura sugere que o diagnóstico pré-natal das MCCs permite intervenções fetais durante o pré-natal e adequado planejamento do parto. Essas ações interferem na morbiletalidade perinatal e no prognóstico dos fetos portadores de cardiopatias, além de auxiliarem a equacionar as vagas nos hospitais de referência e estimarem os gastos na saúde pública e privada.(AU)

The improvement of the ultrasound scan used in the prenatal evaluations provides better images data for the study of the fetal heart. Congenital heart malformations are one of the most leading causes of infant death in the world. Ninety percent of pregnant women do not present any risk factors for Congenital Heart Malformations, so prenatal screening should be performed in all pregnancies, as suggested by the first Brazilian Guideline on Fetal Cardiology. The literature review propose that prenatal diagnosis of congenital heart malformations supports fetal care satisfactory delivery planning and interventions during prenatal. These kindness influences the prognosis of the cardiopathies, perinatal morbidity and mortality and help to reorganize hospital admission and public health care.(AU)

Cirurgias intrauterinas: alternativa de intervenção para as cardiopatias congênitas / Intrauterine surgeries: intervetion alternative for congenital cardiopathies

As cardiopatias congênitas são anormalidades estruturais ou funcionais do sistema cardiovascular, advindas desde o nascimento, mesmo que diagnosticadas posteriormente. Entre as malformações congênitas, as cardiopatias são as principais causas de mortalidade infantil nos Estados Unidos e em outros países desenvolvidos. Com o intuito de reduzir os efeitos progressivos dessas patologias, a intervenção intrauterina tem se destacado como opção terapêutica diante de resultados iniciais satisfatórios. O presente artigo teve por objetivo demonstrar a evolução da cirurgia intrauterina para correção cardíaca, a partir da avaliação dos benefícios ao feto e visando a riscos mínimos e aceitáveis para a mãe. Foi realizada uma pesquisa na base de dados Publisher Medline (PubMed), Scientific Electronic Library Online (SciELO) e Biblioteca Virtual da Saúde (BVS), incluindo artigos publicados entre 2008 e 2018; além da pesquisa efetuada no Manual de Medicina Fetal da SOGIMIG ­ 2018. Os critérios de elegibilidade são amplos. São necessários equipe multidisciplinar, equipamentos sofisticados e aperfeiçoamento da técnica, dessa forma dificulta-se a realização das cirurgias. Entretanto, diante dos resultados já demonstrados, a cirurgia intrauterina apresenta-se como alternativa terapêutica promissora.(AU)

The congenital cardiopathies are structural or functional abnormalities of the cardiovascular system, originated from birth, even when previously diagnosed. Among the congenic malformations, the cardiopathies are the main causes of infant mortality in the United States and in other developed countries. In order to reduce the progressive effects of these pathologies, intrauterine intervention has been highlighted as a therapeutic option in contempt of satisfactory initial results. This article has as goal to demonstrate the evolution of the intrauterine surgery for cardiac correction, based on the evaluation of the benefits to the fetus and aiming at minimum and acceptable risks to the mother. A research was made based on the Publisher Medline (PubMed) data base, Scientific Electronic Library Online (SciELO) and Biblioteca Virtual da Saúde (BVS), including published articles between 2008 and 2018. Beyond the research made on The fetal medicine manual from SOGIMIG ­ 2018. The eligibility criteria are broad. It is necessary a multidisciplinary team, sophisticated equipments and technique improvement, therefore interfering in the performance of surgeries. However, in contempt of the already demonstrated results the intrauterine surgery presents itself as a therapeutic promising alternative.(AU)

How to perform a functional assessment of the fetal heart: a pictorial review

The purpose of this pictorial review was to describe various echocardiographic techniques that can be used for the functional assessment of the fetal heart. The systolic and diastolic assessments of the fetal heart are presented separately, with an emphasis on 2-dimensional Doppler methods and an overview of new technologies. The aim of this summary was to review the tools that can be used by the echocardiographer, and on that basis, to systematize the process of performing a functional assessment.

