Parvovirus Infection in Pregnancy Case File

Parvovirus Infection in Pregnancy Case File

Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD

CASE 19

A 24-year-old G2P1 woman at 22 weeks’ gestation complains of an episode of myalgias and low-grade fever 1 month ago. Her 2-year-old son had high fever and “red cheeks.” On examination, her blood pressure is 110/60 mm Hg, heart rate is 82 beats per minute (bpm), and she is afebrile. The heart and lung examinations are normal. The fundal height is 28 cm and fetal parts are difficult to palpate.

» What is the most likely diagnosis?

» What is the most likely mechanism?

ANSWER TO CASE 19:

Parvovirus Infection in Pregnancy                                            

Summary: A 24-year-old G2P1 woman at 22 weeks’ gestation complains of an episode of myalgias and low-grade fever 1 month ago. Her 2-year-old son had high fever and “red cheeks.” The fundal height is 28 cm and fetal parts are difficult to palpate.

• Most likely diagnosis: Hydramnios, with probable fetal hydrops due to parvovirus B19 infection.
• Most likely mechanism: Fetal anemia due to neonatal parvovirus infection, which inhibits bone marrow erythrocyte production.

ANALYSIS

Objectives

1. Know the clinical presentation of parvovirus infection in children and adults.
2. Understand the possible effects of parvovirus B19 infection on pregnancy.
3. Know the clinical presentation of hydramnios.

Considerations

This 22-year-old woman presents with a history of myalgias and low-grade fever. Her 2-year-old son had “red cheeks” and high fever. This illustrates the difference in the clinical presentation of parvovirus B19 infection in an adult versus that of a child. Adults rarely have high fever, but more often have malaise, arthralgias, and myalgias, and a reticular (lacy) faint rash that comes and goes. Up to 20% of adults will have no symptoms. In contrast, children often develop the classic “slapped cheek” appearance and high fever, which is the manifestation of “fifth disease.” Parvovirus infections in pregnancy may cause a fetal infection, which may lead to suppression of the erythrocyte precursors of the bone marrow. Severe fetal aplastic anemia may result, leading to fetal hydrops. One of the earliest signs of fetal hydrops is hydramnios or excess amniotic fluid. This patient’s uterine size is greater than that predicted by her dates, and fetal parts are difficult to palpate, which are classic findings of hydramnios. An ultrasound examination would confirm the fetal and amniotic fluid effects. The diagnosis of parvovirus B19 infection is made by serology (see Table 19– 1).

Table 19–1 • PREGNANT PATIENT EXPOSED TO PARVOVIRUS B19
IgM	IgG	Diagnosis	Management
Negative	Positive	Prior infection, immune	Reassurance
Negative	Negative	If more than incubation time (20 days) from exposure, then susceptible, not infected	Counsel about perhaps staying away from infected setting
Negative	Negative	If less than 20 days from exposure, then possible early infectiona vs not infected	Repeat IgG and IgM in 4 weeks
Positive	Negative	Probable acute infectiona but possible false-positive IgM	Repeat IgG and IgM in 1-2 weeks, expect both to be positive indicating acute infection

aOnce acute infection is diagnosed, then weekly ultrasounds assessing for hydrops.

APPROACH TO:

Parvovirus Infection in Pregnancy                                           

DEFINITIONS

FIFTH DISEASE: Illness caused by a single-stranded deoxyribonucleic acid (DNA) virus, parvovirus B19, also known as erythema infectiosum.

FETAL HYDROPS: A serious condition of excess fluid in body cavities, such as ascites, skin edema, pericardial effusion, and/ or pleural effusion.

HYDRAMNIOS (OR POLYHYDRAMNIOS): Excess amniotic fluid.

SINUSOIDAL HEART RATE PATTERN: A fetal heart rate pattern that resembles a sine wave with cycles of 3 to 5 per minute, indicative of severe fetal anemia or fetal asphyxia.

CLINICAL APPROACH

Parvovirus B19 infection is common, and up to 50% of adults have been infected during childhood or adolescence. It usually causes minimal or no symptoms in the adult, but may lead to devastating consequences for the fetus. A small, singlestranded DNA virus, parvovirus B19, causes a red “slapped cheek” appearance and fever in children; adults usually are less symptomatic and often have peripheral arthopathy, and a characteristic lacy reticular rash, which comes and goes (Figure 19– 1). The disease is transmissible 5 to 10 days after exposure, and this infectious period ends once symptoms appear.

