Cytomegalovirus (CMV)

Testing algorithm

Not immune Early Acute phase Acute phase or primary infection Chronic phase or Reactivation of latent infection or Reinfection (or non-primary infection)
Description No symptoms Flu-like symptoms or asymptomatic Flu-like symptoms or asymptomatic
CMV IgM - + + + -
CMV IgG - - + + +
CMV IgG Avidity* n.a. Low Low High n.a./High

* A low-avidity anti-CMV IgG detected before the 16th – 18th week of pregnancy, together with a positive anti-CMV IgM, is strong evidence of a recent primary infection, whereas a high avidity index during the first 12 – 16 weeks would be considered a good indicator of past infection. A high avidity result later in gestation cannot rule out a primary infection at an earlier stage of the pregnancy.

n.a. not applicable

Adapted from Revello MG, Gerna G. (2002) Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev. 15(4):680-715. doi: 10.1128/CMR.15.4.680-715.2002.

Adapted from:

  1. Prince HE and Lapé-Nixon M. Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy. Clin Vaccine Immunol. 2014;21:1377-1384.
  2. Revello MG and Gerna G. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev. 2002;15:680-715.
  3. Duff P. Diagnosis and management of CMV Infection in Pregnancy. Perinatology. 2010;1:1-6.
  4. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). Knowledge and Practices of Obstetricians and Gynecologists Regarding Cytomegalovirus Infection During Pregnancy. MMWR. 2008;57903:65-68. [Internet; updated 2008 Jan 24; cited 2024 Mar 4]. Available from: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5703a2.htm.
  5. Davis NL, et al. Cytomegalovirus infection in pregnancy. Birth Defects Research. 2017;109:336-346.
Product Description Tests Product page
Elecsys® CMV IgMa) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of IgM class antibodies to CMV in human serum and plasma 100
Elecsys® CMV IgM b) 300
Elecsys® CMV IgG a) Electrochemiluminescence immunoassay (ECLIA) for the quantitative detection of IgG class antibodies to CMV in human serum and plasma 100
Elecsys® CMV IgG b) 300
Elecsys® CMV IgG Avidity a) Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of CMV IgG avidity in human serum and plasma 50
Elecsys® CMV IgG Avidity b) 50
cobas® CMV c) Nucleic acid amplification test for the quantitative measurement of CMV DNA in human EDTA plasma 120
cobas® CMV d) 96
192

a) for use on the cobas® e 411 analyzer and the cobas® e 601 / 602 modules
b) for use on the cobas® e 402 and cobas® e 801 analytical units
c) for use on the cobas® 4800 System
d) for use on the cobas® 6800/8800 Systems

CMV IgM CMV IgG CMV IgG Avidity CMV DNA Interpretation
1st sample
- - N/A N/A Patient is not immune and susceptible to infection. Pregnant women should take preventive measures and be closely monitored during pregnancy.
- + N/A N/A Infection at least one year previously, and immunity to CMV infection.
+ - N/A N/A Very early stage of infection or false positive (unspecific IgM). Perform follow-up test incl. IgG Avidity (when IgG is reactive) after 2 – 3 weeks to confirm either result.
+ + N/A N/A
2nd sample
+ + low + Acute infection confirmed.
+ + low N/A Acute infection highly suspected – follow-up sample and DNA testing is recommended.
+ + high N/A or - Acute infection not confirmed

* except infants
N/A: not available or not tested

Adapted from:

  1. Munro SC, et al. Diagnosis of and screening for cytomegalovirus infection in pregnant women. J Clin Microbiol. 2005;43:4713-4718.
  2. Duff P. A thoughtful algorithm for the accurate diagnosis of primary CMV infection in pregnancy. Am J Obstet Gynecol. 2007;196:196-197.
  3. Guerra B, et al. Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive cytomegalovirus immunoglobulin M antibody titers. Am J Obstet Gynecol. 2007;196:221 e221-226.
  4. Lazzarotto T, et al. Congenital cytomegalovirus infection: recent advances in the diagnosis of maternal infection. Hum Immunol. 2004;65:410-415.
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Step 1

Perform CMV IgM and IgG tests in parallel

CMV IgM test
CMV IgG test
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Summary

Not immune and susceptible to infection.

Pregnant women should take preventive measures and be closely monitored during pregnancy. Follow up until delivery is possible depending on local guidelines. In case very recent infection is suspected, retest a second sample in 2-3 weeks.

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Summary

Infection occurred at least one year previously.

Immune to CMV infection.

No further testing required.

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Step 2

Test CMV IgM and IgG in parallel in 2nd sample

CMV IgM test
CMV IgG test
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Summary

IgM reaction likely a false positive or possible analytical error.

Continue with serological screening (according to country-specific guidance) and following advices for avoiding infection

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Summary

IgM reaction likely a false positive.

Continue with serological screening (according to country-specific guidance) and following advices for avoiding infection

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Step 3

Test amniotic fluid for CMV DNA

CMV DNA test
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Summary

Fetal infection not confirmed.

