Hydrops fetalis (HF) is the pathological accumulation of fluid in two or more fetal compartments. While immune-mediated HF was historically predominant, non-immune hydrops fetalis (NIHF) is now increasingly common. Advances in genetic testing have revealed monogenic causes, including RASopathies (a group of genetic syndromes caused by dysregulation of the RAS-mitogen-activated protein kinase signalling pathway). We report a young primigravida, referred at 20+3 weeks for unilateral fetal pleural effusion. Serial ultrasound scans showed rapid progression to bilateral effusion, hepatomegaly, polyhydramnios and NIHF. First-trimester screening and non-invasive prenatal testing were low-risk, Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, Herpes simplex serologies and PCR ruled out infection. Whole exome sequencing identified a likely pathogenic heterozygous frameshift mutation in the RASA1 gene (c.723dupT; p.Gly242TrpfsTer23), associated with capillary malformation-arteriovenous malformation type 1 (CM-AVM1). The mother had a subtle congenital capillary haemangioma on her left hand and revealed the same heterozygous variant of RASA1 gene, indicating variable expressibility. This case highlights the importance of considering rare monogenic causes like RASA1-related CM-AVM1 in NIHF, especially when early findings precede florid hydrops and classical RASopathy features are absent.

Mirror syndrome, also known as Ballantyne syndrome, is a rare complication of pregnancy characterized by the combination of generalized fetal hydrops, placentomegaly, and a systemic pathological response in the maternal organism. The clinical presentation in the pregnant woman reflects the severe condition of the fetus, which is a defining feature of this syndrome. This paper examines the etiological factors and pathogenetic mechanisms underlying the development of mirror syndrome, its clinical manifestations, diagnostic criteria, and principles of pregnancy management, and also provides a comparative analysis with preeclampsia as the pregnancy complication with the most similar clinical features.

Fetal pleural effusion is a condition characterized by the accumulation of fluid in the chest cavity of a developing fetus. It may be primary, often caused by lymphatic leakage such as chylothorax, or secondary to immune causes like Rh or ABO incompatibility, as well as nonimmune factors including chromosomal abnormalities, genetic disorders, infections, and congenital heart defects. These effusions may be associated with hydrops fetalis. The preferred prenatal treatment is thoraco-amniotic shunt (TAS), which drains pleural fluid into the amniotic sac. TAS improves lung development and has a survival rate of up to 85% in nonhydropic fetuses. A 34-week pregnant woman (gravida 2, para 1) was referred with suspected fetal lung fluid and diagnosed with fetal pleural effusion by ultrasound. After multidisciplinary evaluation, an ultrasound-guided thoraco-amniotic shunt (TAS) was performed under maternal spinal anesthesia, with fetal analgesia and paralysis achieved using fentanyl and vecuronium. The procedure was successful without complications. The patient delivered by cesarean section at 38 weeks. Postnatal imaging showed the shunt in place without residual effusion. On day six of life, the neonate underwent successful thoracoscopic shunt removal under general anesthesia, with stable intraoperative and postoperative outcomes. Conclusion, Thoraco-amniotic shunt placement and postnatal thoracoscopic removal require careful anesthetic planning and multidisciplinary coordination. Understanding maternal-fetal physiology and neonatal immaturity is essential. With thorough assessment and precise anesthetic management, both intrauterine and neonatal procedures can be performed safely with favorable outcomes.

Hereditary Anemias as a Monogenic Etiology for Nonimmune Hydrops Fetalis.

