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Congenital Cytomegalovirus Infection


A baby is born on the labour ward at 39 weeks gestation. Their weight and head circumference are both on the smaller side (standard deviation of -2 for the gestational age), but they are otherwise well, and their physical examination is unremarkable.

The mother tells you there were no problems during pregnancy. Could they have congenital CMV?

The nurse asks you: “Should we collect some urine for CMV testing?”

Congenital cytomegalovirus (CMV) is the most common infection-related cause of fetal growth retardation and the most common congenital viral infection worldwide.

In developed countries, around 1 in 100-200 babies are born with congenital CMV, while the number may be higher in low-income countries. Around one-fifth of those affected develop long-term health problems, of which hearing loss is the most common.

What are the consequences of congenital CMV?

CMV, also known as human herpesvirus 5 (HHV-5), can be transmitted through bodily fluids such as urine, saliva, blood, and breast milk.

CMV is common; studies suggest that most adults have been infected with it at some point.

During pregnancy, maternal CMV infection can cause spontaneous abortion, intra-uterine death, hydrops fetalis, and foetal growth restriction. It can also cause severe problems in immunocompromised patients, such as HIV-positive individuals and transplant recipients.

Most babies with CMV do not have symptoms.

What are the symptoms of congenital CMV?

Symptoms present at birth include:

  • Babies can be small for gestational age or have experienced fetal growth retardation during pregnancy.
  • Microcephaly: this is also a negative prognostic factor as children with microcephaly are more likely to have neurological symptoms
  • Hepatosplenomegaly
  • Jaundice
  • Thrombocytopenia
  • Petechiae
  • Blueberry muffin rash
  • Eye problems: especially chorioretinitis, strabismus, optic atrophy, haemorrhage in the retina, and cataracts.
  • Intra-cerebral calcifications, most often periventricular
  • Sensorineural hearing loss, either unilaterally or bilaterally
  • (Possibly) biliary atresia

These symptoms can closely resemble congenital Rubella. Some babies, especially those born pre-term, have fulminant disease at birth. Their mortality is around 20-30%.

If CMV is acquired after delivery, pre-term babies may alsorun a more severe course.

What are the long-term consequences of congenital CMV?

In the long term, congenital CMV can cause:

What are the risk factors for congenital CMV?

The following factors increase the risk of acquiring congenital CMV:

  • Families with young children (under the age of five) or contact with young children
  • Lower socio-economic class, especially in the case of crowded homes
  • Poor hygiene practices
  • A primary (first) CMV infection in the mother; 1-3% of women experience a primary CMV infection during their pregnancy, with younger age, having multiple sex partners and maternal HIV seropositivity being significant risk factors. The chance for the fetus to acquire congenital CMV is 35% in the first trimester, 40% in the second, and 75% in the third. Symptoms are often more severe if the infection occurs in early pregnancy.
  • Secondary infection in the mother: The chances of acquiring congenital CMV are around 0.5-1.5% if the mother has been infected before. Because of the high prevalence of CMV in the general population, congenital CMV is more likely to have arisen due to (an often relatively asymptomatic) re-infection than primary infection.

How do we diagnose CMV?

It can be hard to decide who to test for CMV infection. High-quality prospective studies are lacking.

Maternal infection during pregnancy (primary or reinfection) is the strongest predictor of congenital infection.

Symmetric fetal growth retardation (with both weight and head circumference being low) is sometimes quoted in the literature as a sign of congenital cytomegalovirus, but this has not been adequately studied.

A urine PCR is the clinical standard. Testing should be done within 21 days of birth to differentiate congenital from acquired infection. You can also test saliva, but urine PCR should be used as a confirmatory test if the saliva test is positive. CMV serology is of minimal value, just like with other herpes viruses.

If they have CMV, what other tests should we do?

