Seguimiento del derrame pericárdico fetal aislado: ¿debemos preocuparnos? / Isolated fetal pericardial effusion follow-up: Should we worry?

Introducción y objetivos: El derrame pericárdico fetal aparece en diferentes enfermedades como hidropesía fetal, alteraciones estructurales o del ritmo cardiaco, aunque puede observarse de manera aislada. Se ha observado un incremento de su incidencia con relación a la presencia de enfermedades graves. Métodos: Análisis de la totalidad de casos de derrame pericárdico fetal aislado (DPFA) detectados en Aragón y valorados en consulta cardiológica de diagnóstico prenatal de un hospital terciario recogidos durante 10años, así como la evolución de los pacientes hasta la actualidad. Resultados: Se obtuvo una muestra de 38 fetos en 37 gestantes diagnosticados de DPFA con resolución espontánea en el 86,8%. Se registraron 2abortos (interrupciones voluntarias tras diagnóstico prenatal de deleción 22q13 y de primoinfección por citomegalovirus) y una muerte fetal espontánea. Se objetivaron alteraciones patológicas en 10/38 recién nacidos: 2pacientes con metabolopatía, 2pacientes con cromosomopatía, un paciente con hipoplasia pulmonar e hidronefrosis unilateral, un paciente con miocardiopatía hipertrófica y 4pacientes estudiados por alteraciones del desarrollo psicomotor o alteraciones congénitas oftalmológicas o auditivas. La tasa de morbilidad fue del 34,2% y de fallecimiento del 15,7%. La detección de otras alteraciones ecográficas y la alteración en el cribado del primer trimestre se asociaron de forma significativa con la presencia de patología. Conclusiones: El DPFA se ha asociado clásicamente a buen pronóstico, aunque en ocasiones se relaciona con entidades clínicas con elevada morbimortalidad: más de un tercio de los pacientes en nuestra muestra. Se recomienda un seguimiento estrecho pre y posnatal de estos casos para poder realizar una intervención precoz. (AU)

Introduction and objectives: Fetal pericardial effusion appears in different pathologies such as hydrops fetalis, heart structural or rhythm alterations, however, it can be observed in isolation but an increase in its incidence has been observed in relation to the presence of severe pathologies. Methods: Analysis of all cases of IFPE detected in Aragon and assessed in a cardiological consultation for prenatal diagnosis of a tertiary hospital collected over 10years, as well as the evolution of the patients to the present. Results: A sample of 38 fetuses was obtained from 37 pregnant women diagnosed with DPFA with spontaneous resolution in 86.8%. Two abortions (voluntary interruptions after prenatal diagnosis of 22q13 deletion and primary infection by cytomegalovirus) and one spontaneous fetal death were recorded. Pathological alterations were observed in 10/38 newborns: 2patients with metabolic disease, 2patients with chromosomopathies, one patient with pulmonary hypoplasia and unilateral hydronephrosis, one patient with hypertrophic cardiomyopathy, and 4patients studied for alterations in psychomotor development and/or congenital ophthalmological or hearing disorders. The overall morbidity rate was 34.2% and death rate 15.7%. The detection of other ultrasound alterations and the alteration in the first trimester screening were significantly associated with the presence of pathology. Conclusions: IFPE has been classically associated with a good prognosis, although it is sometimes related to clinical entities with high morbidity and mortality: more than a third of the patients in our sample are affected. An exhaustive pre- and posnatal follow-up of these cases is recommended in order to perform an early intervention. (AU)

Prenatal diagnosis of maternal uniparental disomy 16 associated with mosaic trisomy 16 at amniocentesis, and pericardial effusion and intrauterine growth restriction in the fetus.

