Parvovirus B19 in Pregnancy.

Importance: Although the risk of parvovirus B19 infection during pregnancy and subsequent risk of adverse fetal outcome are low, understanding management practices is essential for proper treatment of fetuses with nonimmune hydrops fetalis. In addition, continued investigation into delivery management, breastfeeding recommendations, and congenital abnormalities associated with pregnancies complicated by parvovirus B19 infection is needed. Objective: This review describes the risks associated with parvovirus B19 infection during pregnancy and the management strategies for fetuses with vertically transmitted infections. Evidence Acquisition: Original articles were obtained from literature search in PubMed, Medline, and OVID; pertinent articles were reviewed. Results: Parvovirus B19 is a viral infection associated with negative pregnancy outcomes. Up to 50% of people of reproductive age are susceptible to the virus. The incidence of B19 in pregnancy is between 0.61% and 1.24%, and, overall, there is 30% risk of vertical transmission when infection is acquired during pregnancy. Although most pregnancies progress without negative outcomes, viral infection of the fetus may result in severe anemia, congestive heart failure, and hydrops fetalis. In addition, vertical transmission carries a 5% to 10% chance of fetal loss. In pregnancies affected by fetal B19 infection, Doppler examination of the middle cerebral artery peak systolic velocity should be initiated to surveil for fetal anemia. In the case of severe fetal anemia, standard fetal therapy involves an intrauterine transfusion of red blood cells with the goal of raising hematocrit levels to approximately 40% to 50% of total blood volume. One transfusion is usually sufficient, although continued surveillance may indicate the need for subsequent transfusions. There are fewer epidemiologic data concerning neonatal risks of congenital parvovirus, although case reports have shown that fetuses with severe anemia in utero may have persistent anemia, thrombocytopenia, and edema in the neonatal period. Conclusions and Relevance: Parvovirus B19 is a common virus; seropositivity in the geriatric population reportedly reaches 85%. Within the pregnant population, up to 50% of patients have not previously been exposed to the virus and consequently lack protective immunity. Concern for parvovirus B19 infection in pregnancy largely surrounds the consequences of vertical transmission of the virus to the fetus. Should vertical transmission occur, the overall risk of fetal loss is between 5% and 10%. Thus, understanding the incidence, risks, and management strategies of pregnancies complicated by parvovirus B19 is essential to optimizing care and outcomes. Further, there is currently a gap in evidence regarding delivery management, breastfeeding recommendations, and the risks of congenital abnormalities in pregnancies complicated by parvovirus B19. Additional investigations into optimal delivery management, feeding plans, and recommended neonatal surveillance are needed in this cohort of patients.

Hydrops fetalis caused by a complex congenital heart defect with concurrent hypoplasia of pulmonary blood vessels and lungs visualized by micro-CT in a French Bulldog.

BACKGROUND: Hydrops fetalis (HF) is fluid accumulation in fetus body cavities and subcutaneous tissue. The condition has been described in various farm and companion animal species, including dogs. Most of cases result from a heart defect. Exact nature of this defect is rarely clarified. CASE PRESENTATION: A newborn, male French bulldog puppy with severe HF underwent a full anatomopathological examination to diagnose the primary cause of HF. Based on the anatomopathological examination, fetal ultrasound, and micro-computed tomography, transposition of the great arteries with hypoplasia of the ascending aorta, aortic arch interruption, ostium secundum atrial septal defect, severe tricuspid valve dysplasia, as well as hypoplasia of pulmonary vessels and lungs were diagnosed. CONCLUSIONS: This is the first report of HF caused by severe, complex congenital heart defects with concurrent pulmonary vessel and lung hypoplasia.

Comparing three cardiothoracic ratio measurement techniques and creating multivariable scoring system to predict Bart's hydrops fetalis at 17-22 weeks' gestation.

To assess the diagnostic performance of three cardiothoracic (CT) ratio techniques, including diameter, circumference, and area, for predicting hemoglobin (Hb) Bart's disease between 17 and 22 weeks' gestation, and to create a multivariable scoring system using multiple ultrasound markers. Before invasive testing, three CT ratio techniques and other ultrasound markers were obtained in 151 singleton pregnancies at risk of Hb Bart's disease. CT diameter ratio demonstrated the highest sensitivity among the other techniques. Significant predictors included CT diameter ratio > 0.5, middle cerebral artery-peak systolic velocity (MCA-PSV) > 1.5 multiples of the median, and placental thickness > 3 cm. MCA-PSV exhibited the highest sensitivity (97.8%) in predicting affected fetuses. A multivariable scoring achieved excellent sensitivity (100%) and specificity (84.9%) for disease prediction. CT diameter ratio exhibited slightly outperforming the other techniques. Increased MCA-PSV was the most valuable ultrasound marker. Multivariable scoring surpassed single-parameter analysis in predictive capabilities.

