Nonimmune Hydrops Fetalis.

Nonimmune hydrops fetalis (NIHF) historically has been considered a lethal fetal condition. Understanding NIHF to be a symptom or an end-stage status of a variety of fetal conditions, along with improved fetal diagnostics and interventions, has changed the landscape for at least some fetuses. Understanding the pathophysiologic mechanisms has led to the development of diagnostic algorithms, improved understanding of cause, and therefore fetal or neonatal treatments. Multidisciplinary counseling and shared decision making are critical to supporting families through pregnancy decisions, potential fetal therapeutic interventions, neonatal management decisions, and at times accepting or transitioning to palliative care.

Non-Immune Hydrops, Hypotonia, Encephalopathy, and Liver Failure with Novel Compound Heterozygous AHCY Mutations.

A late-preterm infant with a prenatal diagnosis of non-immune hydrops was born with hypotonia, poor respiratory effort, chylothorax, encephalopathy, coagulopathy, progressive hepatic failure, and refractory pulmonary hypertension. Life support was withdrawn at 7 days of life due to multisystem organ failure. Rapid whole exome sequencing revealed novel compound heterozygous mutations in the gene encoding S-adenosylhomocysteine hydrolase (AHCY); each novel variant was carried by an asymptomatic parent. Reports of neonates with other AHCY mutations describe a pathology of varying severity. AHCY mutations should be considered when seeking an etiology for neonates with the combination of non-immune hydrops, hypotonia, encephalopathy, and liver failure.

Clinical Features of Neonates with Hydrops Fetalis.

OBJECTIVE: The objective of this study was to evaluate the clinical characteristics of neonates with hydrops fetalis to improve recognition of the disease. PATIENTS AND METHODS: The clinical data of 10 neonates with hydrops fetalis were retrospectively studied. Prenatal characteristics, causes, clinical features, and prognosis were explored. RESULTS: Eight neonates presenting abnormal nonstress test suffered from severe neonatal asphyxia at birth and were resuscitated by endotracheal intubation. Nine had skin edema, eight had pleural effusions with one unilateral and seven bilateral. Six had ascites, eight had polyhydramnios, one had multiple malformations and one had chromosome abnormalities. One survived and nine died. Six died due to resuscitation failure in delivery room, two died due to giving up after 1 day and one died due to the treatment failure after 6 months. Causes of hydrops fetalis were a congenital diaphragmatic hemangioma, recurrent atrial premature beats, genetic syndrome suspicious, Down syndrome, congenital pulmonary lymphangiectasia, anemia, paroxysmal supraventricular tachycardia, placental chorioangioma, and idiopathic edema. CONCLUSION: The prognosis varied because of different etiologies of hydrops fetalis. Severe cases frequently had skin edema and high rate of asphyxia at birth and difficult resuscitation. Timely intrauterine interventions were helpful for successful resuscitation. A well-prepared resuscitation team and the effectiveness of resuscitation could correlate to increasing survival rate.

Etiology of non-immune hydrops fetalis: An update.

Hydrops fetalis is an excessive fluid accumulation within the fetal extra vascular compartments and body cavities. Non-immune hydrops fetalis (NIHF), due to causes other than Rh alloimmunization, is the cause in >85% of all affected individuals. Herein we present an update of our earlier systematic literature review [Bellini et al., 2009] using all publications between 2007 and 2013. We excluded most of the initial 31,783 papers by using strict selection criteria, thus resulting in 24 relevant NIHF publications describing 1,338 individuals with NIHF. We subdivided the affected individuals into 14 classification groups based on the cause of NIHF (percentage of the total group): Cardiovascular (20.1%), Hematologic (9.3%), Chromosomal (9.0%), Syndromic (5.5%), Lymphatic Dysplasia (15.0%), Inborn Errors of Metabolism (1.3%), Infections (7.0%), Thoracic (2.3%), Urinary Tract Malformations (0.9%), Extra Thoracic Tumors (0.7%), TTTF-Placental (4.1%), Gastrointestinal (1.3%), Miscellaneous (3.6%), Idiopathic (19.8%). We discuss the results of the review. There may be some shifts in the percentages of etiological categories as compared to the previous review, but the small numbers within each category make drawing firm conclusions hazardous. We highlight the need for multi-center series of NIHF cases collected and classified using the same schemes in diagnostic work-ups to allow for comparisons of larger numbers of cases.