Congenital parvovirus B19 (PB19) infection can lead to severe fetal anemia and hydrops fetalis, necessitating in-utero transfusion (IUT) as a life-saving intervention. This study aimed to identify risk factors associated with unfavorable perinatal outcome following IUT in hydropic fetuses with PB19 infection, with the goal of optimizing transfusion strategies and improving fetal survival. A retrospective, multicenter, international cohort study was conducted across nine specialized fetal medicine centers in France, Belgium and the Czech Republic. This study included pregnant women with a fetus diagnosed with hydrops due to PB19 infection that underwent at least one IUT for severe fetal anemia between January 2014 and May 2024. Clinical, demographic and procedural data were analyzed. The primary outcome was to identify maternal, fetal, obstetric or IUT-related risk factors associated with adverse fetal or neonatal outcome, defined by a composite criterion of unfavorable outcome that included perinatal mortality and/or severe and persistent fetal anomalies, including severe fetal brain injury at follow-up. Statistical analysis was conducted using logistic regression models to assess potential risk factors. Of the 84 eligible cases, 78 pregnancies were included in the final analysis. The rate of perinatal survival without severe brain injury was 59.0% (46/78), while 41.0% (32/78) of cases had an unfavorable outcome, including 20 (25.6%) cases of stillbirth, nine (11.5%) cases of termination of pregnancy, one (1.3%) case of continuation of pregnancy despite severe prenatal neurological findings and two (2.6%) cases of neonatal death. Notably, a higher fetal hemoglobin (Hb) level (> 9.3 g/dL) after the first or second IUT was significantly associated with a reduced risk of unfavorable outcome (adjusted odds ratio (aOR), 0.6 (95% CI, 0.4-0.8)). A femur length Z-score of < -2 was associated with unfavorable outcome (aOR, 5.4 (95% CI, 1.3-27.0)). Transplacental vs transamniotic funicular puncture was not significantly associated with perinatal survival. IUT remains a cornerstone intervention for managing severe fetal anemia caused by PB19 infection; however, rates of perinatal loss continue to be substantial, especially in the presence of severe hydrops. Achieving higher post-transfusion Hb levels appears to be an important factor in improving survival outcomes for hydropic fetuses with PB19 infection. © 2026 International Society of Ultrasound in Obstetrics and Gynecology.

Rare case reports of immunological fetal hydrops and severe fetal anemia due to maternal sensitization with both anti-D and anti-C antibodies necessitating fetal intrauterine treatment.

Severe thalassemia remains a significant public health concern in Southeast Asia. Prenatal screening is an effective strategy for early detection and prevention. This study aimed to determine the prevalence of severe thalassemia and assess the performance of prenatal screening at the Siriraj Thalassemia Center, Siriraj Hospital, Thailand. A retrospective review was conducted using data from January 2018 to December 2023. A total of 18,976 pregnant women underwent initial screening with mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and hemoglobin (Hb) typing. Of these, 12,499 tested positive. Complete screening data from 6,698 male partners identified 18.3% of couples as high-risk. Deoxyribonucleic acid (DNA) analysis and prenatal diagnostic testing were performed for at-risk pregnancies. Among high-risk couples, 75.2% of fetuses were identified by DNA analysis as being at risk for severe thalassemia, and 34.2% were confirmed as affected. The distribution of severe thalassemia types included Hb Bart's Hydrops Fetalis (15.8%), homozygous β-thalassemia (1.6%), and β-thalassemia/Hb E disease (16.8%). The most frequent α-thalassemia genotype in Hb Bart's cases was homozygous α0-thalassemia (--SEA/--SEA; 96.3%). The most common β-thalassemia mutation was a 4-base pair deletion at codons 41/42 (-TTCT; 40.2%). DNA testing for α-thalassemia showed 100% specificity and positive predictive value (PPV). For β-thalassemia, the sensitivity, specificity, PPV, and negative predictive value (NPV) were 97.6%, 98.9%, 96.1%, and 99.3%, respectively. The findings underscore the effectiveness of prenatal screening and diagnosis in identifying severe thalassemia, highlighting their importance for informing prevention strategies and guiding public health planning in high-prevalence settings.

Congenital tricuspid valve regurgitation (TR) is rare, and chordae tendinae rupture is an even more uncommon finding in neonates. We describe a case with intrauterine tricuspid valve chordae tendinae rupture leading to severe TR and hydrops fetalis. Successful tricuspid valve repair using artificial chordae, leaflet approximation, and annular reduction were used as rescue therapy for the neonate.

