SUMMARY:

Maternal immune response is dampened during pregnancy to allow for fetal tolerance. However, this comes at the expense of increased risk of infections, especially concerning congenital infections where maternal-fetal transmission can occur. Cytomegalovirus (CMV), parvovirus B19, varicella-zoster virus (VZV), and toxoplasmosis are common infections and may lead to severe fetal and infant complications.

Jump To:
Cytomegalovirus (CMV)
Parvovirus B19
Varicella Zoster (VZV)
Toxoplasmosis

Cytomegalovirus (CMV)

• Most common congenital infection
• Women working at childcare or with young children are at higher risk
• Routine screening of pregnant women not recommended
• No contraindication to breastfeeding for CMV infected women

Mode of Transmission

• Contact with infectious body fluids
  • Urine | Saliva | Blood | Tears | Semen | Breast milk
• Sexual contact
• Transplacental
• Transplanted organs
• Blood transfusions
• Contact with the maternal genital secretions during delivery

Risk for Vertical Transmission and Congenital CMV

• Risk of transmission
  • Higher after primary infection vs reactivation
  • Greatest in the 3^rd trimester
• More fetal complications if transmitted in 1^st trimester

Incubation

• 28 to 60 days
• Mean: 40 days

Symptoms

• Typically asymptomatic in healthy individuals
• Mononucleosis-like symptoms
  • Fever
  • Myalgia
  • Malaise
  • Abnormal liver function
  • Leukocytosis
  • Lymphocytosis
  • Lymphadenopathy

Congenital CMV

• Most infants are asymptomatic
• Symptoms when present
  • Jaundice
  • Petechiae
  • Thrombocytopenia
  • Hepatosplenomegaly
  • Myocarditis
  • Growth restriction
  • Nonimmune hydrops
  • Deafness
  • Intracranial calcification
  • Microcephaly

Evaluation and Diagnosis

• Serology, Viral culture or PCR of infected fluid
• Seroconversion or 4-fold increase in anti-CMV IgG
• Anti-CMV IgM is not reliable
• Positive IgM and low avidity IgG
  • Confirms primary infection in past 2 to 4 months
• Congenital CMV infection
  • Suspected after documented maternal infection
  • Presence of suggestive symptoms on US
  • Can be detected in amniotic fluid by PCR or culture
  • CMV positive amniotic fluid does not predict severity
  • Cannot be diagnosed by serology

Treatment

• No therapy for maternal or congenital CMV infection
• Antivirals for AIDS or organ transplanted patients
  • Ganciclovir
  • Valganciclovir
  • Foscarnet
• Referral to MFM and ID
• Monitor with serial US

Parvovirus B19

• Routine screening for pregnant women not recommended
• No contraindication to breastfeeding for Parvovirus B19 infected women
• Risk for severe fetal anemia

Transmission

• Respiratory secretion
• Hand to mouth contact
• Blood products
• Transplacental

Vertical Transmission

• Most fetuses recover spontaneously
• May cause
  • Miscarriage
  • Nonimmune hydrops fetalis
  • Stillbirth
• Hydrops fetalis more common with infection <20 weeks of gestation

Incubation

• Individual most contagious
  • Early after exposure
  • Before the start of rash
• Generally safe to go back to work or school after onset of rash

Symptoms

• Adult
  • General reticular rash
  • Arthralgia | Arthropathy
  • Aplastic crisis in patients with hemoglobinopathy | Low reticulocytes count with anemia
• Children
• Erythema infectiosum or 5th disease
• Characteristic red facial rash (also known as ‘slapped cheek’) | Appears a few days after fever or flu-like symptoms
  • Rash can appear elsewhere including chest, back, buttocks, or arms and legs
  • Typically fades within 7 to 10 days

Evaluation and Diagnosis

• During pregnancy, screen with serology after exposure
• IgM and IgG both positive
  • Indicates acute infection
• IgG only positive
  • Indicates lifelong immunity
• IgM and IgG both negative  
  • Repeat serology after 4 weeks
• No monitoring for women with immunity by serology

