Congenital cytomegalovirus — time to diagnosis, management and clinical sequelae in Australia: opportunities for earlier identification

Abstract

Objectives: To report on the burden of disease in Australian infants with congenital cytomegalovirus (cCMV) infection in the era of neonatal hearing screening and improved diagnostic techniques. Design, setting and participants: National data were collected from across Australia via the Australian Paediatric Surveillance Unit (APSU) with monthly reporting by > 1000 clinicians between January 1999 and February 2009. For each reported case, data on investigations and epidemiological and clinical features were analysed. Detailed clinical reviews were performed on 42 infants in two Sydney tertiary paediatric infectious diseases clinics. Results: There were 195 infants with cCMV identified, including 126 definite and 69 probable cases. Of these, 175 (90%) were symptomatic and only 15 were treated with antiviral agents. Identification was delayed beyond 60 days of age in 30 cases (15%). During the period of study, neonatal hearing screening was introduced for most Australian infants. Detection of hearing loss increased from 19% of cCMV cases in 1999–2003 to 31% in 2004–2009. Of 42 infants whose cases were reviewed in detail, 33 (79%) had symptomatic disease. DNA detection of CMV, using polymerase chain reaction testing of newborn screening cards, was useful in retrospective identification, and was strongly correlated with the presence of clinical sequelae (15/18; 83%). Conclusions: Congenital CMV is underdiagnosed, infrequently treated, and often manifests as isolated hearing loss. Delayed diagnoses both before and after the introduction of neonatal hearing screening represent missed treatment and management opportunities and are likely to lead to poorer, life‐long outcomes for these children. Retrospective analysis of newborn screening cards for CMV should be undertaken for infants with sensorineural hearing loss, to identify unrecognised cCMV.

Congenital cytomegalovirus infection is associated with high maternal socio‐economic status and corresponding low maternal cytomegalovirus seropositivity

“…This differs from recent data estimating significantly more cases of congenital CMV (75%) result from non‐primary CMV infection . However, this discrepancy most likely results from the method of case ascertainment used in the APSU programme, which involves recognition by a paediatrician of congenital CMV in young infants, likely biasing cases to those most severely affected . In addition, Wang et al .…”

“…Human cytomegalovirus (CMV) is the leading infectious cause of congenital infection in Australia affecting an estimated 0.64% (0.5–2.2%) of livebirths . Reactivation of latent CMV infection with subsequent fetal transmission precedes a larger number of cases of congenital CMV .…”

Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?

“…For each study, we divided the observed number of symptomatic congenital CMV cases by the expected number of symptomatic cases derived using the appropriate parameters in Table 2. The proportions were 3.8% [47], 12.5% [3], 15.7% [48], and 25.0% [49]. Active clinical surveillance misses some symptomatic cases correctly diagnosed by health care providers; hence, we assigned our parameter the highest percentage (i.e.…”

“…It is a leading cause of childhood hearing loss, cognitive deficit, and vision impairment [2,3]. The number of children with congenital CMV-related disabilities is similar to or greater than the number with better-known conditions such as Down syndrome or spina bifida [4].…”

“…Literature definitions of symptomatic congenital CMV frequently include many children whose symptoms are sufficiently nonspecific that they generally do not prompt the physician to order a CMV test that could lead to a diagnosis of congenital CMV infection. Therefore, in the absence of universal newborn CMV screening, not only asymptomatic infections but also many symptomatic infections go undiagnosed [3]. …”