Nonimmune hydrops fetalis (NIHF) is a severe prenatal condition with a broad etiological spectrum, including chromosomal abnormalities, structural malformations, congenital infections, and inherited metabolic disorders. Early identification of the underlying cause is essential for accurate prognosis, clinical decision-making, and genetic counseling. Here, we report the prenatal diagnosis of a fetus presenting with early-onset NIHF caused by a homozygous missense variant in the SUMF1 gene, detected through first-trimester chorionic villus sampling (CVS). A 27-year-old gravida 5 woman with a history of two previous pregnancies affected by unexplained hydrops fetalis was referred at 12 weeks and 3 days of gestation. Ultrasound examination revealed markedly increased nuchal translucency, generalized hydrops fetalis, and absence of the nasal bone. Given the recurrent phenotype and early gestational presentation, invasive prenatal diagnosis was performed using CVS. Clinical exome sequencing identified a homozygous SUMF1 variant (NM_182760.4: c.538T&gt;A, p.Trp180Arg), which is absent from population databases and has been reported only once in ClinVar as a variant of uncertain significance. Subsequent Sanger sequencing confirmed heterozygous carrier status in both parents and the unaffected sibling, consistent with autosomal recessive inheritance. SUMF1 encodes the sulfatase-modifying factor 1, a critical enzyme required for post-translational activation of all sulfatases. Biallelic pathogenic variants in SUMF1 cause multiple sulfatase deficiency, an ultra-rare lysosomal storage disorder that may present prenatally with hydrops fetalis. The severe and recurrent fetal phenotype observed in this family strongly supports the pathogenic relevance of the identified variant. This case highlights the diagnostic value of early invasive prenatal testing, particularly CVS combined with next-generation sequencing, in pregnancies complicated by early-onset or recurrent NIHF. Early molecular diagnosis enables timely counseling, informed reproductive decision-making, and appropriate planning for future pregnancies.

Objective Parvovirus B19 infection during pregnancy can cause severe fetal anemia, hydrops fetalis, and fetal death. This study describes our experience managing ten cases of severe fetal anemia due to parvovirus B19 infection during the 2023–2024 national outbreak in Israel. Methods This single-center descriptive cohort study included ten singleton pregnancies with fetal anemia (MCA-PSV >1.5 MoM) requiring intrauterine transfusion. Parvovirus B19 infection was confirmed by maternal IgM serology and/or amniotic fluid PCR. For pregnancies <20 weeks of gestation, we implemented a modified intraperitoneal transfusion technique incorporating pre-transfusion ascites drainage. Intravascular transfusions were used for later gestations. Platelet transfusions were administered when thrombocytopenia was present. Serial fetal sonography and neuroimaging were performed throughout the follow-up period. Results Seventy percent of fetuses presented with anemia and hydrops before 20 weeks of gestation. The modified intraperitoneal transfusion technique doubled the mean transfused packed red blood cell volumes compared to the standard technique (40 mL vs. 20 mL; p = 0.009). We performed 15 intraperitoneal transfusions (mean 2.14 per fetus) and 11 intravascular transfusion procedures. One fetal death occurred following intraperitoneal transfusion. Complications included one iatrogenic abdominal wall defect post-intraperitoneal transfusion (successfully repaired postnatally) and one case of transient ascites with hemosiderin deposits (resolved after birth). Two fetuses required platelet transfusions. All surviving infants demonstrated normal neuroimaging. Mean gestational age at delivery was 37 weeks 5 days, with 88% delivered at term. One preterm delivery occurred at 27 weeks due to cervical shortening and contractions, resulting in neonatal complications of prematurity. Conclusion Intensive intrauterine intervention, including ascites drainage and repeated red blood cell and platelet transfusions, may improve fetal outcomes in severe parvovirus B19 anemia. The modified intraperitoneal transfusion technique with pre-transfusion ascites drainage enabled larger transfusion volumes. Early, aggressive intervention appears crucial for optimal outcomes in these challenging cases.