Changing epidemiology of parvovirus B19 in the Netherlands since 1990, including its re-emergence after the COVID-19 pandemic.

Parvovirus B19V (B19V) infection during pregnancy can be complicated by potentially life-threatening fetal hydrops, which can be managed by intrauterine transfusion (IUT). This study investigates the long-term temporal patterns in the epidemiology of B19V and evaluates the impact on fetal hydrops, by combining data on B19V infections from the Dutch Sentinel Surveillance system in the period 1990 to 2023, Dutch blood banking data and hospital data on fetal hydrops. Using wavelet analysis, we identified annual epidemic cycles in the Netherlands in the period 1990-2019 and we identified superimposed multiannual cycles in the period 1990-2009. After 2009, no multiannual cycle could be identified, although the incidence fluctuated and correlates with number of IUT performed. As of 2020, weekly reports of B19V infection demonstrated a historically low incidence and B19V-DNA positive blood donors were nearly absent. From May 2020 to May 2023, no IUT for B19V-related hydrops was performed. In the spring of 2023, B19V infections re-emerged, reaching pre-pandemic epidemic levels. Due to the changes in B19V epidemiology over the last 30 years and the near-absence of B19V during the COVID-19 pandemic, the resulting low immunity levels may lead to rebound outbreaks. Alertness to severe complications such as fetal hydrops is warranted.

The role of fetal therapy in the management of mirror syndrome: a narrative review.

OBJECTIVES: Mirror syndrome (MS) is a condition characterized by the presence of maternal, fetal, and placental edema and is reversible through delivery or pregnancy termination. As fetal hydrops itself may be amenable to treatment, we sought to determine outcomes for MS primarily managed by fetal therapy through a narrative review of the literature and cases managed at our fetal center. STUDY DESIGN: PubMed, Embase, Web of Science, Scopus, and Google Scholar databases were searched through January 2024 using key words: mirror syndrome, Ballantyne's syndrome, fetal hydrops, maternal hydrops, pseudotoxemia, triple edema, maternal recovery, fetal therapy, and resolution. Manuscripts describing primary management by fetal therapy that included maternal and fetal outcomes were identified. Clinical details of MS patients managed with fetal therapy at our center were also included for descriptive analysis. RESULTS: 16 of 517 manuscripts (3.1%) described fetal therapy as the primary intended treatment in 17 patients. 3 patients managed at our center were included in the analysis. Among 20 patients undergoing primary fetal therapy for management of mirror syndrome, median gestational age of presentation was 24 weeks and 5 days gestation; predominant clinical findings were maternal edema (15/20), proteinuria (10/20), pulmonary edema (8/20), and hypertension (8/20); the primary laboratory abnormalities were anemia (8/20) and elevated creatinine or transaminases (5/20). Condition-specific fetal therapies led to resolution of hydrops in 17 (85%) cases and MS in 19 (95%) cases. The median time to hydrops resolution was 7.5 days and to resolution of mirror syndrome was 10 days. Fetal therapy prolonged pregnancy by a median of 10 weeks with a median gestational age of 35 weeks and 5 days at delivery. All women delivered for indications other than mirror syndrome and 19/20 fetuses survived. CONCLUSION: In appropriately selected cases, MS often resolves after fetal therapy of hydrops allowing for safe pregnancy prolongation with good maternal and infant outcomes.

Perinatal Results and Long-Term Follow-Up of Fetal Cardiac Tumors: A 30-Year Historical Cohort Study. / Resultados Perinatais e Seguimento em Longo Prazo de Tumores Cardíacos Fetais: Estudo de Coorte Histórica de 30 Anos.

