Congenital Cytomegalovirus (CMV)

• CMV is the commonest cause of congenital infection.
• It causes a self-limiting infection in immune-competent children and adults, however infection of the developing fetus can cause more serious sequelae.
• Most pregnant women with CMV infection will not pass it to their fetus.
• If fetal infection occurs, around 10-20% of children will develop long-term sequelae.

• Primary (acute) infection during pregnancy may result in fetal infection in up to ~40% of cases, whereas with reactivation/reinfection in women with past CMV it is ~1%.
• However, because past infection in many populations is far more common than acute infection during pregnancy, on a population level, reactivation/reinfection is usually responsible for more congenital CMV infections overall.

• Routine screening in pregnant women is not recommended.
• Test in pregnant women with mononucleosis-like illness.
• Test in pregnant women with fetal USS findings that may suggest congenital infection.
  • Bilateral cerebral periventricular calcifications are the most characteristic findings.
  • A number of other USS findings may be seen, including other CNS abnormalities, hyperechoic bowel, IUGR, ascites/pleural/pericardial effusion, hepatosplenomegaly.

If maternal mononucleosis-like illness) request “CMV serology“:

CMV IgG indicates infection at some point in time (can be acute or past infection)

• Excellent sensitivity – negative result excludes CMV infection (unless tested within the first 2-3 weeks of symptoms)
• Excellent specificity – positive result confirms infection at some stage

CMV IgM is used to diagnose primary (acute) infection

• Good sensitivity – negative result makes primary infection unlikely
• Poor specificity – positive result doesn’t necessarily indicate acute infection
• IgM can remain positive for many months after resolved primary infection, or reappear with other unrelated illnesses
• Because of the importance of diagnosing acute CMV in pregnancy, women with a positive IgM should be discussed with a clinical microbiologist regarding further confirmatory testing (which may include CMV IgG avidity testing).

If abnormal USS findings): request “CMV serology”

CMV IgG indicates infection at some point in time (can be acute or past infection)

• Excellent sensitivity – negative result excludes congenital CMV as cause of USS findings
• Poor specificity – positive result indicates maternal infection at some point in time, but gives no indication as to whether infection may have passed to fetus

If the CMV IgG is positive then the decision on whether to pursue further investigations to determine whether the fetus is infected is complicated and invasive, and should be in conjunction with a maternal fetal medicine specialist.

Factors influencing decisions include:

• Would confirming infection alter management during the pregnancy, or can it wait until baby is born (at which point diagnosis is straightforward)?
• How suggestive of congenital CMV are the USS findings?
• Is the CMV IgM also positive (i.e. possible recent acute maternal infection)?

If antenatal diagnosis is pursued, then amniocentesis for CMV PCR is the test of choice:

• Sensitivity is excellent if performed >20 weeks gestation and >6 weeks after possible primary maternal infection, otherwise sensitivity is lower.

Request “CMV PCR on urine (or saliva)”

If performed within the first 21 days of life

• Excellent sensitivity – negative result excludes congenital CMV infection
• Excellent specificity – positive result confirms congenital CMV infection

If performed after this time period, results can be difficult to interpret, as they could represent post-natally-acquired CMV infection. Discuss with a clinical microbiologist.

CMV PCR/viral load on blood:

• This is seldom used in this context, and only under the guidance of a clinical microbiologist.

CMV PCR on ‘Guthrie’/’newborn blood spot card’

• Has poor sensitivity, but sometimes used under specialist guidance if unable to obtain urine sample in first 21 days of life.

• Confirmation of congenital infection in a fetus or neonate only tells you congenital infection has occurred, it does not tell you whether the infection will cause sequelae or not.
• If primary infection is suspected during pregnancy, the antenatal ‘booking’ sample can often be retrieved for parallel testing to determine if the woman already had past CMV infection.