Cytomegalovirus (CMV) is a double-stranded DNA virus. For infection during pregnancy, intrauterine transmission may cause a congenital cytomegalovirus (cCMV) infection. cCMV is the most common congenital infection. It might result in sensorineural hearing loss (SNHL) or neurodevelopmental impairment. As such, cCMV has been a major public health problem worldwide for decades.
Being a herpesvirus, CMV can establish a lifelong latency with periods of reactivation. Moreover, different viral strains exist. Consequently, maternal seroconversion can be primary or nonprimary (reactivation of a latent virus or infection with a different strain). The risk of intrauterine transmission is considerably lower in a nonprimary infection compared with a primary infection (1% vs 40%). Once infected, the risk of fetal damage is presumed to be the same. A factor contributing to the severity of disease is timing of maternal seroconversion. Most neurodevelopmental sequelae are associated with seroconversion during the first trimester. Sequelae after a second- or third-trimester infection have also been described, albeit with a lower prevalence.
Congenital CMV infection can be asymptomatic or cause a widespread range of symptoms. Newborns may present with dysmaturity, hepatosplenomegaly, microcephaly, or petechiae. Rarely, retinal or optic nerve abnormalities may be found.
Despite the large amount of research on the occurrence and characteristics of cCMV-related hearing loss, it is still unclear which newborns are at risk of hearing loss at birth. Although researchers previously investigated the importance of clinical symptoms and central imaging anomalies as risk factors for hearing loss, uniformity was difficult to reach, mainly due to small sample sizes. The role of a second- or third-trimester infection and viral load remains contradictory. The aim of the study by Elise De Cuyper et al was to identify independent risk factors for cCMV-related congenital hearing loss and predictors of hearing loss severity at birth.
This cross-sectional study of newborns with cCMV infection used data included in the Flemish CMV registry that was collected from 6 secondary and tertiary hospitals in Flanders, Belgium, over 15 years (January 1, 2007, to February 7, 2022). Data were analyzed March 3 to October 19, 2022. Patients were included in the study after confirmed diagnosis of cCMV infection and known hearing status at birth. Patients who presented with other possible causes of sensorineural hearing loss were excluded.
Primary outcome was hearing status at birth. Clinical, neurological, and laboratory findings along with the timing of seroconversion and blood viral load were separately considered as risk factors.
Of the 1033 newborns included in the study (553 of 1024 [54.0%] boys), 416 (40.3%) were diagnosed with symptomatic cCMV infection and 617 (59.7%) with asymptomatic cCMV infection.
A total of 15.4% of the patients (n = 159) presented with congenital hearing loss; half of them (n = 80 [50.3%]) had isolated hearing loss.
The regression model revealed 3 independent risk factors for congenital hearing loss: petechiae at birth (adjusted odds ratio [aOR], 6.7), periventricular cysts on magnetic resonance imaging (MRI; aOR, 4.6), and seroconversion in the first trimester (aOR, 3.1).
Lower viral loads were seen in patients with normal hearing compared with those with congenital hearing loss
This cross-sectional study based on the data from the Flemish CMV registry identified several risk factors for congenital hearing loss on univariate analyses but only 3 independent factors on logistic regression analyses: petechiae at birth, periventricular cysts on MRI, and timing of seroconversion. Petechiae at birth was associated with the highest risk of congenital hearing loss followed by periventricular cysts on MRI. Seroconversion in the first trimester was associated with a higher risk of congenital hearing loss compared with seroconversion during the second or third trimester. The more of these independent risk factors that are present at birth, the higher the risk of congenital hearing loss.
This cross-sectional study based on data from the Flemish CMV registry found that newborns infected with cCMV with petechiae at birth, periventricular cysts on MRI, or a seroconversion in the first trimester are at higher risk of congenital hearing loss. These risk factors may be used by clinicians to counsel parents in the prenatal and postnatal periods about the risk of congenital hearing loss. The importance of viral load as a risk factor for congenital hearing loss remains unclear.
Source: Elise De Cuyper, Frederic Acke, Annelies Keymeulen; JAMA Otolaryngol Head Neck Surg.
doi:10.1001/jamaoto.2022.4109