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Parvovirus B19 (B19V) causes erythema infectiosum, a.k.a., fifth disease. This disease primarily affects children. It is generally self-limiting and subsides after 1-2 weeks. In pregnancy, the virus can cross the placenta and result in a fetal infection. This may lead to severe fetal anemia, hydrops fetalis, a miscarriage, or intrauterine fetal death. The risk of long-term sequelae also appears to be increased. About one-third of pregnant women are not immune to B19V and, therefore, are at risk to contract a primary infection. The seroconversion rate during pregnancy is generally around 1-2%. During a primary infection, maternal-fetal transplacental transmission of B19V occurs in about 30-50% of the cases and the risk of fetal infection increases with advancing gestational age. The risk of severe fetal anemia or hydrops is around 3-4% overall and is around 6-7% if the primary infection occurs before 20 weeks' gestation. Fetal monitoring in women with a primary B19V infection includes regular ultrasound examinations looking for evidence of hydrops fetalis and Doppler measurements of the middle cerebral artery peak velocity. Fetal blood sampling is performed if a significant anemia is suspected and, if such is found, an intrauterine blood transfusion is needed. This article provides an overview of the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and management of B19V infection during pregnancy., (© 2024. The Author(s).)

Ebstein anomaly (EA) is a rare congenital heart defect characterized by abnormal development of the tricuspid valve (TV) and right ventricular myocardium. This study documents 2 dramatic cases of fetal EA characterized by hydrops and cardiomegaly, leading to intrauterine or early neonatal death. These clinical outcomes were associated with morphological abnormalities including severe tricuspid regurgitation, unguarded TV orifice, pulmonary atresia, and flattened right ventricular myocardium. This study highlights that these adverse anatomical features may result in unfavorable clinical outcomes in fetal EA. While timely identification of such features by prenatal ultrasound is crucial for providing accurate prognostic stratification and guiding treatment decisions, fetopsy may be necessary to discern EA among the spectrum of right-heart anomalies., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hydrops fetalis is an abnormal accumulation of fluid in two or more foetal compartments which is easily detected using prenatal ultrasonography. It can be categorised into immune and non-immune. The non-immune hydrops can result from various aetiologies, including cardiovascular, respiratory, genitourinary infections, chromosomal anomalies and metabolic causes. The metabolic causes, including lysosomal storage disorders (LSD), are increasingly being recognised as the causes of non-immune hydrops. The hydrops fetalis associated with metabolic disorders is usually severe with huge ascites, hepatosplenomegaly, thick skin, renal abnormalities, increased nuchal translucency, renal abnormalities and skeletal deformities. In this report, we describe a case of LSD, that is, galactosialidosis presenting as non-immune hydrops and its diagnosis. In utero diagnosis of the disorder without an index case is challenging. The definitive diagnosis is important for planning and management of future conceptions., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Congenital Diaphragmatic Hernia (CDH) associated with hydrops is rare. The aim of this study was to describe the incidence of this combination of anomalies and the postnatal outcomes from a large database for CDH., Study Design: Data from the multicenter, multinational database on infants with prenatally diagnosed CDH (CDHSG Registry) born from 2015 to 2021 were analyzed., Results: A total of 3985 patients were entered in the registry during the study period, 3156 were prenatally diagnosed and 88 were reported to have associated fluid in at least 1 compartment, representing 2.8% of all prenatally diagnosed CDH cases in the registry. The overall survival to discharge for CDH patients with hydrops was 43%. The hydropic CDH group had lower birth weight and gestational age at birth, and increased incidence of right-sided CDH (55%), and rate of non-repair (45%). However, the survival rate for hydropic infants with CDH undergoing surgical repair was 80%. Other associated anomalies were more common in hydropic CDH (50% vs 37%, p = 0.001)., Conclusion: Hydropic CDH is rare, only 2.8% of all prenatally diagnosed cases, and more commonly occurring in right-sided CDH. Survival rates are low, with higher rates of non-repair. However, decision-making regarding goals of care and an aggressive surgical approach in selected cases may result in survival rates comparable to non-hydropic cases., (© 2024. The Author(s).)