Síndrome de hipoplasia del ventrículo izquierdo / Left ventricular hypoplasia syndrome

Antecedentes: el síndrome de hipoplasia del ventrículo izquierdo es un conjunto de alteraciones del corazón fetal que condicionan un hipodesarrollo del corazón izquierdo, que es insuficiente para mantener la circulación sistémica. El corazón derecho se encuentra dilatado e hipertrofiado y soporta la circulación pulmonar y la circulación sistémica fetal a través del conducto arterioso permeable. Representa el 2 a 3% de todas las cardiopatías congénitas. Sin embargo, la incidencia real está subestimada ya que es responsable de abortos espontáneos y otras muertes fetales intrauterinas no diagnosticadas. Reporte de un caso: paciente de sexo femenino, 32 años de edad, con antecedente familiar de importancia (padre con fibrilación auricular). Antecedentes gíneco-obstétricos: un parto céfalo-vaginal, sin complicaciones, de un neonato de sexo masculino que actualmente tiene 6 años de edad. Durante su segunda gesta el feto es diagnosticado de hipoplasia del ventrículo izquierdo y atresia de la válvula mitral a las 34 semanas. Acude al Hospital Metropolitano a las 39 semanas de gestación para terminación de su embarazo mediante parto céfalo-vaginal. El parto no tuvo complicaciones; al nacimiento se confirma el diagnóstico prenatal y el recién nacido fallece en las primeras 72 horas. Conclusiones: el síndrome de hipoplasia del corazón izquierdo es una combinación compleja de malformaciones cardíaca;, debe ser detectado durante la evaluación ecográfica prenatal para planificar su manejo al nacimiento en centros especializados donde sea posible realizar procedimientos con el propósito de mejorar la supervivencia de estos pacientes.

Background: It is a set of alterations of the fetal heart that condition a hypodevelopment of the left heart, which is insufficient to maintain the systemic circulation. The right heart is dilated and hypertrophied and it supports the pulmonary circulation and fetal systemic circulation through patent ductus arteriosus. It represents 2 - 3% of all congenital heart diseases. However, current incidence is underestimated because it produces spontaneous abortions and other undiagnosed intra- uterine fetal deaths. Report of a case: a 32-year-old female patient with an importance family history: father with atrial fibrillation. Obstetric-gynecological antecedents: a cephalo- vaginal delivery without complications who was a male product of 6 years. During her second pregnancy, fetus was diagnosed with left ventricular hypoplasia and mitral valve agenesis at 34 weeks. She went to Metropolitan Hospital at 39.1 weeks to finish her pregnancy due to cephalo-vaginal birth. Delivery occurred without complications, however, the prenatal diagnosis was confirmed and the newborn died in 72 hours. Conclusions: The left heart hypoplasia syndrome is a complex combination of cardiac malformations; it can be detected with a prenatal evaluation with ultrasound which provides an option to pose treatment and also it can guide physicians to prepare for postnatal interventions when it is necessary.

Job Analysis of Maternal Fetal Intensive Care Unit Nurses Using DACUM Technique / 임상간호연구

PURPOSE: This study was performed to establish the role and to analyze the job of MFICU (Maternal Fetal Intensive Care Unit) nurses using DACUM (Developing a curriculum). METHODS: A DACUM workshop was held to define MFICU nurses' role and identify their duties and tasks. A DACUM committee was consisted of 7 nurses, 2 nursing professors and 1 medical doctor and as a result, a survey was developed which contained duties and tasks of MFICU nurse. Pre-test was carried out for the validity, finally collected the data from 97 nurses who worked at 7 MFICU and 10 delivery room. RESULTS: A total of 60 duties, 115 tasks and 822 elements of tasks were defined on the DACUM chart and survey. The importance, frequency and difficulty of the tasks were presented the determinant coefficient (DC), the highest DC duty was ‘Manage maternal ventilator’ (15.09) and the lowest DC was ‘Provide nursing care for leisure to gestation extension mother’ (6.52). Twenty-eight tasks were differentiated between MFICU and delivery nurses significantly. And the most important, frequently, difficulty task perceived by MFICU nurse was ‘Check fetal heartbeat with electronic fetal heart monitor’. CONCLUSION: The organized educational program and policy was needed to develop for MFICU nurses.

