Congenital cytomegalovirus screening by dried blood spot: a systematic review

Congenital human cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss and neurological sequelae in children. Although newborn screening strategies remain controversial, dried blood spots (DBS) collected for routine metabolic screening have been proposed as a low-cost method for large-scale detection. This systematic review assessed studies that evaluated the accuracy of DBS testing for screening newborns for cCMV infection. A systematic review was conducted following the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy and reported in accordance with PRISMA-DTA. The PIRT strategy included the following: Population (newborns undergoing screening for cCMV), Index test (detection of cCMV using DBS samples), Reference standard (confirmatory testing using saliva or urine PCR collected within 21 days of life), Target condition (cCMV infection). Searches were performed in PubMed/MEDLINE, Scopus, Bireme, Embase, LILACS, SciELO, and CENTRAL. The search identified 365 articles; after removing 210 duplicates, 155 were screened by title and abstract, and 9 studies were included. The included studies tested between 1174 and 551,034 DBS samples each. Confirmatory testing used PCR in urine (seven studies) or saliva (two studies). Three studies used paired samples for screening; sensitivity ranged from 28.3% to 79.3%, specificity from 99.9% to 100%. Positive predictive value (PPV) ranged from 39 to 100%, and negative predictive value (NPV) from 99.6% to 99.9%.

Neonatal screening for congenital cytomegalovirus using DBS samples is promising, since it would allow early identification for timely interventions to reduce sequelae.

• Congenital CMV is a leading cause of sensorineural hearing loss and neurodevelopmental sequelae, with many cases asymptomatic at birth. Diagnosis relies on early viral detection, and while saliva/urine PCR is sensitive, newborn screening lacks consensus and feasibility is unknown in many settings.

• DBS PCR emerges as a scalable, feasible low-cost screening alternative for cCMV screening. A few states in the USA and provinces in Canada have implemented newborn cCMV screening programs using DBS, but the sensitivity appears lower than in research studies. Improving DNA extraction and PCR methods are required as well as assessing feasibility of using other specimens (e.g., urine or saliva) for screening.