Abstract: Hemoglobin Bart's hydrops fetalis syndrome (BHFS) represents the most severe form of α-thalassemia, arising from deletion of the duplicated α-globin genes from both alleles. The absence of α-globin leads to the formation of nonfunctional hemoglobin (Hb) Bart's (γ4) or HbH (β4) resulting in severe anemia, tissue hypoxia, and, in some cases, variable congenital or neurocognitive abnormalities. BHFS is the most common cause of hydrops fetalis in Southeast Asia; however, owing to global migration, the burden of this condition is increasing worldwide. With the availability of intensive perinatal care and intrauterine transfusions, an increasing number of patients survive with this condition. The current approach to long-term management of survivors involves regular blood transfusions and iron chelation, a task made challenging by the need for intensified transfusions to suppress the production of nonfunctional HbH-containing erythrocytes. Although our knowledge of outcomes of this condition is evolving, it seems, in comparison to individuals with transfusion-dependent β-thalassemia, those with BHFS may face an elevated risk of complications arising from chronic anemia and hypoxia, ongoing hemolysis, iron overload, and from their respective treatments. Although stem cell transplantation remains a viable option for a select few, it is not without potential side effects. Looking ahead, potential advancements in the form of genetic engineering and innovative therapeutic approaches, such as the reactivation of embryonic α-like globin gene expression, hold promise for furthering the treatment of this condition. Prevention remains a crucial aspect of care, particularly in areas with high prevalence or limited resources., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: We aimed to compare the etiology and perinatal outcomes of non-immune hydrops fetalis diagnosed early- and late-onset at our hospital., Methods: The records of the patients who applied to our department were reviewed, and we reached 42 non-immune hydrops fetalis cases retrospectively and examined the medical records. Hydrops diagnosis week, birth week, accompanying anomalies, and perinatal outcomes were compared as ≤12 weeks (early-onset) and >12 weeks (late-onset)., Results: The prevalence of non-immune hydrops fetalis was 0.05%, and the median week of diagnosis for hydrops was 18 weeks. Consanguinity (16.7%) was found in seven pregnancies, and the other seven patients (16.7%) had a history of hydrops in previous pregnancies. Anomalies of the skeletal system, central nervous system, and gastrointestinal tract accounted for 66.7% of ≤12 weeks in non-immune hydrops fetalis cases. Cardiac abnormalities were more common (26.7%) in patients at > 12 weeks (p=0.078). A statistically significant difference was found between the distribution of week of birth and week of diagnosis (p=0.029). Notably, 66.7% of patients diagnosed before week 12 and 23.3% of patients diagnosed after week 12 delivered their babies before week 24. Spontaneous intrauterine death occurred before week 12 in 45.5% (n=5) of non-immune hydrops fetalis and after week 12 in 39.1% (n=9) of non-immune hydrops fetalis. Notably, 69.2% (n=9) of the patients who had prenatal invasive testing resulted in normal karyotype., Conclusion: In this study, most of the fetuses diagnosed with early-onset non-immune hydrops fetalis were born in the first 24 weeks. Additionally, live birth rates and cardiac anomalies were observed to be higher in late-onset non-immune hydrops fetalis.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia., Methods: PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included "fetal edema," "hydrops fetalis," "glucose 6 phosphate dehydrogenase deficiency," and "fetal anemia." Cases with workup presuming G6PD deficiency as an etiology for NIHF and severe fetal anemia were included. PRISMA guidelines were followed., Results: Five cases of G6PD-related NIHF and one case of severe fetal anemia were identified. Four fetuses (4/6, 66.7%) were male and two fetuses (2/6, 33.3%) were female. Mean gestational age at diagnosis of NIHF/anemia and delivery was 32.2 ± 4.9 and 35.7 ± 2.4 weeks, respectively. Four cases (66.7%) required a cordocentesis for fetal transfusion, and two cases (33.3%) received blood transfusions immediately following delivery. Among the four multigravida cases, two (50%) noted previous pregnancies complicated by neonatal anemia. When reported, the maternal cases included two G6PD deficiency carrier patients and two G6PD-deficient patients. Exposures to substances known to cause G6PD deficiency-related hemolysis occurred in 3/6 (50%) cases., Conclusion: Six cases of NIHF/severe fetal anemia were associated with G6PD deficiency. While G6PD deficiency is an X-linked recessive condition, female fetuses can be affected. Fetal G6PD deficiency testing can be considered if parental history indicates, particularly if the standard workup for NIHF is negative., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objective: To evaluate maternal and perinatal outcomes following fetal intervention in the context of maternal "mirror" syndrome., Study Design: 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., Results: 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 ± 3.8 weeks. 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 13.1 days (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., Conclusion: 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., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Competing Interests: The authors declare that they have no conflict of interest.

Fetal pericardial teratomas are rare. They present with pericardial effusion and hydrops. The definitive management is postnatal resection of the tumor. The exact antenatal management is not known due to its rarity. We present a case of fetal pericardial teratoma with pericardial tamponade. Pericardiocentesis performed at 31 weeks significantly relieved the venous compression, leading to resolution of hydrops and prolonging the gestational age for the definitive management., (© 2024 John Wiley & Sons Ltd.)

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.