Effect of Structured Bed Exercise on Uterine Contractions, Fetal Heart Rate Patterns, and Maternal Psychophysical Symptoms of Hospitalized High-Risk Pregnant Women: A Randomized Control Trial

PURPOSE: This study examined the effect on uterine contraction frequency (UCF), blood pressure (BP), heart rate (HR), fetal heart rate (FHR) patterns and psychophysical symptoms (physical discomfort, anxiety, and depression) of structured bed exercise (SBE) in hospitalized high-risk pregnant women prescribed bed rest. METHODS: Forty-five hospitalized high risk pregnant women at >24 weeks of pregnancy prescribed bed rest were randomly assigned to the experimental or control group. From January to May 2014, data were collected using electronic fetal monitoring and patient monitoring of UCF, BP, HR and FHR patterns, and psychophysical symptoms were measured using the antenatal physical discomfort scale, state-trait anxiety scale, and Edinburgh postnatal depression scale. RESULTS: UCF, BP, HR, and FHR patterns (rate, variability, acceleration, and deceleration) did not differ significantly between the experimental and control groups. The experimental group showed a significant increase in baseline FHR after SBE within the normal range, and after SBE, it reduced to the FHR before SBE. The variability, acceleration and deceleration of FHR before and after SBE did not differ significantly between two groups. Moreover, there was no statistically significant difference before and after SBE in the experimental group. Also, the experimental group showed statistically significant decreases in physical discomfort score. However, there were no significant differences in depression and anxiety score between two groups. CONCLUSIONS: SBE in hospitalized high-risk pregnant women under bed rest did not increase the risk to the fetus, and relieved physical discomfort and anxiety. Therefore, SBE should be considered as a nursing intervention in hospitalized high-risk pregnant women.

Disruption of Planar Cell Polarity Pathway Attributable to Valproic Acid-Induced Congenital Heart Disease through Hdac3 Participation in Mice / 中华医学杂志(英文版)

Background@#Valproic acid (VPA) exposure during pregnancy has been proven to contribute to congenital heart disease (CHD). Our previous findings implied that disruption of planar cell polarity (PCP) signaling pathway in cardiomyocytes might be a factor for the cardiac teratogenesis of VPA. In addition, the teratogenic ability of VPA is positively correlated to its histone deacetylase (HDAC) inhibition activity. This study aimed to investigate the effect of the VPA on cardiac morphogenesis, HDAC1/2/3, and PCP key genes (Vangl2/Scrib/Rac1), subsequently screening out the specific HDACs regulating PCP pathway.@*Methods@#VPA was administered to pregnant C57BL mice at 700 mg/kg intraperitoneally on embryonic day 10.5. Dams were sacrificed on E15.5, and death/absorption rates of embryos were evaluated. Embryonic hearts were observed by hematoxylin-eosin staining to identify cardiac abnormalities. H9C2 cells (undifferentiated rat cardiomyoblasts) were transfected with Hdac1/2/3 specific small interfering RNA (siRNA). Based on the results of siRNA transfection, cells were transfected with Hdac3 expression plasmid and subsequently mock-treated or treated with 8.0 mmol/L VPA. Hdac1/2/3 as well as Vangl2/Scrib/Rac1 mRNA and protein levels were determined by real-time quantitative polymerase chain reaction and Western blotting, respectively. Total HDAC activity was detected by colorimetric assay.@*Results@#VPA could induce CHD (P 0.05); VPA exposure dramatically decreased the expression of Vanlg2/Scrib together with Hdac activity (P 0.05).@*Conclusion@#VPA could inhibit Hdac1/2/3, Vangl2/Scrib, or total Hdac activity both in vitro and in vivo and Hdac3 might participate in the process of VPA-induced cardiac developmental anomalies.

