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Parvovirus B-19 in Pregnancy Parvovirus is a member of the family Parvoviridae. The virus contains a single-stranded DNA. It can only infect humans. 50% of all adults have been infected sometime during childhood or adolescence.
Parvovirus B-19 in Pregnancy Epidemiology Congenital infection rates vary depending on the prevalence in the community. Approximately 50 to 75% of adult women are immune. 20% to 30% of susceptible adults in school settings will become infected. Day-care workers have a 20% to 50% risk of seroconversion. The risk of infection among susceptible adults following household exposure to an infected person is approximately 50%.

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  1. 1. Parvovirus B-19 in Pregnancy By La Lura White MD Maternal Fetal Medicine
  2. 2. Parvovirus B-19 in Pregnancy <ul><li>It is a typical, busy Friday afternoon at the clinic, and Ms. Jones, a 25-year-old G2P1 at 17 weeks' gestation, mentions that her 5-year-old daughter's pediatrician thinks her little girl has fifth disease. </li></ul><ul><li>Your patient asks you if this poses any concern for her or her fetus. What's your next step, and how do you counsel her? </li></ul>
  3. 3. Parvovirus B-19 in Pregnancy <ul><li>Fifth disease, or erythema infectiosum, is caused by parvovirus B19. </li></ul><ul><li>Fifth disease was so named because it was the fifth pink-red rash--following scarlet fever, measles, rubella, and roseola--to be described by physicians. </li></ul><ul><li>The annual incidence of acute parvovirus in pregnancy has been estimated at 1 in 400 pregnancies. </li></ul><ul><li>In approximately 30% of those cases, the infection is transmitted to the fetus. </li></ul><ul><li>Brown and colleagues first reported adverse perinatal outcomes associated with maternal parvovirus infection in 1984. </li></ul>
  4. 4. Parvovirus B-19 in Pregnancy <ul><li>Parvovirus is a member of the family Parvoviridae. </li></ul><ul><li>The virus contains a single-stranded DNA. </li></ul><ul><li>It can only infect humans. </li></ul><ul><li>50% of all adults have been infected sometime during childhood or adolescence. </li></ul>
  5. 5. Parvovirus B-19 in Pregnancy Epidemiology <ul><li>Congenital infection rates vary depending on the prevalence in the community. </li></ul><ul><li>Approximately 50 to 75% of adult women are immune. </li></ul><ul><li>20% to 30% of susceptible adults in school settings will become infected. </li></ul><ul><li>Day-care workers have a 20% to 50% risk of seroconversion. </li></ul><ul><li>The risk of infection among susceptible adults following household exposure to an infected person is approximately 50%. </li></ul>
  6. 6. Parvovirus B-19 in Pregnancy <ul><li>Maternal infection with parvovirus B19 is estimated to occur in 0.25-6% of the susceptible pregnancies. </li></ul><ul><li>Spontaneous abortion may occur as a result of maternal infection in the first trimester (risk, 10%). </li></ul><ul><li>The risk for congenital infection from an infected mother is between 10% to 20% , and is highest in the first and second trimesters. </li></ul><ul><li>The fetus is at greatest risk during the 3 to 6 weeks after maternal infection with parvovirus. </li></ul><ul><li>The overall fetal loss rate associated with maternal infection ranges from 2% to 10%. </li></ul><ul><li>The average time from diagnosis to resolution is about 6 weeks. </li></ul>
  7. 7. Parvovirus B-19 in Pregnancy <ul><li>Transmission is greatest during viremia and before symptoms arise. </li></ul><ul><li>Parvovirus B19 most commonly is transmitted among humans via respiratory secretions and hand-to-mouth contact. </li></ul><ul><li>Blood products also have been linked to infection, with the greatest risk attributed to coagulation factor concentrate transfusion. </li></ul><ul><li>Spread transplacentally to the fetus during active maternal infection (33% transmission rate) can occur any time during pregnancy. </li></ul><ul><li>Seasonal variation has been noted as well, with higher rates of infection during the late winter, spring, and early summer than at other times of the year. </li></ul>
  8. 8. Parvovirus B-19 in Pregnancy <ul><li>There essentially are 2 phases of parvovirus infection. </li></ul><ul><li>Viral replication in the bone marrow, viremia, and viral shedding in the throat characterize the first phase. </li></ul><ul><li>Occurs 5 to 10 days after exposure, is when the infection is most contagious. </li></ul><ul><li>Individuals often are unaware that they have parvovirus during this period, which increases the risk of exposure to others. </li></ul>
