Making Decisions in Congenital Cytomegalovirus Infection

Congenital CMV (cCMV) infection - CMV, or Cytomegalovirus, is a common virus that can infect people of all ages. Congenital CMV is when a baby has been infected before birth.

Symptomatic cCMV - babies born with cCMV with signs of damage caused by the infection at birth. Each research study might use slightly different signs and symptoms to decide which babies are ‘symptomatic’. This makes it difficult to compare each study. 

Asymptomatic cCMV - babies born with cCMV but without signs of damage caused by the infection at birth. Some research studies tested large populations of healthy newborn babies to find those with ‘asymptomatic’ cCMV infection. 

Sensorineural hearing loss - Damage to the inner ear or nerves that pass signals from the ear to the brain which causes hearing loss. 

Neurodevelopmental disorder – A group of conditions affecting the brain, typically becoming apparent early in development, that produce impairments of personal, social, academic, or everyday functioning.

Neurodiversity - people with or without neurodevelopmental disorders who think and behave differently than the majority of others. Some examples of conditions are Autism Spectrum Disorder, Attention Deficit Disorder, Dyslexia and Dyspraxia.

If a mother acquires CMV infection during pregnancy, the risk of passing the virus to her unborn baby is higher during later stages of pregnancy. However, infection during early pregnancy is more likely to have severe consequences for the baby (Yinon 2010). A study of 74 cases of cCMV infection found that the risk of complications for the baby (hearing loss, learning difficulties, cerebral palsy, seizures, eye involvement) was doubled when the mother was infected before the 13th week of pregnancy compared to when the mother was infected after the 13th week of pregnancy. (Pass 2006)

One study followed 176 children with cCMV for at least five years and found that all moderate and serious problems were apparent in the first year of life. Milder problems (e.g. hearing loss in one ear, mild language delay, mild movement impairment) were identified later on (between two and seven years of age). 

This study showed that babies who have signs and symptoms of cCMV infection at birth are more likely to develop long-term difficulties than those who were found to have cCMV infection but no signs or symptoms at birth. It should be noted that this study looked at babies born between 1977 and 1986, before effective treatment for CMV was available. (Townsend 2013) 

Currently, we do not have enough information about outcomes into adulthood; existing studies have only followed babies up until around seven years.

The main hearing impairment associated with cCMV is called sensorineural hearing loss (SNHL).

When followed up until five years of age, SNHL was found in approximately 1 in 10 asymptomatic babies compared to 4 in 10 symptomatic babies. The timing of hearing loss and severity of hearing loss was variable with no reliable way to predict any deterioration. (Bartlett 2017) 

There is also a risk that hearing can get worse over the first few years of life (see ‘Why do we treat cCMV?’ below). This is why all children with cCMV, regardless of whether they have treatment for cCMV or not, will have hearing follow up until school age.  

Babies with significant changes on their brain MRI scan are more at risk of neurodevelopmental disorders. In some cases, the type of changes on the scan might suggest a particular risk of difficulties affecting movement or other functions. However, often it is very difficult to predict the clinical outcome from the scans. Some babies may have more subtle neurodevelopmental problems, such as neurodiversity or mild learning difficulties, which are not seen on MRI scans and may only be detected as a child grows up. 

Most studies looking at children with asymptomatic cCMV reported no difference in the rate of neurodevelopmental problems compared to the general population. Children with symptomatic cCMV perform worse on neurodevelopmental assessment. In a review of 5 studies, the rates of neurodevelopmental problems in children with symptomatic cCMV was reported in up to 6 in 10 children. (Bartlett 2017) 

A study In Sweden and the UK followed up 176 babies with untreated cCMV (symptomatic and asymptomatic) until at least five years of age. They found that most (8 out of 10) children had no developmental problems, only 1 in 20 were reported as having severe problems. (Townsend 2013) 

A smaller study from Holland compared a group of 133 children with cCMV (symptomatic and asymptomatic) to a group of 274 children without cCMV. They found that developmental delays were diagnosed more often in cCMV-positive children than cCMV-negative children in the following areas: movement, ability to learn, and speech and language. There was no significant difference in rates of neurodiversity (Autism Spectrum Disorder, ADHD) between the two groups although this might be due to the small number of children in the study. (Korndewal 2017)

Visual impairment related to cCMV is a rare complication (approximately 1 in 100). (Korndewal 2017, Townsend 2013) Chorioretinitis (inflammation of the back of the eye), optic atrophy (damage to the nerve connecting the eye to the brain), and cataracts (clouding of the lens in the eye) have all been described in cCMV. (Karamchandani 2022) 

There is limited evidence on eye involvement related to cCMV presenting later in childhood. It is rare if no abnormality is noted shortly after birth but late complications of cCMV are possible, notably visual impairment and strabismus (squint). (cCMV consensus guideline)

There have been two randomised controlled clinical trials informing decision about cCMV treatment. In both trials, treatment was started in the first month of life and only babies born after 32 weeks gestation were included. 