Effect of histone acetylation/deacetylation imbalances on key gene of planar cell polarity pathway / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of histone acetylation/deacetylation imbalances on embryonic hearts of mice and its effect on key genes of planar cell polarity (PCP) pathway-Vangl2, Scrib and Rac1 in H9C2 cells.</p><p><b>METHODS</b>Forty pregnant C57/B6 mice were randomly assigned into three groups: blank group (n=10), vehicle group (n=10), and valproic acid (VPA)-treated group (n=20). In the VPA-treated group, VPA, a histone deacetylase (HDAC) inhibitor, was administered to each individual dam intraperitoneally at a single dose of 700 mg/kg on embryonic day 10.5 (E10.5). The vehicle and blank groups received equivalent saline or no interventions, respectively. Dams were sacrificed on E15.5, and death rates of embryos were evaluated. Subsequently, embryonic hearts of survival fetus were removed to observe cardiac abnormalities by hematoxylin-eosin (HE) staining. H9C2 cells were cultured and allotted to the blank, vehicle, and VPA-treated groups: the VPA treated group received VPA exposure at concentrations of 2.0, 4.0 and 8.0 mmol/L; the vehicle and blank groups received equivalent saline or no interventions, respectively. HDAC1-3 as well as Vangl2, Scrib and Rac1 mRNA and protein expression levels were determined by quantitative real-time PCR and Western blot, respectively. The total HDAC activity was analyzed by colorimetric assay.</p><p><b>RESULTS</b>The fetus mortality rate after VPA treatment was 31.7%, with a significantly higher rate of cardiac abnormalities in comparison with the controls (P<0.05). In comparison with the blank and vehicle groups, HDAC1 mRNA was significantly increased at various concentrations of VPA treatment at all time points of exposure (P<0.05), together with a reduction of protein level after 48 and 72 hours of exposure (P<0.05). The inhibition of HDAC2 mRNA after various concentrations of VPA incubation was pronounced at 24 hours of exposure (P<0.05), while the protein levels were reduced at all time points (P<0.05). HDAC3 mRNA was prominently induced by VPA (4.0 and 8.0 mmol/L) at all time points of treatment (P<0.05). In contrast, the protein level was inhibited after VPA treatment (P<0.05). In comparison with the blank and vehicle groups, Vangl2 mRNA as well as Scrib mRNA/protein expression levels were markedly reduced after 48 and 72 hours of VPA treatment (P<0.05), together with a reduction of protein level in Vangl2 at 72 hours (P<0.05). Compared with the blank and vehicle groups, a significant repression in the total HDAC activity was observed in the VPA-treated group at concentrations of 4.0 and 8.0 mmol/L after 24 hours of treatment (P<0.05), and the effect persisted up to 48 and 72 hours, exhibiting pronounced inhibition at all concentrations (P<0.05).</p><p><b>CONCLUSIONS</b>VPA might result in acetylation/deacetylation imbalances by inhibiting HDAC1-3 protein expression and total HDAC activity, leading to the down-regulation of mRNA and protein expression of Vangl2 and Scrib. This could be one of the mechanisms contributing to congenital heart disease.</p>

First reported case of fetal aortic valvuloplasty in Asia

Prenatal intervention of severe fetal aortic valve stenosis by ultrasound-guided percutaneous balloon valvuloplasty has been performed to prevent the progression to hypoplastic left heart syndrome, and achieve biventricular circulation in neonates. Here we report a case of fetal aortic valvuloplasty prenatally diagnosed with aortic stenosis at 24 weeks of gestation and showed worsening features on a follow-up echocardiography. Prenatal aortic valvuloplasty was performed at 29 weeks of gestation, and was a technical success. However, fetal bradycardia sustained, and an emergency cesarean delivery was performed. To the best of our knowledge, this is the first reported case of fetal aortic valvuloplasty which was performed in Asia.

