Syphilis Infection: An Uncommon Etiology of Infectious Nonimmune Fetal Hydrops with Anemia.

An increased prevalence of syphilis has been observed in many developed countries over the last decade. During pregnancy, syphilis can affect the fetus through development of nonspecific symptoms such as microcephaly, ascites, hepatosplenomegaly, dilated and echogenic bowel, placentomegaly, and, uncommonly, fetal hydrops. Congenital syphilis also leads to hematologic abnormalities such as anemia, thrombocytopenia, leukopenia, and leukocytosis. We present a case of nonimmune fetal hydrops with anemia related to syphilis infection. Diagnosis was confirmed by a maternal serological test and microbiological testing on amniotic fluid, umbilical cord, and placental tissues. The patient was treated with penicillin and the fetus received an intrauterine red blood cell transfusion, but fetal death occurred shortly after. Such a presentation is mostly related to parvovirus B19, and syphilis etiology is poorly mentioned because physicians have rarely seen early congenital syphilis in the past. However, given the increasing prevalence of this disease in the adult population, clinicians should remain alert to the various presentations of congenital syphilis.

Early detection by magnetic resonance imaging of fetal cerebral damage in a fetus with hydrops and cytomegalovirus infection.

We discuss the use of magnetic resonance imaging (MRI) to reveal early fetal neurological involvement of cytomegalovirus (CMV) infection. A woman presented at 21 weeks of pregnancy with active CMV infection. Cerebral ultrasound examination had been normal. An MRI scan revealed a thickened germinal matrix, which was histologically confirmed, associated with underdevelopment of the gyri. Brain MRI proved particularly useful in identifying the findings not disclosed by routine ultrasound during pregnancy and subsequently confirmed at histology.

Long-term outcome after fetal transfusion for hydrops associated with parvovirus B19 infection.

OBJECTIVE: To evaluate neurodevelopmental status of children treated with intrauterine red blood cell and platelet transfusion for fetal hydrops caused by parvovirus B19. METHODS: Maternal and neonatal records of all intrauterine transfusions for congenital parvovirus B19 infection in our center between 1997 and 2005 were reviewed. Congenital B19 virus infection was confirmed by the presence of parvovirus B19-specific immunoglobulin M or parvovirus B19 DNA in fetal blood samples. All children underwent a general pediatric and neurological examination. Primary outcome measure was neurodevelopmental status (developmental index by Bayley Scales of Infant Development or Snijders-Oomen test). Secondary outcome measure was general health status of surviving children. RESULTS: A total of 25 intrauterine transfusions were performed in 24 hydropic fetuses. Median fetal hemoglobin concentration, platelet count, and blood pH before intrauterine transfusions were 4.5 g/dL (range 2.4-11.4 g/dL), 79x10(9)/L (range 37-238x10(9)/L) and 7.36 (range 7.31-7.51), respectively. Sixteen survivors aged 6 months to 8 years were included in the follow-up study. Eleven children (68%) were normal, and 5 children (32%) demonstrated a delayed psychomotor development with an suboptimal neurological examination (mild delay n=3, severe delay n=2). Neurodevelopmental status did not correlate with pre-intrauterine transfusion hemoglobin, platelet, or blood pH values. Growth and general health status were normal in all. Two children had minor congenital defects. CONCLUSION: Neurodevelopmental status was abnormal in 5 of 16 survivors and was not related to the severity of fetal anemia and acidemia. We hypothesize that fetal parvovirus B19 infection may induce central nervous system damage. LEVEL OF EVIDENCE: III.

Immunoelectron microscopic identification of human parvovirus B19.

A mildly macerated, hydropic fetus was delivered spontaneously at 25 weeks gestation by a multigravidous black mother. At autopsy, gross and microscopic evidence suggested fetal anemia, and excessive extramedullary erythroblastosis was present generally. Erythroid precursor cells in the pulmonary capillary circulation contained eosinophilic nuclear inclusions consistent with human parvovirus B19 infection. Transmission electron microscopy on osmicated Epon lung sections showed lucent, granular chromatin corresponding to the inclusions. In rare foci only these sections contained paracrystalline arrays of 20-nm virions. In the same cells, similar virions were seen within the cytoplasm, both randomly distributed and in paracrystalline aggregates. Postembedding immunoelectron microscopy, done on formalin-fixed lung embedded in a hydrophilic resin, showed positive labelling over the nuclear inclusions, and also localized the viral capsid antigen to cytoplasmic virion aggregates. The nuclear aggregates suggest that the virus would reach the circulation after cell lysis whereas those in cytoplasm suggest that parvovirus also may be excreted from infected cells before they lyse.

