Diagnosis and investigations

Investigation and Diagnosis of Congenital Cytomegalovirus (CMV)

• cCMV may be diagnosed by urine or saliva PCR in the first 21 days of life
  • after that time it becomes difficult to distinguish congenital infection from postnatal infection
  • when based on clinical suspicion alone
    • 90% of symptomatic cases go undiagnosed at birth
    • implementation of systematic neonatal cCMV screening, either universal or targeted to infants with hearing loss, increases diagnosis of both symptomatic and asymptomatic cases
    • incidental findings or delayed onset symptoms may also lead to a diagnosis later in infancy or childhood
      
      
• neonates
  • test neonates with clinical signs suggestive of cCMV or with confirmed sensorineural hearing loss (SNHL) - congenital CMV infection is the leading non-genetic cause of SNHL in early childhood, accounting for 21% of children with hearing loss at birth and 24% of those with hearing loss at 4 years of age (2)
    • CMV testing may be performed in the hospital after birth or as an outpatient, using urine or saliva PCR before 21 days of age ( ideally before 14 days)
    • after 21 days, it is challenging to distinguish congenital from postnatal CMV infection, which is not typically associated with long term sequelae
  • guidance give preference to the use of urine rather than saliva for CMV PCR because of possible false positives in saliva from CMV shed in breastmilk
    • saliva PCR is performed on a sample obtained from a cheek swab, and it can be performed as a point-of-care test
    • false positives can be reduced by collecting the sample 60 minutes or more after breastmilk consumption.
    • a positive saliva PCR result should be confirmed with urine PCR
      
      
• infants and children older than 21 days
  • clinical suspicion for cCMV may be raised by a delayed onset or recognition of symptoms, especially SNHL
  • CMV PCR can be performed on a stored residual dried blood spot left over from newborn screening sensitivity of this approach is low (30-85%);
    a negative result cannot definitively rule out cCMV (1)
  • if no dried blood spot is available, a definitive diagnosis of cCMV cannot be made
  • if definitive diagnosis of cCMV cannot be made, additional testing may lend support for or against a presumptive diagnosis
    • the following tests and parameters may be useful (1):
      • 1) evaluate for findings consistent with cCMV through cranial imaging, eye examination, and/or laboratory studies
      • 2) rule out other possible contributors to the clinical presentation (eg, genetic causes of hearing loss)
      • 3) test for previous exposure to CMV by measuring CMV IgG
    • a positive result cannot differentiate between congenital and postnatal disease, but a negative result substantially diminishes the likelihood of cCMV
      • for children <18 months
        • a positive urine or saliva CMV PCR confirms previous exposure to the virus (we caution against using IgG in this age group because of the potential for persistence of maternal antibodies in the infant)
      • for children older than 18 months
        • a positive CMV IgG suggests previous exposure to the virus
      • shedding of CMV in urine and saliva of a child with cCMV may not persist indefinitely, making those tests less reliable in older children

Reference:

1. Pesch MH et al. Congenital cytomegalovirus infection.BMJ 2021;373:n1212 | doi: 10.1136/bmj.n1212
2. Mack I et al.Symptomatic Congenital Cytomegalovirus Infection in Children of Seropositive Women. Front Pediatr. 2017 Jun 9;5:134.