Hydrops Fetalis Research Articles

Maternal "mirror" syndrome: Evaluating the benefits of fetal therapy.

To evaluate maternal and perinatal outcomes following fetal intervention in the context of maternal "mirror" syndrome. A multicenter retrospective study of all cases of fetal hydrops complicated by maternal "mirror" syndrome and treated by any form of fetal therapy between 1995 and 2022. Medical records and ultrasound images of all cases were reviewed. "Mirror" syndrome was defined as fetal hydrops and/or placentomegaly associated with the maternal development of pronounced edema, with or without pre-eclampsia. Fetal hydrops was defined as the presence of abnormal fluid collections in ≥2 body cavities. Twenty-one pregnancies met the inclusion criteria. Causes of fetal hydrops and/or placentomegaly included fetal lung lesions (n=9), twin-twin transfusion syndrome (n=6), severe fetal anemia (n=4), and others (n=2). Mean gestational age at "mirror" presentation was 27.0±3.8weeks. Maternal "mirror" syndrome was identified following fetal therapeutic intervention in 14 cases (66.6%). "Mirror" symptoms resolved or significantly improved before delivery in 8 (38.1%) cases with a mean interval from fetal intervention to maternal recovery of 13.1days (range 4-35). Three women needed to be delivered because of worsening "mirror" syndrome. Of the 21 pregnancies treated (27 fetuses), there were 15 (55.5%) livebirths, 7 (25.9%) neonatal deaths and 5 (18.5%) intra-uterine deaths. Following successful treatment and resolution of fetal hydrops, maternal "mirror" syndrome can improve or sometimes completely resolve before delivery. Furthermore, the recognition that "mirror" syndrome may arise only after fetal intervention necessitates hightened patient maternal surveillance in cases of fetal hydrops.

Nonimmune Hydrops Fetalis and Early Skeletal Changes in Congenital Syphilis: Case Series and Review of Literature

Nonimmune Hydrops Fetalis and Early Skeletal Changes in Congenital Syphilis: Case Series and Review of Literature

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

BackgroundHydrops 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 presentationA 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.ConclusionsThis is the first report of HF caused by severe, complex congenital heart defects with concurrent pulmonary vessel and lung hypoplasia.

Congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disease due to the deficient, but not absent, activity of uroporphyrinogen III synthase (UROS), the fourth enzyme in the heme biosynthesis pathway. Biallelic variants in the UROS gene result in decreased UROS enzymatic activity and the accumulation of non-physiologic Type I porphyrins in cells and fluids. Overproduced uroporphyrins in haematopoietic cells are released into the circulation and distributed to tissues, inducing primarily hematologic and dermatologic symptoms. The clinical manifestations vary in severity ranging from non-immune hydrops fetalis in utero to mild dermatologic manifestations in adults. Here, the biochemical, molecular and clinical features of CEP as well as current and new treatment options, including the rescue of UROS enzyme activity by chaperones, are presented.

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program

BackgroundMucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.MethodsThis disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022.ResultsAs of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and − 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died.ConclusionsTo date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.

β-arrestin1/2 are essential for embryonic lymphatic vessel development

Lymphatic dysfunction can lead to fetal loss due to interstitial edema known as hydrops fetalis during development and lymphedema in adulthood. Lymphedema affects an estimated 250 million individuals worldwide, yet there is no effective treatment available. Numerous studies have established G protein-coupled receptors (GPCRs) as key lymphangiogenic signaling pathways and ideal druggable therapeutical targets. β-arrestins (β-arrestin 1 and 2) are ubiquitously expressed cytosolic adaptor proteins which perform a wide range of functions in GPCR pathways, such as promoting agonist-induced internalization and forming signaling scaffolds with internalized GPCRs in endosomes. However, the roles of β-arrestins in lymphatic vessel development and function remain undefined. We hypothesize that β-arrestin1/2 are essential in embryonic lymphatic vessel development. To test this hypothesis, I used an inducible β-arrestin1fl/fl (Arrb1 fl/fl), β-arrestin2fl/fl (Arrb2 fl/fl);Prox1 CreERT2 mouse line. β-arrestin1 and 2 were deleted by oral gavage of tamoxifen at embryonic day 10.5 (E10.5) and E12.5, critical points for developmental lymphangiogenesis. Compared to Arrb1/2fl/flembryos, the Arrb1/2fl/fl;Prox1CreERT2 embryos exhibit profound hydrops fetalis, subcutaneous hemorrhages, and increased embryonic lethality between E14.5 and E16.5. At E15.5, the Arrb1/2fl/fl;Prox1CreERT2 embryos with edema show decreased weight indicating growth restriction compared to controls. Jugular lymphatic sacs are enlarged and filled with blood in Arrb1/2fl/fl;Prox1CreERT2 embryos compared to controls. Dermal lymphatic vessel length in the Arrb1/2fl/fl;Prox1CreERT2 embryos is shorter than controls. Collectively, our results demonstrate that loss of β-arrestin1/2 expression in lymphatics causes mid-gestational arrest in lymphatic development and fetal growth restriction, indicating that β-arrestins are required for developmental lymphangiogenesis in mammals. American Physiological Society postdoctoral Fellowship (to YT) and NIH R01 HL129086 (to KMC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Parvovirus B19 in Pregnancy.