Antenatal fetal surveillance

• Women with acute infection by serology should be monitored for fetal complications
  • Serial monitoring every 1 to 2 weeks for 8 to 12 weeks after exposure
  • Follow relevant management guidelines if any of the following are found
    • Ascites | Cardiomegaly | Placentomegaly | Growth restriction | Hydrops fetalis
  • Doppler assessment for peak systolic velocity of fetal middle cerebral artery to predict fetal anemia
• Fetal blood sampling for hematocrit if
  • Hydrops fetalis
  • Severe fetal anemia
• Evidence of fetal infection such as hydrops fetalis
  • Perform PCR of amniotic fluid

Treatment

• Supportive care
• Many recover spontaneously
• Intrauterine blood transfusion in severe fetal anemia

Noted Increase in US Cases in Summer 2024

• Recommended increase suspicion if patient
  • Symptomatic
  • With known exposure
• Have a low threshold to test those at higher risk and symptomatic
  • Pregnancy
  • Severely immunocompromised: Leukemia | Other cancers | Organ transplant recipients | HIV infected | On chemotherapy
  • Chronic hemolysis: Sickle cell disease | Thalassemia | Hereditary spherocytosis
• Counsel pregnant individuals to report exposure to their providers
  • Exclusion of pregnant women from workplace during endemic not recommended
  • Excluding individuals with acute infection will not eliminate exposure
• Promote CDC recommendations for core prevention strategies
  • Practicing good hand hygiene
  • Taking steps for cleaner air (see ‘Learn More – Primary Sources’ for CDC guidance regarding ventilation to prevent viral infection)

Varicella Zoster (VZV)

• Uncommon in pregnant women
• Breast Feeding
  • No breast lesions: Mothers can breastfeed
  • Breast lesions: Temporarily stop breastfeeding

Note: Mothers should feed expressed breast milk but no direct breastfeeding if active varicella developed 5 days before to 2 days after delivery

Transmission

• Highly contagious
• Respiratory droplets
• Direct contact
• Transplacental
• Infectivity begins
  • 48 hours before rash
  • Lasts until vesicles crust
• Vaccinated people may develop lesions that do not crust
  • Contagious until no new lesions for 24 hours

Vertical Transmission | Congenial varicella syndrome

• Risk is low
• Symptoms
  • Skin scarring
  • Limb hypoplasia
  • Chorioretinitis
  • Microcephaly
• Neonatal infection
  • High neonatal death rate
  • Occurs when maternal disease develops 5 days before to 2 days after delivery

Incubation

• 10 to 20 days
• Mean: 14 days

Symptoms

• Primary infection: Chickenpox
  • Fever
  • Malaise
  • Maculopapular pruritic rash that becomes vesicular
• Reactivated: Shingles | Herpes zoster
  • Dermatomal distribution rash
• More benign in children
• Complications
  • Adults: Encephalitis | Pneumonia
  • Children: Bacterial infection of skin or soft tissues

Evaluation | Diagnosis

• Clinical diagnosis
• Document immunity in early pregnancy  
  • History of prior infection
  • Vaccination
• Document immunity with serum varicella IgG if no prior infection or vaccination
• Prior infection confers lifelong immunity
• Infected individuals
  • Isolated with airborne and contact precautions

Treatment

• Oral acyclovir
  • Reduces duration of lesions
  • Best started within 24 hours of rash
• Oral acyclovir safe in pregnancy
• Maternal acyclovir does not affect fetal risk of congenital varicella syndrome
• Varicella-zoster immunoglobulin (VZIG)
  • Given to infants born to mothers with varicella developed 5 days before to 2 days after delivery
• VZIG during pregnancy
  • No immunity to VZV
  • Exposed to someone with active infection
  • Ideally administer within 96 hours of exposure
    • Can give up to 10 days after exposure
• IV acyclovir
  • Infants developing varicella within first 2 weeks of life