The first, in 2003, enrolled 100 babies with cCMV and signs of CMV disease affecting the nervous system (small head size, changes seen on brain imaging, eye involvement, and/or hearing impairment). Half the patients were treated with six weeks of IV ganciclovir, an antiviral medication, while half did not receive treatment. The data collected were for 42 patients. No baby receiving ganciclovir had hearing deterioration at six months compared with 4 in 10 of the babies who received no treatment. Assessment at one year of age showed that 2 in 10 of those given treatment had deterioration in hearing compared to 7 in 10 of those without treatment. (Kimberlin 2003) 

This suggests that ganciclovir is effective for reducing the risk of hearing deterioration in those with cCMV however its effects may be less pronounced when considering longer term hearing loss outside of the first six months of age.

The second trial, compared six weeks versus six months of oral valganciclovir (a drug which is converted to ganciclovir in the body) in 86 babies with symptomatic cCMV disease. This showed that a six month course was associated with slightly improved hearing and neurodevelopmental outcomes at two years of age. 

The benefit of six months versus six weeks treatment on hearing was more marked when there was CMV disease affecting the nervous system at the start of treatment (small head size, changes seen on brain imaging, eye involvement, and/or hearing impairment) compared to those infants with no nervous system involvement. 

Developmental outcomes were measured using Bayley Scales of Infant and Toddler Development (Bayley III). Infants receiving a six month treatment course showed slightly better language and understanding scores on assessment at two years. Benefits were similar in those with nervous system involvement versus no nervous system involvement at birth. (Kimberlin 2015)

Short-term

There are risks associated with taking ganciclovir or valganciclovir. While on the treatment, your baby may experience reduced white cells (neutrophils) which affects about 2 in 10 babies. This is most likely to occur in the first month of treatment and may require pausing treatment for a short while to allow recovery. Low platelets and liver inflammation can also occur in about a third of babies. These problems can be easily managed by temporarily stopping treatment to allow recovery, before restarting. 

Long-term

The long-term risks are less well understood. There is no long term follow up data on use of ganciclovir or valganciclovir in babies with cCMV. We know from animal studies that fertility and long-term risk of cancers may be affected, but we do not know whether, or how, this applies to humans. (FDA Valacyte leaflet)

Treatment of premature babies

Evidence of benefit from randomised controlled trials is only available for treatment started in infants over 32 weeks gestation. (Kimberlin 2003, 2015) There is little evidence to guide decisions about treatment of preterm infants and advice will vary depending on the exact circumstances. Your team will discuss with you in detail to reach a decision. 

Treatment of older babies or children

Evidence of benefit from randomised controlled trials is only available for treatment started in the first month of life, in infants over 32 weeks gestation. (Kimberlin 2003, 2015) We do not, therefore, know if treatment outside this period is beneficial. In some circumstances, particularly where the infant is not much more than one month old, treatment will be considered. Your team will discuss this with you in detail.

The two trials looking at treatment for cCMV recruited only patients who had symptoms of cCMV at birth therefore we do not have any evidence for the effectiveness of antiviral medication on those babies born with cCMV who show no signs or symptoms at birth. This is an area of research that we hope to prioritise in the future.

We need further evidence about congenital CMV infection to help us make decisions about which babies to treat, for how long, and to understand the longer-term risks both of infection and of treatment. A registry is open, to allow collection of data about babies with cCMV and help increase understanding about these issues. Your team will discuss this with you and ask whether you are happy to enrol your baby in this registry. 

To find out more, visit our page: 'What to Expect After Congenital Cytomegalovirus Diagnosis'.

Bartlett AW, McMullan B, Rawlinson WD, Palasanthiran P. Hearing and neurodevelopmental outcomes for children with asymptomatic congenital cytomegalovirus infection: A systematic review. Medical Virology 2017; 27(5) 

Consensus Guideline for the diagnosis and management of congenital cytomegalovirus infection. August 2015 

Karamchandani U, Ahmed U, Rufai SR, Tan N, Tan W, Petrushkin H, Solebo AL. Long-term ocular and visual outcomes following symptomatic and asymptomatic congenital CMV infection: a systematic review protocol. BMJ Open. 2022 May 18;12(5) 

Kimberlin DW, Lin CY, Sánchez PJ, et al.; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003;143:16–25. 

Kimberlin DW, Jester PM, Sánchez PJ, et al.; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372:933–943. 

Korndewal MJ, Oudesluys-Murphy AM, Kroes ACM, van der Sande MAB, de Melker HE, Vossen ACTM. Long-term impairment attributable to congenital cytomegalovirus infection: a retrospective cohort study. Dev Med Child Neurol 2017;59:1261–8. 

Pass RF, Fowler KB, Boppana SB, et al. Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J Clin Virol 2006;35:216– 220 

Townsend CL, Forsgren M, Ahlfors K, et al, Long Term Outcomes of Congenital CMV Infection in Sweeden and the United Kingdom. Clinical Infectious Diseases 2013;56(9):1232–9 

Valcyte Safety Data. Available online  

Yinon Y, Farine D, Yudin MH; Screening, diagnosis, and management of cytomegalovirus infection in pregnancy. Obstet Gynecol Surv, 2010. 65(11)

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