[Human parvovirus B19 (HPV-B19), a clinical overview with emphasis of rheumatologic manifestations]. / Humanes Parvovirus B19 (HPV-B19), eine klinische Ubersicht mit Betonung der rheumatologischen Manifestationen.

The human parvovirus B19 (HPV-B19) causes a spectrum of diseases: Erythema infectiosum (fifth disease), aplastic crises in patients with chronic hemolytic anemias, chronic bone marrow failure in patients with congenital or acquired immune deficiency, vascular purpura, hydrops fetalis, abortion, intrauterine fetal death and HPV-19-arthropathy. In this review we will discuss the clinical pattern, the diagnostic questions and therapeutic possibilities particularly relating to rheumatic manifestations.

Human parvovirus B19 infection and unbalanced translocation in a case of hydrops fetalis.

In a case of hydrops fetalis, serological examination showed a recent maternal human parvovirus B19 infection. Amniocentesis revealed a unique unbalanced translocation between chromosomes 3 and 11 of the fetus. The mother proved to have a balanced reciprocal translocation between chromosomes 3 and 11. A grossly macerated hydropic male fetus was delivered with a flat nose and low implanted deformed ears. Histopathological examination revealed nuclear inclusion bodies in fetal erythroid cells, confirming human parvovirus B19 infection. Parvovirus B19 DNA was demonstrated by in situ hybridization in the nuclei of heart muscle cells. Our finding of two different disorders in one case illustrates the importance of a complete evaluation of every case of hydrops fetalis, especially concerning counselling on the outcome of future pregnancies. The human parvovirus B19 infection will not recur due to the acquired immunity of the mother, whereas the balanced reciprocal translocation will endanger future pregnancies.

The frequency of human parvovirus B19 infection in nonimmune hydrops fetalis.

Intrauterine infection of human parvovirus B19 has recently been identified as an etiology for nonimmune hydrops fetalis (NIHF) and fetal death. To examine the frequency of B19 infection in cases of NIHF, forty two cases of NIHF of unknown cause were tested for the presence of B19 antibodies by enzyme-linked immunosorbent assay (ELISA) and B19 DNA by polymerase chain reaction (PCR). Three maternal sera were positive for B19 IgM antibody and one fetal serum was positive for B19 DNA. Overall, four (10%) of the 42 cases were positive for B19 infection. All of the four cases positive for B19 infection were found during or just before an outbreak of erythema infectiosum and the incidence was calculated at 36% if only cases found during the outbreak were collected. In all four cases of B19 infection, NIHF was diagnosed at 20 to 23 weeks of gestation, which suggested that B19 infection might be a particular threat to the fetus during this stage of gestation. In conclusion, B19 infection may contribute to 10% of cause unknown NIHF and the incidence may be higher if cases during outbreaks are exclusively collected.

Hidrops fetal no inmunológico: experiencia de 33 casos / Non immunological fetal hydrops: experience in 33 cases

En un estudio retrospectivo de autopsias perinatales efectuadas durante 11 años en el Hospital Sam Borja Arriarán, se encontró 33 casos de hidrops fetal no inmunológico, correspondiendo al 1,83 por ciento de las autopsias perinatales; la incidencia fue de 1 caso por cada 3.624 nacidos vivos. Entre las etiologías destacan las causas infecciosas y las anormalidades genéticas o cromosómicas, ambas con un 27,3 por ciento cada una; en un 15,2 por ciento se encontró algún trastorno del embarazo, especialmente gestaciones múltiples y no hubo casos idiopáticos. En todos se observó anemia severa y marcada eritropoyesis extramedular. En un 58 por ciento de los casos hubo hipoplasia pulmonar y en un 31 por ciento hipoplasia renal. La placenta estuvo aumentada de tamaño en el 100 por ciento de los casos estudiados. Entre los mecanismos implicados en la génesis del estado hidrópico están la anemia crónica, la hipoproteinemia y la insuficiencia cardíaca

A report of human parvovirus B19 infection in hydrops fetalis. First Australian cases confirmed by serology and immunohistology.