Vaccination

• Live attenuated vaccines over 2 doses
• Appropriate for the following
  • No history of prior infection
  • No vaccination
  • No immunity on serology
• First dose of vaccine
  • Upon completion or termination of pregnancy
• Second dose 4 to 8 weeks after the first
• Conception should be delayed for 3 months after last dose
• Vaccine is safe for breastfeeding mothers

Toxoplasmosis

• Routine screening for healthy pregnant women not recommended
• Prenatal serological screening for
  • HIV infected
  • Immunocompromised
• Breastfeeding is encouraged unless bleeding or cracked nipples

Transmission

• Zoonotic | Cats
• Foodborne
  • Consumption of contaminated food
  • Undercooked food
• Contact with infected animals
• Transplacental

Incubation

• 5 to 18 days

Symptoms

• Usually asymptomatic | Asymptomatic cervical lymphadenopathy
• Other symptoms
  • Fever
  • Night sweat
  • Myalgia
  • Hepatosplenomegaly

Vertical Transmission | Congenital toxoplasmosis

• Parasitemia causes transplacental transmission
• Infection in late gestation increases risk of transmission
• Infection in early gestation is associated with severe disease
• Mostly asymptomatic in infected newborns
• Other symptoms
  • Chorioretinitis
  • Deafness
  • Neurodevelopmental delay | Seizure
  • Rash
  • Hepatosplenomegaly | Ascites
  • Ventriculomegaly
  • Periventricular calcifications

Evaluation

• Serological testing
  • Serum IgM and IgG
  • Low sensitivity and specificity
  • Used for initial evaluation during pregnancy
• Low risk of transplacental transmission 
  • Positive IgG and
  • Negative IgM
• Recent infection or false positive result
  • Positive IgG and
  • Positive IgM
• No infection or recent acute infection before seroconversion
  • Negative IgG and
  • Negative IgM
• In suspected acute infection
  • Repeat testing 2 to 3 weeks for increased IgG
• In confirmed serological maternal infection test for IgG avidity
  • Low avidity means infection occurred within the past 5 months
• Fetal infection
  • Amniocentesis should be offered in suspected cases
  • PCR of amniotic fluid is preferred
  • Amniocentesis should be performed < 18 weeks

Treatment

• Healthy individuals recover spontaneously
• Maternal infection acquired <18 weeks and no fetal infection suspected
  •  Spiramycin
• Maternal infection acquired ≥18 weeks and fetal infection confirmed or suspected
• Combination: Pyrimethamine | Sulfadiazine | Folinic acid
• Infants with symptomatic congenital toxoplasmosis treated for 1 year with combination of
  • Pyrimethamine | Sulfadiazine | Folinic acid

KEY POINTS:

• Pregnant women with Parvovirus B19 infection
• Monitor for fetal anemia with serial US
• Oral acyclovir for VZV treatment safe in pregnancy
  • Should be given if lesions develop
• Pregnant patients not immune to VZV and exposed to person with chickenpox
  • Administer VZIG within 96 hours of exposure
• Pregnant patient with acute toxoplasmosis < 18 weeks without fetal infection
  • Administer spiramycin to reduce fetal infection risk
• Fetal infection with toxoplasmosis acquired ≥18 weeks
  • Administer combination of pyrimethamine, sulfadiazine and folinic acid to mother

Learn More – Primary Sources

ACOG Practice Bulletin 151: Cytomegalovirus, Parvovirus B19, Varicella Zoster, and Toxoplasmosis in Pregnancy

CDC: Parvovirus B19 in Pregnancy

CDC: Clinical Overview of CMV and Congenital CMV

Breastfeeding In Parvovirus infected mothers

ACOG Practice Advisory: Increase in Human Parvovirus B19 Activity in the United States

CDC: Clinical Overview of Chickenpox (Varicella)

CDC: Breastfeeding with shingles

CDC: Contraindications to breastfeeding

CDC: Clinical care of Toxoplasmosis

CDC: Toxoplasmosis and breastfeeding

CDC: Taking Steps for Cleaner Air for Respiratory Virus Prevention

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