Delays in diagnosis and treatment initiation for congenital cytomegalovirus infection - Why we need universal screening

Abstract

IntroductionCongenital cytomegalovirus (cCMV) is the leading cause of neurodevelopmental and hearing impairment from in-utero infection. Late diagnosis results in limited treatment options and may compromise long-term outcome.MethodsA retrospective audit of infants with cCMV referred to a Tertiary Pediatric Infectious Diseases center from 2012–2021. Data collected included timing of diagnostics, treatment initiation and reasons for delays.Results90 infants with confirmed cCMV were included, 46/90 (51%) were symptomatic at birth. Most common reasons for diagnostics in asymptomatic infants were failed newborn hearing screening (17/44, 39%) and antenatal risk-factors (14/44, 32%). Median age at cCMV diagnosis was 3 (range 0–68) and 7 (0–515) days, with median referral age 10 (1–120) and 22 (2–760) days for symptomatic and asymptomatic infants respectively. There was a significant risk of delay in diagnosis (>21 days) for asymptomatic infants [RR 2.93 (1.15–7.45); p = 0.02]. Of asymptomatic infants who received treatment, 13/24 (54%) commenced it within 28 days of life, a significant delay in treatment compared to 30/36 (83%) symptomatic infants [RR 2.75 (1.18–6.43); p = 0.02]. The commonest reason for delayed treatment initiation was delayed first diagnostic test for both symptomatic 4/6 (67%) and asymptomatic infants 9/11 (82%).ConclusionsDelays in diagnosis and treatment for cCMV are unacceptably frequent and significantly higher in asymptomatic infants. Our study highlights the need for increased awareness among healthcare professionals, reconsideration of age-targets for Newborn Hearing Screening, and research that addresses the barriers to implementation of universal screening, which would ultimately facilitate prompt diagnosis and management of all infants with cCMV.

Performance evaluation of fully automated cobas® 6800 CMV PCR for the detection and quantification of cytomegalovirus DNA in neonatal urine and saliva, and adult urine, saliva, and vaginal secretion

“…These include (1) a shorter turnaround time due to the removal of the need to refer samples to, and a delay in receiving results from, reference laboratories, (2) a reduction in the number of user's intervention and risk of errors as samples are pipetted directly from primary containers and processed by fully automated sample‐to‐result processes, and (3) the removal of the need to remove reagents for storage which reduces hands‐on time and prevents contamination (Supporting Information: Table ). These improvements will support a timely management of patients and universal screening for cCMV 12,13 . However, the benefits are contingent on a laboratory access to the cobas® CMV assay and a minimum of 350 µL sample volume, which may not be realistic for some laboratories or patients such as low birth weight infants.…”

“…If implemented, the assay may reduce the delay in initiating antiviral therapy for cCMV, and support a timely management of CMV infection in neonates and adults. 8,12,13 In the context of diagnosing cCMV in neonates, a sensitive and specific test is required. The cobas ® assay was found to be fit for this purpose.…”

“…These improvements will support a timely management of patients and universal screening for cCMV. 12,13 However, the benefits are contingent on a laboratory access to the cobas ® CMV assay and a minimum of 350 µL sample volume, which may not be realistic for some laboratories or patients such as low birth weight infants. In addition, as with all automated solutions, loss of clinical samples is possible due to instrument failure.…”

“…[9][10][11] The need to improve CMV diagnostics to support timely patient management and universal screening has been reported. 12,13 In pregnant women, testing for CMV shedding in urine, saliva, and vaginal secretion not only allows the detection of maternal infection and prediction of the risks of vertical transmission, but may also support early discussion for further investigation and potential medical referral. 5,6,14 Until very recently, a rapid, fully automated, and high throughput CMV test to support clinicians' decision-making and patient management for congenital and prenatal CMV was not available.…”

“…The methodological variations partially have limited the portability and comparison of PCR results 14–16 . In addition, the inefficient laboratory processes and long test turnaround time have contributed to suboptimal patient care 12 . For laboratories that do not have access to a locally validated test (such as ours), samples were referred to reference laboratories for testing which resulted in further delays.…”