Congenital Cytomegalovirus Infection and Permanent Hearing Loss in Rural North Indian Children

Abstract

Background Congenital cytomegalovirus infection (cCMV) is a leading non-genetic cause of permanent congenital or early-onset hearing loss (PCEHL). Although cCMV rates are high despite near-universal seroimmunity, the contribution of cCMV to PCEHL in the developing world is unclear. Methods Neonates at a rural north Indian hospital were screened for cCMV by saliva PCR and hearing by distortion product otoacoustic emission (DPOAE) testing. CMV positive infants and those not passing newborn hearing screening (NHS) were evaluated by auditory brainstem response to confirm PCEHL. Infants with cCMV and those with PCEHL were tested for mutations within the GJB2 gene. Results Of the 1720 infants screened, 40 (2.3%) did not pass NHS and 20 (1.2%) were CMV positive. ABR testing confirmed unilateral or bilateral PCEHL in 11 (0.64%) children who either did not pass NHS or CMV positive. PCEHL was 20-fold higher in neonates with cCMV (2/20, 10%) than those without (9/1700, 0.5%; p<0.01). None of 11 infants with PCEHL had connexin 26 mutations. Conclusion PCEHL incidence is high in India, with cCMV contributing significantly despite near universal seroimmunity. Our findings also demonstrate the feasibility and the utility of simultaneous newborn screening for both cCMV and hearing loss in a resource-limited setting.

Etiology of Prelingual Hearing Loss in the Universal Newborn Hearing Screening Era: A Scoping Review

“…A total of 20 studies, published from 2004 to 2020, were included in this review. These studies were conducted from 1998 to 2018 and reported data on etiology of hearing loss among children who had undergone UNHS in the following countries: Australia, 10,11 Belgium, 12,13 Brazil, 14 China, 15 Croatia, 16 India, 17 Ireland, 18 Israel, 19 Italy, 20 Japan, 21 Norway, 22 Taiwan, 23,24 United Kingdom, 25 and the United States 26-29 ( Table 1 ). Altogether, the 20 studies included 2149 children with congenital hearing loss, of which 1787 (83.2%) had etiologic investigation.…”

“…12,24 The prevalence of congenital hearing loss ranged from 1.0 to 6.4 per 1000 newborns screened. 17,22 The number of children diagnosed with hearing loss ranged from 6 to 548 ( Table 2 ). 15,24 The proportion of those who had an etiologic investigation ranged from 23% 27 to 100% in 13 studies.…”

“…27 One study investigated mutations in 8 connexin genes and the SLC26A4 gene. 23 CMV PCR testing was performed on saliva and urine 10,14,19 ; saliva, urine, and/or dried bloodspot 11,18,25 ; saliva or urine 24,29 ; saliva 17,26,28 ; urine 24 ; or dried blood spot. 12,13 Two studies also performed CMV viral culture and serology.…”

Vaccination against the human cytomegalovirus

“…The natural history of congenital CMV infection in LMIC has not been well defined except for the data from prospective newborn screening studies in Brazil. These studies demonstrate that the prevalence of CMV-associated hearing loss is similar to that seen in the U.S. and northern Europe [18], [19]. The frequency and severity of other neurodevelopmental sequelae in these populations have not been well characterized.…”

“…A number of studies in populations in resource-limited settings over the past decade have demonstrated that congenital CMV infection is an important cause of childhood morbidity [6], [7], [17], [18], [19]. As a higher prevalence of congenital CMV infection is seen in populations with high and often near-universal seroimmunity, a substantial number of infants born in the LMICs are CMV-infected.…”