Congenital cytomegalovirus infection in Finland

Cytomegalovirus (CMV) is the most common congenital infection in developed countries. Only about 10% of the infected infants have symptoms due to CMV at birth. About half of these symptomatic infants will develop long-term sequelae, such as hearing loss or neurological impairment. Most congenitally infected infants are asymptomatic, and their prognosis is clearly better. The aim of this doctoral thesis was to evaluate the burden of congenital CMV infection (cCMV) in Finland. In the first study, we evaluated the CMV seroprevalence in Finland. We examined CMV antibodies of 200 randomly collected samples from the Finnish Maternity Cohort serum bank at three time points: 1992, 2002, and 2012. The seropositivity rate decreased significantly from 84.5% (95% CI 78.7–89.2) in 1992 to 71.5% (95% CI 64.7–77.6) in 2012. The outcome of symptomatic cCMV infection was evaluated retrospectively from a cohort of 26 children diagnosed in Finnish tertiary hospitals from 2000 to 2012. Long-term sequelae occurred in 58% (15/26), neurologic abnormality in 50% (12/24), and hearing loss in 42% (8/19) of the children. Of the children whose mothers had suffered from primary CMV infections in the first trimester, 86% (6/7) developed long-term sequelae. Of the children whose mothers had experienced non-primary CMV infections during the pregnancy, 64% (9/14) developed long-term sequelae. None of the 5 children whose mothers had had primary CMV infections in the second or third trimester had developed any long-term sequelae. To evaluate the prevalence of cCMV, and the outcome of asymptomatic cCMV, we screened 19,868 infants with a saliva CMV PCR test in four Helsinki area hospitals from September 2012 to January 2015. Confirmed cCMV infection occurred in 40 children, corresponding to a prevalence of 2 in 1,000 (95% CI 1.4–2.6). No differences in the Griffiths Mental Development Scales or hearing outcome could be found between cCMV positive and healthy controls at 18 months age. In addition, no CMV-related findings were detected in the ophthalmologic examinations. Among cCMV positive children, viral shedding to urine was more persistent than to saliva. At 18 months age all urine samples tested (33/33) were positive for CMV culture, but only 24% (9/37) saliva samples had positive CMV PCR. In conclusion, the disease burden of cCMV was relatively low in Finland. The prevalence was only 2 in 1,000, and the outcome of the asymptomatic infants was favourable. However, the morbidity of the symptomatic infection was remarkable. Over half of the infants from the retrospective cohort with CMV-related symptoms at birth developed long-term sequelae. In the positive screening samples, the genotype distribution for CMV glycoproteins gB, gH, and gN was similar to that reported from other populations and does not therefore explain the low burden of the disease in Finland.