Objectives: Non-immune hydrops fetalis (NIHF) is the pathological accumulation of fluids in fetal compartments, without maternal isoimmunization. Fetal interventions (e.g. shunting, fetal paracentesis, fetal thoracocentesis, fetal pleurodesis) are used to alleviate fluid accumulations, but the outcome is uncertain because the underlying causes of NIHF vary. We aimed to explore the etiology and long-term outcome of NIHF after fetal intervention., Methods: This was a retrospective review of fetuses with NIHF, defined by the presence of fetal ascites, pleural or pericardial effusion, skin edema or cystic hygroma, or a combination of these features, who underwent intervention at our institution during the period 2012-2021. Clinical surveillance, genetic analysis and viral infection screening were used to define the etiology. Chart reviews and telephone interviews were conducted to assess the long-term outcomes., Results: In total, 55 fetuses were enrolled and 46 cases had final follow-up data after delivery. Etiology was identified in 33 cases, including four for which the underlying causes were not identified initially using small-gene-panel tests but which were later diagnosed with monogenic disorders by whole-exome sequencing (WES). Twenty-three cases with follow-up survived, having a follow-up period of 2-11 years at the time of writing, of which 17 were healthy. All 11 cases initially presenting as congenital chylothorax survived with favorable outcome., Conclusions: The etiologies of NIHF are heterogeneous, and the long-term (spanning 2-11 years) outcome of fetal intervention varies, according to the underlying etiology, with cases caused by congenital chylothorax having the best prognosis. Genome-wide tests, such as WES, may be helpful in determining the underlying condition in cases caused by a genetic disorder, and this may affect fetal therapy approaches in the future. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To describe the maternal outcomes of a prospective cohort of non-immune hydrops fetalis (NIHF) pregnancies with negative standard-of-care evaluations., Methods: This study was a secondary analysis of a prospective cohort study of NIHF pregnancies with negative work-ups (infection, alloimmune anemia, fetomaternal hemorrhage, and chromosomal disorders). Outcomes were obstetric complications, including pre-eclampsia, mirror syndrome, preterm birth, polyhydramnios, postpartum hemorrhage, and maternal mental health., Results: Forty pregnancies were included. Four patients developed pre-eclampsia (4/40, 10.0%); three occurred postpartum. None was diagnosed with mirror syndrome. Of the 31 continued pregnancies, 16 (51.6%) resulted in early fetal death or stillbirth and 15 (48.4%) resulted in live births. Of the 15 live births, 8 (53.3%) were delivered by primary cesarean delivery; 5 (62.5%) were for hydrops fetalis. Eleven live births (73.3%) were delivered preterm; 9 (81.8%) were indicated, most commonly for fetal indications (7/9, 77.8%). Polyhydramnios occurred in 14/40 (35.0%) cases. Where EBL was recorded (n=37), there were 5 (13.5%) cases of postpartum hemorrhage and an additional 3 (8.1%) had uterine atony without hemorrhage. Eighteen patients (18/40, 45.0%) had new-onset or exacerbated depression or anxiety symptoms., Conclusion: Our study identified several important adverse outcomes of pregnancies complicated by NIHF with negative standard-of-care evaluations, including a high rate of postpartum pre-eclampsia and worsened mental health. We identified a higher rate of cesarean delivery and preterm birth, both primarily for fetal indications. We also observed the known relationship between polyhydramnios, hemorrhage, and atony, but noted that this risk included pregnancies concluding in dilation and evacuation. Counseling after a diagnosis of NIHF should include these adverse outcomes., (© 2023 International Federation of Gynecology and Obstetrics.)

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., (Copyright © 2023 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Supraventricular tachyarrhythmia (SVT) is the most common form of fetal tachyarrhythmias. The presentation can vary from ill-defined, non-sustained episodes of tachyarrhythmia to frank non-immune hydrops. The standard of care is transplacental therapy by treating the mother with oral antiarrhythmic drugs, followed by direct fetal therapy in refractory cases. We report a case of primigravida in her late 20s, who presented at 28.1 weeks of gestation with fetal hydrops and SVT. She was initially managed with oral digoxin and flecainide, but due to worsening hydrops, risk of fetal demise and extreme prematurity, further management by direct fetal therapy was given in terms of intramuscular digoxin and intraperitoneal flecainide. Following which, the fetus had a favourable outcome. This case highlights the possible role of direct fetal therapy in refractory cases of SVT., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Fetuses with large lung lesions including congenital cystic adenomatoid malformations (CCAMs) are at risk for cardiopulmonary compromise. Prenatal maternal betamethasone and cyst drainage for micro- and macrocystic lesions respectively have improved outcomes yet some lesions remain large and require resection before birth (open fetal surgery, OFS), at delivery via an Ex Utero Intrapartum Treatment (EXIT), or immediately post cesarean section (section-to-resection, STR). We sought to compare prenatal characteristics and outcomes in fetuses undergoing OFS, EXIT, or STR to inform decision-making and prenatal counseling., Methods: A single institution retrospective review was conducted evaluating patients undergoing OFS, EXIT, or STR for prenatally diagnosed lung lesions from 2000 to 2021. Specimens were reviewed by an anatomic pathologist. Lesions were divided into "CCAMs" (the largest pathology group) and "all lung lesions" since pathologic diagnosis is not possible during prenatal evaluation when care decisions are made. Prenatal variables included initial, greatest, and final CCAM volume-ratio (CVR), betamethasone use/frequency, cyst drainage, and the presence of hydrops. Outcomes included survival, ECMO utilization, NICU length of stay (LOS), postnatal nitric oxide use, and ventilator days., Results: Sixty-nine percent (59 of 85 patients) of lung lesions undergoing resection were CCAMs. Among patients with pathologic diagnosis of CCAM, the initial, largest, and final CVRs were greatest in OFS followed by EXIT and STR patients. Similarly, the incidence of hydrops was significantly greater and the rate of hydrops resolution was lower in the OFS group. Although the rate of cyst drainage did not differ between groups, maternal betamethasone use varied significantly (OFS 60.0%, EXIT 100.0%, STR 74.3%; p = 0.0378). Notably, all OFS took place prior to 2014. There was no difference in survival, ventilator days, nitric oxide, NICU LOS, or ECMO between groups. In multiple variable logistic modeling, determinants of survival to NICU discharge among patients undergoing resection with a pathologic diagnosis of CCAM included initial CVR <3.5 and need for <3 maternal betamethasone doses., Conclusion: For CCAMs that remain large despite maternal betamethasone or cyst drainage, surgical resection via OFS, EXIT, or STR are viable options with favorable and comparable survival between groups. In the modern era there has been a shift from OFS and EXIT procedures to STR for fetuses with persistently large lung lesions. This shift has been fueled by the increased use of maternal betamethasone and introduction of a Special Delivery Unit during the study period and the appreciation of similar fetal and neonatal outcomes for STR vs. EXIT and OFS with reduced maternal morbidity associated with a STR. Accordingly, efforts to optimize multidisciplinary perinatal care for fetuses with large lung lesions are important to inform patient selection criteria and promote STR as the preferred surgical approach in the modern era., Level of Evidence: Level IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We report three cases of fetalis hydrops associated with nondeletional α-thalassemia. Two cases were caused by hemoglobin (Hb) H-Quong Sz disease, and one caused by homozygous Hb Constant Spring. Fetal hydrops occurred in the late second trimester in all three cases. Our study indicates that for pregnancies at risk for fetal nondeletional Hb H disease, strict ultrasound follow-up is particularly important. Even without techniques of intrauterine transfusion treatment, early prenatal diagnosis can enable parents to make timely decisions.