BACKGROUND: This was a 30-year retrospective cohort study that approximates closely to the natural history of cardiac tumors diagnosed in the fetus, since there was no case of pregnancy interruption. OBJECTIVE: To assess morbidity and mortality in the perinatal period and at long term in fetuses diagnosed with cardiac tumor. Our secondary objective was to assess the evaluating factors of perinatal and postnatal results. METHODS: This was a retrospective cohort study with 74 pregnant women with an echocardiographic diagnosis of fetal cardiac tumor at two referral centers between May 1991 and November 2021. A descriptive analysis was performed, and data were expressed as absolute (n) and relative (%) frequencies, median and interquartile range. Fisher's exact test was used to evaluate the association of echocardiographic characteristics and clinical manifestations with perinatal and postnatal results. Global survival was calculated using the Kaplan-Meier method and the curves were compared by the log-rank test. The time of follow-up, calculated in months, corresponded to the time elapsed from hospital discharge to current status (survived/ censoring or death). The level of significance was set at 5% (p<0.05). RESULTS: Rhabdomyoma is the most common type of cardiac tumor (85%), with a high morbidity (79.3%) and overall mortality of 17.4%. The presence of fetal hydrops was a predictor of death. CONCLUSION: The presence of fetal hydrops had an impact on mortality, and hence is an important factor in counselling and determining the prognosis. Most deaths occurred before hospital discharge.

FUNDAMENTO: Seguimento de coorte retrospectiva de 30 anos que se aproxima da história natural dos tumores cardíacos diagnosticados no feto uma vez que nenhum caso foi submetido à interrupção da gestação. OBJETIVO: Avaliar a morbidade e mortalidade perinatal e em longo prazo em fetos com diagnóstico de tumor cardíaco. Como objetivo secundário avaliar os fatores que influenciaram os resultados perinatais e pós-natais. MÉTODO: Estudo de coorte retrospectiva envolvendo 74 gestantes com diagnóstico ecocardiográfico fetal de tumor cardíaco acompanhadas em dois serviços de referência no período de maio de 1991 a novembro de 2021. Foi realizada análise descritiva dos dados por meio de frequências absolutas (n) e relativas (%), mediana e intervalos interquartis. Para avaliar a associação entre as características ecocardiográficas e as manifestações clínicas com os resultados perinatais e pós-natais, foi aplicado o teste exato de Fisher. O cálculo da sobrevida global foi realizado pelo método de Kaplan-Meier e a comparação de curvas pelo teste de log-rank. O tempo de seguimento, calculado em meses, foi definido a partir da data de alta do hospital à data do status atual (vivo/censura ou óbito). O nível de significância considerado foi de 5% (p<0,05). RESULTADOS: o rabdomioma é o tipo mais frequente (85%) de tumor cardíaco; apresenta alta morbidade (79,3%) e mortalidade geral de 17,4%; a presença de hidropisia fetal preditiva de óbito. CONCLUSÃO: A presença de hidropisia fetal teve impacto na mortalidade, sendo fator importante para aconselhamento e estabelecimento de prognóstico. A maioria dos óbitos ocorrem antes da alta hospitalar.

Retrospective study and implementation of a low-cost LAMP-turbidimetric assay for screening α0-thalassemia (SEA deletion): preventing and controlling Hb Bart's hydrops fetalis syndrome in Thailand.

Homozygous α0-thalassemia (SEA deletion) or Hb Bart's hydrops fetalis syndrome is a significant public health issue in Thailand and Southeast Asia. A prevention and control program has been implemented in this region. This study focuses on retrospective laboratory data collected between January 2021 and April 2023 at a single center. Additionally, we developed a low-cost LAMP-turbidimetric assay to propose in the screening strategy. A total of 3,623 samples underwent screening tests (MCV, MCH, and DCIP), including 1,658 couple screenings (84.25%) and 310 single pregnant screenings (15.75%). Negative screenings, which did not require further investigation, were found in 75.51% for couple screenings and 46.58% for single pregnant screenings. At hemoglobin (Hb) analysis identified 129 couples which had fetuses at risk of severe thalassemia, whereas molecular analysis during the retrospective period revealed 210 samples with different genotypes. These remaining samples were validated using the low-cost LAMP-turbidimetric assay to detect α0-thalassemia (SEA deletion). The developed LAMP turbidimetric assay demonstrated a sensitivity and specificity of 100% (36/36 × 100) and 97.7% (170/174 × 100), respectively, when compared with gap-PCR. Furthermore, we propose a strategy involving the addition of the low-cost LAMP-turbidimetric assay before performing the gold standard. This strategy represents a cost-saving of USD 2,608 based on 210 samples that required DNA analysis. Finally, the developed LAMP turbidimetric assays offer advantages such as reduced time, workload, cost savings, no need for highly developed instruments, and a straightforward interpreting process. Therefore, implementation of LAMP assays into routine settings would be improve the efficiency of prevention and control program for severe thalassemia disease in this region.