OBJECTIVE: To present the first Australian cases of fetal hydrops induced by parvovirus B19. CLINICAL FEATURES: Autopsies on two cases of intrauterine fetal death with hydrops fetalis and pallor revealed evidence of myocarditis and widespread characteristic inclusion-bearing cells, predominantly erythroblasts. The diagnosis of hydrops fetalis induced by parvovirus B19 was confirmed in both cases by immunohistological localisation of the viral inclusions by means of a monoclonal antibody to the VP1 and VP2 proteins of parvovirus B19. A low level of parvovirus B19 IgM antibodies was detected in the second case. CONCLUSIONS: It is possible that our relatively small population and lack of familiarity with the histopathological features may have led to underdiagnosis rather than a true absence of fetal parvovirus B19 infection in Australia. The condition can be diagnosed and treated antenatally and therefore should be included in the differential diagnosis of causes of hydrops fetalis.

Diagnosis and incidence of fetal parvovirus infection in an autopsy series: II. DNA amplification.

This study evaluates the practical utility of the polymerase chain reaction (PCR) as a diagnostic method for intrauterine fetal parvovirus infection in cases of hydrops fetalis. Paraffin-embedded, formalin-fixed fetal tissues from cases of hydrops fetalis were assessed for parvovirus B19 by histology and PCR in conjunction with 32P hybridization. Of 673 fetal and neonatal autopsies performed at Women and Infants' Hospital for the years 1985 through 1990, 32 cases were determined to have hydrops fetalis, of which five were positive for parvovirus infection by both histology and the PCR. PCR was not used in seven (22%) of the 32 hydrops cases because 1 microgram of DNA was not available for study. Histology was as sensitive as PCR in detecting parvovirus B19 in fetal autopsy tissues from cases of hydrops fetalis, and could be used reliably in each case to diagnose parvovirus infection. In our hands, histology is as sensitive as PCR and less labor-intensive. We would reserve PCR for cases without inclusions and with a strong suspicion of parvovirus infection, or for fluids in which histological analysis is not available.

Diagnosis and incidence of fetal parvovirus infection in an autopsy series: I. Histology.

This study was undertaken to obtain additional information about the incidence and characteristics of fetal parvovirus B19 infection in an unselected autopsy series, and to assess the distribution and quantitation of inclusions in various organs. Autopsy records from 673 fetal and neonatal autopsies performed at Women and Infants' Hospital during 1985 through 1990 were reviewed. Thirty-two cases of hydrops fetalis were identified, and, of these, 5 had parvovirus infection. This gives an incidence of fetal parvovirus infection resulting in hydrops fetalis of 0.7% among all autopsies, and a 16% incidence among cases of hydrops. Thirty-five percent of the cases of hydrops had malformations; a muscular ventricular septal defect was noted in one of the 5 cases of parvovirus infection. All 5 parvovirus cases had characteristic erythroid nuclear inclusions, and these inclusions were resistant to tissue degenerative changes. The most reliable tissue for histologic diagnosis was the liver, followed by heart and lung. Only 2 of 5 placentas had diagnostic inclusions, making examination of the placenta alone insufficient for ruling out fetal parvovirus infection.

Detection of parvovirus B19 in fetal autopsies.

In a 10-year retrospective study we examined the incidence of parvovirus B19 (B19)-related hydrops fetalis in fetal autopsies (n = 1,299) carried out between 1982 and 1991. Intrauterine death had occurred in 399 cases (30.7%); in 42 (10.5%) of these hydrops fetalis was diagnosed. Of these 42 hydropic fetuses, parvovirus B19 infection was identified in 6 (14.3%) cases by the presence of typical erythroblastic nuclear inclusions in hematoxylin-eosin stained tissue and the diagnosis was confirmed by in situ hybridization using a Digoxigenin-labelled B19 DNA probe. The study shows that the overall incidence of B19-associated intrauterine death associated with hydrops fetalis is low. However, B19 infection should be considered in all cases of hydrops fetalis.

Long-term outcome in fetal hydrops from parvovirus B19 infection.