  9. 9. Parvovirus B-19 in Pregnancy <ul><li>Most children with parvovirus infection feel well. Some develop mild, cold-like signs and symptoms early in the illness: </li></ul><ul><li>Sore throat </li></ul><ul><li>Slight fever </li></ul><ul><li>Upset stomach </li></ul><ul><li>Headache </li></ul><ul><li>Fatigue </li></ul><ul><li>Itching </li></ul>
  10. 10. Parvovirus B-19 in Pregnancy <ul><li>The hallmark of the second phase is the appearance of a rash and associated arthralgias. </li></ul><ul><li>The rash, which usually is maculopapular or papulovesicular, typically waxes and wanes over a period of several days or weeks, reappearing after exercise, warm baths, or sun exposure. </li></ul><ul><li>Eventually it may extend to the arms, trunk, thighs and buttocks, areas where the rash has a pink, lacy, slightly raised appearance. </li></ul><ul><li>Seen most frequently among preschool and school-age children in the United States </li></ul>
  11. 11. Parvovirus B-19 in Pregnancy <ul><li>In the absence of a rash, nonspecific flu-like symptoms and symmetrical joint pain. </li></ul><ul><li>An adult who has not previously been infected with parvovirus B19 can be infected and become ill, and develop a rash, or joint pain or swelling, or both. The joint symptoms usually resolve in a week or two, but they may last several months. </li></ul><ul><li>33% of infected individuals are asymptomatic. </li></ul><ul><li>Individuals are no longer infectious once they enter the second phase because by that time their immune system has begun producing antigen-antibody complexes. </li></ul>
  12. 12. Parvovirus B-19 in Pregnancy <ul><li>Pathogenesis: </li></ul><ul><li>The primary site of Parvovirus B19 infections is within erythroid precursor cells and it has an affinity for the late normoblast stage and the cardiac myocytes and also causes a decrease in the number of platelets. </li></ul><ul><li>Following Parvovirus B19 infection, erythrocytes will lyse arresting erythropoiesis. </li></ul><ul><li>Lymphocyte, granulocyte and platelet counts may also fall during infection. </li></ul>
  13. 13. Parvovirus B-19 in Pregnancy <ul><li>The B19V incubation period is usually 4-14 days. </li></ul><ul><li>Hydrops fetalis has been reported with maternal B19 infection and appears to be due primarily to fetal anemia and resulting cardiac failure induced by the anemia and the fetal myocarditis. </li></ul><ul><li>Parvovirus B19 causes up to 27% cases of non-immune hydrops in anatomically normal fetuses. </li></ul><ul><li>Parvovirus causes fetal anemia by hindering erythropoiesis in a manner similar to that seen in anemic adults. </li></ul>
  14. 14. Parvovirus B-19 in Pregnancy <ul><li>Infected pregnant women may exhibit a transient and mild anemia because of the predilection of the virus for destroying erythroid precursor cell lines. </li></ul><ul><li>This slight decrease in hemoglobin is observed within a few days of infection. </li></ul><ul><li>Individuals with sickle cell disease, other hemoglobinopathies, immunocompromised individuals,(transplant patients, HIV positive) or are at risk for transient aplastic crisis and may require hospitalization. </li></ul>
  15. 15. Parvovirus B-19 in Pregnancy Diagnosis <ul><li>Pregnant women who have symptoms of parvovirus infection or who are asymptomatic but who know they have been exposed to the infection should undergo diagnostic serology. </li></ul><ul><li>The enzyme-linked immunosorbent assay (ELISA) and Western blot analysis appear is a reliable methods for detecting IgG and IgM antibodies in maternal serum. </li></ul><ul><li>Both antibodies are produced in response to the parvovirus infection. </li></ul><ul><li>The sensitivity and specificity of IgM for confirming the presence of acute infection are 100% and 89%, respectively. </li></ul>
  16. 16. Parvovirus B-19 in Pregnancy <ul><li>Acute infection is diagnosed when a gravida is IgM positive. </li></ul><ul><li>IgM antibodies usually are present by the third day after development of the rash and may persist for 1 to several months after exposure. </li></ul><ul><li>Titers usually begin to decline by 30 to 60 days after infection. </li></ul><ul><li>IgG antibodies appear 7 days after infection, and the patient then remains IgG positive throughout life. </li></ul>