If the diagnosis is confirmed, perform the following:

  • Blood count, liver function, and renal function testing
  • Brainstem-evoked response audiological testing (otoacoustic emission testing is not sensitive enough to detect central auditory hearing loss such as seen in congenital CMV)
  • Ophthalmic assessment
  • A brain ultrasound
  • A brain MRI if the brain ultrasound has abnormalities or if there are neurological abnormalities during physical examination. A brain MRI is performed regardless of the result of the cranial ultrasound in some countries.
  • One should consider performing a quantitative PCR in blood to investigate the viral load, as a lower viral load is associated with better outcomes.
  • Lumbar puncture should not be performed routinely.

Repeated audiology testing should be performed in CMV-positive infants until the age of six, as hearing loss can develop later on in life.

If they present late with features suggestive of congenital CMV, think about using their stored dried blood spot (Guthrie) cards to make a retrospective diagnosis. Remember, though, that a negative result does not completely rule out the diagnosis. and it is not universally available.

Some countries use buccal swabs or Guthrie blood spots for universal CMV screening, but this is controversial. The vast majority of CMV-positive babies are completely unaffected.

Can we treat congenital CMV?

The evidence base for congenital CMV treatment is rather slim. It is generally agreed that one should treat those with evidence of symptoms or laboratory findings (that cannot be explained otherwise). There is just one clinical study that suggests it is effective to treat patients with isolated hearing loss.

First-choice treatment is oral valganciclovir. Children usually require six months of treatment – trials are underway to investigate whether this treatment duration can be lowered. If valganciclovir is not tolerated or not feasible, you can use intravenous ganciclovir.

Common side effects of both valganciclovir and ganciclovir include neutropenia (20-60%) and thrombocytopenia. Ganciclovir can also produce hepatotoxicity. Most local guidelines include regular assessments of blood counts and liver function tests because of this.

There are lots of attempts to develop a CMV vaccine underway. Most of these efforts are aimed at pregnant women and immunocompromised people.

A clean slide with an illustrarion of bubbles on it showing two key take home points to think about when considering congenital CMV infections.


Barlinn R et al. Maternal and congenital cytomegalovirus infections in a population-based pregnancy cohort study. APMIS 2018;126:899-906,

De Vries JJC et al. Congenital cytomegalovirus infection in the Netherlands: birth prevalence and risk factors. J Med Virol 2011;83:1777-82.

Dollard SC et al. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol 2007;17:355-63.

Emery VC and Lazzarotto T. Cytomegalovirus in pregnancy and the neonate. F1000 Res. 2017;6:138.

Faraci M et al. Fetal Growth Restriction: Current Perspectives. J Prenat Med 2011;5:31-3.

Fleisch B et al. Knowledge gaps and emerging research areas in intrauterine growth restriction-associated brain injury. Front. Endocrinol 2019;10:188.

Jansen MAE et al. Determinants of ethnic differences in cytomegalovirus, Epstein-Barr virus, and herpes simplex virus type 1 seroprevalence in childhood. J Ped 2016;170:126-34.

Kimberlin DW et al. 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.

Kliegman R (editor). Nelson textbook of pediatrics. Edition 21. Philadelphia, PA: Elsevier, 2020.

Korndewal MJ et al. Disease burden of congenital cytomegalovirus infection at school entry age: study design, participation rate and birth prevalence. Epidemiol Infect 2016;144:1520-7.

Korndewal MJ et al. Long-term impairment attributable to congenital cytomegalovirus infection: a retrospective cohort study. Dev Med Child Neurol 2017;59:1261-8.

Levit Y et al. Assessment of risk indicators for targeted cytomegalovirus screening in neonates. Neonatology 2020;117:750-5.

Luck S et al. Congenital cytomegalovirus: a European expert consensus statement on diagnosis and management. Ped Inf Dis J 2017;36:1205-13.

Park HW et al. Incidence of postnatal CMV infection among breastfed preterm infants: a systematic review and meta-analysis. J Korean Med Sci 2021;36:e84

Rozhnova G et al. Short- and long-term impact of vaccination against cytomegalovirus: a modeling study. BMC Med 2020;18:174.


  • Marijn is a resident in paediatrics at the Sophia Children's Hospital in Rotterdam, the Netherlands. He is interested in infectious diseases, neonatology, and acute medicine. In his free time he likes to play tennis, read books, and worship his two cats.



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