Parvovirus B19 infection in the fetus is associated with anemia and hydrops and can result in fetal death. Fetal transfusion has been used in an attempt to improve outcome; however, it is associated with its own perinatal morbidity. We report two cases of fetal parvovirus B19 infection that were confirmed by polymerase chain reaction for parvovirus B19 deoxyribonucleic acid in umbilical cord blood. Ultrasonographic signs of compromise were observed at 30 and 24 weeks of gestation. Both fetuses were hydropic and one fetus was also anemic. Serial sonograms demonstrated that the hydrops resolved spontaneously over 3 to 5 weeks after diagnosis. One infant was delivered at 32 weeks of gestation as a result of idiopathic preterm labor. The other infant was delivered at term. Both infants appeared relatively normal at birth and have developed normally in the first year of life. Thus fetal hydrops in association with parvovirus B19 infection does not always lead to poor long-term outcome. A conservative approach without in utero therapy may be appropriate for the management of some of these fetuses.

Prenatal diagnosis of human parvovirus B19 in nonimmune hydrops fetalis by polymerase chain reaction.

OBJECTIVE: Nonimmune hydrops fetalis is a potentially lethal condition reflecting the clinical manifestation of several pathologic processes. Recently maternal infection by human parvovirus B19 has been reported to result in nonimmune fetal hydrops. We sought to develop a rapid and sensitive test to detect the presence of this agent in utero. STUDY DESIGN: Using a cloned isolate of the virus, we developed an assay based on enzymatic amplification of a segment of the human parvovirus B19 genome that allows direct detection of this agent in samples of fetal blood and amniotic fluid. RESULTS: The method detected as few as 100,000 genome equivalences and was specific for the viral genome alone. We used this assay to evaluate nine fetuses initially seen with nonimmune hydrops. Three cases were found to be positive for the human parvovirus B19 genome. CONCLUSION: The method is powerful in that it is rapid, sensitive, and simple. This assay may have general applicability in evaluation of nonimmune hydrops and in documentation of the natural history of fetal human parvovirus infections.

Spontaneous resolution of nonimmune hydrops fetalis secondary to human parvovirus B19 infection.

Many instances of nonimmune hydrops fetalis ascribed to human parvovirus B19 have been reported. The leading proposed pathophysiologic mechanism of hydrops in affected fetuses is viral invasion of red blood cell progenitors, causing a profound reticulocytopenic fetal anemia. Although the natural history of fetal parvovirus infection remains to be elucidated fully, there have been recent reports of funipuncuture and intrauterine blood transfusions to diagnose and manage this problem. We report two pregnancies in which parvovirus-related hydrops fetalis was observed to resolve without intervention, followed by uncomplicated vaginal deliveries of healthy infants. These observations emphasize the need for further investigation before recommending routine fetal blood transfusion in affected cases.

Immunohistological detection of human parvovirus B19 in formalin-fixed, paraffin-embedded tissues.

Human parvovirus B19 is a cause of aplastic crises in patients with haemolytic anaemias, prolonged bone marrow failure in the immunosuppressed, and fetal death secondary to non-immune hydrops. The immunohistological detection of parvovirus B19 in formalin-fixed, paraffin-embedded tissues has not previously been reported, and definitive diagnosis of infection in such specimens has relied on the use of specialized DNA hybridization and amplification techniques. A new monoclonal antibody to B19 capsid proteins, R92F6, was found to be capable of labelling infected cells in paraffin-embedded tissues from all 19 cases of parvovirus-related fetal hydrops tested, and in bone marrow from a child with congenital immunodeficiency and chronic parvovirus infection. Viral antigen was detected both in cytoplasmic and in nuclear distributions using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique without preceding proteolytic digestion. The viral epitope recognized appears to be highly conserved, as specimens were obtained over a 13-year period from widely spaced locations in the U.K. Antibody R92F6 should facilitate rapid diagnosis of parvovirus B19 infection in routinely processed and archival specimens.

Fetal survival after human parvovirus B19 infection: spectrum of intrauterine response in a twin gestation.

We report the first known symptomatic survivors of congenital parvovirus infection. One fetus was hydropic and the other was growth retarded. There was no evidence of anemia. The antenatal diagnosis of congenital infection requires a multifaceted approach, which includes serology, cultures, and electron microscopy.

Diagnosis of human parvovirus B19 infections by polymerase chain reaction.

The polymerase chain reaction (PCR) was used for detecting parvovirus B19 DNA in clinical specimens. A pair of oligonucleotide primers spanning the PstI-fragment of the B19 virus genome was used for PCR, and a PCR product of 727 bp was amplified. B19 virus DNA was detected in all sera (n = 26) of individuals in the incubation period and acute phase of infection. PCR was useful for detecting viral B19 DNA in amniotic fluid and fetal blood of hydropic fetuses, confirming fetal B19 virus infection.