School-aged children are commonly affected, and frequently transmit the virus to adults. Exposure to an infected household member carries a 50% risk of infection, and the risk is 20% to 50% in child care settings. Specific immunoglobulin M (IgM) antibody confirms the diagnosis. Although there is no universal consensus about how to follow pregnant women who are infected with parvovirus B19, one

commonly used strategy includes fetal ultrasounds every 1 to 2 weeks for 8 to 12 weeks after a positive IgM assay. Because the virus may cause an aplastic anemia by destroying erythroid precursors in the bone marrow, Doppler assessment is used to assess for severe fetal anemia. If evidence of hydrops or severe anemia is present, fetal blood should be sampled to obtain a hematocrit for fetal transfusion.

Figure 19–1. Fifth disease. Lacy reticular rash of erythema infectiosum. (Reproduced with

permission from Kasper DL, et al. Harrison’s Principles of Internal Medicine. 16th ed. New York:

McGraw-Hill; 2005:1056.)

Approximately half of pregnant women will have had parvovirus infection and be immune. IgG and IgM serologies are helpful (see Table 19– 1). Less than 5% of those susceptible pregnant women who are infected after 20 weeks’ gestation will have fetuses complicated by anemia, but pregnancies at <20 weeks have a higher risk of fetal loss. There is no vaccine available for parvovirus.

Parvovirus infection may lead to spontaneous abortion, stillbirth, and hydrops. Hydrops fetalis is defined as excess fluid located in two or more fetal body cavities, and many times is associated with hydramnios (see Table 19– 2 for causes of hydramnios); pregnancies <20 weeks’ gestation are at particular risk. Parvovirus is the most common infectious cause of nonimmune hydrops (fetal cardiac arrhythmias are the most common cause of nonimmune hydrops overall). Theories about the mechanism of the hydrops include the observation that severe anemia may cause heart failure, or induction of the hematopoietic centers in the liver to replace normal liver tissue, leading to low serum protein. The anemia is usually transient. If hydrops does not develop within 8 weeks of maternal infection, it is unlikely to occur.

Table 19–2 • CAUSES OF HYDRAMNIOS

Fetal central nervous system anomalies Fetal gastrointestinal tract malformations Fetal chromosomal abnormalities Fetal nonimmune hydrops Maternal diabetes Isoimmunization Multiple gestation Syphilis

Middle cerebral artery (MCA) Doppler waveforms can be used to assess for possible fetal anemia with elevated systolic velocity. For those patients who are susceptible and are exposed to parvovirus, serology is obtained to assess for possible infection, and serial ultrasound and MCA Doppler examinations are recommended until about 10 weeks postexposure.

For severely affected fetuses, intrauterine transfusion is one option, while mild cases may sometimes be observed. Other causes of fetal anemia are isoimmunization, such as an Rh-negative woman who is sensitized to develop anti-D antibodies, a large fetal-to-maternal hemorrhage, or thalassemia. An unusual fetal heart rate pattern, called a sinusoidal pattern, is associated with severe fetal anemia or asphyxia.

The possibility of exposure to parvovirus B19 may be a source of anxiety for pregnant women. Exclusion from the workplace (eg, school or daycare) during endemic periods is not recommended, however, pregnant women may be advised to avoid people exposed to fifth disease. Routine serologic screening is not recommended, and such screening should be reserved for pregnant women with symptoms of parvovirus B19 infection, recent exposure to people with confirmed or suspected fifth disease.

Other Congenital Infections

Cytomegalovirus (CMV) is a DNA virus and is the most common congenital infection in the United States, affecting 1% of neonates; most are asymptomatic. Affected infants can have microcephaly, periventricular calcifications, deafness, chorioretinitis (blindness), seizures, and interstitial pneumonia. Exposure is from blood, urine, or saliva and especially from school-aged children. Vertical transmission can occur with primary or secondary infections. Transmission is highest in the third trimester, but neonatal effects are worse in the first trimester. Serology and PCR are helpful in diagnosis. Ultrasound may show abdominal/ liver calcifications, cerebral ventriculomegaly, intracranial calcifications, microcephaly, and IUGR. Since there is no treatment, prevention remains the mainstay: careful handwashing, avoid sharing utensils especially with children (see also Table 19–3).

Toxoplasmosis is caused by the intracellular parasite Toxoplasma gondii. Exposure can be from undercooked meat or oocysts from the feces of infected cats. Vertical transmission increases with gestational age, but severity is worse in early pregnancy. Serology is not consistent and PCR is the best method for diagnosis. Ultrasound may show ventriculomegaly, intracranial calcifications, microcephaly, ascites, hepatosplenomegaly, and IUGR. Pregnant women infected with toxoplasmosis are treated with spiramycin to reduce transplacental transfer; although recommended by the CDC, spiramycin is not commercially available, but can be obtained through the FDA. Fetal infection is treated with pyrimethamine and sulfadiazine. Most neonates are asymptomatic at birth, but can later develop chorioretinitis (85% by an age of 20 years) and hearing loss. The classic triad is hydrocephalus, intracranial calcifications, and chorioretinitis. The keys in prevention are pet care precautions (avoid changing cat litter), handwashing, and meat preparation.