Chromosomal abnormalities associated with fetal pleural effusion (I): General overview.

Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides an overview of chromosomal abnormalities associated with fetal pleural effusion which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.

Syndromic and single gene disorders associated with fetal pleural effusion (I): Noonan syndrome, RASopathy and congenital lymphatic anomalies.

Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides an overview of syndromic and single gene disorders associated with fetal pleural effusion that is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.

Chromosomal abnormalities associated with fetal pleural effusion (II): Specific and non-specific chromosome aberrations.

Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides a comprehensive view of specific and non-specific chromosome aberrations associated with fetal pleural effusion which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.

A singleton pregnancy with placental chorioangioma and hydrops fetalis complicated with mirror syndrome and ritodrine-induced side effects: a case report.

BACKGROUND: Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma. CASE PRESENTATION: A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion. CONCLUSION: Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.

Novel premature termination codon in the FOXP3 gene as the cause of familial hydrops fetalis in males.

A 19-year-old, G1P0, pregnant person was referred at 20w2d gestation for evaluation due to non-immune hydrops fetalis (NIHF), which was confirmed at the time of evaluation. Amniocentesis was performed at 20 w4d, and FISH, karyotype, chromosomal microarray, and exome sequencing (ES) were ordered. Trio ES identified a novel hemizygous c.142 C > T (p.Arg48*; maternally inherited) variant in the FOXP3 gene, resulting in a premature termination codon and establishing the diagnosis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Intrauterine fetal demise (IUFD) was diagnosed at 21w3d. CVS was performed at 12w1d in a subsequent pregnancy (male fetus) and the known familial variant was identified. NIHF was identified at 18w1d. Ultrasound at 19w2d revealed IUFD. This is the first report of this variant in a diagnosis of IPEX syndrome, presenting with NIHF and male fetal demise. Genotype-phenotype correlations are not available in many cases of IPEX syndrome, as the same genotype can be present with variable severity in different individuals. Given the near identical presentations in this family, we anticipate a more severe phenotype with this variant. We propose a novel variant resulting in an early premature termination codon as an explanation for the severe presentation of IPEX syndrome in two successive fetuses in this family.

Neonatos con diagnóstico prenatal de hidrops fetal: experiencia durante 10 años en un centro de tercer nivel / Neonates with a prenatal diagnosis of hydrops fetalis: A 10-year experience in a tertiary care center

Introducción: El hidrops fetal (HF) es una condición rara con una alta mortalidad. Este estudio analiza la evolución obstétrica y perinatal de los diagnósticos prenatales de HF, relacionándola con la etiología y el tratamiento intrauterino (TIU) recibido. Pacientes y métodos: Se revisaron 164 gestantes con diagnóstico prenatal de HF entre 2011 y 2021. Se registraron intervenciones prenatales, hallazgos clínicos, etiologías y resultados de los recién nacidos vivos. Resultados: Se realizó un estudio invasivo prenatal en el 79,3% de los pacientes. Las etiologías mayoritarias fueron alteraciones genéticas (31%), infecciones TORCH y por parvovirus B19 (9,7%), y cardiopatías estructurales (9,1%). En el 25,6% se realizó TIU, y entre todas las gestaciones, el 74,4% fueron interrumpidas. Las alteraciones genéticas tuvieron tasas más altas de interrupción legal del embarazo respecto a otras etiologías (p<0,01). Del total, solo nacieron el 25,6% de los fetos, la mayoría pretérmino. Los que recibieron TIU gozaron de mayores tasas de supervivencia perinatal y al año de vida (p<0,001). De entre aquellos nacimientos, las cardiopatías estructurales presentaron las peores tasas de supervivencia, mientras que las causas con mejor pronóstico fueron las taquiarritmias. La supervivencia al año de vida entre aquellos recién nacidos vivos fue del 70%, pero el 58,6% asociaron morbilidad significativa al alta. Conclusiones: A pesar de los avances en el manejo del HF, el mal pronóstico obstétrico, la mortalidad perinatal y la morbilidad de los supervivientes siguen siendo significativos. Estos datos son importantes para asesorar a las familias que reciben un diagnóstico prenatal de HF.(AU)