Thoracoamniotic shunting (TAS) in fetuses with macrocystic congenital pulmonary airway malformation (CPAM) is mostly performed with pigtail shunts like the rocket shunt or the Harrison fetal bladder stent. The aim of this study was to assess the prenatal course, perinatal outcome and complications of TAS for severe macrocystic CPAM using the Somatex® intrauterine shunt. This was a two center (Cologne/Bonn) observational retrospective study of fetuses that underwent TAS using the Somatex® intrauterine shunt for severe macrocystic CPAM with and without hydrops between 2016-2024. Outcome parameters were perinatal survival, complications, gestational age at delivery and visibility of the shunt outside the skin after birth. During the study period, 25 fetuses were treated with the Somatex® shunt (13 = Cologne, 12 = Bonn), including 24 singletons and one fetus of a monochorionic-diamniotic twin pregnancy Mean gestational age at intervention was 24.7weeks (range 19-30). The mean diameter of the dominant cyst within the lesion was 34mm (range 18-55). Fetal hydrops prior to TAS (ascites and fetal scalp oedema) was present in 36% (9/25). Dislocation in the further course of pregnancy occurred in 8% (2/25) with the need for reintervention in two cases. Resolution of hydrops and regression of the lesion occurred in 96% (24/25). Mean gestational age at delivery was 38.3weeks (range 26-41), the preterm birth rate < 37weeks was 20% (5/25), 12% (3/25) were due to PPROM. Live birth rate was 100% and 92% (23/25) of neonates survived the neonatal period. Of the 12 liveborns delivered at the two study centers, in one case the shunt (8.3%) was dislocated in the amniotic cavity, 5 (41.7%) had a visible shunt outside the skin, whereas in the other 6 (50.0%) cases the shunt was covered with skin at birth. TAS in macrocystic CPAM with the Somatex® shunt has a high technical success rate leading to high neonatal survival rates even in cases associated with hydrops. The intrauterine course and neonatal outcome are comparable to TAS for fetal macrocystic CPAM using other types of shunts. Therefore, the choice of the shunt in macrocystic CPAM can be made freely at the discretion of the physician in charge, the availability of devices and economic factors. Due to the short length of 25mm and its straight design, the outer end of the Somatex® shunt is covered by skin at birth in up to 50% of cases, which may complicate its removal.

Idiopathic infantile arterial calcification is a rare autosomal recessive disorder characterised by extensive calcification and proliferation of the intimal layer of the large and medium sized arteries. The diagnosis is usually made at autopsy or in the neonatal period, when there is cardiac failure. Prenatal diagnosis is possible in the latter half of pregnancy when there are hyperechoic vessel walls, hypertrophied ventricular musculature, and nonimmune fetal hydrops. The number of cases diagnosed before birth is low. This study presents a 27-week pregnant patient diagnosed with widespread calcification in the aorta and pulmonary arteries, severe pericardial effusion, and hydrops fetalis during fetal echocardiographic examination. This case report reminds paediatric cardiologists, radiologists, and perinatologists that they should be familiar with widespread arterial calcification. It emphasises that idiopathic infantile arterial calcification, a very rare condition, should be considered among the etiologic factors when hydrops fetalis is detected on ultrasound.

Placental chorio-angiomas are rare benign vascular tumours of the placenta which are usually small and clinically insignificant, but large lesions can cause serious fetal complications such as anaemia, hydrops fetalis and an adverse perinatal outcome. We report the case of a 29-year-old multigravida diagnosed at 28 weeks' gestation with a large placental chorioangioma accompanied by sonographic evidence of fetal anaemia and hydrops fetalis. Despite two intra-uterine transfusions which led to partial improvement, the hydrops persisted, necessitating a preterm caesarean delivery at 31 weeks. The newborn required prolonged neonatal intensive care for respiratory distress, hydrops, thrombocytopenia and bronchopulmonary dysplasia, but there was satisfactory growth and neurodevelopment at 12 months of age. This case highlights the importance of early diagnosis and timely, individualised fetal therapy in managing large chorio-angiomas, and underscores how coordinated care through public-private partnership in a resource-limited setting can support effective continuity of antenatal and neonatal management, leading to a favourable perinatal outcome.

Background: Hemoglobin is composed of globin polypeptide chains, which serve as immunogens to induce the production of antibodies. Objectives: This review article aims to describe the use of antibodies against human hemoglobins for the identification of thalassemia and hemoglobinopathies. Materials and methods: Literature review to discusses the nature of normal human hemoglobin, hemoglobin switching, thalassemia and hemoglobinopathies, laboratory diagnosis, general properties of antibodies, production of antibodies against human hemoglobins, and clinical applications of these antibodies in identifying thalassemia and hemoglobinopathies.Antibody-based detection of hemoglobin is highly useful in diagnosing thalassemia and hemoglobinopathies. Results: Polyclonal antibodies against HbF have been applied in sandwich ELISA to accurately detect HbF levels. Monoclonal antibodies against HbH and Hb Bart’s have been produced and utilized in sandwich ELISA for detecting α-thalassemia. In addition, monoclonal antibodies against hemoglobin containing α-globin chains were developed and applied in sandwich ELISA to identify infants with Hb Bart’s hydrops fetalis, a condition in which no α-globin chains are produced. For detecting β-thalassemia carriers, monoclonal antibodies against HbA2 were produced, and sandwich ELISA was employed to measure HbA2 levels, which are elevated in these individuals. Conclusion: Antibody-based diagnosis of thalassemia and hemoglobinopathies enhances the quality of screening platforms and makes diagnosis of these disorders more reliable.

