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Non-Immnue Hydrops Fetalis

Parvovirus B19

Two fetuses with small (arrows) and large (asterisk) ascites due to parvovirus infection and early non-immune hydrops


Ascites is seen in two fetuses with seropositive parvovirus infection in the mother. No other findings of non-immune hydrops were seen.



Hydrops fetalis is a condition characterized by excessive fluid accumulation within fetal extravascular compartments and body cavities (Chinn). It is manifest by varying degrees of fetal anasarca, ascites, pleural effusion, pericardial effusion, polyhydramnios and placentomegaly. While the condition of hydrops was first reported over 100 years ago, it was not until 1939 and 1940 when sensitizing blood group antigens were discovered and shown to be a major factor in the etiology of hydrops fetalis. (Levine)(Landsteiner). In 1943 Potter described a clinical entity that affected non-Rh sensitized pregnancies and was characterized by fetal anasarca, placental edema and fetal serous effusions. Potter recognized that this entity, since termed non-immune hydrops fetalis did not represent a specific disease but rather a late manifestation of many severe diseases. At that time, non-immune hydrops represented less than 20% of all cases of hydrops fertalis. Since the introduction of Rhogam in 1968 for Rh isoimmunization, the number of cases of Rh disease has decreased significantly worldwide. As such, cases of non-immune hydrops are a much larger proportion of reported cases of hydrops fetalis; as high as 90% of cases. The prevalence of non-immune hydrops is approximately 1 in 1500 to 1 in 4000 deliveries and the cause varies considerably. (Macafee) (Maidman) The ethnicity of the patient may influence the prevalence of disease. (Tercanli) For example, the most common cause of non-immune hydrops in Southeast Asia is homozygous alpha-thalassemia, whereas in whites cardiac, infectious and chromosomal causes are the most frequent. While a wide range of etiologies exist for hydrops, the major pathophysiologic mechanisms common to most conditions are a combination of anemia, hypoproteinemia and cardiac failure.

Parvovirus B19
Epidemiology and Pathophysiology

In this case, parvovirus B-19 was the etiology for the hydrops. Human parvovirus B19 (B19) is the only known parovirus virus pathogenic to humans (CDC). It was first discovered accidentally in 1974 in England in blood specimens (batch #B19) from adult blood donors who were asymptomatic or had mild symptoms during an evaluation of hepatitis B antigen detection tests. The name parvovirus B19 was used to avoid possible confusion with the human papilloma virus (HPV) family. Parvoviruses B1-18 do not exist (Kumar). Soon after its discovery, studies established B19 as the causative agent of a mild childhood illness erythema infectiosum (EI), or fifth disease, described clinically in 1889 and characterized by rash. Due to the nature of the rash it has also been referred to as “slapped cheek” disease. Epidemiologic data revealed that the illness associated with infection tended to occur in outbreaks similar to measles and rubella. The principal mode of spread are respiratory secretions. Parvovirus B19 is also the cause of transient aplastic crisis in patients with chronic hemolytic anemia, although anemia may go unrecognized in otherwise healthy adults. B19 can cross the placenta of women infected during pregnancy and was first reported to be associated with fetal death and hydrops fetalis in 1984. (CDC) Parvovirus B19 infection occurs worldwide, most commonly in outbreaks in late winter and early spring. The incubation period is usually 4-14 days but can be as long as 20 days; in volunteer studies, rash occurred 17-18 days after inoculation.(CDC) The most sensitive test to detect recent infection is the IgM-antibody assay. B19 IgM antibody can be detected in approximately 90% of cases by the third day after symptoms of begin. The titer and the percentage of positives begin to decline 30-60 days after onset. B19 IgG antibody is usually present by the seventh day of illness and persists for years. Parvovirus B19 may be transmitted from mother to fetus transplacentally in approximately 30% of maternal infections (CDC). The fetus affected by B19 resembles adults and children with chronic hemolytic anemias due to decreased erythrocyte production. High output cardiac failure, secondary to anemia, leads to fluid accumulation and hydrops fetalis. Myocarditis leading to heart failure may contribute to the development of fetal hydrops.Maternal infection with parvovirus B19 is estimated to occur in 0.25-6% of susceptible pregnancies. It has been estimated that fetal death occurs in 9% of these cases. After exposure, there is a minimal or no risk of transmission if the mother has positive IgG titers for parvovirus B19 and maternal IgM is negative indicating maternal reinfection. Parvovirus B19 infection during pregnancy causes up to 27% cases of non-immune hydrops in anatomically normal fetuses. (von Kaisenberg and Jonat) The virus is believed to cause arrest of maturation of red blood cell precursors at the late normoblast stage and also causes a decrease in the number of platelets. The risk of fetal death attributable to parvovirus infection following documented maternal infection (B19 IgM-antibody positive) is uncertain but has been estimated to be <10%. in cases in which the mother has clear-cut symptoms, the pregnancy was lost on an average of 4-6 weeks after the onset of the maternal illness, with the risk highest for infection in the first 20 weeks of pregnancy. The overall risk of fetal loss following maternal exposure is much less than previously thought, and may be less than 3% in the first 20 weeks of gestation or approximately 10% if the mother is actually infected (Berry). Although some of the animal parvoviruses are teratogens, there is no evidence that the rate of congenital anomalies following B19 infection exceeds background rates. B19-associated congenital anomalies have not been reported among several hundred live-born infants of B19-infected mothers. One aborted fetus with eye anomalies and histologic evidence of damage to multiple tissues born to a B19-infected woman has been reported.