The many faces of hydrops.

PURPOSE: Fetal hydrops arises from multiple disease processes and can portend a grim prognosis. We reviewed our experience with hydropic fetuses to understand relevant antenatal anatomic and physiologic predictors of survival. METHODS: We reviewed fetal ultrasounds and echocardiograms of hydropic fetuses evaluated from 1996 to 2013. RESULTS: Overall neonatal survival in 167 fetuses was 44% (range, 0-75%) and was influenced by the underlying disease process. The anatomic distribution of fluid varied and was not significantly different between survivors and nonsurvivors. Univariate analysis indicated that resolution of hydrops and delivery at a later gestational age were predictive of survival (OR: 5.7 (95% CI: 2.5-13.2) and OR: 1.3 (95% CI: 1.1-1.4), respectively). Fetal intervention also improved survival in some diseases. Echocardiograms were reviewed to group fetuses with similar cardiac physiology and defined categories with high or low/normal cardiothoracic ratio (CTR). Among patients with a high CTR, the cardiovascular profile score was predictive of survival (p=0.009). CONCLUSION: Survival in hydrops depends on the underlying disease, available fetal therapies to resolve hydrops, and the gestational age of delivery and not on the specific anatomic manifestations of hydrops. In hydropic fetuses with high CTRs, the cardiovascular profile score may be a useful prognostic indicator.

Mirror syndrome associated with fetal leukemia.

Mirror syndrome describes the association of fetal and placental hydrops with maternal edema. This case is the first reported case of mirror syndrome relative to fetal leukemia. We suggest that fetal leukemia can have a major impact on mirror syndrome, and provide a brief review of the literature related to this syndrome.

Association of nonimmune hydrops fetalis with familial hemophagocytic lymphohistiocytosis in identical twin neonates with perforin His222Arg (c665A>G) mutation.

BACKGROUND: This is the first study demonstrating that nonimmune hydrops fetalis (NIHF) in identical twin neonates is associated with biallelic gene defect causing familial hemophagocytic lymphohistiocytosis. OBSERVATIONS: Preterm male twins (31(4/7) wk) with NIHF and hepatosplenomegaly gradually developed pancytopenia, hyperferritinemia, hyponatremia, hypoalbuminemia, and elevated alanine aminotransferase, aspartate aminotransferase, bilirubin, and lactate dehydrogenase levels. Suspected sepsis led to antibiotic therapy. Upon detection of hemophagocytosis in bone marrow, multiorgan failure and pulmonary bleeding led to death. Homozygous His222Arg (c665A>G) mutation was identified in Perforin. CONCLUSIONS: Familial hemophagocytic lymphohistiocytosis should be considered in first days of NIHF cases to have chance for HLH-2004 therapy. Missense mutations of Perforin codon His222 may lead to intrauterine presentation.

Placental expression of anti-angiogenic proteins in mirror syndrome: a case report.

Mirror syndrome is a rare disorder in which fetal hydrops is associated with maternal oedema, proteinuria and hypertension. The aetiology of the maternal condition is unknown, but it is thought to be related to preeclampsia. Few descriptions exist of placental morphology in mirror syndrome, but placentomegaly is consistently observed. In this case placental morphology showed villous oedema and syncytial nuclear aggregates where villi were in direct contact. Immunoperoxidase staining for VEGFR1 and Endoglin was more intense in mirror syndrome compared to gestational-age matched controls,and at a similar level to a case of preeclampsia. Placentally-derived anti-angiogenic factors may be involved in the pathogenesis of mirror syndrome.

Placental origins of angiogenic dysfunction in mirror syndrome.