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. This review describes the risks associated with parvovirus B19 infection during pregnancy and the management strategies for fetuses with vertically transmitted infections. Original articles were obtained from literature search in PubMed, Medline, and OVID; pertinent articles were reviewed. 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. 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.

Management of Fetal Hemolytic Disease Due to Anti-Rh17 With the D−Phenotype [ID 2683500

INTRODUCTION: The rare blood D− haplotype produces multiple Rh antibodies against red blood cell antigens such as anti-Rh17 or anti-Hr0 antibodies if a patient is sensitized to Rh antigens. METHODS: This report discusses successful management of a pregnancy in a 28-year-old woman with high anti-Rh17 titers leading to hemolytic disease of the fetus (HDFN). The combination of a D− allele and the weak D 45 allele has not been reported previously, and it may be that the hybrid allele expresses D antigen epitopes such that the D antigen is not weakened. During the studied pregnancy, the patient received plasmapheresis and intravenous immunoglobulin (IVIG) infusions along with intrauterine transfusions (IUTs) when absolutely necessary. She underwent uncomplicated repeat cesarean delivery at 32 5/7 weeks of gestation resulting in a female infant weighing 2,020 g. Patient informed consent was obtained for this case report. CONCLUSION: This patient with the D−/D− blood phenotype leading to anti-Rh17 antibodies after her first pregnancy was managed successfully. Her baby with HDFN and several instances of hydrops fetalis, was successfully managed and treated. The patient’s blood donations for IUTs and maternal plasma exchange therapies promoted efficiency and favorable outcomes for the baby, but did put the mother in an anemic blood range.

Estudo comparativo de análise ultrassonográfica e anatomopatológica de fetos caninos apresentando hidropisia fetal

Fetal hydrops is a pathological condition that is incompatible with the life of the affected animal and can lead to fetal distortions. The diagnosis is frequent in routine dog neonatology and can be made by gestational ultrasound and/or necroscopic study. To carry out this study, we analyzed three stillborn fetuses from French bulldog dogs with hydrops using echographic and anatomopathological techniques. Ultrasound was used to check for the presence of fluid in tissues such as the subcutaneous tissue, the abdominal and thoracic cavity and the intraencephalic tissue. The necroscopic study revealed morphological changes in the brain and the presence of hydropericardium. This confirmed that ultrasound can accurately identify subcutaneous and intracavitary fluids, as well as verify the brain morphology of fetuses. However, there is evidence of limitations to the ultrasound technique, given that alterations such as hydropericardium and encephalic morphological changes were not detected during the ultrasound study.

Ultrasound-guided laser photocoagulation for the treatment of fetal bronchopulmonary sequestration. Report of two successful cases in Venezuela.

Bronchopulmonary sequestration is a malformation of the respiratory system consisting of non-functioning bronchial and pulmonary tissue, separated from the tracheo-bronchial tree and fed by a blood vessel from the systemic circulation. The incidence is 1 in 5000 births, ranging from 0.15% to 6.45% of pulmonary pathologies. The prognosis is generally favorable, with spontaneous regression of the lesion reported in 50% to 75% of patients. It can cause mass effect, compressing the heart and lung to the point of generating hemodynamic changes and heart failure. There are multiple procedures for treatment and management, mainly in large cases and hydropic fetuses, to improve perinatal prognosis. We present the first two cases of bronchopulmonary sequestration treated in Venezuela by laser photocoagulation of the nutrient vessel and their perinatal evolution, with 100% survival and without any complications recorded in the perinatal period.

