Background The natural history of congenital CMV infection is scarcely known in populations with high maternal CMV seroprevalence. This study evaluated birth prevalence, clinical findings at birth, and hearing outcome in infected children from such a population. Methods Infants consecutively born were screened for the presence of CMV in urine and/or saliva within the first two weeks. Neonatal clinical findings were recorded and infected children were tested to document hearing function during follow-up. A subset of mothers of infected infants was prenatally tested for the presence of anti-CMV IgG antibodies. Results Congenital CMV infection was confirmed in 87/8047 infants (1.08%; 95%CI: 0.86–1.33). Seven (8.1%; 95%CI: 3.3–15.9) infants had at least one clinical finding suggestive of CMV infection and 4 (4.6%; CI95%: 1.3–11.3) had ≥ 3 findings of systemic disease. Sensorineural hearing loss was found in 5/58 (8.6%; CI95%: 2.9–19.0) children tested at a median age of 21 months. Bilateral profound hearing loss was observed in two children and hearing threshold was >60 dBHL in all five children with hearing loss, including two children born to mothers with probable non primary CMV infection. Conclusions The results of this first large newborn screening study in a population with high CMV seroimmunity provide additional evidence that congenital CMV disease occurs in populations with high seroprevalence rates with a similar incidence of CMV-related hearing loss to that reported in offspring of women from populations in the developed countries with lower rates of seroimmunity to CMV.

Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.

Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congenitally infected infants. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with ∼25% of the genome being devoid of polymorphisms. These low diversity regions were distributed across 26 loci that were preferentially located in DNA-processing genes. Furthermore, by developing, to our knowledge, the first genome-wide mutation and recombination rate maps for HCMV, we show that genomic diversity is positively correlated with these two rates. In contrast, median levels of viral genomic diversity did not vary between putatively single or mixed strain infections. We also provide evidence that HCMV populations isolated from vascular compartments of hosts from different continents are genetically similar and that polymorphisms in glycoproteins and regulatory proteins are enriched in these viral populations. This analysis provides the most highly detailed map of HCMV genomic diversity in human hosts to date and informs our understanding of the distribution of HCMV genomic diversity within human hosts.human cytomegalovirus | HCMV | congenital CMV | virology | evolution

Background The burden of CMV-associated sensorineural hearing loss (SNHL) in populations with CMV seroprevalence approaching 100% is unknown. The purpose of this study was to assess the rate, associated factors and predictors of SNHL in CMV-infected infants identified by newborn screening in a highly seropositive maternal population. Methods Newborns with positive saliva CMV-DNA and confirmed by virus isolation in the first two weeks of life were enrolled in a prospective follow-up study to monitor hearing outcome. Results Of 12,195 infants screened, 121 (1%) were CMV-infected and 12 (10%) had symptomatic infection at birth. Hearing function could be assessed in 102/121 children who underwent at least one ABR testing at a median age of 12 months. SNHL was observed in 10/102 (9.8%; 95%CI: 5.1–16.7) children. Median age at the latest hearing evaluation was 47 months (12 to 84 months). Profound loss (>90dB) was found in 4/5 children with bilateral SNHL while all 5 children with unilateral loss had moderate to severe deficit. The presence of symptomatic infection at birth (OR 38.1; 95%CI: 1.6– 916.7) was independently associated with SNHL after adjusting for IUGR, gestational age, gravidity and maternal age. Among 10 infants with SNHL, six (60%) were born to mothers with non-primary CMV infection. Conclusions Even in populations with near universal immunity to CMV, congenital CMV infection is a significant cause of SNHL demonstrating the importance of CMV as a major cause of SNHL in children worldwide. As in other populations, SNHL is more frequently observed in symptomatic CMV infection.

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Close monitoring of HIV-1-exposed infants, especially those who are anemic at birth or whose mothers have more-advanced HIV-1 disease or who smoked during pregnancy, remains important.

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The frequency of congenital CMV infection in preterm newborn infants from mothers with a high seropositive rate was similar to that found in term infants. No significant difference was found between the proportion of symptomatic infants among preterm and term infants. Our finding of symptomatic congenital CMV infection underscores the need of further evaluation of correlates of congenital symptomatic infection in highly immune populations.