Table 19–3 • INTRAUTERINE INFECTIONS
Infectious Agent	Presentation	Transmission	Diagnosis	Treatment
Parvovirus	Fetal anemia, hydrops, miscarriage	Fetal loss high <20 weeks’ gestation; 5% anemia if >20 weeks	Serology	Delivery if near term; intrauterine transfusion
Cytomegalovirus	Microcephaly, periventricular calcifications, deafness, chorioretinitis, seizures	Highest in third trimester; worse effects in first trimester	Serology and PCR	None; prevention is key
Toxoplasmosis	Classic triad: hydrocephalus, intracranial calcifications, chorioretinitis; hearing loss	Any gestational age but worse outcome in first trimester	PCR	Pyrimethamine and sulfadiazine
Rubella	Classic triad: cataracts, sensorineural deafness, and cardiac defects; also microcephaly and thrombocytopenia	Severe effects when <8 weeks’ gestation; 50% risk 9-20 weeks, no effects after 20 weeks	Serology and PCR	None; prevention via immunization

Rubella

Rubella is caused by a ribonucleic acid (RNA) togavirus. Maternal infection in the first 8 weeks of pregnancy confers an 80% risk of major congenital defects, between 9 and 12 weeks’ gestation of 50%, and virtually no risk at 20+ weeks. The classic triad of congenital rubella is cataracts, sensorineural deafness (60%), and cardiac defects (pulmonary artery stenosis and patent ductus arteriosus). Microcephaly, thrombocytopenic purpura, and IUGR can be seen. Prevention is through immunization of susceptible patients.

COMPREHENSION QUESTIONS

19.1 A 24-year-old G1P0 woman at 27 weeks’ gestation is noted to have a fetal size greater than her dates. A fetal ultrasound performed reveals fetal hydrops. The fetal heart tones are in the range of 140 bpm. Middle cerebral artery Doppler studies indicate increased flow. Which of the following is the most likely etiology?

A. Fetal cardiac tachyarrhythmia

B. Immune thrombocytopenia purpura

C. Rh isoimmunization

D. Intrauterine growth restriction

E. Gestational diabetes

19.2 A 32-year-old G2P1 woman at 32 weeks’ gestation is seen in consultation at the maternal fetal medicine center of a hospital. A diagnosis of hydramnios is made on the basis of an amniotic fluid volume of 32 cm (normal 5 to 25 cm). Which of the following is the most likely cause of the patient’s condition?

A. Fetal duodenal atresia

B. Fetal renal disease

C. Uteroplacental insufficiency

D. Hemolysis elevated liver enzymes, low platelets (HELLP) syndrome

E. Immune thrombocytopenia purpura

19.3 A 22-year-old school teacher at 28 weeks’ gestation has a history of a faint rash and low-grade fever. She states that fifth disease is spreading in her school. Serology is obtained for parvovirus B19 revealing that the IgM is negative, and the IgG is negative. Which of the following statements is most accurate?

A. This patient is immune to parvovirus B19 and does not need to be concerned.

B. This patient is not infected with parvovirus B19, and is susceptible.

C. This patient is infected with parvovirus B19 and is at risk for fetal hydrops.

D. There is insufficient information to draw a conclusion about whether this patient is infected.

Please match the most likely infectious agent (A-E) to the clinical scenario (19.4-19.7):

A. CMV

B. Parvovirus B19

C. Rubella

D. Syphilis

E. Toxoplasmosis

19.4 A 25-year-old G1P0 woman at 30 weeks’ gestation is noted on ultrasound to have fetal IUGR with estimated fetal weight of 2nd percentile. There microcephaly and periventricular calcifications are noted.

19.5 A 30-year-old G2P1 woman delivers an infant at term. The neonate is noted to have an abnormal light reflex. Also a machine like murmur is noted on auscultation.

19.6 A 36-year-old G3P2 woman undergoes ultrasound examination for size greater than dates. The ultrasound shows fetal ascites, increased amniotic fluid, hydrocephalus, and intracranial calcifications.

19.7 A 19-year-old G1P0 woman is at 7 weeks’ gestation and develops a perinatal infection. The obstetrician explains that this particular infection has a very high transmission rate and fetal effects in the first trimester.

