Nonimmune Hydrops Fetalis in the Liveborn: Series of 32 Autopsies

Nonimmune hydrops fetalis (NIHF) or generalized soft tissue edema and cavity effusions may be due to cardiovascular diseases, congenital infections, genitourinary malformations, thoracic masses, placental conditions, chromosomal abnormalities, and idiopathic. We report 32 cases of NIHF from among 429 neonates who underwent autopsies (incidence 7.45%). Sixteen cases (50%) had cardiovascular disease; all were due to low output cardiac failure; 7 had structural congenital heart disease. Three of the children with congenital heart disease also had chromosomal abnormalities: 2 had trisomy 18 and 1 had Noonan syndrome. Among myocardial conditions were five subjects with cardiomyopathies (1 of each of the following types): oncocytic, dilated, endocardial fibroelastosis, cardiac glycogenosis, and carnitine deficiency; 3 had myocarditis, and 1 had cardiac rhabdomyomas. Congenital infections were due to cytomegalovirus in 3 cases, bacteria in 2, and parvovirus in 1. The mechanism of NIHF in these cases might be a combination of decreased myocardial contractility due to myocarditis and fetal anemia. Genitourinary diseases were present in 5 newborns: Two had congenital nephrotic syndrome, 1 had VACTER association, 1 had prune-belly syndrome, and 1 had urogenital sinus malformation. Intrathoracic lesions were found in 2 babies (pulmonary sequestration and diaphragmatic hernia). One twin died of volume overload due to twin transfusion syndrome. Only 2 newborns were classified as idiopathic. Our study shows that cardiovascular diseases that lead to heart failure or impaired venous return are more common in the liveborn (50%), whereas congenital infections are more common in the stillborn with NIHF.     

Nonimmune Hydrops Fetalis, Hydramnios, Microcephaly, and Intracranial Meningeal Hemangioendothelioma

Necropsy findings in a male stillborn at 31 weeks gestational age included nonimmune hydrops, hydramnios, and microcephaly secondary to a hemangioendotheliomatous malformation at the tentorium. The vascular lesion was composed by large and small tortuous endothelium-lined vessels and leiomuscular septa. The lesion is thought to be related to the more frequent arteriovenous malformation of the vein of Galen.     

Cardiac Abnormalities and Nonimmune Hydrops Fetalis: a Coincidental, Not Causal, Relationship

Few conditions associated with nonimmune hydrops fetalis have had a demonstrable causal relationship. Congenital heart disease is often said to be a cause of nonimmune hydrops fetalis and antenatal closure of the foramen ovale is the cardiac abnormality most frequently reported in association with hydrops. In order to examine the role of congenital heart disease in hydrops, and, in particular, that of antenatal closure of the foramen ovale, we reviewed all autopsy cases with hydrops fetalis over an 11 year period and compared cardiac anomalies with those of nonhydropic controls. The incidence of various congenital heart malformations was not significantly different among these groups, suggesting that factors in addition to cardiac anomalies must be considered in the pathogenesis of nonimmune hydrops fetalis.     

Parvovirus Infects Cardiac Myocytes in Hydrops Fetalis

Parvovirus infection during pregnancy is an important cause of hydrops fetalis. It is attributed to anemia caused by viral-induced destruction of red blood cells. Infection of other organs has been reported including the heart, liver, and lungs. Few of these reports, however, convincingly demonstrate virions within the functional parenchyma of the tissue. This is of particular concern regarding myocardium in the context of hydrops fetalis which is, in part, due to cardiac failure. The problem in routine pathology practice is that most fetuses with the infection are macerated. This, in part, probably explains the paucity of published information on cardiac involvement. This study examined five cases of fatal hydrops fetalis with variable maceration with serologically proven parvovirus B19 infection. Transmission electron microscopy of cardiac tissue demonstrated intranuclear virions in both erythroid precursor cells and in cardiac myocytes in three of these cases. In each of these, immunogold electron microscopy provided confirmatory evidence of parvovirus infection. Virions were not identifiable where maceration had caused disintegration of nuclei in the myocytes. In addition, virions were absent in the three negative control cases where retroplacental hemorrhage was confirmed as the cause of death.This study suggests that parvovirus infection of cardiac myocytes may play a more important role in causing hydrops fetalis than previously realized. It also demonstrates that maceration should not discourage the use of electron microscopy.     