ObjectiveTo evaluate the surgical efficacy and prognosis of radiofrequency ablation (RFA) in the treatment of microcystic congenital pulmonary airway malformation (CPAM) complicated by fetal hydrops, with the CLM volume ratio (CVR) exceeding 2.0 and refractory to conservative treatment with maternal steroid administration.MethodsWe collected data from fetal microcystic CPAM cases with CVR > 2.0, complicated by fetal hydrops, and refractory to maternal steroid therapy, who underwent RFA at our hospital from June 2020 to June 2024.ResultsThe study comprised five fetuses, all diagnosed with microcystic CPAM complicated by fetal hydrops. All fetuses had a mean CVR of 3.8 (range, 2.2–5.3) and were complicated by fetal hydrops. All cases received two courses of maternal steroid before the RFA procedure. Among the five cases, three newborns were delivered at a mean gestational age of 36.6 weeks (range 35.2–38.7 weeks), and two cases of IUFD occurred postoperatively.ConclusionFor microcystic CPAM complicated with fetal hydrops and refractory to maternal conservative steroid administration, ultrasound-guided RFA serves as an effective salvage option for intrauterine treatment. Nevertheless, intrauterine interventional procedures should be performed with extreme caution, given the potential risks of IUFD.

Management of Chronic Myeloid Leukemia During Pregnancy: Review of Evidence and Treatment Algorithm.

Non-deletional α-thalassemia variants, particularly hemoglobin Constant Spring (Hb CS) and hemoglobin Pakse, are prevalent in northeastern Thailand and neighboring regions. Homozygous Hb CS and compound heterozygous Hb CS/Hb Pakse can present with a wide clinical spectrum. In this study, 49 patients with these α-globin variants—with or without co-inheritance of beta-thalassemia—were evaluated. Genotypes included homozygous Hb CS (n = 27), homozygous Hb CS with Hb E (n = 8), compound heterozygous Hb CS/Hb Pakse (n = 10), compound heterozygous Hb CS/Hb Pakse with Hb E (n = 3), and homozygous Hb Pakse (n = 1). Fetal anemia with hydrops fetalis occurred in 25 patients; 21 underwent intrauterine transfusions (IUTs), resulting in favorable postnatal outcomes in most cases. Two patients with homozygous Hb CS died from complications of severe anemia and prematurity. Early neonatal jaundice occurred in 27 patients, most requiring phototherapy. Direct hyperbilirubinemia was observed in 10 patients; most recovered with supportive care and transfusion, though one died from progressive cholestasis. Twenty four patients required 1–2 postnatal transfusions, with only two requiring later transfusion. Four patients with childhood anemia were initially misdiagnosed with iron deficiency anemia before confirmation of α-thalassemia variants. After the first few months of life, patients typically exhibit mild hypochromic microcytic anemia, elevated red cell distribution width, and reticulocytosis, with basophilic stippling more prominent in Hb CS. During follow-up (3–160 months, median 66), no patients developed hepatosplenomegaly, iron overload, or gallstones. These α-thalassemia variants may cause severe fetal anemia requiring IUT but generally evolve into transfusion-independent mild anemia. Early detection and targeted intervention can improve outcomes in high-prevalence regions.