Perinatal Outcomes of Intrauterine Interventions for Fetal Sacrococcygeal Teratoma Based on Different Surgical Techniques-A Systematic Review.

Background: This study aims to evaluate the outcomes of fetal sacrococcygeal teratoma (SCT) submitted to prenatal interventions. Methods: We performed a systematic literature review of fetal SCT patients and compared the outcomes between open fetal surgery and percutaneous intervention. In addition, we also compared the results of SCT fetuses who did not undergo any surgical intervention (NI). Results: We identified 16 cases of open fetal surgery (OS), 48 cases of percutaneous fetal intervention (PI), and 93 NI patients. The survival rate was 56.2% in OS, 45.8% in PI (p = 0.568), and 71.0% in NI patients. The gestational age at delivery was earlier in cases where there was no survival compared to cases where the fetuses did survive across all evaluated cohorts (OS: p = 0.033, PI: p < 0.001, NI: p < 0.001). The gestational weeks at delivery in OS and PI fetuses were more similar; however, OS tended to be performed later on in pregnancy, and the affected fetuses had more severe presented findings. In our evaluation, we determined that the presence of fetal hydrops and cardiac failure had no significant impact on survival in SCT cases. In NI patients, polyhydramnios was much higher in fetuses who did not survive compared to their surviving cohorts (p < 0.001). Conclusions: In conclusion, gestational age at delivery can affect the short-term prognosis of fetuses affected with sacrococcygeal teratomas. Regardless of the mode of delivery or the necessity for intervention during the fetal period, monitoring for complications, including polyhydramnios, can prevent premature delivery.

Staged biventricular repair in a premature neonate with critical aortic stenosis, severe mitral regurgitation, and fetal hydrops: a case report

BackgroundThe surgical management of critical aortic stenosis, mitral regurgitation, and left ventricular dysfunction is a significant clinical challenge. Whether left ventricular function will recover to support systemic circulation after the relief of aortic stenosis is a concern. In this setting, surgical or balloon aortic valvotomy combined with bilateral pulmonary artery banding and atrial septectomy may allow time for left ventricular adaptation, while the systemic circulation is supported by the right ventricle through the ductus arteriosus. We describe the case of a premature neonate with critical aortic stenosis, severe mitral regurgitation, and fetal hydrops who successfully underwent staged biventricular repair after bilateral pulmonary artery banding, atrial septectomy, balloon aortic valvuloplasty, and stent implantation for ductus arteriosus.Case presentationA 29-year-old female was referred to our hospital at 25 weeks of gestation with fetal echocardiography findings of critical aortic stenosis, severely impaired left ventricular function, severe mitral regurgitation, and restrictive foramen ovale. At 33 weeks of gestational age, the baby was born via cesarean delivery. Prostaglandin E1 infusion was immediately initiated, and the neonate underwent emergecy bilateral pulmonary artery banding and atrial septectomy. On the second day, a balloon aortic valvuloplasty was performed. The neonate underwent stent implantation to open the ductus arteriosus and multiple-balloon aortic valvuloplasty. At 4 months of age, he underwent biventricular repair consisting of surgical aortic valvuloplasty, atrial septal defect closure, bilateral pulmonary artery debanding, and ductus arteriosus ligation. At 1 year of age, he underwent the Ross –Konno procedure. Six years after the operation, the patient’s general condition was stable, and the patient is doing well.ConclusionsStaged biventricular repair was successfully achieved in a premature neonate with fetal hydrops and critical aortic stenosis associated with severe mitral valve regurgitation and left ventricular dysfunction.