OBJECTIVE: We present prenatal diagnosis of maternal uniparental disomy (UPD) 16 associated with mosaic trisomy 16 at amniocentesis, and pericardial effusion and intrauterine growth restriction (IUGR) in the fetus. CASE REPORT: A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, and the result was 47,XX,+16[2]/46,XX[54]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 14% mosaicism for trisomy 16 and a paternally inherited 319-kb microdeletion of 15q11.2 encompassing the genes of TUBGCP5, CYFIP1, NIPA2 and NIPA1. Prenatal ultrasound revealed persistent left superior vena cava, pericardial effusion and severe IUGR. Cordocentesis at 23 weeks of gestation revealed a karyotype of 46,XX, but polymorphic DNA marker analysis revealed maternal UPD 16. Repeat amniocentesis was performed at 27 weeks of gestation and revealed a karyotype of 46, XX in 21/21 colonies. Molecular cytogenetic analysis on uncultured amniocytes revealed 22.4% mosaicism (26/116 cells) for trisomy 16 on interphase fluorescence in situ hybridization (FISH) analysis, and 20% mosaicism for trisomy 16 on aCGH. Polymorphic DNA marker analysis on the DNAs extracted from uncultured amniocytes and parental bloods revealed maternal UPD 16. The pregnancy was subsequently terminated, and a fetus was delivered with facial dysmorphism and severe IUGR. The umbilical cord had a karyotype of 47,XX,+16[28]/46,XX[16]. Polymorphic DNA marker analysis on placenta confirmed a maternal origin of trisomy 16. CONCLUSION: Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may present in mosaic trisomy 16 at amniocentesis. Prenatal diagnosis of mosaic trisomy 16 should alert the association of maternal UPD 16 which may be associated with congenital heart defects and severe IUGR on prenatal ultrasound.

Vertical Transmission of Chikungunya Manifesting as Foetal Pericardial Effusion.

Chikungunya fever is believed to be a self-limiting illness, which can result in significant disability, but with a very low mortality. Chikungunya is uncommonly believed to be associated with serious manifestations. The present case is of a pregnant lady who had transient fever for two days in the third trimester, following which she developed foetal pericardial effusion and intrauterine growth restriction. After two weeks of the fever, in view of non-reactive non-stress test, breech and foetal pericardial effusion, patient was taken up for caesarean section. The neonate was positive for Chikungunya, detected by RT-PCR, while the mother tested positive for Chikungunya IgM antibodies. A diagnosis of Chikungunya pericardial effusion was made in the neonate, presumably acquired vertically secondary to the maternal Chikungunya infection occurring in the third trimester, which was also contributory to intrauterine growth restriction. No case of vertical transmission of Chikungunya has been reported in India, and foetal pericardial effusion has not been reported in world literature.

Comparative analysis of cardiovascular effects of selenium nanoparticles and sodium selenite in zebrafish embryos.

Selenium acts as an important element in the prevention and treatment of cardiovascular diseases but their health-related effects have not been fully explored. As a novel attempt, zebrafish embryos were treated separately with SeNPs (5-25 µg/ml) and sodium selenite (5-25 µg/ml) starting at early blastula stage. Abnormalities were also observed in the morphology of the zebrafish embryos. The SeNPs-treated embryos exhibited concentration-dependent increased in mortality, pericardial edema, and cardiac arrhythmia. In contrast, sodium selenite showed no significant malformation effect in developing zebrafish embryos. The results of the present study conclude that the SeNPs were more toxic than sodium selenite. The results also suggest that lower concentrations of SeNPs and sodium selenite can be used as possible therapeutic agents for cardiovascular-related problems.

Overexpression of miR-19b impairs cardiac development in zebrafish by targeting ctnnb1.

BACKGROUND: MicroRNAs are broadly accepted as crucial regulators of cardiovascular development, and dysregulation of their expression has been linked to cardiac disease. MicroRNA cluster miR-17-92 has been implicated in cardiac development and function, yet its defined mechanisms of action in this context are uncertain. Here, we focused on miR-19b, a key component of the miR-17-92 cluster proven to induce cardiomyocyte proliferation in vitro. We aimed to identify the biological significance of miR-19b in cardiac development and its underlying molecular mechanism of action in vivo. METHODS: We micro-injected zebrafish embryos with different concentrations (0, 2, 4 and 8 µm) of miR-19b mimics or a negative control, and assessed the embryo malformation rate, mortality rate, hatching rate and heart abnormalities at 72 hours post-fertilization (72 hpf). RESULTS: We found that overexpression of miR-19b impacted left-right symmetry and cardiac development of zebrafish embryos, characterized by pericardial edema, slower heart rate and cardiac looping defects in a dose-dependent manner. Moreover, several important signaling molecules in the Wnt signaling pathway were abnormally expressed, suggesting that overexpression of miR-19b induces the inhibition of the Wnt signaling pathway by directly targeting ctnnb1. Interestingly, the deformed cardiac phenotype was partially rescued by treatment with the GSK3ß inhibitor lithium chloride. CONCLUSION: Our findings suggest that miR-19b regulates laterality development and heart looping in zebrafish embryos by targeting ctnnb1.

Fetal right-ventricular hypertrophy with pericardial effusion and maternal untreated hyperthyroidism.

