Managing Fetal Anemia: A Case of Parvovirus Infection in Pregnancy

A gravida 2, para 1-0-0-1 woman aged 27 years with chronic hypertension and a previous cesarean delivery in Brazil presented to her scheduled anatomy ultrasonogram for routine prenatal care at 20 weeks and 1 day’s gestation. On imaging, the fetus had ascites and a small pericardial effusion diagnostic of fetal hydrops (Fig. 1). Middle cerebral artery (MCA) Dopplers were performed and noted to be significantly elevated, indicating fetal anemia (Fig. 2). This finding was reviewed with the patient. Her medical and surgical histories were unremarkable, except that she reported having experienced a flu-like illness about 3 to 4 weeks before her ultrasonogram, with symptoms including coughing, sneezing, headaches, arthralgias in bilateral knees, shortness of breath, and lower abdominal pain. The differential diagnosis included an infectious, cardiac, or genetic etiology. The combination of her recent symptomatology and ultrasonogram findings led to a leading differential diagnosis of parvovirus infection. Serum testing with parvovirus serologies was obtained. The parvovirus IgM returned positive, confirming parvovirus infection.At 20 weeks’ gestation, she was transferred to a tertiary care center where she underwent a percutaneous umbilical blood sampling (PUBS) to confirm suspicion of fetal anemia. The PUBS was performed without complication, and fetal anemia was confirmed with a hematocrit of 9.7% (reference range, 35%–48%). The fetus underwent an intrauterine blood transfusion with 15 cc of irradiated, O-negative, cytomegalovirus-negative blood. Several hours after the procedure, she reported diffuse abdominal pain and had decreased fetal movement. Bedside ultrasonogram found absent cardiac activity, confirming intrauterine fetal demise.The patient was counseled extensively regarding mode of delivery, including induction of labor vs dilation and evacuation. She underwent dilation and evacuation procedure under ultrasonogram guidance. She recovered with no physical concerns. She was discharged the same day with physician and social services follow-up.A fetal autopsy was offered to the patient at the time of counseling for the dilation and evacuation. The patient declined an autopsy after the procedure.Parvoviridae are a class of small, nonenveloped DNA viruses.1 Human parvovirus B19 is the predominant strain affecting humans. About 30% to 60% of adults have positive antibodies to parvovirus.2 Similarly, about 35% to 53% of pregnant patients have evidence of immunity from previous infection, given serologic evidence of IgG to the virus.3 The incidence of B19 infection is highest in schoolteachers (16%) and daycare workers (9%).4 Notably, the Centers for Disease Control and Prevention (CDC) issued a statement in August 2024 stating there is an increase in the cases of B19 infection in the United States as well as 14 other European countries.5 Thus, this should increase clinical suspicion for patients with common parvovirus symptoms.Parvovirus infection can present as erythema infectiosum, or fifth disease, classically characterized with a “slapped cheek” rash on the face and lacy rash along the trunk. Although adults can manifest with a rash, the classic appearance on the face or the trunk is rare. These dermatologic findings are usually accompanied by systemic symptoms, most commonly arthralgias in the adult population. The recommended treatment is routine supportive care, given the virus is self-limiting, especially in immunocompetent individuals.6 However, in pregnancy, there are unique considerations for the fetus exposed to parvovirus B19.If there is a clinical suspicion of parvovirus B19 in a pregnant patient, assessing serologic IgG and IgM antibodies is recommended.6 Patients with seropositive IgM antibodies indicate active parvovirus infection. Counseling should be tailored depending on the gestational age at the time of parvovirus diagnosis.6Pregnant patients presenting with active infection before 20 weeks’ gestation should be counseled that the PUBS procedure is not typically feasible given limited visualization and the smaller size of fetal structures. Typically, after 20 weeks’ gestation, patients may have weekly ultrasonograms to monitor for ultrasonographic evidence of hydrops fetalis (ie, edema, ascites, cardiomegaly, and polyhydramnios). Additionally, MCA peak systolic velocity Doppler is measured to assess anemia, with the anemia characterized as a peak systolic blood velocity more than 1.5 multiples of the median. The usual duration of time for testing is about 10 to 11 weeks after the infection. It is less likely for the fetus to develop fetal hydrops if the infection has not occurred 8 weeks after infection in the pregnant person.6 Susceptible pregnant patients (no history of exposure, schoolteachers, and daycare workers) should be recommended to engage in proper hand hygiene and to avoid sharing food or drinks.6Hydrops fetalis is a known but fortunately infrequent result of parvovirus B19 infection in pregnancy. Hydrops fetalis is ultrasonographic evidence of fluid accumulation around the soft tissues and serous cavities of the fetus.7 There is a wide variety of possible causes. These include immune-mediated (eg, isoimmunization) and nonimmune-mediated causes, such as congenital infections, abnormalities in hemoglobin function, or anatomic malformations such as congenital heart or lung defects. Parvovirus B19 infection is cytotoxic to red blood cells, which results in profound fetal anemia. The likelihood of fetal loss is directly correlated with the severity of the anemia in the fetus.Fortunately, most cases of parvovirus infection in pregnancy resolve spontaneously without fetal infection or fetal sequelae. Studies suggest the rate of hydrops fetalis associated with parvovirus B19 infection before and after 20 weeks of gestation is 11% and less than 1%, respectively.8 One study from Sweden demonstrated that the risk of third trimester stillbirth from B19 infection was very low, citing 93 deaths out of 33 759 deliveries.9 Additionally, infection in the first trimester will increase the risk of adverse outcomes.A fetus with evidence of mild-to-moderate anemia is usually self-limited and typically resolves spontaneously without long-term sequalae. Because the anemia caused by parvovirus is transient, there is low utility in determining the fetal hemoglobin levels, unless there is ultrasonographic evidence of hydrops. Two of the primary modalities for monitoring fetal anemia include the MCA peak systolic blood velocity and ductus venosus velocity; the MCA is usually preferred given its accessibility for measurement via ultrasonogram.Patients with elevated MCA Doppler ultrasonograms are recommended to have a PUBS procedure, in addition to an intrauterine fetal blood transfusion. The evidence demonstrates that intrauterine transfusion improved the survival rate of fetal parvovirus infection to 82% with transfusion vs 55% without intrauterine transfusion.10 Although intravenous immunoglobulin has been used to treat patients infected with parvovirus B19, there is no recommendation for its use in the management of infected pregnant patients outside of a research protocol.Given the high risk of neonatal compromise in the setting of hydrops, it is critical to have coordinated efforts between the obstetrics team and the neonatologists arrange for a coordinated delivery planning with prepared respiratory support and mechanical ventilation. Additional preparation for resuscitation includes paracentesis, thoracentesis, or infusion of blood products, depending on the gestational age and severity of clinical manifestations of the parvovirus infection in the infant. Additionally, mental health support should be considered for the parents. Fetal hydrops can be psychologically altering events, and mental health should be prioritized postpartum.A fetus can succumb to complications stemming from parvovirus-induced hemolytic anemia at a previable gestational age. Although most parvovirus infections do not cause anemia and hydrops, a minority of parvovirus infections in pregnancy will result in adverse outcome for the fetus despite appropriate surveillance and treatment.American Board of Pediatrics Neonatal-Perinatal Content SpecificationDevelopment of immune defenses in the fetus and neonate.Assessment of fetal well-being.