Cytomegalovirus Flashcards
Ref: Evidence-Based MFM, Creasy & Resnik, Dr. Gibbs' lecture
What is the structure of CMV?
Double-stranded virus of herpes family
What is the most common cause of viral intrauterine infection?
CMV. Affects 0.5 - 2.5% of all neonates in different parts of the world.
How is CMV transmitted?
Contamination from urine, saliva, blood, semen, cervical excretions.
Risk factors for CMV infection?
Low SES Exposure to infected individuals Multiple partners Extremes of age Multiparity Blood transfusion 0.1-0.4% per unit of cellular blood products containing leukocytes In most cases, pregnant women acquire CMV by exposure to children in their home or occupational exposure to children
Symptoms of CMV infection
Usually asymptomatic, or symptoms so mild that it goes undiagnosed. May include a mononucleosis-like or flu-like syndrome, malaise, fatigue, lymphadenopathy, persistent fever, lymphocytosis, incr transaminases
Rarely - HSM, cough, headache, rash, GI sx
CMV incubation period
4-8w
CMV viremia period
3-12 months (infants can shed virus for up to 6 yrs)
In whom does serious CMV disease occur?
Fetuses
Immunocompromised adults
Does CMV transmission occur with primary or recurrent infection?
Both, but 99.5% of infections occur following primary maternal infection.
What percentage of IgG negative women will acquire CMV infection during pregnancy?
2%
What percentage of pregnant women with a primary CMV infection transmit it to their fetus?
1/3 (range 30-75%)
When is the transmission rate of CMV highest in pregnancy?
3rd trimester
The severity of CMV disease is highest in what trimester of pregnancy?
1st trimester
What percentage of CMV-infected infants develop sequelae?
15-20% (about 5-8% of infants of infected mothers develop sequelae)
How does recurrent CMV infection occur?
Occurs w/ immunosuppression and during pregnancy
Recurrent infxn in pregnancy is usu asx and primarily caused by reactivation of the endogenous virus, but can also be caused by a low-grade chronic infection or reinfection by a different CMV strain.
What is the risk of vertical transmission with recurrent CMV infection?
1.4%
What percentage of neonates infected from recurrent maternal infection will have sequelae?
<10% (usu have no sx at birth, and do not have CMV+ urine)
What are the clinical neonatal findings of symptomatic congenital CMV infection?
Jaundice
Petechiae ("blueberry muffin baby")
Thrombocytopenia
Hepatosplenomegaly
Growth restriction
Microcephaly
Intracranial calcifications
Nonimmune hydrops
Preterm birthWhat are the late complications of neonatal CMV disease?
Hearing loss Mental retardation Delay in psychomotor development Chorioretinitis Optic atrophy Seizures Expressive language delays Learning disabilities
What is the most common cause of congenital sensorineural hearing loss?
CMV
What is the long-term mortality rate in neonatal CMV disease?
10-30%
Diagnosis of congenital CMV infection in amniotic fluid
Quantitative PCR count of >/= 10^3 genome equivalents/mL is a certain sign of infxn
>/= genome equivalents/mL can predict symptomatic infection
If no ultrasonographic abnl due to CMV are seen, what is the incidence of postnatal neurologic abnormalities?
15-20%
How effective is hygiene in preventing CMV seroconversion in pregnancy?
Avoiding intimate contact w/ children, frequent handwashing, and glove use is associated with an 84% decrease in CMV seroconversion during pregnancy, esp in women who work in day care.
Is there a vaccine available for CMV?
A live-attenuated CMV vaccine is available, but may be reactivated, and safety issues have not been resolved. In a trial including CMV-seronegative women of childbearing age, a glycoprotein B vaccine demonstrated a 50% efficacy in preventing CMV infection.
What is chance of an affected neonate after maternal seroconversion, with a nl US?
5%
What is chance of an affected neonate after maternal seroconversion, with an abnl US?
35%
What is chance of an affected neonate after maternal seroconversion, with positive AF PCR and a nl US?
15%
What is chance of an affected neonate after maternal seroconversion, with a positive AF PCR and an abnl US?
80%
How long does CMV IgM persist after seroconversion?
4-8 months
How sensitive is CMV IgM testing?
75%. If first test is negative, consider a second test at 18-20w, and a third, if needed, at 30-32w.
How can CMV IgM/IgG testing be used to assure no risk of primary infection?
IgM negative, IgG positive, with a high IgG avidity index (>65%).
Fetal ultrasound findings in congenital CMV infection
Growth restriction Oligohydramnios Ventriculomegaly Choroid plexus cyst (unilateral) Pleural effusion Brain and liver calcification Fetal hydrops
What are US findings that increase the risk for neonatal CMV infection?
Microcephaly
Hydrocephaly
Intracranial calcifications
Periventricular “halo” - assoc w/ white-matter lesions
Ultrasound detects fetal abnormalities in what percent of congenitally CMV-infected fetuses?
Only 15%
Is CMV-specific IgM+ only found in primary disease?
No, CMV IgM can be found in 10% of women with recurrent disease
What is the sensitivity of CMV PCR in amniotic fluid?
80-100%. It increases after 21w, and after a minimum of 6w interval following maternal primary infxn, so if amnio performed before this interval, it should be repeated later.
How is CMV infection diagnosed in the neonate?
Based on CMV PCR in body fluids, esp urine.
Is there therapy to prevent fetal CMV infxn in pregnancy?
- No randomized trials exist (yet). In a nonrandomized study, CMV hyperimmune globulin IV 100 U/kg q mo until delivery to the mother w/ primary CMV infection was associated with a decrease in infected neonates from 40% to 16%.
- Maternal CMV hyperimmune globulin 200 U/kg IV to the mother (with additional AF or umbilical cord infusions for persistent US findings) for CMV DNA + fetuses was associated with a decrease in symptomatic CMV disease at birth from 50% in controls to 3%.
- A trial demonstrated reduction of hearing loss in neonates with proven congenital CMV infection with CNS involvement when tx was begun within one month of birth.
- Valacyclovir (8g/day orally for 7 weeks) given to women with congenitally CMV-infected fetuses at about 30w was associated with about a 50% normal child outcome at 1 to 5 years of age in one study.
How is CMV transmitted perinatally?
Transplacentally, in the birth canal, through breast milk