ANSWERS

19.1 C. Rh isoimmunization can lead to significant fetal anemia if the baby is Rh positive. With the use of RhoGAM, this is a rare event today. Other causes of isoimmunization, such as anti-Kell disease, are still a concern. Middle cerebral artery Doppler studies indicating increased velocity of flow are consistent with significant fetal anemia. This is due to cerebral autoregulation. Fetal cardiac arrhythmias, especially supraventricular tachycardia, are associated with nonimmune hydrops, but this would not affect the bone marrow and cause anemia. ITP is associated with maternal thrombocytopenia, and rarely fetal thrombocytopenia. IUGR is usually associated with polycythemia. Gestational diabetes does not typically affect the hemoglobin level.

19.2 A. Hydramnios is associated with problems with fetal swallowing or intestinal atresias, or associated with hydrops. Fetal duodenal atresia, diagnosed by the “double bubble” on ultrasound, is associated with hydramnios. Fetal renal disease or placental insufficiency is associated with oligohydramnios. With ITP in pregnancy, antiplatelet antibodies may cross the placenta and cause neonatal thrombocytopenia. HELLP syndrome is a serious, possibly deadly syndrome associated with preeclampsia. Rather than polyhydramnios, oligohydramnios is associated with HELLP.

19.3 D. IgM and IgG serology is the most common method to diagnose acute fifth disease. Typically, in the acute setting, if the IgG is positive and IgM is negative, it indicates that the patient has been exposed to parvovirus previously and is immune. When the IgG is negative and IgM is positive, then it usually means acute parvovirus infection; sometimes a false-positive IgM can occur, so the IgG and IgM are repeated in 1 to 2 weeks at which time the IgG should be positive with a true infection. When the IgG and IgM are both negative, then the patient typically will not be infected and susceptible, provided sufficient time has elapsed past incubation period. In this case, the patient has some symptoms of parvovirus infection in a high-risk setting, so although both IgG and IgM are negative, it would be wise to repeat it in 4 weeks to ensure that the incubation period (up to 20 days) has elapsed and antibodies have formed.

19.4 A. CMV affected infants can have microcephaly, periventricular calcifications, deafness, chorioretinitis (blindness), seizures, and interstitial pneumonia.

19.5 C. The classic triad of congenital rubella is congenital cataracts, cardiac defects, and deafness. The abnormal light reflex suggests cataracts. The machine-like murmur which is continuous is consistent with PDA.

19.6 E. The classic triad of congenital toxoplasmosis is cerebral ventriculomegaly, chorioretinitis, and intracranial calcifications.

19.7 C. Rubella has a very high transmission rate in the first trimester (50%) and high rate of fetal anomalies.

    CLINICAL PEARLS    

» Parvovirus infection in pregnancy can cause fetal anemia leading to hydrops fetalis. » Hydramnios is one of the earliest manifestations of fetal hydrops. » A parvovirus infection in the adult commonly leads to subtle findings of myalgias, malaise, and the reticular rash, whereas an infected child often has high fever and a “slapped cheek” appearance. » Some causes of hydramnios include gestational diabetes, isoimmunization, syphilis, fetal cardiac arrhythmias, and fetal intestinal atresias. » A pregnant woman who is diagnosed with a parvovirus infection will have weekly ultrasound examinations for 12 weeks to assess for fetal hydrops/hydramnios. » The classic triad of congenital rubella is heart defects, cataracts, and deafness. The rate of vertical transmission in the first trimester is 50%. » Congenital CMV is the most common perinatal infection worldwide. Affected infants have IUGR, microcephaly, periventricular calcifications, and hepatosplenomegaly. » Careful handwashing is important in the prevention of CMV infection. » The classic triad of congenital toxoplasmosis is cerebral ventriculomegaly, chorioretinitis, and intracranial calcifications.

REFERENCES

American College of Obstetricians and Gynecologists. Cytomegalovirus, parvovirus B19, varicella zoser, and toxoplasmosis in pregnancy. ACOG Practice Bulletin 151. Washington, DC; 2015. 

Castro LC, Ognyemi D. Common medical and surgical conditions complicating pregnancy. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 5th ed. Philadelphia, PA: Saunders; 2010:191-218. 

Centers for Disease Control and Prevention. Pregnancy and fifth disease. Atlanta, GA: CDC; 2012. http:/ / www.cdc.gov/ parvovirusb19/ pregnancy.html; Accessed 15.07.2015. 

Cunningham F, Leveno KJ, Bloom SL, et al. Amnionic fluid. In: Cunningham F, Leveno KJ, Bloom SL, et al. Williams Obstetrics. 24th ed. New York, NY: McGraw-Hill Education; 2013. http:/ / accessmedicine. mhmedical.com; Accessed 15.06.2015.

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