Prenatal Diagnosis of Right Dominant Heart in Fetuses: A Tertiary Center Experience over a 7-year Period / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Right dominant heart (RDH) in fetuses can occur with a number of cardiac as well as noncardiac anomalies. Analysis of the enlargement of the right cardiac chamber in the fetus remains a major challenge for sonographers and echocardiographers. The aim of this study was to report the experience with prenatal diagnosis of RDH in the fetuses over a 7-year period.</p><p><b>METHODS</b>Fetuses with prenatal diagnosis of RDH from July 2009 to July 2016 were evaluated in two different categories: according to the gestational age, Group I (n = 154, second trimester) and Group II (n = 298, third trimester); and according to the fetal echocardiography diagnosis, Group A (n = 452, abnormal cardiac structure) and Group B (n = 90, normal cardiac structure). Differences in categorical variables were assessed by Chi-square exact test and continuous variables were evaluated by independent Student's t-test or Mann-Whitney U-test depending on parametric or nonparametric nature of the data.</p><p><b>RESULTS</b>Over a 7-year period, 452 fetuses were referred for the assessment of suspected RDH. Left-sided obstructive lesions were observed most frequently in the fetuses with RDH. When comparing Group I with Group II and Group A with Group B, the latter groups exhibited significant differences in the right/left ventricle (RV/LV) ratio (1.435 vs. 1.236, P = 0.002; 1.309 vs. 1.168, P = 0.047), RV width Z-score (1.626 vs. 1.104, P < 0.001; 1.553 vs. 0.814, P = 0.014), and above +2 cutoff percentages (14.3% vs. 22.5%; P = 0.038; 21.5% vs. 12.2%, P = 0.046). Multivariable logistic regression revealed no variables associated with perinatal survival.</p><p><b>CONCLUSIONS</b>The study demonstrates that RDH warrants careful attention to the possible presence of a structural cardiac anomaly, especially left-sided obstructive lesions. A diagnosis of RDH is best supported by a combination of the RV Z-score and RV/LV ratio. Most of the fetuses with RDH and structurally normal hearts had favorable outcomes.</p>

Anormalidades del tamaño del corazón fetal / Anomalies in the fetal heart disease

Introducción: el corazón fetal es la víscera más difícil de estudiar, debido a que es un órgano móvil con una anatomía compleja y presenta un número importante de anomalías posibles. Objetivos: exponer al alcance de los especialistas dedicados al diagnóstico prenatal una revisión de las posibles causas que modifican el tamaño del corazón fetal. Métodos: la evaluación de su tamaño se realiza a partir de la vista ecocardiográfica de las cuatro cámaras la cual es obtenida realizando un barrido ultrasonográfico desde el abdomen hasta el tórax. Cuando el tamaño es normal, ocupa un tercio del tórax fetal y la circunferencia cardíaca equivale aproximadamente a la mitad de la circunferencia torácica durante todo el curso del embarazo. Resultados: las anomalías del tamaño del corazón pueden ser ocasionadas por disminución o por incremento del radio cardiotorácico. En relación con su incremento es muy importante definir si este es debido a un crecimiento global del corazón o si está afectada una cavidad auricular, ventricular o ambas. En cuanto a la disminución del tamaño este siempre será debido a compresiones intratoráxicas. Conclusiones: la evaluación ecocardiográfica del corazón fetal resulta posible en casi la totalidad de los casos y aporta un elemento de valor al examen prenatal del feto(AU)

