Abstract / Summary
The purpose of this research was to evaluate the implementation and relative diagnostic accuracy of dried blood spot (DBS) and dried saliva spot (DSS)-based newborn screening for congenital cytomegalovirus infection (cCMV). This prospective paired-sample pilot studied consecutive births at 10 centers using DBS and DSS specimens from 12 February 2024 to 31 May 2025, using laboratory-developed qPCR assays. Newborns who screened positive on either specimen were offered urine qPCR confirmatory testing. Among 45,597 births, 39,047 newborns (86%) had satisfactory results in both specimens. Of the 150 newborns who screened positive, 39 underwent confirmatory urine testing within 21 days of life, and 24 had cCMV. As a percentage of DBS sensitivity, DSS screening displayed a non-significant relative sensitivity (rSe) of 109% [95CI: 97–123%]. The DSS relative false positive rate was 700% [95CI: 175–2795%] the DBS rate. Each newborn with cCMV identified by DSS but not DBS was associated with 6 additional false positives [95CI: 1.32–27.3]. Calculating rSe including newborns with urine CMV qPCR confirmation after day 21 showed DSS to be 128% [95CI: 111–147%] more sensitive than DBS. In this pilot of DSS screening for cCMV, DSS did not significantly increase sensitivity for cCMV and had an increased false positive rate. Screening with DSS extended turnaround times. Often, DSS screening for cCMV was not achieved within timeframes necessary to offer newborns a definitively diagnostic test to confirm congenital infection. The performance profile of DSS-based screening did not support population-wide implementation of DSS in our program.