Cytomegalovirus

Question 1

What is the structure of CMV?

Answer 1

Double-stranded virus of herpes family

Question 2

What is the most common cause of viral intrauterine infection?

Answer 2

CMV. Affects 0.5 - 2.5% of all neonates in different parts of the world.

Question 3

How is CMV transmitted?

Answer 3

Contamination from urine, saliva, blood, semen, cervical excretions.

Question 4

Risk factors for CMV infection?

Answer 4

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

Question 5

Symptoms of CMV infection

Answer 5

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

Question 6

CMV incubation period

Answer 6

4-8w

Question 7

CMV viremia period

Answer 7

3-12 months (infants can shed virus for up to 6 yrs)

Question 8

In whom does serious CMV disease occur?

Answer 8

Fetuses

Immunocompromised adults

Question 9

Does CMV transmission occur with primary or recurrent infection?

Answer 9

Both, but 99.5% of infections occur following primary maternal infection.

Question 10

What percentage of IgG negative women will acquire CMV infection during pregnancy?

Answer 10

2%

Question 11

What percentage of pregnant women with a primary CMV infection transmit it to their fetus?

Answer 11

1/3 (range 30-75%)

Question 12

When is the transmission rate of CMV highest in pregnancy?

Answer 12

3rd trimester

Question 13

The severity of CMV disease is highest in what trimester of pregnancy?

Answer 13

1st trimester

Question 14

What percentage of CMV-infected infants develop sequelae?

Answer 14

15-20% (about 5-8% of infants of infected mothers develop sequelae)

Question 15

How does recurrent CMV infection occur?

Answer 15

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.

Question 16

What is the risk of vertical transmission with recurrent CMV infection?

Answer 16

1.4%

Question 17

What percentage of neonates infected from recurrent maternal infection will have sequelae?

Answer 17

<10% (usu have no sx at birth, and do not have CMV+ urine)

Question 18

What are the clinical neonatal findings of symptomatic congenital CMV infection?

Answer 18

Jaundice
Petechiae ("blueberry muffin baby")
Thrombocytopenia
Hepatosplenomegaly
Growth restriction
Microcephaly
Intracranial calcifications
Nonimmune hydrops
Preterm birth

Question 19

What are the late complications of neonatal CMV disease?

Answer 19

Hearing loss
Mental retardation
Delay in psychomotor development
Chorioretinitis
Optic atrophy
Seizures
Expressive language delays
Learning disabilities

Question 20

What is the most common cause of congenital sensorineural hearing loss?

Answer 20

CMV

Question 21

What is the long-term mortality rate in neonatal CMV disease?

Answer 21

10-30%

Question 22

Diagnosis of congenital CMV infection in amniotic fluid

Answer 22

Quantitative PCR count of >/= 10^3 genome equivalents/mL is a certain sign of infxn
>/= genome equivalents/mL can predict symptomatic infection

Question 23

If no ultrasonographic abnl due to CMV are seen, what is the incidence of postnatal neurologic abnormalities?

Answer 23

15-20%

Question 24

How effective is hygiene in preventing CMV seroconversion in pregnancy?

Answer 24

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.

Question 25

Is there a vaccine available for CMV?

Answer 25

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.

Question 26

What is chance of an affected neonate after maternal seroconversion, with a nl US?

Answer 26

5%

Question 27

What is chance of an affected neonate after maternal seroconversion, with an abnl US?

Answer 27

35%

Question 28

What is chance of an affected neonate after maternal seroconversion, with positive AF PCR and a nl US?

Answer 28

15%

Question 29

What is chance of an affected neonate after maternal seroconversion, with a positive AF PCR and an abnl US?

Answer 29

80%

Question 30

How long does CMV IgM persist after seroconversion?

Answer 30

4-8 months

Question 31

How sensitive is CMV IgM testing?

Answer 31

75%. If first test is negative, consider a second test at 18-20w, and a third, if needed, at 30-32w.

Question 32

How can CMV IgM/IgG testing be used to assure no risk of primary infection?

Answer 32

IgM negative, IgG positive, with a high IgG avidity index (>65%).

Question 33

Fetal ultrasound findings in congenital CMV infection

Answer 33

``` Growth restriction Oligohydramnios Ventriculomegaly Choroid plexus cyst (unilateral) Pleural effusion Brain and liver calcification Fetal hydrops ```

Question 34

What are US findings that increase the risk for neonatal CMV infection?

Answer 34

Microcephaly Hydrocephaly Intracranial calcifications Periventricular "halo" - assoc w/ white-matter lesions

Question 35

Ultrasound detects fetal abnormalities in what percent of congenitally CMV-infected fetuses?

Answer 35

Only 15%

Question 36

Is CMV-specific IgM+ only found in primary disease?

Answer 36

No, CMV IgM can be found in 10% of women with recurrent disease

Question 37

What is the sensitivity of CMV PCR in amniotic fluid?

Answer 37

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.

Question 38

How is CMV infection diagnosed in the neonate?

Answer 38

Based on CMV PCR in body fluids, esp urine.

Question 39

Is there therapy to prevent fetal CMV infxn in pregnancy?

Answer 39

- 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.

Question 40

How is CMV transmitted perinatally?

Answer 40

Transplacentally, in the birth canal, through breast milk