Hydrops Fetalis and Neonatal Leukemia in Down Syndrome

Four newborn infants with Down syndrome and manifestations of neonatal leukemia are described. One of the four was stillborn, two died shortly after birth, and a fourth survived and all evidence of leukemia disappeared in the first month of life. Three of the four cases had hydrops fetalis, and a fourth was a macerated stillborn. Nine other similar reported cases are reviewed. We conclude that neonatal leukemia in Down syndrome is a form of leukemia that is usually transient, with spontaneous recovery, but may be fatal at or around the lime of birth with manifestations of hydrops fetalis, hepatosplenomegaly, and/or progressive liver disease.     

Left Ventricular Noncompaction: A Rare Cause of Hydrops Fetalis

We present a case of isolated left ventricular noncompaction (LVNC), a severe congenital cardiomyopathy, which presented in the neonatal period as fetal hydrops. To our knowledge, this is the first child with LVNC presenting with hydrops fetalis to survive infancy. Once considered a uniformly fatal and extremely rare form of cardiomyopathy, LVNC has recently been shown to be more common than previously reported, with a varying range of clinical severity. Although long-term morbidity and mortality are not clearly known, recent work suggests better survivability than once reported.     

Acid Hematin Pigmentation of the Cornea in Stillborn Fetuses

During the postmortem histopathologic evaluation of eyes from stillborn fetuses we noted the presence of a prominent undescribed corneal pigment in 18 of 55 stillborn fetuses. The corneal pigment was frequently associated with documented meconium-stained amniotic fluid, and in no instance was a stained cornea coupled with recorded clear amniotic fluid. Pigmented corneas came from stillborn fetuses with a longer duration of intrauterine death than nonstained corneas. The pigment stained black with the Fontana-Masson stain, was birefringent, and treatment of tissue sections with 5% potassium permanganate and 5% oxalic acid as well as with saturated alcoholic picric acid solution removed the pigment indicating that it is acid hematin. The most likely cause of the acid hematin-stained corneas was tissue acidity created in utero with prolonged intrauterine death.     

Role of Amiodarone in the Treatment of Fetal Supraventricular Tachyarrhythmias and Hydrops Fetalis

We report three consecutive hydropic fetuses with fetal tachyarrhythmias treated with amiodarone—two in combination with digoxin and one with digoxin, procainamide, and propranolol. Sinus rhythm was achieved in one case and ventricular rate control was achieved in two cases. All fetuses treated with amiodarone gradually improved. Observed side effects of amiodarone were a maternal rash in one mother and transient neonatal hypothyroidism in one infant. We conclude that amiodarone might be effective and safe for fetal tachyarrhythmias and impending hydrops. The small number of patients suggests that a multicenter cooperative approach is required in order to determine if this is correct.     

Noncompaction Cardiomyopathy in a Neonate Presenting With Hydrops Fetalis and Pulmonary Hypertension

Noncompaction cardiomyopathy (NCCM) is a recently recognized form of cardiomyopathy with a variable clinical presentation. This report describes NCCM of a newborn presenting with hydrops fetalis and pulmonary hypertension. To date, this has not been described in the literature. As knowledge of this condition grows, the need to recognize NCCM becomes more important.     

Placental Chorioangioma as the Cause of Non-Immunologic Hydrops Fetalis; a Case Report

Background

Chorioangiomas are the most common benign tumors of the placenta originating from primitive angioblastic tissues. It comprises near 1 percent of placental tumors. Clinical manifestations in the newborn are rare and usually associated with tumors greater than 5 cm in diameter and consist of polyhydramnios, fetal anemia, massive edema with pleural effusion, ascites and intrauterine growth retardation. We present a case with large chorioangioma as the cause of non-immunologic hydrops fetalis with a successful outcome.

Case Presentation

The patient was a female newborn with history of polyhydramnios, symptoms of congestive heart failure and associated anemia, thrombocytopenia and coagulopathy. The pathophysiology and management of the complications of hydrops fetalis with chorioangioma are discussed

Conclusion

Chorioangioma of the placenta has potentially serious perinatal risks and so the pregnancy needs to have regular surveillance. The chance of developing complications is directly related with the tumor size.     

Congenital Erythropoietic Porphyria: Prenatal Diagnosis and Autopsy Findings in Two Sibling Fetuses

Congenital erythropoietic porphyria is an autosomal recessive disease characterized by a deficiency of uroporphyrinogen III cosynthetase activity, with diffuse tissue accumulation of specific type I porphyrins. The diagnosis of this disease was made in two fetuses, who were siblings, and from a Caucasian nonconsanguinous family. The first fetus died in utero with hydrops fetalis and anemia, but without an etiopathogenic diagnosis. In the second case, the diagnosis was based on pink fluorescence of the amniotic fluid examined fortuitously in sunlight. DNA analysis showed that the fetus was heteroallelic for the mutation C73R. The autopsy showed brown skin, and at histological examination, porphyrin pigment was deposited in many tissues. Retrospectively, similar deposits were found in the tissues of the first fetus. Received October 14, 1999; accepted July 12, 2000.     