Sonographic Findings

Sonographically detectable markers of fetal compromise include increased (> 95th centile) cardiac biventricular outer diameter, pericardial or pleural effusions, ascites, abdominal wall edema, bilateral hydroceles, amniotic fluid volume disorders, hydrocephalus, microcephaly, intracranial and hepatic calcification and sporadic cases of contractures. (von Kaisenberg and Jonat) (Sheikh) (Weiner). Recently, Doppler interrogation of the fetal middle cerebral arteries has been utilized (similar to that done for Rh isoimmunization) to assess fetal anemia in mothers with parvovirus infection. Fetal anemia caused by parvovirus infection is detected non-invasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery. (Cosmi) The increased blood velocity in fetuses with anemia that is caused by parvovirus infection could be explained by an increased cardiac output because of a decline in blood viscosity. In a recent study by Cosmi et al the sensitivity of the middle cerebral artery peak systolic velocity (>1.50 MoM) for the prediction of anemia because of parvovirus infection was 94.1%; the specificity was 93.3%; the positive and negative predictive values were 94.1% and 93.3%, respectively. They concluded that: “The MCA-PSV may be a useful adjunct to ultrasound scanning. If the MCA-PSV values are <1.50 MoM, we suggest weekly ultrasound scans for 12 weeks after the exposure to follow those fetuses that potentially are at high risk for anemia and hydrops. In cases with no signs of hydrops and elevated MCA-PSV (>1.50 MoM), the surveillance should be intensified with more frequent scans (2-3 per week) to detect the earliest signs of hydrops.”


Unless the mother demonstrates symptoms of parvovirus infection, the only clue to disease may be the coincidental finding of fetal hydrops during a routine scan. In a review by von Kaisenberg and Jonat they suggested key monitoring parameters of affected fetuses to be: MCA Doppler, cardiomegaly and ductus venosus blood flow. In their review of the literature treatment options for confirmed cases of fetal parvovirus B19 infection include: 1 expectant management using close ultrasound surveillance and intrauterine transfusion, if required; 2 cordocentesis in all fetuses and transfusions in those with anemia; 3 immediate delivery after 33 weeks; 4 termination of pregnancy of non-viable fetuses with severe hydrops (although this last option is rarely recommended. (von Kaisenberg and Jonat) The results of a survey and review of the management and outcome of parvovirus infection in pregnancy was reported by Rodis et al in 1998. They reported that approximately 63% of cases of nonimmune hydrops caused by parvovirus resolve either spontaneously or after intrauterine transfusions. “Importantly, of the 164 hydropic fetuses transfused, 137 (83.5%) survived. The fact that essentially all the fetal deaths after transfusion occurred within 48 hours of the procedure suggests that either these fetuses were moribund at the time of the fetal transfusion or died as a result of procedure-related complications.”(Rodis)


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Peter W. Callen, M.D.
Professor of Radiology, Obstetrics, Gynecology and Reproductive Science
University of California Medical Center, San Francisco, California