  17. 17. Parvovirus B-19 in Pregnancy <ul><li>Women who are IgG negative should undergo repeat testing in 3 to 4 weeks with paired samples. </li></ul><ul><li>This provides both the physician and the pathologist with a baseline for comparison. </li></ul><ul><li>If IgG and IgM remain negative, the fetus is not at risk </li></ul><ul><li>If seroconversion is documented in the second sample, however, fetal surveillance is indicated. </li></ul><ul><li>Perform Polymerase Chain Reaction (PCR) to detect Parvovirus B-19 DNA in maternal sera. </li></ul>
  18. 18. Parvovirus B-19 in Pregnancy <ul><li>Monitoring and treating the infected fetus </li></ul><ul><li>Women with documented seroconversion should undergo an initial targeted fetal ultrasound to identify or rule out congenital anomalies. </li></ul><ul><li>Should perform weekly ultrasounds for 8 to 10 weeks after maternal infection. </li></ul><ul><li>If the physician finds hydrops at sonography--the presence of which indicates that the fetus has parvovirus-induced anemia--cordocentesis (for B19-specific IgM). </li></ul><ul><li>Percutaneous umbilical blood sampling [PUBS]) is indicated to assess fetal blood in preparation for intrauterine red blood cell transfusion to treat the anemia. </li></ul><ul><li>Send fetal blood for IgG testing or for PCR (sensitivity, 100%) after 22 weeks, as IgG antibodies do not appear in the fetal circulation until this gestational age. </li></ul>
  19. 19. Parvovirus B-19 in Pregnancy <ul><li>At the time of fetal blood sampling, which carries a complication rate of approximately 1%, blood is sent to the lab to determine mean corpuscular volume (MCV), hematocrit, leukocyte count, and platelet count. </li></ul><ul><li>Thrombocytopenia may accompany fetal anemia, and fetal hemorrhage from the cordocentesis site has been reported. </li></ul><ul><li>Karyotype may be obtained from fetal blood or amniocytes if there is a high risk of aneuploidy. </li></ul>
  20. 20. Parvovirus B-19 in Pregnancy <ul><li>Middle cerebral artery time-averaged mean velocity for the detection of anemia as the cause of fetal hydrops. </li></ul><ul><li>The mean (z score) of middle cerebral artery time-averaged mean velocity for fetuses with normal hemoglobin was 1.1 +/- 0.81 and for the fetuses with anemia was 4.71 +/- 2.16 (P <.001). </li></ul><ul><li>The sensitivity for the increased middle cerebral artery time-averaged mean velocity to predict fetal anemia was 91%, and the specificity was 100%. </li></ul>Flow velocity waveform in the fetal middle cerebral artery in a severely anemic fetus at 22 weeks (left) and in a normal fetus (right). In fetal anemia, blood velocity is increased
  21. 21. Parvovirus B-19 in Pregnancy <ul><li>Reversed flow in the ductus venosus Doppler have been reported that could be explained by both end-stage heart failure and regurgitation secondary to tricuspid insufficiency. </li></ul>
  22. 22. Parvovirus B-19 in Pregnancy <ul><li>Intrauterine red blood cell transfusion is indicated if fetal anemia is confirmed. </li></ul><ul><li>When aggressive management with serial transfusions is employed, fetal survival may be as high as 60% to 80% compared to only a 15% to 30% survival rate without such intervention. </li></ul><ul><li>Overall perinatal survival associated with nonimmune hydrops ranges from 50% to 98%. </li></ul>
  23. 23. Parvovirus B-19 in Pregnancy <ul><li>Ultrasound-guided PUBS is performed and an immediate fetal Hct performed. </li></ul><ul><li>If the Hct is less than 25%, then irradiated, CMV-free, Oneg packed red blood cells are transfused via the spinal needle or catheter into the fetal umbilical vein. </li></ul><ul><li>Combined intravascular/intraperitoneal transfusion can be utilized, which allows a more gradual increase in fetal Hct than intravascular transfusion alone. </li></ul><ul><li>Fetuses with severe degrees of anemia may require transfusion in stages in order to avoid cardiac decompensation and bradycardia. </li></ul><ul><li>Published formulas assist in estimating the volume of blood to be transfused. </li></ul>
  24. 24. Parvovirus B-19 in Pregnancy <ul><li>Rodis and colleagues surveyed members of the Society for Maternal-Fetal Medicine in 1997 regarding their management of parvovirus infection and its sequelae in pregnancy. </li></ul><ul><li>539 cases of parvovirus-induced nonimmune hydrops reported. </li></ul><ul><li>Of the perinatologists surveyed, 89% utilized ultrasonography for the initial management of parvovirus infection in pregnancy. </li></ul><ul><li>7.5% utilized amniocentesis to send fluid for polymerase chain reaction (PCR) testing. </li></ul><ul><li>2% utilized fetal blood sampling. </li></ul><ul><li>Outcomes of these 539 cases revealed that nonimmune hydrops secondary to parvovirus infection resolved spontaneously in 34% of the cases. </li></ul>
