Urine viral load and correlation with disease severity in infants with congenital or postnatal cytomegalovirus infection

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Abstract

Background

A correlation between cytomegalovirus (CMV) load in urine and severity of disease in congenitally infected infants has previously been reported. CMV load in postnatally infected infants has not been studied before.

Objective

To investigate CMV load in urine of infants with postnatal or congenital infection and correlate this with clinical symptoms of CMV disease and cerebral abnormalities.

Study design

Infants admitted to our NICU between July 2000 and February 2010, and diagnosed with congenital or postnatal CMV infection were included. Clinical symptoms of CMV infection, cranial ultrasonography (cUS) and magnetic resonance imaging (MRI) findings were evaluated. CMV urine loads of postnatally infected infants were analyzed and compared with CMV urine loads of congenitally infected infants.

Results

Seventeen infants with congenital CMV infection and 45 infants with postnatal CMV infection were included. Thirteen/17 (76%) congenitally infected infants had clinical symptoms of CMV infection at birth and 11/17 (65%) had cerebral abnormalities diagnosed by neuro-imaging. None of the four asymptomatic infants had cerebral abnormalities. Of the postnatally infected infants 43/45 (96%) did not develop any clinical symptoms of CMV infection, but in 23/45 (51%) cerebral abnormalities such as lenticulostriate vasculopathy and germinolytic cysts were identified. The median CMV load in postnatally infected infants was significantly lower than in congenitally infected infants (1.0 × 105 copies/ml versus 8.5 × 106 copies/ml, p < 0.001, respectively).

Conclusions

CMV load in urine is significantly lower in infants with postnatal CMV infection than in infants with congenital CMV infection irrespective of clinical symptoms of CMV infection or cerebral abnormalities.

Section snippets

Background

Cytomegalovirus (CMV) is the most common cause of congenital infection in newborns with a reported incidence of 0.2–2%.1, 2 These infants may be at risk of developing neurodevelopmental sequelae, including sensorineural hearing loss (SNHL). Previous studies have shown that high CMV load in blood and urine correlate with symptomatic CMV disease3, 4, 5, 6 and development of adverse sequelae.7 In contrast to congenital CMV infection, acquisition of CMV in the postnatal period, mostly through

Objectives

We aimed to study the relationship between urine viral load in preterm infants with postnatal CMV infection and severity of disease, based on clinical symptoms of CMV disease and cerebral involvement determined by cranial ultrasonography (cUS) and magnetic resonance imaging (MRI). Furthermore, we aimed to compare the CMV urine load of these infants with the CMV urine load of congenitally infected infants.

Congenital CMV infection

From July 2000 until February 2010 all infants diagnosed with congenital CMV infection and admitted to the level 3 neonatal intensive care unit (NICU) of the University Medical Center Utrecht, The Netherlands, were included. Congenital CMV infection was confirmed by positive CMV PCR of urine collected within 2 weeks after birth. Symptomatic congenital CMV infection was diagnosed using CMV PCR of urine when signs and symptoms of CMV infection were present at birth (microcephaly, growth

Congenital CMV infection

Seventeen (eleven term and six preterm) infants were diagnosed with congenital CMV infection (Table 1). Urine was collected shortly after birth in all infants (median age 1 day, range 0–12 days). Thirteen of 17 (76%) infants were symptomatic: growth retardation (2/17), microcephaly (1/17), hepatitis (2/17), hepatosplenomegaly (4/17), petechia (4/17), thrombocytopenia (8/17), neutropenia (1/17), seizures (1/17) and abnormal hearing test at birth (4/17). Eleven of 17 infants (65%) had cerebral

Discussion

Our data are the first showing that CMV load in urine of infants with postnatally acquired CMV infection is significantly lower than CMV load in urine of infants with congenital CMV infection.

Postnatally acquired CMV infection is common among preterm infants who receive breast milk from CMV seropositive mothers.10, 15 Short-term consequences of postnatal CMV infection in these preterm infants have been described previously.9, 10, 11 Long-term consequences of this infection with regard to

Funding

None.

Competing interests

None.

Ethical approval

The Medical Ethics Committee of the hospital approved this study.

Acknowledgements

None.

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