This study was performed to evaluate surgical outcomes in patients prenatally diagnosed with severe Ebstein's anomaly and a circular shunt. This retrospective study included 13 patients diagnosed with severe Ebstein's anomaly accompanied by a circular shunt on foetal echocardiography between 2012 and 2024 at our institution. All patients were delivered by planned caesarean section. Foetal hydrops was present in 4 patients. At birth, chest radiographs showed cardiothoracic ratios ranging from 90% to 100%, and echocardiography demonstrated severe pulmonary and tricuspid regurgitation in all cases. Surgical strategies-including main pulmonary artery ligation and the modified Starnes procedure-were evaluated based on perioperative clinical course, incorporating chest X-rays, echocardiograms, laboratory data, and urine output. The median follow-up after the modified Starnes procedure was 3.46 years (interquartile range, 2.9 years). All patients underwent surgical intervention on the day of birth: main pulmonary artery ligation in 7 and a modified Starnes procedure in 6. Of those who initially underwent ligation, 4 patients required conversion to the modified Starnes procedure on postoperative day 1, 2 patients on day 3, and 1 patient on day 6. One patient died of infection after the Glenn procedure. Of the remaining 12 patients, 7 completed Fontan circulation, and 5 were awaiting the Fontan. The 5-year postoperative survival rate was 92.3%. Surgical outcomes for severe Ebstein's anomaly with a circular shunt were excellent. However, the main pulmonary artery ligation as an initial palliation did not stabilize haemodynamics. Early implementation of the modified Starnes procedure appears critical to overcoming the haemodynamically unstable period immediately after birth.

Introduction: the ABO and rhesus systems remain the most clinically significant blood group antigens on red blood cell membranes. Rhesus isoimmunization occurs when maternal Rh antibodies in a RhD-negative woman react with red blood cells of an RhD-positive fetus, leading to adverse fetal and neonatal outcomes. Methods: a cross-sectional review of 194 medical records of RhD-negative pregnant women managed at Kenyatta National Hospital (KNH) between 2013 and 2019 was conducted. Data on sociodemographic, obstetric, and clinical characteristics were extracted and analyzed using SPSS version 23. Multivariable logistic regression was performed to determine associations between Rh isoimmunization and adverse pregnancy outcomes. Adjusted odds ratios (aORs) with 95% confidence intervals were calculated, and p&lt;0.05 was considered statistically significant. Results: the mean age (SD) of participants was 30.1 years, and the mean gestational age at delivery was 38.9 weeks. Most participants were multigravida (69.1%) and married (91.2%). The prevalence of Rh isoimmunization was 4.1%. Isoimmunized women had significantly higher odds of miscarriage (aOR 5.64, 95% CI 1.48-21.53; p=0.01), hydrops fetalis (aOR 8.72, 95% CI 2.10-36.12; p&lt;0.001), intrauterine foetal death (aOR 9.83, 95% CI 2.75-35.12; p&lt;0.001), low birth weight &lt;2500g (aOR 7.40, 95% CI 1.93-28.43; p=0.004), and poor APGAR score &lt;7 at 5 minutes (aOR 10.26, 95% CI 2.98-35.32; p&lt;0.001). Neonates of isoimmunized mothers were also more likely to require neonatal intensive care unit (NICU) admission (aOR 6.92, 95% CI 1.41-33.84; p=0.02). Conclusion: the prevalence of Rh isoimmunization among RhD-negative women at KNH was 4.1%. Isoimmunization was significantly associated with miscarriage, hydrops fetalis, IUFD, low birth weight, poor APGAR scores, and NICU admission. Strengthening routine anti-D prophylaxis and improving documentation of its administration after pregnancy loss or delivery are critical to reducing isoimmunization and related complications.

Lymphatic malformations are rare congenital anomalies that range from small, self-limited lesions to large, rapidly expanding masses capable of causing serious perinatal complications, including hydrops fetalis, polyhydramnios, airway obstruction, and fetal demise. Although most lesions are managed expectantly or postnatally, in utero interventions have been attempted in highly select cases where lesions threaten pregnancy viability or safety of delivery. Reported approaches include the perinatal option of ex utero intrapartum therapy, intrauterine ultrasound-guided cyst aspiration for decompression, intrauterine intralesional sclerotherapy with agents such as OK-432, and more recently, maternal pharmacologic therapy targeting the mTOR pathways. This review summarizes the available literature describing prenatal management of these lesions, including procedural techniques, maternal and fetal outcomes, and emerging strategies. Together, these findings highlight the potential promise and the caution necessary in translating postnatal therapeutic advances for lymphatic malformations to the prenatal setting.