Shunt migration is a rare but significant complication of thoracoamniotic shunting, an intervention widely used for fetal pleural effusion. We describe a case of a term infant noted antenatally to have fetal hydrothorax that was managed with thoracoamniotic shunting but complicated by shunt migration. We also present the current literature on risk factors, complications and management of intrathoracic shunt migration. The majority of shunt migration cases are managed conservatively with no untoward postnatal sequelae, but surgical removal of the migrated shunt has been used for associated clinical complications, if visceral damage is suspected or if postnatal thoracic surgery is indicated for other reasons. We advocate an approach of conservative management for asymptomatic infants, where possible, to avoid unnecessary surgical and anaesthetic risks to very young, often already compromised children. However, further studies are still required to determine optimal management after shunt migration has occurred to ensure the best outcome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of this paper is to explore whether the cardiovascular profile score (CVPS) correlates with fetal outcome in patients with non-immune hydrops fetalis (NIHF) and cardiac anomalies. In this retrospective study, we included fetuses with NIHF and the suspicion of a cardiac anomaly in prenatal ultrasound. The CVPS was calculated using information obtained by fetal echocardiographic examination. Feto-neonatal mortality (FNM) was defined as intrauterine fetal demise or death in the first 6 months of life. We reviewed 98 patients, who were referred to the Department of Obstetrics and Gynecology of the Johannes Gutenberg University in Mainz with the diagnosis of NIHF between January 2007 and March 2021. By eighteen of them, the suspicion of a cardiac anomaly was raised. After exclusion of six pregnancies (one termination of pregnancy and five because of incomplete data), 12 cases were left for analysis. Mean gestational age at which the CVPS was calculated was 29 + 2 weeks. Two fetuses died in utero. Of the remaining ten hydropic fetuses, three newborns died in the neonatal period, and seven survived after a 6-month surveillance period. Median CVPS of all fetuses was 6 points. Surviving fetuses showed statistically significantly higher CVPS values (median 8 points) than fetuses with FNM (median 5 points, p value = 0.009). Our results point towards a positive association between CVPS and fetal outcome in fetuses with NIHF and cardiac anomalies. The CVPS appears to be a useful marker in the assessment of heart failure in utero., (© 2023. The Author(s).)

Intrapericardial teratoma is a germ-cell tumor that typically arises from the base of the heart. This rare cardiac tumour is the second most common tumor diagnosed in fetuses and newborn. Although benign, it can be massive in size causing direct compression on the heart and associated with significant pericardial effusion resulting life-threatening complications such as cardiac tamponade, heart failure, foetal hydrops, and sudden death. Early antenatal diagnosis and surgical intervention improve the survival. We present a case of immature intrapericardial teratoma diagnosed at 25 weeks of gestation but required multiple foetal pericardiocentesis and premature delivery due to massive pericardial effusion. The importance of multidisciplinary team approach to ensure successful management was highlighted in this case report.

Purpose: Evaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20 +0  weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection., Methods: A retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results., Results: A total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19 +3 (13 +0 -31 +4 ) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20 +0  weeks of gestation., Conclusion: IUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome., (© 2022. The Author(s).)