The American Association for Thoracic Surgery (AATS) 2024 expert consensus document: Management of neonates and infants with Ebstein anomaly

ObjectivesSymptomatic neonates and infants with Ebstein anomaly (EA) require complex management. A group of experts was commissioned by the American Association for Thoracic Surgery to provide a framework on this topic focusing on risk stratification and management. MethodsThe EA Clinical Congenital Practice Standards Committee is a multinational and multidisciplinary group of surgeons and cardiologists with expertise in EA. A citation search in PubMed, Embase, Scopus, and Web of Science was performed using key words related to EA. The search was restricted to the English language and the year 2000 or later and yielded 455 results, of which 71 were related to neonates and infants. Expert consensus statements with class of recommendation and level of evidence were developed using a modified Delphi method, requiring 80% of members votes with at least 75% agreement on each statement. ResultsWhen evaluating fetuses with EA, those with severe cardiomegaly, retrograde or bidirectional shunt at the ductal level, pulmonary valve atresia, circular shunt, left ventricular dysfunction, or fetal hydrops should be considered high risk for intrauterine demise and postnatal morbidity and mortality. Neonates with EA and severe cardiomegaly, prematurity (<32 weeks), intrauterine growth restriction, pulmonary valve atresia, circular shunt, left ventricular dysfunction, or cardiogenic shock should be considered high risk for morbidity and mortality. Hemodynamically unstable neonates with a circular shunt should have emergent interruption of the circular shunt. Neonates in refractory cardiogenic shock may be palliated with the Starnes procedure. Children may be assessed for later biventricular repair after the Starnes procedure. Neonates without high-risk features of EA may be monitored for spontaneous closure of the patent ductus arteriosus (PDA). Hemodynamically stable neonates with significant pulmonary regurgitation at risk for circular shunt with normal right ventricular systolic pressure should have an attempt at medical closure of the PDA. A medical trial of PDA closure in neonates with functional pulmonary atresia and normal right ventricular systolic pressure (>20-25 mm Hg) should be performed. Neonates who are hemodynamically stable without pulmonary regurgitation but inadequate antegrade pulmonary blood flow may be considered for a PDA stent or systemic to pulmonary artery shunt. ConclusionsRisk stratification is essential in neonates and infants with EA. Palliative comfort care may be reasonable in neonates with associated risk factors that may include prematurity, genetic syndromes, other major medical comorbidities, ventricular dysfunction, or sepsis. Neonates who are unstable with a circular shunt should have emergent interruption of the circular shunt. Neonates who are unstable are most commonly palliated with the Starnes procedure. Neonates who are stable should undergo ductal closure. Neonates who are stable with inadequate pulmonary flow may have ductal stenting or a systemic-to-pulmonary artery shunt. Subsequent procedures after Starnes palliation include either single-ventricle palliation or biventricular repair strategies.

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.

Prenatal Management and Perinatal Outcome in a Large Series of Hydrops Fetalis

Introduction: Nonimmune hydrops fetalis (NIHF) is the most frequent etiology of hydrops fetalis (HF), accounting for around 95% of cases. It associates high perinatal mortality and morbidity rates. The aim of the study was, first, to investigate etiology, prenatal management, and perinatal outcome in a large single-center series of HF; second, to identify prenatal prognostic factors with impact on perinatal outcome. Materials and Methods: Observational retrospective study of 80 HF diagnosed or referred to a single tertiary center between 2012 and 2021. Clinical characteristics, etiology, prenatal management, and perinatal outcome were recorded. Adverse perinatal outcome was defined as intrauterine fetal death (IUFD), early neonatal death (first 7 days of life) and late neonatal death (between 7 and 28 days). Results: Seventy-six of the 80 cases (95%) were NIHF, main etiology being genetic disorders (28/76; 36.8%). A total of 26 women (32.5%) opted for termination of pregnancy, all of them in the NIHF group. IUFD occurred in 24 of 54 patients (44.4%) who decided to continue the pregnancy. Intrauterine treatment was performed in 29 cases (53.7%). There were 30 newborns (55.6%). Adverse perinatal outcome rate was 53.7% (29/54), significantly higher in those diagnosed <20 weeks of gestation (82.4% < 20 weeks vs. 40.5% ≥ 20 weeks; p = 0.004). Survival rate was higher when fetal therapy was performed compared to the expectantly managed group (58.6% vs. 32%; p = 0.05). Intrauterine blood transfusion and thoraco-amniotic shunt were the procedures that achieved the highest survival rates (88.9% and 100%, respectively, p = 0.003). Conclusion: NIHF represented 95% of HF with genetic disorders as the main etiology. Most of them were diagnosed before 20 weeks of gestation, with worse prognosis than cases detected later in gestation. Rates of TOP, IUFD, and early neonatal death were higher in NIHF. Intrauterine therapy, when indicated, improved the perinatal outcome.