Unusual Electrocardiogram Findings in a Preterm Infant After Fetal Tachycardia with Hydrops Fetalis Treated with Flecainide

Fetal tachycardia and signs of hydrops fetalis were diagnosed at 29 weeks of gestation. The heart rate normalized by combined treatment with digoxin and flecainide and was followed by improvement of the hydrops. Premature labor led to delivery at 33 weeks of gestation. The newborn infant showed mild respiratory distress and was in a hemodynamically stable condition. Marked QT segment anomalies on the electrocardiogram during the first postnatal days resolved completely within 3 weeks. They were unlikely to be attributable to myocarditis or myocardial infarction. We speculate that these anomalies were caused by the maternal flecainide therapy.     

Successful Management of Severe Tricuspid Regurgitation Associated with Hydrops Fetalis in a Case of Dysplastic Tricuspid Valve

We report a case with hydrops fetalis and severe tricuspid regurgitation due to dysplastic tricuspid valve, diagnosed in utero and followed after birth. The patient was successfully managed on the basis of useful echocardiographic informations.     

Intrathyroidal Thymic Tissue: An Autopsy Study in Fetuses with Some Emphasis on Pathological Implications

Fifty-eight human thyroid glands obtained at autopsy from fetuses with proven retrosternal thymus were systematically studied for the presence of intrathyroidal thymic tissue. The latter was found in one thyroid lobe in each of three fetuses (5.1%). It was located in a subcapsular position in two cases (3.4%) and lying deep in thyroid tissue in one (1.7%). Our findings would support a IV-V pharyngeal pouch origin for some accessory thymic tissue and would provide an explanation of the histogenesis of intrathyroid thymomas.     

Value of the Perinatal Autopsy: Critique

In consenting to a perinatal autopsy, the primary motive of parents may be to find the exact cause of death. A critical review on the value of perinatal autopsies was performed to see whether parents could be counseled regarding their main motive. A literature search was performed in MEDLINE, EXCERPTA MEDICA, and the Cochrane library. We evaluated the value of the autopsy by comparing the clinical and autopsy diagnoses in stillbirths, neonatal deaths, and therapeutic terminations. Clinicopathologic concordance was divided into four categories: (1) change in diagnosis, (2) additional findings, (3) complete confirmation, and (4) inconclusive. We sought information on factors that may influence the value of perinatal autopsies: the type and definitions of perinatal loss; autopsy rate; level of hospital; expertise of pathologists; autopsy protocol used; whether patients were inborn or referred; and antenatal diagnosis. From the 27 articles that met our review criteria, the autopsy revealed a change in diagnosis or additional findings in 22% to 76% of cases. If confirmation of clinical findings is included, then the value of the perinatal autopsy was as high as up to 100%. Factors that could influence this rate were reported variably by investigators. When centers report their experience of the value of the perinatal autopsy, information on the factors that may influence their reports should be provided as well. Clinicians can confidently advise parents of the usefulness of the perinatal autopsy in ascertaining the cause of death or for counseling their future pregnancies.     

Demonstration of Respiratory Syncytial Virus in an Autopsy Series

Respiratory syncytial virus (RSV) antigen was demonstrated in formalin-fixed, paraffin-embedded autopsy tissue using an immunoperoxidase technique. Eighteen autopsy cases were selected on the basis of one of the following criteria: a positive culture for RSV, antemortem or postmortem; positive ELISA test for RSV, antemortem or postmortem; or postmortem histology suggestive of paramyxovirus infection. Controls included three cases from which parainfluenza or influenza virus had been cultured and a case in which the clinical diagnosis of measles was firmly established. Sections of formalin-fixed, paraffin-embedded tissue were stained with a rabbit anti-RSV antibody (Dako) using an immunoperoxidase technique. Staining was achieved in 12 cases. This included 6 of 7 cases selected because of positive cultures or ELISA tests for RSV. The other 6 cases in which RSV was identified by the described technique lacked culture or ELISA confirmation. Granular and globular staining was seen in the cytoplasm of respiratory epithelial cells and syncytial giant cells. None of the control cases stained for RSV. The histology of RSV lungs was consistent with changes described in the literature for RSV infection, although pneumonic consolidation and syncytial giant cells were more prominent in this series.