Continue pregnancy monitoring.

Thoroughly evaluate the newborn. Perform postnatal diagnosis.

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Summary

Fetal infection confirmed.

Discuss options for possible pregnancy outcomes.

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Step 2

Perform CMV IgM and IgG tests
in parallel 2nd sample

CMV IgM test
CMV IgG test
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Summary

Result is implausible.

Investigate for possible analytical errors.

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Step 3

Perform CMV IgG Avidity test

IgG Avidity test
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Step 4

Determine gestation period

20 weeks gestation
≤ >
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Summary

No further testing required
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Summary

Retrospectively screen with a 1st trimester bood and perform IgG avidity.

Retrospectively screen a 1st trimester blood sample and perform CMV IgG avidity test.

No further testing required if high avidity in first sample (Step 1). High risk of transmission if low avidity in first sample (Step 1).

Test amniotic fluid sample for CMV DNA after 20-21 weeks of gestation and at least 8 weeks after maternal infection.

Consider referring patient to an expert CMV laboratory. Possible additional testing includes maternal viremia assessment (CMV DNA in urine and blood), fetal ultrasounds and MRI, or amniocentesis.

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Step 4

Test amniotic fluid for CMV DNA

CMV DNA test
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Summary

Fetal infection not confirmed.

Continue pregnancy monitoring.

Thoroughly evaluate the newborn. Perform postnatal diagnosis.

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Summary

Fetal infection confirmed.

Discuss options for possible pregnancy outcomes.

Back
Next Restart simulation
Step
Result
Interpretation
1
CMV IgM test = ...
CMV IgG test = ...
waiting for input
1
CMV IgM test = negative
CMV IgG test = negative
Not immune and susceptible to infection.
1
CMV IgM test = negative
CMV IgG test = positive

Infection occurred at least one year previously.

Immune to CMV infection.

1
CMV IgM test = positive
CMV IgG test = negative
Very early stage of infection or false positive (unspecific IgM).
Test new sample 2-3 weeks later.
1
CMV IgM test = positive
CMV IgG test = positive
Possible acute infection (or false-positive/ persisting IgM, or reactivation).
Obtain a new specimen after 2-3 weeks and repeat IgG and IgM testing.
2
CMV IgM test = ...
CMV IgG test = ...
waiting for input
2
CMV IgM test = negative
CMV IgG test = negative
IgM reaction likely a false positive or possible analytical error.
2
CMV IgM test = negative
CMV IgG test = positive
Acute infection or implausible results.
Investigate for possible analytical errors.

Test amniotic fluid for CMV DNA.

Consider referring patient to an expert CMV laboratory. Possible additional testing include IgG Avidity, maternal viremia assessment (PCR in urine/blood), fetal ultrasound and MRI, and amniocentesis.

Consider starting antiviral treatment.
2
CMV IgM test = positive
CMV IgG test = negative
IgM reaction likely a false positive.
2
CMV IgM test = positive
CMV IgG test = positive
Acute infection strongly suggested due to seroconversion.
Test amniotic fluid for CMV DNA.

Consider referring patient to an expert CMV laboratory. Possible additional testing include IgG Avidity, maternal viremia assessment (PCR in urine/blood), fetal ultrasound and MRI, and amniocentesis.

Consider starting antiviral treatment.
3
CMV DNA test = ...
waiting for input
3
CMV DNA test = negative
Fetal infection not confirmed.
3
CMV DNA test = positive

Fetal infection confirmed.

2
CMV IgM test = ...
CMV IgG test = ...
waiting for input
2
CMV IgM test = negative
CMV IgG test = negative

Implausible result.

2
CMV IgM test = negative
CMV IgG test = positive

Possible acute infection or false-positive IgM result.​​​​​​​
​​​​​​​Test for CMV IgG Avidity.

2
CMV IgM test = positive
CMV IgG test = negative

Implausible result.

2
CMV IgM test = positive
CMV IgG test = positive

Initial results confirmed.
Test for CMV IgG Avidity.

3
CMV IgG Avidity test = ...
waiting for input
3
CMV IgG Avidity test = low
Primary infection highly suspected. High risk of transmission.
Test amniotic fluid sample for CMV DNA after 20-21 weeks of gestation and at least 8 weeks after maternal infection.

Consider referring the patient to an expert CMV laboratory. Possible additional testing includes maternal viremia assessment (PCR in urine and blood), fetal ultrasounds and MRI, and amniocentesis.

Consider starting antiviral treatment.
3
CMV IgG Avidity test = high
Determine gestation period.
4
Gestation = ...
waiting for input
4
Gestation = ≤ 20 weeks
No further testing required.
4
Gestation > 20 weeks

Retrospectively screen a 1st trimester blood sample, and perform CMV IgG avidity test.

4
CMV DNA test = ...
waiting for input
4
CMV DNA test = negative

Fetal infection not confirmed.

4
CMV DNA test = positive
Fetal infection confirmed.
End of test sequence