Diagnosing congenital Cytomegalovirus infection: don’t get rid of dried blood spots

Abstract

Background: Congenital Cytomegalovirus (cCMV) is a serious global public health issue that can cause irreversible fetal and neonatal congenital defects in symptomatic or asymptomatic newborns at birth. In absence of universal cCMV screening, the retrospective diagnosis of cCMV infection in children is only possible by examining Dried Blood Spot (DBS) samples routinely collected at birth and stored for different time spans depending on the newborn screening regulations in force in different countries. In this article, we summarize the arguments in favor of long-term DBS sample storage for detecting cCMV infection. Main text: CMV infection is the most common cause of congenital infection resulting in severe defects and anomalies that can be apparent at birth or develop in early childhood. Sensorineural hearing loss is the most frequent consequence of cCMV infection and may have a late onset and progress in the first years of life. The virological diagnosis of cCMV is essential for clinical research and public health practices. In fact, in order to assess the natural history of CMV infection and distinguish between congenital or acquired infection, children should be diagnosed early by analyzing biological samples collected in the first weeks of life (3 weeks by using viral culture and 2 weeks by molecular assays), which, unfortunately, are not always available for asymptomatic or mildly symptomatic children. It now seems possible to overcome this problem since the CMV-DNA present in the blood of congenitally infected newborns can be easily retrieved from the DBS samples on the Guthrie cards routinely collected and stored within 3 days from birth in the neonatal screening program for genetic and congenital diseases. Early collection and long-term storage are inexpensive methods for long-term bio-banking and are the key points of DBS testing for the detection of cCMV. Conclusion: DBS sampling is a reliable and inexpensive method for long-term bio-banking, which enables to diagnose known infectious diseases-including cCMV-as well as diseases not jet recognized, therefore their storage sites and long-term storage conditions and durations should be the subject of political decision-making.

Congenital Cytomegalovirus Infection Burden and Epidemiologic Risk Factors in Countries With Universal Screening

“… 17 Therefore, screening studies based on CMV polymerase chain reaction of dried blood spots will probably underestimate cCMV prevalence, but with improved methods, this form of testing may become more useful. 49 , 104 To assess possible differences in the estimates due to the biological specimens used for screening for cCMV, we conducted subgroup analysis comparing studies that carried out screening using urine and/or saliva samples with those that used only blood or serum. There was a significant difference in the cCMV prevalence rates between the biological specimens used for screening: 0.79% (95% CI, 0.63%-1.00%) for urine or saliva vs 0.31% (95% CI, 0.22%- 0.46%) for blood or serum only ( P < .001 for subgroup differences) (eFigure 3 in the Supplement ).…”

Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment

“…Despite all of this, some authors provided evidence of the high sensitivity of DBS for the retrospective diagnosis of cCMV in children developing neurological sequelae in the first few years of life. Moreover, it is clear that some serious health problems (such as SNHL, cortical development, pachygyria, cholestasis) would have been lessened as a result of DBS retrospective diagnosis [ 71 , 72 ]. Finally, some authors reported the usefulness of DBS to identify children at risk of developing long-term sequelae [ 73 , 74 ].…”

Acute Febrile Illness as a Manifestation of Cytomegalovirus Infection in Extremely Low-Birth Weight Babies—A Case Series

“…In some countries, dried blood spots (DBS) taken in the first week of life for newborn screening are stored and used for retrospective diagnosis of congenital CMV infection even if the baby presents after the perinatal period. 5 However, long-term DBS storage and virological diagnosis from DBS are not feasible in all settings.…”