先天性巨细胞病毒感染gH基因分型与临床特征的关系

Relationship between gH genotyping and clinical characteristics of children with congenital cytomegalovirus infection

目的探讨人巨细胞病毒(HCMV)gH基因分型与先天性巨细胞病毒感染临床特征的关系。方法采用队列研究,选取2013年7月至2015年12月在浙江大学医学院附属儿童医院新生儿科及新生儿重症监护室(NICU)住院确诊为先天性巨细胞病毒感染的21例患儿,检测尿液、痰液或血液HCMV gH基因分型,根据gH基因分型结果将患儿分为gH1组和gH2组。收集患儿新生儿期住院资料和3~5年随访资料。应用χ^2检验、t检验、非参数检验分析gH基因分型与患儿临床表现、实验室检查、听力损失、神经系统预后的相关性。结果21例患儿中gH1型14例(67%)、gH2型7例(33%),未发现混合感染病例。两组男性比例(9/14比3/7,Fisher概率法,P=0.397)、出生体重[(2 609±686)比(3 021±451)g,t=-1.436,P=0.167]差异均无统计学意义。gH1组出生胎龄小于gH2组[38(29~40)比39(38~40)周,Z=-2.18,P=0.029]。40耳(20例)进行新生儿期脑干诱发电位听力测试,gH1组中重度及以上听力损失比例高于gH2组(4/22比0/18,χ^2=5.145,P=0.023)。神经系统影像学检查Alarcon评分gH1组低于gH2组[(0.4±0.3)比(1.3±1.1)分,t=-2.459,P=0.024]。gH2组出现运动或语言发育落后的概率与gH1组差异无统计学意义(4/7比4/14,Fisher概率法,P=0.346)。结论gH1型感染较gH2型感染新生儿出生胎龄小。新生儿期中重度及以上听力损失以gH1型感染为主。gH2型先天性感染患儿出现神经系统损害的可能性较大。

Objective To study the relationship between human cytomegalovirus (HCMV) envelope glycoprotein gene H and clinical features of children with congenital cytomegalovirus infection. Methods A cohort study was conducted. Newborns diagnosed with congenital cytomegalovirus infection, hospitalized in the Department of Neonatology and Neonatal Intensive Care Unit (NICU) of the Children′s Hospital, Zhejiang University School of Medicine, were included from July 2013 to December 2015.HCMV-DNA gH typing in urine, sputum or blood was conducted. Patients then were divided into gH1 group and gH2 group according to gH genotypes. Patients′ data during hospitalization in newborn and 3-5 years of follow-up were collected.The relationships between gH genotype and clinical manifestations, laboratory examinations, hearing loss and neurological prognosis were analyzed by chi-square test, t test and non-parametric test. Results A total of 21 cases were enrolled as congenital HCMV infection and followed-up for 3-5 years. Among them, 14 (67%) were gH1 type and 7 (33%) were gH2 type. No mixed infection was found. In the two groups, there were no significant differences in the ratio of males (9/14 vs. 3/7,P=0.397), or birth weight ((2 609±686) vs.(3 021±451) g, t=-1.436, P=0.167). Gestational age of gH1 group was younger than that of gH2 group (38 (29-40) vs. 39(38-40) weeks, Z=-2.18, P=0.029). Moderate to severe hearing loss detected by neonatal auditory brainstem response were found in 40 ears (20 cases). It was higher in gH1 group than that in gH2 group (4/22 vs.0/18,χ^2=5.145, P=0.023). In the imaging examination of the nervous system, the Alarcon score of gH1 group was lower than that of gH2 group (0.4±0.3 vs. 1.3±1.1, t=-2.459,P=0.024).No significant statistical difference was found in the probability of motor or language development lag in gH2 group and gH1 group (4/7 vs.4/14, P=0.346). Conclusions Compared with gH2 infection, gH1 infection in children has a younger gestational age. The major type of hearing loss in neonatal period is gH1 infection. Children with gH2 congenital infections are more likely to suffer from nervous systems damage.