What are the diagnostic criteria for Congenital Cytomegalovirus (CMV) infection?

From the Guidelines

Congenital CMV diagnosis must be performed using a specimen collected in the neonatal period, before 21 days of age, to distinguish it from an acquired post-natal CMV infection. This approach is crucial for early identification and intervention, as most infants with congenital CMV are born without clinical signs, and the infection is often underdiagnosed in routine practice 1. The diagnosis of congenital CMV can be achieved through viral culture or PCR testing of urine or saliva samples, with urine samples being preferred due to their high viral load.

Key considerations for congenital CMV diagnosis include:

• The use of specimens collected within the first 21 days of life to ensure accurate diagnosis 1
• The preference for urine samples over saliva samples due to higher viral loads
• The role of PCR testing in providing rapid results within 24-48 hours
• The potential for blood testing for CMV-specific IgM antibodies as a supplementary diagnostic tool, although it is less sensitive than direct viral detection

After 21 days, distinguishing between congenital and postnatal infection becomes challenging due to the possibility of breast milk transmission. In such cases, testing should include PCR of dried blood spots (if available) or assessment for CMV DNA in tissues. Additionally, neuroimaging, preferably using MRI, should be performed in confirmed cases to evaluate for brain abnormalities. Other evaluations, such as comprehensive hearing assessment, ophthalmologic examination, complete blood count, liver function tests, and CSF analysis if neurologic symptoms are present, are also essential for managing congenital CMV. Early diagnosis is critical, as antiviral treatment with ganciclovir or valganciclovir may be indicated for symptomatic infants, particularly those with CNS involvement, to potentially improve hearing and neurodevelopmental outcomes 1.

From the Research

Congenital CMV Diagnosis

• Congenital cytomegalovirus (CMV) infection is the most common cause of viral infection in newborn babies, affecting 1 in 200 of all live born infants in high-income countries and 1 in 71 in low- and middle-income countries 2.
• The risk of intrauterine transmission is highest when primary infection occurs during pregnancy, with a higher rate of vertical transmission in mothers with older gestational age at infection 3.
• Testing for CMV is usually offered only to women who develop symptoms of influenza, glandular fever or hepatitis (liver inflammation) during pregnancy, or for those whom a routine ultrasound scan detects fetal anomalies that suggests possible CMV infection 2.
• The UK National Screening Committee recommends against universal antenatal or newborn screening for CMV 2.

Diagnostic Methods

• PCR testing of saliva is sensitive but has a risk of yielding false-positive results in infants without congenital CMV 4.
• Dried blood spot (DBS) PCR testing is an alternative, but the technique remains suboptimum 4.
• CMV-specific IgM (CMV-IgM) detection has a high positive predictive value, but may not be sufficient for clinical use due to the considerable number of false-negative cases 5.
• CMV IgG avidity testing and analysis of stored frozen first-trimester maternal blood samples provide valuable insights, but have limitations 6.

Screening and Treatment

• Universal newborn screening for congenital CMV infection is likely to have the greatest overall benefit, allowing for early identification and interventions such as antiviral therapy and anticipatory audiological monitoring 4.
• Targeted screening is typically based on the outcome of a newborn hearing screen, and can be influenced by findings of other signs suggestive of congenital CMV 4.
• Treatment with antiviral medicine (valganciclovir or ganciclovir) can reduce hearing loss in 5 out of 6 babies, and improve long-term brain development outcomes in some 2, 3.
• Valganciclovir is reserved for congenitally-infected neonates with symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss 3.