Introduction: Hydrops fetalis (HF) is a rare condition with a high mortality. This study analysed the obstetric and perinatal outcomes of antenatally diagnosed HF according to its aetiology and the possibility of intrauterine treatment (IUT). Patients and methods: We carried out a retrospective review of the health records of 164 pregnant women with a prenatal diagnosis of HF in a tertiary care centre between 2011 and 2021. We analysed prenatal interventions, clinical findings, aetiologies and obstetric and live-born infant outcomes. Results: An invasive prenatal study had been performed in 79.3% cases. The most common aetiologies were genetic disorders (31%), TORCH and parvovirus B19 infections (9.7%) and structural heart diseases (9.1%). Intrauterine treatment was performed in 25.6%, and 74.4% of pregnancies were terminated. Pregnancies with a prenatal diagnosis of genetic or chromosomal disorders had higher rates of elective termination compared to other aetiologies (P<.01). Among all pregnancies, only 25.6% resulted in live births (LBs), most of them preterm. Perinatal and 1-year survival rates were higher in the group that received IUT (P<.001). Among the LBs, structural heart diseases had the worst survival rates, while the aetiology with the best outcomes was tachyarrhythmia. Survival at 1year of life among those born alive was 70%, but 58.6% of these infants had significant morbidity at discharge. Conclusions: Despite advances in the management of FH, the poor obstetric prognosis, perinatal mortality and morbidity of survivors is still significant. These data are important for the purpose of counselling families when HF is diagnosed antenatally.(AU)

Neonates with a prenatal diagnosis of hydrops fetalis: A 10-year experience in a tertiary care center.

INTRODUCTION: Hydrops fetalis (HF) is a rare condition with a high mortality. This study analysed the obstetric and perinatal outcomes of antenatally diagnosed HF according to its aetiology and the possibility of intrauterine treatment (IUT). PATIENTS AND METHODS: We carried out a retrospective review of the health records of 164 pregnant women with a prenatal diagnosis of HF in a tertiary care centre between 2011-2021. We analysed prenatal interventions, clinical findings, aetiologies and obstetric and live-born infant outcomes. RESULTS: An invasive prenatal study had been performed in 79.3% cases. The most common aetiologies were genetic disorders (31%), TORCH and parvovirus B19 infections (9.7%) and structural heart diseases (9.1%). Intrauterine treatment was performed in 25.6%, and 74.4% of pregnancies were terminated. Pregnancies with a prenatal diagnosis of genetic or chromosomal disorders had higher rates of elective termination compared to other aetiologies (P < .01). Among all pregnancies, only 25.6% resulted in live births (LBs), most of them preterm. Perinatal and 1-year survival rates were higher in the group that received IUT (P < .001). Among the LBs, structural heart diseases had the worst survival rates, while the aetiology with the best outcomes was tachyarrhythmia. Survival at 1 year of life among those born alive was 70%, but 58.6% of these infants had significant morbidity at discharge. CONCLUSIONS: Despite advances in the management of FH, the poor obstetric prognosis, perinatal mortality and morbidity of survivors is still significant. These data are important for the purpose of counselling families when HF is diagnosed antenatally.

PIEZO Ion Channels in Cardiovascular Functions and Diseases.

The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is primed with mechanosensory structures that respond and adapt to changes in mechanical stimuli. Since their discovery in 2010, PIEZO ion channels have dominated the field of mechanobiology. These have been proposed as the long-sought-after mechanosensitive excitatory channels involved in touch and proprioception in mammals. However, more and more pieces of evidence point to the importance of PIEZO channels in cardiovascular activities and disease development. PIEZO channel-related cardiac functions include transducing hemodynamic forces in endothelial and vascular cells, red blood cell homeostasis, platelet aggregation, and arterial blood pressure regulation, among others. PIEZO channels contribute to pathological conditions including cardiac hypertrophy and pulmonary hypertension and congenital syndromes such as generalized lymphatic dysplasia and xerocytosis. In this review, we highlight recent advances in understanding the role of PIEZO channels in cardiovascular functions and diseases. Achievements in this quickly expanding field should open a new road for efficient control of PIEZO-related diseases in cardiovascular functions.