Congenital Cytomegalovirus Infection as a Cause of Sensorineural Hearing Loss in a Highly Immune Population

Aparecida Y. Yamamoto, MD; Marisa Marcia Mussi-Pinhata, MD; Myriam de Lima Isaac, MD; Fabiana R. Amaral, MD; Cristina G. Carvalheiro, MD; Davi C. Aragon, MSc; Alessandra K. da Silva Manfredi, MSc; Suresh B. Boppana, MD; William J. Britt, MD.


Pediatr Infect Dis J. 2011;30(12):1043-1046. 

In This Article

Patients and Methods

Study Population

Between March 2003 and May 2009, 121 infants with congenital CMV infection were identified from a prospective screening of 12,295 newborns in 2 public hospitals of Ribeirão Preto, State of São Paulo, Brazil. The first maternity hospital (MATER) provides care for low-risk parturients. The second hospital, Clinical Hospital of Faculty of Medicine of Ribeirão Preto, University of São Paulo, not only serves as a referral center for high-risk parturients but also provides care for low-risk parturients. Infants with congenital CMV infection were identified by the detection of CMV DNA in saliva or urine specimens collected within the first 2 weeks of life and confirmed by virus isolation in tissue culture.[8] The study was approved by the Research Ethics Committee of the University Hospital (Processes 4782/2002, and 9145/2004), and written informed consent was obtained from all mothers.

Newborn Evaluation and Definition of Congenital CMV Disease

All infants identified as congenitally infected underwent a clinical evaluation, ophthalmological examination, and computed tomography (CT) scan of the brain. Congenitally infected neonates were classified as small for gestational age (<fifth percentile) or appropriate for gestational age (≥fifth percentile) according to a standard reference curve.[9] Microcephaly was defined as described previously.[7] Infants were classified as symptomatic if they presented with at least one of the following findings suggestive of congenital infection including petechiae, cholestatic jaundice (conjugated bilirubin level >2 mg/dL), hepatosplenomegaly, purpura, microcephaly, seizures, chorioretinitis, or abnormal cranial CT.[7,10] Infants who were small for gestational age were not classified as having symptomatic infection if they did not exhibit any of the typical CMV-related findings.[10]

Audiologic Evaluation

The audiologic protocols consisted of an auditory brainstem evoked response (ABR) testing for all congenitally CMV-infected infants within the first year of age and children younger than 3 years of age. During follow-up visits, pure tone conditioned play audiometry measurement was performed in children older than 3 years of age. The ABR register was performed using a standard protocol after infant's sedation with chloral hydrate when necessary.[11] All infants underwent otoscopic examination to detect middle-ear disorders before testing. The ABR threshold was defined as the lowest level at which the wave V could be detected and replicated. SNHL was suspected when the first ABR test showed air conduction thresholds above 30 dB in an infant with normal middle ear function. Confirmation of SNHL was made after at least 2 ABR evaluations performed on different occasions. A child was considered to have normal hearing when the first ABR threshold was ≤30 db and confirmed by subsequent ABR and/or pure tone audiometry measurements.

In March 2006, a newborn hearing screening program consisting of transient otoacoustic emission (OAE) testing (Accu- Screen, Madsen, Denmark) of all infants born at the study hospital was instituted. The results of the OAE screening test was reported as pass or fail.

Definition of Maternal CMV Infection

Maternal CMV infection was considered primary when a CMV-specific immunoglobulin G (IgG) seroconversion occurred during pregnancy or when the first prenatal serum specimen contained CMV IgG antibodies of low avidity with a subsequent increase in the avidity index in the sample obtained at delivery. Women with CMV IgG antibodies before pregnancy and those with high avidity CMV IgG antibodies without CMV IgM within the first 25 weeks of gestation were classified as having nonprimary CMV infection.[12]

Statistical Analysis

Statistical analysis was performed by logistic regression models using the LOGISTIC procedure of SAS 9.0 statistical package, SAS Institute. Associations between newborn findings, maternal characteristics, and hearing loss were analyzed initially by crude odds ratios (ORs) with 95% confidence intervals for each OR. To avoid confounding effects, multiple logistic regression models were performed simultaneously for each variable and adjusted ORs were calculated to determine the predictors independently associated with hearing loss.


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