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When and how to treat neonatal CMV infection


Key points

  • Congenital cytomegalovirus (CMV) is the leading infectious cause of hearing loss and neurologic deficits, affecting up to 1% of live births worldwide.

  • Symptomatic congenital CMV infection should be treated with ganciclovir or valganciclovir for 6 months to reduce or ameliorate long-term neurologic deficits, including hearing loss and developmental delay.

  • Studies suggest that some infants with asymptomatic or mild congenital CMV infection at birth may benefit from treatment, but more studies are needed.

  • In premature infants, postnatal CMV infection can cause severe sepsis-like disease and may contribute to long-term neurologic impairment and bronchopulmonary dysplasia.

  • Premature infants with symptomatic postnatal CMV infection should be strongly considered for treatment.

  • There is not enough evidence at this time to recommend routine treatment of asymptomatic premature infants with postnatal CMV infection.

  • Universal screening of all newborns for CMV is warranted to identify congenitally infected infants who will benefit from enhanced neurodevelopmental monitoring and treatment.

Clinical significance

Cytomegalovirus (CMV) is the most common infection in the newborn, affecting between 0.5% and 2.3% of live births worldwide. , The seroprevalence of CMV in adults ranges from 45% to 100%, depending on geographic location, socioeconomic status, and race. Infants can acquire CMV infection in utero (congenital CMV), through maternal secretions at birth (perinatal), or after birth via breastfeeding (postnatal CMV). Historically, only congenital CMV was thought to cause clinically significant illness and lead to neurodevelopmental impairment in infants; however, new studies have shown that postnatal CMV infection in premature infants can cause severe disease and contribute to long-term sequelae. Although the infection types can be similar, the risk factors for transmission, severity of disease, long-term sequelae, and treatment recommendations differ based on route of infection (congenital vs. postnatal). We will therefore discuss these two modes of viral transmission separately.

Congenital CMV transmission and outcomes

The highest risk of acquiring congenital CMV occurs in fetuses whose mothers have no prior immunity to CMV (primary infection, ∼40% transmission rate); however, transmission can occur with reactivation of a latent infection or with maternal infection with a new strain of CMV (1%–2% transmission rate). , In fact, because of the high global prevalence of CMV seropositivity among women of childbearing age, the majority of congenital CMV infections occur in infants of women with prior immunity to CMV.

Only 10% to 15% of infants with congenital CMV are symptomatic at birth. Symptoms range from mild to life-threatening multiorgan dysfunction and can include intrauterine growth restriction (IUGR), petechiae, jaundice, hepatosplenomegaly, microcephaly, chorioretinitis, and sensorineural hearing loss (SNHL). , Long-term sequelae include intellectual disability, seizures, chorioretinitis, optic nerve atrophy, psychomotor and speech delays, learning disabilities, and dental defects. , Of those infants who are asymptomatic at birth, 10% to 20% will develop neurologic impairment by 2 years of age, most commonly SNHL. SNHL associated with CMV has a fluctuating and progressive course, with some children not developing symptoms until 6 years of age. , Infants with congenital CMV from a primary maternal infection are more likely to have severe sequelae. , , Mortality in infants secondary to congenital CMV is 100 to 200 cases in the United States annually. Overall, congenital CMV is the leading cause of developmental impairment and the leading nongenetic cause of SNHL. ,

Postnatal CMV transmission and outcomes

Infants acquire postnatal CMV through virus shed in maternal breast milk. , In the past, CMV was frequently transmitted to hospitalized infants through blood transfusions, but the use of CMV-seronegative or leukoreduced blood has essentially eliminated this mode of transmission. Although harmless in full-term infants, postnatal CMV infection in very-low-birth-weight (VLBW; <1500 g birth weight) infants can result in a severe sepsis-like illness characterized by pneumonitis, enteritis, hepatitis, and thrombocytopenia and may lead to long-term neurologic impairment. In a meta-analysis of 17 studies, the risk of postnatal CMV infection in VLBW infants in the United States was approximately 6.5%, with 1.4% developing a sepsis-like syndrome. In most neonatal intensive care units (NICUs), the true prevalence is likely underestimated because CMV is not routinely evaluated for during sepsis evaluations.

There is still debate regarding the outcomes of postnatally acquired CMV and if premature infants who survived a postnatal CMV infection, such as full-term infants after postnatal infection, have no long-term consequences. Gunkel et al. followed 356 infants <32 weeks gestational age prospectively for 6 years, of whom 49 (14%) were CMV positive and 307 were CMV negative. The infants’ neurodevelopment was assessed at 16 months, at 24 to 30 months, and at 6 years. The authors noticed no difference at 24 to 30 months, but at 6 years of age infected children scored slightly lower on formal neurodevelopmental testing. They did not observe significant differences in motor development, and none of the infected children developed sensorineural hearing loss. Another prospective study that followed infants with and without a diagnosis of postnatal CMV initially showed that there were no differences in neurodevelopmental outcome between the two groups. Yet, again, when the same population was followed longer, significant differences in neurodevelopment could be found beginning at 6 years of age. Further, a retrospective study on outcome data from over 300 NICUs found that VLBW infants with a diagnosis of postnatal CMV had an increased risk of bronchopulmonary dysplasia (BPD) at 36 weeks’ corrected gestational age when compared with birth-weight–matched uninfected infants. Other studies showed a variable association of postnatal CMV with BPD in premature infants. A large, multicenter, prospective study is needed to fully determine the risk that postnatal CMV poses to premature infants and determine how best to prevent virus transmission or disease in this population.

Treatment of congenital CMV

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