  25. 25. Parvovirus B-19 in Pregnancy <ul><li>Another 29% resolved following intrauterine transfusion. </li></ul><ul><li>In 6%, fetal demise occurred following transfusion. </li></ul><ul><li>All cases of fetal death after transfusion occurred within 48 hours of the procedure, suggesting that either the fetus was simply too moribund to tolerate the transfusion or that demise was secondary to procedure-related complications. </li></ul><ul><li>The incidence of fetal death when anemia and hydrops were managed expectantly, i.e., without intrauterine transfusion, was 30%. </li></ul>
  26. 26. Parvovirus B-19 in Pregnancy <ul><li>Since several case reports have documented spontaneous resolution of non-immune hydrops in fetuses with confirmed congenital Parvovirus B-19 infection. </li></ul><ul><li>Therefore, medical therapy for the fetus is not always necessary for fetal survival. </li></ul><ul><li>The principal intervention for treatment of fetal non-immune hydrops from congenital Parvovirus B-19 infection has been intrauterine fetal transfusion. </li></ul><ul><li>If PUBS confirms significant fetal anemia, then fetal transfusion can accelerate the natural resolution of non-immune hydrops in these fetuses. </li></ul><ul><li>A proposal for IgG therapy has recently been made in the British literature. </li></ul>
  27. 27. Parvovirus B-19 in Pregnancy <ul><li>Diagnosis </li></ul><ul><li>During the first trimester fetuses with parvovirus B19 infection can present with increased nuchal translucency and congenital anomalies (Ventriculomegaly, Mild hydrocephaly, microcephaly) </li></ul><ul><li>In second and third trimesters fetal infection by parvovirus B19 can be suspected by the use of ultrasound with the presence of: </li></ul><ul><li>Fetal hydrops </li></ul><ul><li>Ascites </li></ul><ul><li>Pleural or pericardial effusion </li></ul><ul><li>Skin thickening </li></ul><ul><li>Cardiomegaly (increased cardiac biventricular outer diameter) </li></ul>
  28. 28. Parvovirus B-19 in Pregnancy <ul><li>Hypertrophic myocardiopathy </li></ul><ul><li>Hyperechoic bowel </li></ul><ul><li>Hepatomegaly </li></ul><ul><li>Abdominal wall edema </li></ul><ul><li>Bilateral hydroceles </li></ul><ul><li>Intracranial calcifications </li></ul><ul><li>Intrauterine growth restriction </li></ul><ul><li>Stillbirth </li></ul><ul><li>Decreased movement in severe cases </li></ul><ul><li>Placentomegaly </li></ul><ul><li>Amniotic fluid volume disorders  </li></ul>
  29. 29. Parvovirus B-19 in Pregnancy <ul><li>Hydrothorax </li></ul>
  30. 30. Parvovirus B-19 in Pregnancy <ul><li>Ascites </li></ul>
  31. 31. Parvovirus B-19 in Pregnancy <ul><li>Scalp edema </li></ul>
  32. 32. Parvovirus B-19 in Pregnancy <ul><li>Pericardial effusion </li></ul>
  33. 33. Parvovirus B-19 in Pregnancy <ul><li>Ascites, enlarged liver, cardiomegaly </li></ul>
  34. 34. Parvovirus B-19 in Pregnancy <ul><li>Edema of face and abdominal distension. </li></ul><ul><li>The thoracic cavity is filled by the pericardial sac distended by effusion and cardiomegaly. </li></ul><ul><li>There is massive hepatomegaly. </li></ul>
  35. 35. Parvovirus B-19 in Pregnancy <ul><li>In the event of in utero fetal demise, order maternal serology for parvovirus B19. </li></ul><ul><li>If the maternal serology is positive, the physician should send placental tissue for PCR analysis. </li></ul><ul><li>Although autolysis often makes it very difficult for the pathologist to identify signs of myocarditis at fetal autopsy, viral particles can be visualized by electron microscopy in tissue. </li></ul>
  36. 36. Parvovirus B-19 in Pregnancy <ul><li>Because Parvovirus B-19 is a DNA virus, chronic recurrent pediatric infection in infants with congenital Parvovirus infection has been reported. </li></ul><ul><li>Therefore, confirmed cases of congenital Parvovirus infection should be reported to the child's pediatrician following deliver to allow for pediatric monitoring of potential chronic infection. </li></ul><ul><li>There are isolated case reports of congenital deformities among infants with congenital Parvovirus infection, but the pattern of abnormalities does not suggest a syndrome. </li></ul>
