| Objective:To explore the risk factors of hearing loss in young infants caused by cytomegalovirus(CMV)infection and to investigate the effectiveness of ganciclovir-based antiviral therapy on hearing loss in young infants with CMV infection.Methods:(1)From January 2015 to December 2017,a total of 153 infants with CMV infection and underwent brainstem auditory evoked potential(BAEP)examination were included in this study.Diagnosis of CMV infection is based on the diagnostic protocol formulated by the infectious digestive group of the Branch of Chinese Medical Association.Infants were separated into hearing loss group and normal hearing group,based on the BAEP results.(2)Details of hearing loss were recorded and compared between groups divided according to birth moment(?28 group,>28?60 group and>60?90 group)and congenital infection or perinatal infection(congenital infection group and perinatal infection group).(3)General information,fetal underlying diseases,details of pregnancy,results of laboratory tests and clinical information were compared between hearing loss group and normal hearing group.Univariate and multivariate logistic regressions were used to analyze the influencing factors and ROC curve was used to analyze the predictive value of risk factors for hearing loss in children with CMV infection.(4)Infants with CMV infection were given antiviral therapy.Those with CMV infection and hearing loss given Ganciclovir as the main management in respect of clinical intervention were formed Ganciclovir group,while others not given Ganciclovir were formed control group.Ganglioside,mouse nerve factor,liver protection and phototherapy were also used as adjuvant therapies.During the treatment,routine blood tests,liver and kidney functions were monitored.BAEP and related therapeutic indexes were reviewed at 6-month old and 12-month old.Efficacy of antiviral therapy during the hospital was analyzed.Results based on BAEP tests were compared between the two groups before and after treatment.Prognosis of the hearing loss of two groups was also evaluated at 6-month old and 12-month old.Results1.Details of hearing loss of infants with CMV infections:A total of 153 children(within 3 months)with CMV infection underwent BAEP.57 children suffered from(37.25%)hearing impairment,with 43 cases(75.43%)bilateral and 14 cases(24.56%)unilateral.Thereinto,42 cases(73.68%)were found with mild hearing impairment,11 cases(19.30%)with moderate hearing impairment and 4 cases(7.02%)with severe hearing impairment.2.Comparisons of hearing loss between groups divided according to birth moment and congenital infection or perinatal infection:40 infants(38.83%),10 infants(27.03%)and 7 infants(53.85%)were found with hearing loss in<28 day group,29?60 day group and 61?90 day group,respectively.Distributions and degrees of hearing loss were not statistically different between the three groups.53 infants(46.09%)were found with hearing loss in congenital infection group,and 4 infants(10.53%)were found in perinatal infection group.Infants with congenital infection were more likely to have hearing loss(including bilateral hearing loss)than those with perinatal infection(P<0.05).Distributions of unilateral hearing loss and degrees of hearing impairment were not significantly different between the two groups.3.Comparisons between hearing loss group and normal hearing group:Comparing with those with normal hearing,gestational age(P=0.007)and birth weight(P=0.038)in infants with hearing loss were significantly smaller,while hospital stay was significantly longer(P<0.001).No significant difference was found in other general information including gender and age.In respect of laboratory tests,incidences of positive CMV-IgM in blood,high CMV-DNA viral load blood and urine,thrombocytopenia and abnormal cranial MRI results were significantly larger in hearing loss group than normal control.In respect of clinical manifestations and complications,incidences of petechiae,brain retardation,cholestasis and combined with malformations in infants with hearing loss were larger than those with normal hearing(P<0.05).4.Analysis of factors related to hearing loss in infants caused by CMV infection:Comparisons showed that incidences of premature birth,low birth weight,long hospital