UNLABELLED: BACKGROUNDL: Mirror syndrome is characterized by preeclampsia-like syndrome in pregnancies complicated by fetal hydrops. We describe a case of mirror syndrome associated with angiogenic dysfunction in maternal plasma and the placenta. CASE: A pregnant patient with known fetal hydrops presented at 22 weeks gestation with features of severe preeclampsia. Measurements of plasma anti- and proangiogenic factors were consistent with a profound antiangiogenic state. Immunohistochemistry of the placenta for antiangiogenic proteins showed a pattern similar to that seen in patients with severe preeclampsia. CONCLUSION: Angiogenic imbalance may also be responsible for the preeclampsia-like condition seen in mirror syndrome.

Angiogenic and antiangiogenic factors before and after resolution of maternal mirror syndrome.

Mirror syndrome is a rare condition that involves fetal hydrops, placentomegaly and severe maternal edema. The pathogenesis of this syndrome mimics endothelial dysfunction observed in pre-eclampsia. We report a case of maternal mirror syndrome caused by bilateral fetal hydrothorax that resolved after intrauterine pleuroamniotic shunt placement. At the time of the clinical manifestation there was an antiangiogenic state similar to that seen in pre-eclampsia, which resolved after fetal treatment. Our findings suggest that mirror syndrome is a manifestation of a broad spectrum of pathological conditions that induces an antiangiogenic state.

Fetal and neonatal presentation of long QT syndrome.

This report describes a fetus presenting with intrauterine tachycardia and hydrops fetalis. Soon after birth the neonate was noted to be in torsades de pointes that responded dramatically to medical management. Long QT syndrome (LQTS) was diagnosed on electrocardiogram obtained soon after birth. The prognosis is poor when LQTS presents in utero or during the first week of life. However, our infant did well with medical management and has remained free of arrhythmias at follow-up.

[Non-immune hydrops fetalis--clinical experience in newborn infants].

INTRODUCTION: Non-immune hydrops fetalis is a condition of excessive accumulation of extravascular fluid without identifiable circulating antibody to erythrocytes membrane antigens. In newborn infants it is characterized by skin oedema and pleural, pericardial or peritoneal effusion. In the era of routine Rh immunization for the prevention of foetal erythroblastosis, non-immune pathophysiologic mechanisms are presented in 76-87% of all hydropic newborns. Non-immune hydrops fetalis can be associated with numerous and various disorders. The mortality rate may exceed 50%. This study was aimed at presenting our clinical experience in treating newborn infants with non-immune hydrops fetalis. MATERIAL AND METHODS: A retrospective-prospective study included newborn infants with non-immune hydrops fetalis, who were treated in the Neonatal Intensive Care Unit of Mother and Child Health Institute of Serbia between January 1, 2001 and October 31, 2010. All valid data about aetiology, diagnosis, clinical course and outcome were recorded. RESULTS: The diagnosis of non-immune hydrops fetalis was made in 11 newborns. The etiologic diagnosis was established in 8 patients: anaemia due to fetomaternal transfusion in 4 patients and conatal cytomegalovirus infection, intracranial haemorrhage, isolated pulmonary lymphangiectasia and diffuse skin and mediastinal lymphangiomatosis in the remaining 4 patients. CONCLUSION: Non-immune hydrops of newborn infant is associated with a high mortality rate and requires complex diagnostic and therapeutic procedures. An optimal management of neonates with non-immune hydrops fetalis demands a multidisciplinary approach to the treatment in a neonatal intensive care unit.

Clinical features of the complete closure of the ductus arteriosus prenatally.