Objective: Nonimmune hydrops fetalis (NIHF) is associated with poor perinatal outcomes including preterm birth (PTB). However, the frequency and causes of PTB in this population are not well understood. We hypothesized that NIHF frequently results in PTB due to medically indicated delivery for fetal distress., Study Design: This was a secondary analysis of a prospectively enrolled cohort of pregnancies with NIHF that underwent exome sequencing if standard testing was nondiagnostic. The primary outcome was frequency of PTB at <37 weeks' gestation. Secondary outcomes were reasons for PTB, fetal predictors of PTB, and frequency of neonatal death following PTB., Results: Fifty-six cases were included, with a median gestational age at delivery of 32.8 weeks (interquartile range [IQR]: 30.3-35.0). Overall, 86% (48/56) were delivered preterm. Among 48 PTBs, 18 (38%) were spontaneous, 9 (19%) were medically indicated for maternal indications (primarily preeclampsia), and 21 (44%) were medically indicated for fetal indications (nonreassuring antenatal testing or worsening effusions). Neither fetal genetic diagnosis nor polyhydramnios was associated with PTB., Conclusion: More than four-fifths of pregnancies with NIHF result in PTB, often due to nonreassuring fetal status. These data are informative for counseling patients and for developing strategies to reduce PTB in pregnancies with NIHF., Key Points: · Pregnancies complicated by nonimmune hydrops fetalis often result in preterm birth.. · Preterm birth in these cases is most often medically indicated for fetal benefit.. · Fetal genetic conditions and polyhydramnios may be associated with preterm birth in cases of NIHF.., Competing Interests: None declared., (Thieme. All rights reserved.)

A boy, aged 3 hours, was admitted due to a prenatal diagnosis of fetal hydrops at 3 hours after resuscitation for birth asphyxia. Prenatal examination at 5 months of gestation showed massive ascites in the fetus, and after birth, the boy had the manifestations of systemic hydroderma, massive ascites, coarse face, and hepatomegaly. Genetic testing revealed heterozygous mutations in the SLC17A5 gene, and there was a significant increase in urinary free sialic acid. Placental pathology showed extensive vacuolization in villous stromal cells, Hofbauer cells, cytotrophoblast cells, and syncytiotrophoblast cells in human placental chorionic villi. The boy was finally diagnosed with free sialic acid storage disorders (FSASDs). This is the first case of FSASDs with the initial symptom of fetal hydrops reported in China. The possibility of FSASDs should be considered for cases with non-immune hydrops fetalis, and examinations such as placental pathology and urinary free sialic acid may help with early diagnosis and clinical decision making.

Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major ("homozygous alpha-thalassemia-1") or hemoglobin Bart's disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart's hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart's hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart's hydrop fetalis.

Introduction:  Prenatal ultrasound-guided laser coagulation (USLC) for complicated bronchopulmonary sequestrations has been described but a consensus on the procedure and on the following management is still lacking. We present our experience and provide a literature review., Methods:  Retrospective review of patients treated in our center. Literature review and combined analysis of perinatal data were performed., Results:  Five cases were treated at our center, all presenting with severe hydrothorax. Four met the criteria for fetal hydrops. Four cases underwent postnatal computed tomography (CT) scan: in one case, there was no evidence of persistent bronchopulmonary sequestration. The other three underwent thoracoscopic resection, in two, a viable sequestration was found. Including our series, 57 cases have been reported, with no mortality and a success rate of 94.7%. Mean gestational age (GA) at the procedure was 28 ± 3.4 weeks and mean GA at birth and birth weight (BW) were 38.6 ± 2.3 weeks and 3,276 ± 519.8 g, respectively. In 80.6% of the cases investigated postnatally, a residual mass was found, 50% of cases who showed prenatal arterial flow cessation had a persistent sequestration postnatally, and 26.3% of cases underwent postnatal sequestrectomy. Both patients in our series had pathology examination confirming a viable bronchopulmonary sequestration., Conclusion:  Prenatal USLC seems to be a valid option for bronchopulmonary sequestration complicated by severe hydrothorax and/or fetal hydrops. Authors believe that this procedure should aim to reverse fetal distress and allow pregnancy continuation, and it should not be considered a definitive treatment. The currently available data do not support changes of the common postnatal management., Competing Interests: None declared., (Thieme. All rights reserved.)