stay,thrombocytopenia,positive CMV-IgM in blood,high CMV-DNA viral load in blood and urine and cholestasis,brain retardation,abnormal cranial MRI results and combined with malformations in hearing loss group were significantly greater than those in normal group(P<0.05).Multivariate logistic regression analysis showed that younger age,premature birth,low birth weight,thrombocytopenia,positive CMV-IgM in blood,and high CMV-DNA viral load in blood and urine were risky factors for hearing loss in infants with CMV infection(OR=1.223,P=0.002,95%CI:1.078?1.388;OR=1.886,P=0.010,95%CI:1.167?3.048;OR=1.629,P=0.001,95%Cl:1.082?2.837;OR=1.779,P=0.001,95%CI:1.135?3.026;OR=2.368,P=0.026,95%CI:1.628?3.391;OR=2.517,P=0.042,95%CI:1.931?3.886)?5.ROC curve analysis of the influencing factors to predict the clinical value of hearing loss in CMV infected infants:Six independent risky factors of hearing impairment in infants with CMV infection were selected.The predictive value of CMV-DNA viral load in blood and urine was the greatest,AUC area was 0.802(95%CI:0.772?0.879)and 0.816(95%CI:0.787?0.886).CMV-DNA viral load in urine had the biggest sensitivity of 85.96%,while CMV-DNA viral load in blood had the best specificity of 79.17%.Conjoint analysis of the six risky factors showed the area of AUC was 0.822(95%CI:0.752-0.893),and the sensitivity and specificity were 73.68%and 80.21%,respectively.6.Results of clinical intervention:Before discharge,CMV-DNA viral load in blood and urine and CMV-IgM in blood were decreased,platelet count was increased,incidences of liver damage,cholestasis,jaundice,gastroenteritis,ecchymosis,anemia,ANC reduction,pneumonia and myocardial damage were decreased(P<0.05),while incidences of hearing impairment,growth retardation and brain retardation did not show significant changes(P>0.05).Proportions of elevated hearing threshold and elevated hearing threshold with abnormal wave in Ganciclovir group were decreased after treatment before discharge(P<0.05),while the BAEP results did not show significant changes in control group.Two of the 57 infants with CMV infection and hearing loss were lost to follow-up at 6-month-old.Compared with pre-treatment,the BAEP results of elevated hearing threshold?prolonged ?,?,? waves latency?poor waveform differentiation?elevated hearing threshold with abnormal waves?elevated hearing threshold with prolongation of?,?,? waves latency?elevated hearing threshold with poor waveform differentiation?elevated hearing threshold with poor waveform differentiation accompanied with prolongation of ?,?,? waves latency were significantly improved(P<0.05)except incidence of elevated hearing threshold with disappearance of ?,?,? waves in Ganciclovir group,while all the BAEP results did not show significant changes in control group.The total effective rate in Ganciclovir group was significantly higher than that in control group(54.77%vs.15.38%during hospitalization,P=0.042,95.24%vs.30.77%at 6 months,P<0.05).The degree of hearing impairment in Ganciclovir group was gradually reduced from pre-treatment to 6-month-old follow-up(P<0.05),while no significant changes in control group.At 12-month old,the prognosis of hearing impairment in Ganciclovir group was significantly better than control group(P<0.05).7.Changes of laboratory parameters at 6-month-old follow-up:Compared with pre-treatment,platelet count was significantly increased and CMV-DNA viral load in blood and urine were significantly decreased at 6-month-old follow-up(P<0.05).8.Drug safety monitoring:During treatment with ganciclovir,9 infants(21.43%)were found with neutrophilic granulocytopenia,6 infants(14.29%)with rise of ALT or AST and 1 infant(2.38%)with thrombocytopenia.However,the above complications disappeared after symptomatic treatment,without withdrawal of ganciclovir.Conclusion:Hearing loss in young infants with CMV infection is affected by many factors,including gestational age,birth weight,thrombocytopenia,high level of IgM in blood,and CMV-DNA viral load in blood and urine.Analysis based on the six risky factors has the greatest predictive value for hearing loss.Ganciclovir could effectively prevent and decrease hearing impairment in infants with CMV infection,with good drug safety. |
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