  37. 37. Parvovirus B-19 in Pregnancy <ul><li>TREATMENT: </li></ul><ul><li>No maternal treatment often too late when recognized for prophylaxis and no medical management that prevents parvovirus B19 infection. </li></ul><ul><li>Treatment for fetuses with suspected congenital Parvovirus B-19 infection includes: </li></ul><ul><li>Watchful waiting (conservative management) </li></ul><ul><li>High-dose IgG therapy </li></ul><ul><li>Intrauterine fetal transfusion </li></ul>
  38. 38. Parvovirus B-19 in Pregnancy <ul><li>Parvovirus exposure: </li></ul><ul><li>Serology for Ig G and Ig M. </li></ul><ul><li>If negative, repeat 3-4 weeks paired serum. </li></ul><ul><li>If still negative, no fetal risk. </li></ul><ul><li>If positive, fetus at risk. </li></ul>
  39. 39. Parvovirus B-19 in Pregnancy <ul><li>Fetal surveillance, weekly US, MCA Doppler. </li></ul><ul><li>Assessment for 8-10 weeks. </li></ul><ul><li>Hydrops yes: cordocentesis, fetal transfusion. </li></ul><ul><li>Hydrops no: further evaluation. </li></ul>
  40. 40. Parvovirus B-19 in Pregnancy <ul><li>Prevention </li></ul><ul><li>There are no known measures to treat or control parvovirus B19 infection. </li></ul><ul><li>No reliable vaccine or treatment for mother: </li></ul><ul><li>Frequent hand washing is recommended as a practical and probably effective method to reduce the spread of parvovirus. </li></ul><ul><li>Excluding persons with fifth disease from work, child care centers, schools, or other settings is not likely to prevent the spread of parvovirus B19, since ill persons are contagious before they develop the characteristic rash. </li></ul>
  41. 41. Parvovirus B-19 in Pregnancy <ul><li>Recommendations </li></ul><ul><li>CDC does not recommend that pregnant women should routinely be excluded from a workplace where a fifth disease outbreak is occurring. </li></ul><ul><li>Rather, CDC considers that the decision to stay away from a workplace where there are cases of fifth disease is an personal decision for a woman to make, after discussions with her family, physician, and employer. </li></ul>
  42. 42. Parvovirus B-19 in Pregnancy <ul><li>Because of the high prevalence of parvovirus B19 IgG among adults, most pregnant women are not at risk for parvovirus infection, even during an epidemic of erythema infectiosum. </li></ul><ul><li>If a pregnant woman has symptoms of erythema infectiosum, with or without arthropathy, parvovirus B19 infection should be suspected. </li></ul><ul><li>Information concerning the fetal outcomes of reported cases of infection in pregnancy should be provided, however, the risk of adverse effects on the fetus requires careful surveillance. </li></ul><ul><li>Therapeutic abortion is not indicated, because the intrauterine infection is more embryocidal than teratogenic. </li></ul>
  43. 43. Parvovirus B-19 in Pregnancy <ul><li>Management guidelines for pregnant women with symptomatic infection : </li></ul><ul><li>Monitoring of maternal serum IgM and Ig G. </li></ul><ul><li>Monitoring of maternal serum for elevated levels of a-fetoprotein may indicate fetal aplastic crisis, preliminary study has suggested that fetal loss is unlikely if the level stays within normal limits. </li></ul><ul><li>If the levels are increased, then serial ultrasonography may be useful to detect hydrops fetalis. </li></ul><ul><li>In cases of hydrops fetalis fetal blood samples may reveal the severity of the aplastic crisis; if severe, in-utero transfusions or early delivery and transfusions may be beneficial. </li></ul>
  44. 44. Parvovirus B-19 in Pregnancy <ul><li>During prenatal visits </li></ul><ul><li>Should inquire about any viral syndromes to which the gravida has been exposed or about any symptoms that may have been caused by a virus. </li></ul><ul><li>When a patient's medical history is suspicious for parvovirus exposure or infection, the physician should obtain serology to make a definitive diagnosis. </li></ul><ul><li>Thorough counseling when the infection is first diagnosed facilitates informed decision-making and encourages patient compliance with the management protocol, which is key to achieving a successful pregnancy outcome. </li></ul><ul><li>Patients are more likely to return for frequent screening, such as weekly ultrasounds, if they understand the reasoning behind the screening and the actions to be taken. </li></ul>
  45. 45. Parvovirus B-19 in Pregnancy <ul><li>High index of suspicion </li></ul><ul><li>Look for me! </li></ul>