Giant chorioangiomas are a potentially life-threatening condition that may require intrauterine therapy. We describe a case of a large chorioangioma (>4cm) diagnosed at 30 weeks of gestation causing severe fetal anemia and hydrops. An intrauterine blood transfusion was performed at 31 weeks with reversal of the anemia and hydrops. The neonate was born at 37 weeks showing respiratory distress syndrome that required neonatal intensive care unit admission but was discharged at 30 days of life. Further evaluation at two months of age showed no signs of abnormal neurodevelopment. When timely indicated, intrauterine transfusion of a hydropic fetus with anemia due to a giant chorioangioma is a potentially life-saving therapy that shows good neurodevelopment of the surviving fetus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Significant progress in prenatal care has decreased the incidence of rhesus incompatibility, which may result in hemolytic disease of the fetus and newborn (HDFN). This case report describes an unusual presentation of HDFN in a preterm infant delivered by caesarean section with isolated massive abdominal fluid collection as the leading clinical sign in addition to severe anemia. The immediate drainage of ascites provided transient clinical stabilization with improved pulmonary function in the delivery suite. After admission to the neonatal intensive care unit (NICU), HDFN treatment was initiated. This case report shows the importance of adequately trained staff including neonatologists, pediatricians and NICU nurses in the delivery suite to provide neonatal intensive care for HDFN., (© 2021. The Author(s).)

Objective: Nonimmune hydrops fetalis (NIHF) is defined as the accumulation of excess fluid in two or more body cavities in the fetus without blood incompatibility between mother and baby. We aimed to present our prenatal and postnatal management of intrauterine pleural effusions associated with NIHF., Study Design: A total of 60 patients diagnosed with NIHF with intrauterine pleural effusion were analyzed retrospectively. Gestational age of delivery or fetal demise, the intrauterine treatment procedure including extrauterine intrapartum treatment (EXIT), chest tube, and medical treatment methods in fetuses with chylothorax analyzed., Results: Thirty-nine patients (65%) were born alive between 26 and 38 weeks. A thoracoamniotic shunt was placed in one patient during the intrauterine period. Seven patients were placed bilaterally during the postnatal period, all without the umbilical cord being clamped during delivery. But 25 patients died within the first few days following birth. A total of four patients had chylothorax. Two patients who did not respond to medical treatment (somatostatin) were injected with thoracic local batticon and cured. A total of 14 patients were discharged with healing., Conclusion: Cases of progressive prenatal pleural effusions associated with NIHF have a high risk for fetal and neonatal death. We think that extreme prematurity increases postnatal mortality because it negatively affects the development of the lung and heart. A close obstetric follow-up and a multidisciplinary approach are required for the management to be selected., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Fetal supraventricular tachycardia (SVT) is rare and proposed predictors of postnatal outcomes in fetal SVT have not been validated. Valid predictors can guide postnatal management., Objectives: The authors correlated fetal characteristics to the incidence of postnatal SVT and compared SVT outcomes in infants with and without a history of fetal SVT., Methods: Mother-fetus dyads with fetal SVT and a structurally normal heart were described and compared with a second cohort of infants with a postnatal diagnosis of SVT., Results: SVT was observed in 78 fetuses and 76 survived to delivery. Maternally administered transplacental antiarrhythmics were used in 49 mother-fetus dyads. Rhythm control was achieved in 37 of 49 (76%). Among fetuses with intermittent SVT, there was no ventricular dysfunction or hydrops. Postnatal SVT occurred in one-half of infants (37 of 76), and 94% presented within the first 2 days of life. The following fetal characteristics were associated with postnatal SVT on univariable analysis: sustained SVT (87% vs 56%), ventricular dysfunction (41% vs 15%), lack of conversion to sinus rhythm (49% vs 10%), and earlier gestational age at delivery (37.6 weeks vs 38.9 weeks; P ≤ 0.01 for each comparison). Compared with infants with a postnatal diagnosis of SVT, infants with a fetal diagnosis presented earlier (median age 0 days vs 17 days; P &lt; 0.01) and had a lower incidence ventricular dysfunction at presentation (5% vs 42%; P &lt; 0.01)., Conclusions: One-half of infants with fetal SVT had postnatal SVT, nearly all within 2 days of life. These data and predictors of postnatal SVT may influence parental counseling and postnatal clinical decision-making., Competing Interests: Funding Support and Author Disclosures NUCATS is funded in part by a Clinical and Translational Science Award (CTSA) grant from the National Institutes of Health. UL1TR001422. This study was supported, in part, by the National Institutes of Health/National Heart, Lung, and Blood Institute K23HL130554 and philanthropic donors. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To review prenatal diagnosis and outcome of alpha thalassaemia major through universal antenatal screening., Method: This was a retrospective study on ultrasound features, antenatal diagnosis, in-utero intervention and long term outcome of pregnancies at risk of Haemoglobin Bart's hydrops foetalis syndrome attending prenatal diagnosis from 2000 to 2019 at Tsan Yuk Hospital in Hong Kong., Results: Among 390 foetuses from 373 at-risk pregnancies, 122 (31%) prenatal invasive procedures were performed and 65 affected foetuses were diagnosed antenatally. For foetuses with ultrasound features of anaemia, the diagnostic yield of BHFS was 73%. Cardiomegaly carried a positive predictive value of 65.2% while its absence had the highest negative predictive value (96.0%). Three women having affected foetuses continued pregnancy and received intrauterine transfusion beginning 20 weeks of gestation. All babies were born alive and non-hydropic. They were managed with regular transfusion and cured by haematopoietic stem cell transplantation., Conclusions: Absence of ultrasound features of anaemia had high negative predictive value for alpha thalassaemia major. Couple at risk of having affected foetus could be offered serial ultrasound surveillance. Invasive testing for pregnancies with features of foetal anaemia provided high diagnostic yield. Intrauterine transfusion corrected foetal anaemia and allowed long term transfusion free survival without significant neurological sequelae following postnatal transplant therapy., (© 2022 John Wiley & Sons Ltd.)