Introduction: Fetus heart is the most difficult viscera to be studied, due to the fact that it is a moving organ with a complex anatomy and an important amount of possible anomalies. Objective: To provide the specialists devoted to the prenatal diagnose with a review of the possible causes that modify the fetus heart size. Methods: The heart size is evaluated from an echocardiographic image of its four chambers, which is obtained in an ultrasonic scanning¨from the abdomen to the thorax. When the size is normal, it occupies one third of the fetal thorax and the cardiac circumference is roughly equal to half the thorax circumference throughout the pregnancy. Results: Heart size anomalies could be caused by a drop or an increase of the cardiothoracic radius. It is very important to define whether the increase is due to a global growth of the heart or to an affected atrial or ventricular cavity, or both. Size decreases will always be connected to an intrathoracic compression. Conclusions: Echocardiographic assessment of the fetal heart is possible in almost all cases and provides a valuable element to the fetus prenatal testing(AU)

Validación de un modelo de predicción de necesidad de cirugía cardiovascular o cateterismo terapéutico neonatal en fetos con cardiopatías congénitas / Validation of a prediction model for need of neonatal cardiac surgery or catheter-based therapy in fetuses with congenital heart defects

INTRODUCCIÓN: el diagnóstico prenatal de las cardiopatías congénitas, con nacimiento en centros especializados, permite disminuir la morbimortalidad. Se ha desarrollado un modelo predictivo de necesidad de tratamiento cardíaco intervencionistaneonatal (TCIN) (cirugía cardiovascular y/o cateterismo cardíacoterapéutico) a partir de hallazgos en vistas ecográficas de pesquisa del corazón fetal. Con este modelo sería posible seleccionar a quienes requieren derivación prenatal. OBJETIVOS: Validar dicho modelo predictivo. MÉTODOS: Se llevó a cabo un estudio de cohorte de validación, prospectivo y multicéntrico. Se realizó análisis de regresión logística univariado y multivariado, valoración de calibración del modelo mediante test de Hosmer-Lemeshow, y de discriminaciónmediante valoración de área bajo la curva ROC (Receiver OperatingCharacteristic). RESULTADOS: En 58 (51,8%) de 112 pacientes incluidos se requirió TCIN. La adecuación del ajuste del modelo no resultó estadísticamente significativa (p 0,232), y la discriminación fue buena (área bajo la curva ROC 0,833; IC95%: 0,757-0,909). Para un punto de corte de 0,3 (a partir del cual el riesgo de necesidad de TCIN resultó significativo en el modelo original), hubo sensibilidad de 96,6%, especificidad de 55,6%, valor predictivo positivo de 70% y negativo de 93,8%. CONCLUSIONES: La aplicación del modelo estudiado en fetos con cardiopatías congénitas es factible, presenta una capacidad diagnóstica satisfactoria y constituye una herramienta útil para el manejo perinatal.

INTRODUCTION: prenatal diagnosis of congenital heart diseases allows timely in-utero referral to specialized centersand reduces the risk of morbidity and mortality. A model was developed to predict the need of neonatal cardiac surgery or catheter-based therapy in fetuses with congenital heart defects.With this model, based on fetal cardiac ultrasonographic findings, it would be possible to select patients in need of prenatal referral. OBJECTIVES: To validate such predictive model. METHODS: A prospective multicenter cohort validation study was conducted.Univariate and multivariate logistic regression analysis was performed, evaluating calibration by Hosmer-Lemeshow test and discrimination by area under the curve (AUC) of the receiver operating characteristic (ROC). RESULTS: In 58 (51.8%) of the 112 patients, neonatal cardiac surgery or catheter-based therapy was needed. There was no significant difference between observed and predicted event rates (p 0.232), and discrimination wassatisfactory (AUC of the ROC 0.833; CI95%: 0.757-0.909). For a cut-off probability of 0.3 (that showed significant risk of need for neonatal cardiac invasive therapy in the original model), sensitivity was 96.6%, specificity 55.6%, positive predictive value 70% and negative predictive value 93.8%. CONCLUSIONS: Theapplication of this predictive model in fetuses with congenital heart defects is feasible, shows a good diagnostic ability and can be a useful tool for perinatal management.