Uncontrolled/untreated maternal hyperthyroidism has been associated with fetal tachycardia. We report a case of right-ventricular (RV) hypertrophy with pericardial effusion related to untreated maternal Graves' disease. A 33-year-old G4P1021 woman with uncontrolled Graves' disease presented at 29 weeks gestation with abdominal pain and vaginal bleeding. Fetal echocardiogram showed severe RV hypertrophy and a pericardial effusion. The infant was born prematurely, and initial transthoracic echocardiogram showed severe RV hypertrophy and a small pericardial effusion. The infant had clinical findings consistent with congenital thyrotoxicosis and was treated for this. Follow-up imaging at 4 weeks showed improvement of the cardiac hypertrophy and pericardial effusion. This article describes the presentation of fetal RV hypertrophy with congenital thyrotoxicosis and underscores the importance of screening for this prenatally in mothers with uncontrolled or untreated hyperthyroidism.

Fetal right ventricular diverticulum with pericardial effusion: report of a new case treated by in utero pericardiocentesis.

Right ventricular diverticulum associated with pericardial effusion was diagnosed in a male fetus at 13 weeks of gestation. Screening for infectious, chromosomal, or structural disease was negative. Because there was concern about pulmonary hypoplasia, fetal pericardiocentesis was performed at 17 weeks of gestation. The pericardial fluid did not reaccumulate, and the diverticulum decreased and finally disappeared before the third trimester. The diverticulum could not be seen on the neonatal echocardiography scan performed on the full-term live baby, who was delivered vaginally. The child is doing well at 11 months of age. Given the good outcome of this case, in utero drainage should be considered in similar cases.

Therapy for foetal pericardial tumours: survival following in utero shunting, and literature review.

We report the first case of foetal pericardial teratoma, treated successfully in utero by pericardio-amniotic shunting, and review the relevant literature. Foetal treatment improves survival in case of hydrops. Foetal pericardio-amniotic shunting could possibly be an alternative to serial pericardiocentesis.

Fluoranthene, but not benzo[a]pyrene, interacts with hypoxia resulting in pericardial effusion and lordosis in developing zebrafish.

Previous research has documented several PAHs that interact synergistically, causing severe teratogenicity in developing fish embryos. The coexposure of CYP1A inhibitors (e.g. FL or ANF) with AHR agonists (e.g. BaP or BNF) results in a synergistic increase in toxicity. As with chemical CYP1A inhibitors, it has also been shown that CYP1A morpholinos exacerbate BNF-induced embryotoxicity. We hypothesized that a hypoxia-induced reduction in CYP1A activity in BNF or BaP-exposed zebrafish embryos would similarly enhance pericardial effusion and other developmental abnormalities. BaP, BNF, ANF, and FL exposures, both individually and as BaP+FL or BNF+ANF combinations, were performed under hypoxia and normoxia. CYP1A activity in the BaP+hypoxia and BNF+hypoxia embryos was reduced by approximately 60% relative to normoxia embryos. Although CYP1A activity was significantly reduced, we did not observe any increase in pericardial effusion in either group. An unexpected yet particularly interesting result of these experiments was the observed interaction of both FL and ANF with hypoxia. Relatively high, yet environmentally relevant concentrations of FL (100-500 microg L(-1)) interact with moderate hypoxia (7.3% DO) through an unknown mechanism, resulting in pericardial effusion and severe lordosis. Additionally, ANF exposures (100 microg L(-1)) which are not normally teratogenic caused dramatic pericardial effusion, but not lordosis, when embryos were coexposed to hypoxia. These results suggest that reduced CYP1A activity may not exclusively underlie observed developmental toxicity, and that hypoxia may exacerbate the developmental toxicity of some PAH mixtures.

CYP1A/regucalcin gene expression and edema formation in zebrafish embryos exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin.

In this study, zebrafish eggs were exposed to a relatively low concentration (50 pg/mL) of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) for 72 h and then transferred to vehicle/TCDD-free water for the remainder of the experiments. Mortality, heart rates, edema severity, CYP1A, and regucalcin gene expressions were investigated to study TCDD-induced toxicity in zebrafish during the early life stage. Results indicated that the 50 pg/mL TCDD caused severe and visible developmental toxicity. Further research of the long term and low concentration of TCDD exposure is required.

Prenatal rupture of a left ventricular diverticulum: a case report and review of the literature.

