Human parvovirus B19 infection during pregnancy--value of modern molecular and serological diagnostics.

BACKGROUND: Over 95% of fetal complications (fetal hydrops and death) occur within 12 weeks following acute parvovirus B19 (B19) infection in pregnancy. Therefore, weekly fetal ultrasound monitoring is generally recommended for this time period. However, in the majority of women, typical symptoms of acute infection (rash or arthropathy) are absent, and during epidemics, B19 infection may be diagnosed incidentally by antibody screening of women at risk. OBJECTIVE: To assess the diagnostic value of currently available molecular and serological methods for reliable diagnosis of primary B19 infection in pregnancy. STUDY DESIGN: Large panels of well-characterized acute-phase or convalescent sera were used to investigate the ability of a VP2 IgM EIA, a Light-Cycler-based B19-DNA PCR, a VP1-IgG avidity EIA and two VP2-IgG epitope-type specificity [ETS] EIAs to pinpoint the time of primary B19 infection in pregnancy. RESULTS: The duration of low-level IgM positivity varied greatly (range 4-26 weeks). Samples collected within the first 2 weeks of infection showed high-level viremia (mean 1.75 x 10(8) geq/ml). During follow-up, low-level DNAemia (mean 9.7 x 10(4)geq/ml) persisted for at least 18 weeks in 91% (20/22) of patients. Considering the first 12 weeks after onset of disease the window of greatest risk for fetal complications, the "acute" phase was extended to cover this full period. In this case, performing the avidity and ETS-EIA sequentially, the positive predictive value was 100% in patients showing concordant avidity and ETS-EIA results. CONCLUSIONS: In the presence of low IgM titres and/or low-level DNAemia the use of supplementary serological assays such as VP1-IgG avidity EIA and VP2-ETS-EIA is advisable for restriction or avoidance of unnecessary fetal ultrasound examinations or invasive diagnostics; and in general for strengthening the reliability of B19 serodiagnosis of pregnant women.

Risk of fetal hydrops and non-hydropic late intrauterine fetal death after gestational parvovirus B19 infection.

BACKGROUND: Risk assessment of parvovirus B19 (B19)-associated fetal complications following gestational B19 infection remains controversial. OBJECTIVES: To determine the risk of fetal hydrops or non-hydropic late intrauterine fetal death following acute maternal B19 infection at defined gestational weeks. STUDY DESIGN: Observational cohort study of pregnant women with serologic evidence of acute B19 infection. If available, fetal or neonatal tissue samples from cases complicated by fetal loss or hydrops were investigated for the presence of B19 DNA by polymerase chain reaction (PCR) and/or in situ hybridization (ISH). RESULTS: Of 236 women with known pregnancy outcome, 228 had a live birth and 8 a fetal loss. The observed rate of fetal hydrops for all pregnant women was 4.2% (10/236) (95% confidence interval [CI], 2.1-7.7) and 10.6% (10/94) (95% CI, 5.2-18.7) for those infected between 9 and 20 weeks gestation. Tissue samples from 8 hydrops cases were investigated by PCR or ISH and all were B19 DNA positive. Fetal death occurring during or after gestational week 22 was only observed in one case which was associated with B19-derived fetal hydrops. CONCLUSIONS: Our findings demonstrate that although adverse fetal outcome is a rare complication of gestational B19 infection, a relevant risk of fetal hydrops exists particularly for women infected between 9 and 20 weeks' gestation. Cases of B19-derived non-hydropic late intrauterine fetal death were not observed in the present study.

No detection of human bocavirus in amniotic fluid samples from fetuses with hydrops or isolated effusions.

BACKGROUND: Human bocavirus (HBoV) is a recently identified parvovirus associated with respiratory disease in infants. Animal bocaviruses have been shown to cause intrauterine infection, fetal anasarca and abortion in late gestation. OBJECTIVES: To investigate whether HBoV infection is associated with fetal hydrops, fetal anemia or isolated fetal effusions. STUDY DESIGN: We determined the prevalence of HBoV and parvovirus B19 (B19) DNA in amniotic fluid samples from fetuses with hydrops, anemia or isolated effusions using different real-time PCR protocols, and the HBoV IgG and IgM positivity rate in pregnant women with fetal hydrops or normal ultrasound findings by a non-commercial virus-like particle-based enzyme immunoassay. RESULTS: None of 87 amniotic fluid samples tested was HBoV DNA positive. Twelve of 60 fetuses with hydrops or anemia were found B19 DNA positive. Anti-HBoV IgG antibodies were detected in 100% (19/19) and 94% (47/50) of serum samples from pregnant women with fetal hydrops and normal ultrasound findings, respectively. All serum samples were found negative for anti-HBoV IgM. CONCLUSION: We suggest that HBoV is not a common cause of fetal hydrops, anemia or isolated effusions. This has to be confirmed by further studies of proven gestational HBoV infection.

Improved diagnosis of gestational parvovirus B19 infection at the time of nonimmune fetal hydrops.

BACKGROUND: In the diagnosis of parvovirus B19 infection, the detection of virus-specific IgG in the absence of virus-specific IgM is considered to indicate past immunity. METHODS: We determined the diagnostic value of a high-quality B19 IgM EIA, compared with that of a VP1 IgG avidity EIA, a VP2 IgG epitope-type specificity (ETS) EIA, and real-time polymerase chain reaction (PCR) in the diagnosis of maternal B19 infection during nonimmune fetal hydrops. RESULTS: Serum samples from 101 pregnant women with confirmed B19-induced fetal hydrops were collected at the time of invasive prenatal diagnosis. The samples were investigated for B19 IgM, VP1 IgG avidity, and VP2 IgG ETS. With the B19 IgM EIA, 78 women (77.2 %) showed positive results, 15 (14.9%) showed negative results, and 8 (7.9 %) showed equivocal results. According to the combined B19 IgG avidity and IgG ETS EIA results, only 5 (5%) of 101 women were classified as having past immunity. Available serum samples (n = 24) that had nondiagnostic results in the antibody assays were further investigated by PCR. All were B19 DNA positive (mean load, 2.5 x 10(4) genome equivalents/mL; range, 2.5 x 10(3) - 7.8 x 10(6)). CONCLUSIONS: At the time of B19-induced hydrops, detection of B19 DNA in maternal blood had the best diagnostic sensitivity for identifying maternal B19 infection. However, given the long persistence of B19 DNAemia, supplementary measurement of VP1 IgG avidity and VP2 IgG ETS improves the precision of diagnosis and management of pregnant women affected by the B19 virus.