Objectives: The prognosis of nonimmune hydrops fetalis (NIHF) is still poor with a high mortality and morbidity rate despite progress in perinatal care. This study was designed to investigate etiology and outcome of NIHF., Methods: A retrospective review of 90 NIHF cases from 2007 to 2019 was conducted at University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Demographics, genetic results, prenatal and postnatal outcomes including one year survival as well as autopsy data were extracted. Etiology of hydrops was classified using 13 previously established categories. In 4 patients observed between 2016 and 2019, we used a next-generation-sequencing (NGS) panel for genetic evaluation., Results: Ninety NIHF cases were identified, with a median gestational age (GA) at diagnosis of 14 weeks. There were 25 live-born infants with a median GA of 34 weeks at birth, 15 patients survived to one year. There was aneuploidy in more than one third of the cases. All 90 cases were subclassified into etiologic categories with chromosomal 35, idiopathic 15, syndromic 11, cardiovascular 9, inborn errors of metabolism 6, lymphatic dysplasia 3, thoracic 3, infections 3, gastrointestinal 3 and hematologic 2. The NGS panel was used in 4 cases and 4 diagnoses were made., Conclusions: In 90 cases with NIHF we identified an aneuploidy in more than one third of the cases. Improved techniques, such as possibly specific genetic analysis, could reduce the high rate of unexplained cases of NIHF., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Gaucher disease type 2 is the most progressive and the rarest form of Gaucher disease, defined as the acute neuronopathic type. We presented two GD2 patients who died before three months of age due to severe septicemia, respiratory and liver failure. One was homozygous for a novel GBA variant c.590 T > A (p.197 K), and the second homozygous for the known GBA mutation c.1505G > A (p.R502H). Ichthyosis, hydrops fetalis, apnea, myoclonic seizures, and hepatosplenomegaly occurred in both patients, but hypertrophic cardiomyopathy was observed only in the second and unilateral cataract in the first patient. Due to the disease's early and rapid neurological progression, we did not administer ERT to our patients. It is strongly believed that early diagnosis is essential, and prenatal diagnosis makes genetic counselling possible for future pregnancies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Omenn syndrome (OS) is a rare variant of severe combined immunodeficiency characterized by susceptibility to severe opportunistic infections and peculiar manifestations, such as protein-losing erythroderma, alopecia, hepatosplenomegaly, lymphadenopathies, and severe diarrhea. The typical form of the disease is caused by hypomorphic mutation of the recombination-activating genes (RAG1 and RAG2), which are critical in initiating the molecular processes leading to lymphocyte and immunoglobulin receptor formation. Affected patients lack B cells, whereas autoreactive oligoclonal T cells infiltrate the skin, gut, spleen, and liver. In the absence of hematopoietic stem cell transplantation, patients with OS usually succumb early in life because of opportunistic infections. The incidence of OS is estimated to be <1 per 1 000 000; however, the actual frequency is difficult to ascertain. We report 2 siblings affected by OS due to a homozygous frameshift mutation (NM&#95;000448.3:c.519delT, p.E174Sfs*26) in the RAG1 gene presenting with nonimmune hydrops fetalis (NIHF). To the best of our knowledge, this is the first reported association between OS and NIHF. NIHF specifically refers to the presence of ≥2 abnormal fluid collections in the fetus, without red blood cell alloimmunization. A broad spectrum of pathologies is associated with NIHF; however, in ∼20% of the cases, the primary cause remains unclear. Understanding the etiology of NIHF is essential for guiding clinical management, determining prognosis, and informing parents regarding recurrence risk. Our case contributes to expanding the spectrum of OS presentation and highlights the importance of a complete immunologic and genetic workup in otherwise unexplained cases of NIHF., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Umbilical cord hemangioma is a rare tumor that can be associated with significant fetal and perinatal complications. Although usually described as a single anomaly, sometimes these tumors are reported in association with other vascular lesions. We report an unusual case of simultaneous occurrence of two umbilical cord hemangiomas and vascular malformation of the transverse mesocolon in a stillborn fetus with hydrops. To our knowledge, this is the first report of two simultaneously occurring umbilical cord hemangiomas. Moreover, presence of associated vascular malformation of transverse mesocolon could support the hypothesis of underlying predisposition to the development of vascular tumors.