Congenital left ventricular diverticulum is a rare malformation. We report a case of a ruptured congenital left ventricular diverticulum in a 24-week-old fetus. The fetus was referred for a large and circumferential pericardial effusion confirmed by cross-sectional echocardiography in our tertiary fetal cardiology unit. Pericardiocentesis removed 25 mL of old hematic fluid. The fetus died 5 days later. The pathological examination showed a ruptured submitral fibrous diverticulum of the posterior wall of the left ventricle. There is no previous report in the literature of prenatal rupture of a cardiac diverticulum. The submitral location and the fibrous wall of the diverticulum is uncommon. As regards this case, we reviewed the diagnostic criteria and the outcome of 11 cases of prenatal cardiac diverticulum reported in the literature.

Isolated pericardial effusion and transient abnormal myelopoiesis in a fetus with Down's syndrome.

Isolated pericardial effusion was detected in a fetus at 34 weeks of gestation. A male infant weighing 2,044 g was born by cesarean section because of a non-assuring fetal heart rate pattern at 35 weeks of gestation. Transient leukocytosis (36,100/microl) with 49% blast cells was seen in this neonate. The infant's karyotype was 47, XY + 21. The pericardial effusion disappeared after treatment with prednisolone at a dose of 2 mg/kg/day. Hypothyroidism was subsequently found. Thus, the subject patient with Down's syndrome developed isolated pericardial effusion, transient abnormal myelopoiesis (TAM), and hypothyroidism. Because more than 20% of the infants with TAM and Down's syndrome develop acute nonlymphocytic leukemia in early childhood, he is being closely observed.

Early prenatal diagnosis of ventricular diverticulum complicated by serous pericardial effusion.

An unusual case of apical diverticulum complicated by serous pericardial effusion and diagnosed ultrasonographically at 13 weeks of gestation is described. A therapeutic abortion was induced at 14 weeks and the complete post-mortem examination did not show additional malformation. Cardiac diverticulum is a rare malformation that occurs as an isolated defect or as part of a complex midline thoraco-abdominal defect. Only two prenatally diagnosed cases have been previously reported in the literature and none with associated hydropericardium.

Isolated pericardial effusion: an indication for fetal karyotyping?

The outcome and associations of 35 consecutive cases of isolated pericardial effusion detected in the fetus are presented. In all cases included in the study, there was no evidence of a structural abnormality or a rhythm disturbance detectable antenatally. Karyotyping revealed that 26% of cases had trisomy 21 and 31% of the total had some form of chromosomal anomaly. Our study shows that the outlook for isolated pericardial effusion is good. However, there is a high incidence of associated karyotypic anomalies, in particular trisomy 21. Fetal karyotyping is therefore recommended in these cases.

Thoraco-amniotic shunting.

Thoraco-amniotic shunting was performed in 51 singleton pregnancies for decompression and chronic drainage of fetal pleural effusions (n = 47), pericardial effusion (n = 1), or pulmonary cysts (n = 3). Five fetuses had chromosomal defects and in 4 the parents elected termination of pregnancy. All 18 non-hydropic fetuses and 14 of the 28 with hydrops survived. Thoraco-amniotic shunting is useful for diagnostic evaluation and treatment of fetuses with pathologic collection of intrathoracic fluid.

The prenatal diagnosis of congenital heart disease--a practical approach for the fetal sonographer.

With the widespread use of diagnostic ultrasound to evaluate the human fetus, it is now possible to diagnose a number of anomalies of varying organ systems. Although most anomalies of the central nervous, gastrointestinal, genitourinary, and skeletal systems are recognizable at birth, serious ones involving the cardiovascular system are often silent until the neonate demonstrates signs of cardiovascular compromise. Because an ever increasing number of fetuses are routinely scanned during pregnancy, it becomes imperative to incorporate a simple, logical approach to screen for cardiovascular disease during each fetal examination. The approach outlined in this paper would suggest that one method is the routine examination of the four-chamber view. Although there are a number of fetal and maternal risk factors which predispose to congenital heart disease, we have diagnosed a number of anomalies simply on the basis of the "screening" four-chamber examination in the "low-risk" fetus. For this reason, an attempt to examine the four-chamber view of the fetal heart should be done during each routine fetal examination. If an abnormality is noted, then a Level II, or consultative echocardiographic examination should be carried out. If a fetus at risk for congenital heart disease is being examined, a complete examination of the cardiovascular system (Levels I and II) should be performed. If the above approaches are integrated into obstetrical scanning, in the not too distant future it will be commonplace to diagnose cardiovascular anomalies prior to birth and thus provide the best care during the transition from the intrauterine to the extrauterine environment for the potentially cardiovascularly compromised neonate. The experience gained in our laboratory during the past 5 years strongly suggests that what is "today's research will become tomorrow's clinical tool."