Prenatal Diagnosis and Prognosis of Abdominal Arteriovenous Fistulae: A Comprehensive Case Series and Systematic Review.

This study had two main objectives. Firstly, we conducted a thorough literature review on the prenatal diagnosis of abdominal congenital arteriovenous fistulas (CAVFs) involving the abdominal aorta and hepatic arteries. Secondly, we aimed to provide detailed descriptions of eight additional cases diagnosed at our medical center and assess the outcome of this anomaly for informed counseling. We conducted a systematic search of online databases using specific keywords like "outcome", "ultrasound", "intrahepatic fistulae", and "fetal venous anomalies", focusing on studies published between 1998 and 2023. We selected 10 relevant articles and analyzed 13 cases. Additionally, we conducted a five-year prospective study in two referral centers, identifying eight CAVF cases with an incidence rate of 0.16%. Among the 21 cases evaluated, 11 resulted in live births, all of which received treatment. However, four cases (36.3%) had poor postnatal outcomes and neonatal demise due to heart failure. Prenatal signs of poor fetal hemodynamics, including cardiomegaly or hydrops, were observed in 52.3% of cases, regardless of outcome. Our findings highlight the rarity of this vascular malformation and emphasize the importance of effective treatment to avoid unfavorable outcomes. The long-term effectiveness of prenatal treatment or postnatal embolization remains uncertain, with liver transplantation being considered the most reliable treatment option.

Central conducting lymphatic anomaly: from bench to bedside.

Central conducting lymphatic anomaly (CCLA) is a complex lymphatic anomaly characterized by abnormalities of the central lymphatics and may present with nonimmune fetal hydrops, chylothorax, chylous ascites, or lymphedema. CCLA has historically been difficult to diagnose and treat; however, recent advances in imaging, such as dynamic contrast magnetic resonance lymphangiography, and in genomics, such as deep sequencing and utilization of cell-free DNA, have improved diagnosis and refined both genotype and phenotype. Furthermore, in vitro and in vivo models have confirmed genetic causes of CCLA, defined the underlying pathogenesis, and facilitated personalized medicine to improve outcomes. Basic, translational, and clinical science are essential for a bedside-to-bench and back approach for CCLA.

Glucose phosphate isomerase deficiency demasked by whole-genome sequencing: a case report

BackgroundGlucose-6-phosphate isomerase deficiency is a rare genetic disorder causing hereditary nonspherocytic hemolytic anemia. It is the second most common glycolytic enzymopathy in red blood cells. About 90 cases are reported worldwide, with symptoms including chronic hemolytic anemia, jaundice, splenomegaly, gallstones, cholecystitis, and in severe cases, neurological impairments, hydrops fetalis, and neonatal death.Case presentationThis paper details the case of the first Danish patient diagnosed with glucose-6-phosphate isomerase deficiency. The patient, a 27-year-old white female, suffered from lifelong anemia of unknown origin for decades. Diagnosis was established through whole-genome sequencing, which identified two GPI missense variants: the previously documented variant p.(Thr224Met) and a newly discovered variant p.(Tyr341Cys). The pathogenicity of these variants was verified enzymatically.ConclusionsWhole-genome sequencing stands as a potent tool for identifying hereditary anemias, ensuring optimal management strategies.

Non-immune hydrops fetalis: etiology, pathogenesis, features of diagnosis and treatment in the fetus and newborn

Non-immune hydrops fetalis is a polyetiological disease characterized by high perinatal mortality. The development of non-immune fetal hydrops is associated with diseases of the cardiovascular and lymphatic systems, genetic and chromosomal diseases, infectious agents and many other reasons. In this regard, there is no single approach to the treatment of this extremely dangerous pathological condition, which requires the joint work of specialists from different specialties: obstetricians-gynecologists, neonatologists, cardiologists, surgeons, hematologists and geneticists. This article provides a review of current literature data on the etiology, pathogenesis, clinical manifestations, treatment and outcomes of non-immune hydrops fetalis.

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

BackgroundRitodrine 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 presentationA 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.ConclusionOur 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.