OBJECTIVE: Prenatal constriction of the ductus arteriosus associated with maternal drug ingestion was reported several decades ago. There are fewer reports of the complete closure of the ductus arteriosus; therefore, the clinical features of the latter are poorly understood. The aim of this study is to clarify the clinical features of complete ductal closure and postnatal pulmonary hypertension by performing echocardiography of the fetus. PATIENTS: We diagnosed four fetuses with complete ductal closure by performing fetal echocardiography and reviewed the prenatal and postnatal medical records of the mother and fetus. RESULTS: One mother each had bronchial asthma, ulcerative colitis, and idiopathic thrombocytopenic purpura, and they had received nonsteroidal anti-inflammatory drugs and/or corticosteroids during pregnancy. The fourth mother did not have basal disease and had not ingested any drugs. Fetal diagnosis was performed at 32-38 weeks of gestation. All fetuses had right heart dilatation with tricuspid regurgitation in the absence of any cardiac defects, and Doppler echocardiography indicated that the right ventricular pressure was elevated. Two of the fetuses had fetal hydrops, which suggested severe right heart dysfunction. All fetuses were delivered by emergent cesarean delivery. After birth, all the infants developed persistent pulmonary hypertension and required oxygen inhalation. Of these, three required mechanical ventilation, and two, nitric oxide inhalation. All infants improved within 2 weeks, and they had no neurological and cardiac complications after discharge. CONCLUSION: Right heart dilatation and severe tricuspid regurgitation in the absence of a cardiac defect in the fetus strongly suggested ductal dysfunction. Careful evaluation of ductal patency and right ventricular function can lead to precise early diagnosis and good prognosis.

Hydrops fetalis in a neonate with down syndrome, transient myeloproliferative disorder and hepatic fibrosis.

Transient myeloproliferative disorder is a self limiting disorder characterized by leukocytosis with the presence of megakaryoblasts in the peripheral blood and bone marrow, anemia, thrombocytopenia, and organomegaly. It occurs in approximately 10% of newborn infants with Down syndrome. Hepatic fibrosis is seen in the severe form of transient myeloproliferative disorder with Down syndrome that is characterized by diffuse intralobular sinusoidal fibrosis and extramedullary hematopoesis. We describe a patient with hydrops fetalis, Down syndrome, and transient myeloproliferative disorder. We suggest that patients with the severe form of transient myeloproliferative disorder should be examined for hepatic fibrosis.

Prenatal management of placental chorioangioma: value of the middle cerebral artery peak systolic velocity.

Placental chorioangiomas are benign tumors of the placenta. Large chorioangiomas may cause severe complications such as fetal anemia, hydrops and fetal death. We report the use of sonographic findings and peak systolic velocity in the middle cerebral artery in the diagnosis and management of fetal anemia without the occurrence of hydrops fetalis in a pregnant woman with a large placental chorioangioma. Successful intrauterine blood transfusion was performed at 26 weeks. Spontaneous thrombosis of the main supplying blood vessel of the chorioangioma was detected at 33 weeks. The child was delivered at 39 weeks of pregnancy in normal clinical condition.

Impact of selective laser ablation of placental anastomoses on the cardiovascular pathology of the recipient twin in severe twin-twin transfusion syndrome.

OBJECTIVES: We investigated the impact of selective laser ablation on the cardiovascular pathology of the recipient twin in twin-twin transfusion syndrome. STUDY DESIGN: Fetal echocardiograms and medical records were reviewed from 22 pregnancies with severe twin-twin transfusion syndrome where echocardiography was performed before and after laser. RESULTS: Before laser, cardiomegaly associated with right and/or left ventricular hypertrophy without ventricular dilatation, was observed in most cases. Right ventricular and left ventricular systolic dysfunction (shortening fraction <28%) was present in 59% and 27%, respectively, and diastolic dysfunction (based on inflow and venous Dopplers) in 73%. Shortly after laser, biventricular systolic function improved significantly and diastolic function tended to improve (50%, P = .06). Functional pulmonary atresia, secondary to right ventricular systolic dysfunction, resolved in 2 of 2 cases at post-laser echocardiography. On serial assessment, diastolic function was normal in 7 of 10, hydrops regressed in 4 of 5, and neither progressive myocardial hypertrophy nor anatomical right ventricular outflow obstruction were found. CONCLUSIONS: Selective laser ablation in severe twin-twin transfusion syndrome acutely improves biventricular systolic function and tends to improve diastolic function in the recipient twin.