Objective: To describe the etiology of isolated fetal ascites and associated perinatal outcomes, and to assess the progression of isolated fetal ascites to fetal hydrops., Data Sources: PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases were searched using the following keywords: "fetus" OR "foetal" OR "fetal" OR "foetus" AND "ascites" from inception to February 2020. The search was limited to the English language., Methods of Study Selection: A total of 1,983 articles were identified through the search strategy. All studies containing five or more cases of isolated fetal ascites were included., Tabulation, Integration, and Results: Eleven studies, involving 315 cases of isolated fetal ascites, were eligible for inclusion in this systematic review. All included studies were evaluated using the tool for evaluating the methodologic quality of case reports and case series described by Murad et al. Data were summarized using narrative review and descriptive statistics. Two-tailed Fisher exact P values calculated from hypergeometric distribution were used to compare outcome by etiology. CIs were calculated with Clopper-Pearson exact binomial interval. The etiologies of isolated fetal ascites are genitourinary (24%), gastrointestinal (20%), viral or bacterial infections (9%), cardiac (9%), genetic disorders not otherwise categorized (8%), chylous ascites (6%), metabolic storage disorders (3%), other structural disorders (4%), other causes (4%) and idiopathic (13%). Survival is most favorable for cases of isolated fetal ascites as a result of chylous (100%), idiopathic (90%), gastrointestinal (77%) and genitourinary (77%) etiologies. Survival is least favorable for fetuses with isolated fetal ascites as a result of structural disorders (25%), cardiac etiology (32%) and metabolic storage disorders (33.3%). When pregnancy terminations were excluded, survival rates were similar between fetuses diagnosed at or after 24 weeks of gestation compared with those diagnosed at less than 24 weeks (74% vs 61%, P=.06). Progression of fetal ascites to fetal hydrops occurred in 6.6% (95% CI 3.6-9.6%) (17/259) of cases when pregnancies that were terminated were excluded., Conclusion: Isolated fetal ascites has a diverse etiology. Outcome is related to the etiology of isolated fetal ascites. In the majority of cases, fetal ascites does not progress to fetal hydrops., Systematic Review Registration: PROSPERO, CRD42020213930., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Rhabdoid tumor is a highly aggressive sarcoma found in young children that occurs in the kidney, central nervous system and soft tissue sites. Rarely, it presents in the fetus or neonate and is associated with a dismal prognosis. We report a case of a 28-week gestation fetus presenting with hydrops fetalis who died soon after delivery, found at autopsy to have a rhabdoid tumor of the thoracic cavity with placental metastases and provide a review of the literature of congenital sarcomas.

We performed a systematic review of the literature to evaluate the incidence and types of lysosomal storage disorders (LSD) in case series of nonimmune hydrops fetalis (NIHF). PubMed, Ovid, and clinicaltrials.gov were reviewed for case series evaluating the workup of NIHF diagnosed in utero or in the neonatal period in human subjects from 1979 to August 2020. Retrospective case series with at least five cases of fetal and/or neonatal NIHF with its workup mentioned were identified. Idiopathic NIHF was defined as NIHF without an apparent cause after initial standard-of-care workup. In total, 22 case series with 2678 total cases of NIHF were identified. The overall incidence of LSD was 6.6% (177/2663) in NIHF cases that were tested for any LSD, and 8.2% (177/2151) in idiopathic NIHF cases. The most common LSD identified in cases of NIHF were mucopolysaccharidosis type VII, galactosialidosis, infantile sialic acid storage disease, Gaucher disease, GM1 gangliosidosis, and sialidosis. More than 40% of the most common LSD causes of NIHF have a potential postnatal treatment. LSD testing for NIHF allows for early diagnosis, better counseling and appropriate management, planning for possible early treatment, and counseling for recurrence risk., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 22-year-old pregnant woman was referred to our fetal medicine unit due to severe fetal growth restriction at 26 weeks of gestation. An extensive detailed ultrasound revealed signs of bilateral periventricular hyperechogenicity, suggesting fetal infection potentially due to cytomegalovirus (CMV). Doppler ultrasound showed a high peak systolic velocity in the middle cerebral artery. Percutaneous umbilical cord blood sampling confirmed fetal CMV infection and severe fetal anaemia. We present this case to highlight the importance of fetal anaemia, which can be fatal regardless of whether it is associated with generalised oedema or hydrops fetalis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the etiology and outcome of non-immune hydrops fetalis (NIHF) according to gestational age at diagnosis and intrauterine treatment., Study Design: A total of 122 NIHF cases were included. Medical records and ultrasonographic images were reviewed. The etiology, outcome, and intrauterine treatment were assessed., Results: The etiology was determined in 100 cases, and Hb Bart's disease was the most common. Two cases each of homozygous Southeast Asian ovalocytosis (SAO) and hemoglobin Constant Spring (Hb CS) were found. NIHF diagnosed in early gestation (<24 weeks) had a higher rate of chromosomal abnormalities and fetal demise. Intrauterine treatment was given in 18 cases, and 50% had successful live births., Conclusion: Hb Bart's disease was the most common cause of NIHF. SAO and Hb CS were associated with hydrops. NIHF in gestational age <24 weeks was associated with chromosomal abnormalities and fetal demise. Intrauterine treatment should be offered in selected cases., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)