Prevalence and Clinical Manifestations of Congenital Cytomegalovirus Infection in a Screening Program in Madrid (PICCSA Study)

Abstract

Background: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Up to 15%–20% of infected newborns will develop long-term sequelae such as hearing loss and neurologic abnormalities. The aim of this study was to investigate the prevalence of congenital CMV infection (cCMV) and associated clinical abnormalities in Spain. Methods: A prospective screening for cCMV by viral load in saliva was performed. Saliva samples were obtained within the first 72 hours of life in a maternity ward in Madrid (Spain), during a 1-year period. All positive screening tests were confirmed with viral load in urine. Clinical, laboratory, auditory, visual and cerebral imaging assessments were performed in all children with cCMV. Results: Of the 4097 neonates born during the study period, 3190 (78%) were included. CMV viral load in saliva was detectable in 24/3190 (0.75%) children, and congenital infection was confirmed in 15/3190 (0.47%, CI 95%: 0.29%–0.77%). Positive predictive value was 62.5% (CI 95%: 46.5%–76.1%). Two infants presented symptoms at birth. Eight (53.3%) children showed abnormalities in magnetic resonance imaging; most of them isolated white matter abnormalities. Newborns with abnormalities in magnetic resonance imaging showed higher viral loads in blood and saliva (P = 0.04). Conclusions: One in 200 neonates born in our hospital presented a cCMV infection. CMV viral load in saliva has been shown to be a simple and highly accepted screening method but should be confirmed by CMV detection in urine. In spite of the fact that half of infected children had abnormalities in cerebral imaging, diagnosis during the neonatal period would have been impossible without a screening program in most cases.

Letter to the Editor on the original article: Lower prevalence of congenital cytomegalovirus infection in Portugal: possible impact of COVID-19 lockdown?

“…The prevalence of cCMV in our study is very similar to that reported in Portugal, and far from the 0.6% that has been described in a meta-analysis in high-income countries [3]. Unfortunately, historical estimates of cCMV to compare with from our region are not available, but a recent study in Madrid reported a 0.47% prevalence rate [4]. It is likely that the lockdown measures and behavioral interventions to reduce SARS-CoV-2 transmission in Spain during 2020-2021 also impacted on CMV transmission and cCMV prevalence.…”

Comparison of detection strategies for screening and confirming congenital cytomegalovirus infection in newborns in a highly seroprevalent population: a mother-child cohort study

“…The kappa value between saliva and urine testing was low (0.31) in a study from Indonesia [30] . Inconsistent saliva and urine results were also reported in studies from Spain and Germany [ 31 , 32 ]. The discrepant results were obtained from populations in different regions, where the dominant infection types (primary infection, reinfection or reactivation) in pregnant women are potentially very different.…”

Maternal CMV seroprevalence rate in early gestation and congenital cytomegalovirus infection in a Chinese population

“…Of these newborns, the majority had a low viral load in saliva or urine. The nonnegligible false-positive result in screening is an issue also reported in other studies [ 19–22 ], which is the reason to recommend confirmatory testing using subsequent samples in the current consensus [ 1 , 23 ]. Herein, we confirmed the newborns’ cCMV status according to the consensus’s suggestion; however the long-term clinical outcomes of these questionable newborns will be followed up in the future to better understand their cCMV status.…”