Feasible alternatives to DBS in the retrospective diagnosis of congenital cytomegalovirus infection

Background: Retrospective diagnosis of congenital cytomegalovirus (cCMV) infection may be challenging mainly because of the high variable sensitivity of PCR on dried blood spots (DBS) samples.

Objectives: To compare cytomegalovirus (CMV) viral load (VL) values in different samples obtained at birth from infants with cCMV infection. To evaluate dried umbilical cord (DUC) samples as an alternative to DBS.

Study design: Saliva and/or urine, peripheral blood (PB), and DBS from 16 infants with confirmed cCMV infection were collected at birth. CMV VL were determined by DNA extraction and real-time polymerase chain reaction (rt-PCR). In two cases, VL was determined from DUC samples.

Results: Six (37.5 %) of the 16 infants were symptomatic, and 10 (62.5 %) were asymptomatic. The CMV VL found in saliva (median: 1,958,525 [IQR: 597,683-3,483,843] IU/mL) and in urine (median: 691,865 [IQR: 188,489.5-3,175,696] UI/mL) were both higher than those found in PB (median: 1115 [IQR: 364-4,002] IU/mL), p: 0.0001). Symptomatic infants presented 100 % of detectable VL in PB and 50 % in DBS. Asymptomatic infants showed 75 % of detectable VL in PB and 30 % in DBS. The VL in DUC were 22,341, 9754 IU/mL and 994 IU/mL.

Conclusions: When VL was detectable in PB, the values were lower than in saliva or urine, in both symptomatic and asymptomatic cases of cCMV. The low sensitivity in DBS samples could be due to low blood volume content, making CMV VL undetectable even when using optimised extraction and PCR protocols. In our limited experience, DUC could play a complementary diagnostic role when DBS VL is undetectable.