高胆红素血症新生儿听力筛查结果与血清胆红素水平的相关性.pdf

Hainan Med J,Aug.2023,Vol.34,No.15海南医学2023年8月第34卷第15期高胆红素血症新生儿听力筛查结果与血清胆红素水平的相关性李丽娟，杨引通，秦燕西安市人民医院(西安市第四医院)耳鼻咽喉头颈外科，陕西西安710004【摘要】目的探讨高胆红素血症新生儿(NHB)听力筛查结果与血清胆红素(SB)水平的相关性。方法回顾性分析2018年2月至2019年2月西安市人民医院耳鼻咽喉头颈外科收治的320例NHB患儿的临床资料。根据SB水平分为轻中度组(SB342 mol/L，n=96)、重度组(342 mol/LSB427 mol/L，n=148)和极重度组(SB427 mol/L，n=76)，采用脑干听觉诱发电位(AABR)和瞬态耳声发射(TEOAE)联合作为初筛检查方法，对于初筛未通过的患儿采用1 000 Hz鼓室声导抗测试进行复筛，比较三组患儿的听力异常率，同时比较黄疸发生时间48 h(n=164)及48 h(n=156)两组间的听力异常率，并采用Pearson相关性分析SB水平与听力筛查结果间的关系。结果重度组及极重度组患儿的SB水平分别为(401.7420.38)mol/L、(458.5926.25)mol/L，高于轻中度组的(328.6410.27)mol/L，同时血清白蛋白(ALB)水平及PH低于轻中度组，差异均有统计学意义(P0.05)；轻中度组患儿初筛及复筛的异常率(8.33%)最低，重度组(21.62%)次之，极重度(34.21%)最高，且极重度组听力异常率高于轻中度组与重度组，差异均有统计学意义(P48 h组的11.54%，差异有统计学意义(P0.05)；经Pearson相关性分析结果显示，NHB患儿的听力异常率与SB水平呈正相关(r=0.578，P0.05)，与黄疸出现时间呈负相关(r=-0.443，P48 h的患儿听力异常率较低，且随着SB水平的升高，黄疸发生时间的提前，NHB新生儿听力异常的风险会随之增加。【关键词】新生儿；高胆红素血症；听力筛查；脑干听觉诱发电位；瞬态耳声发射；血清胆红素；听力异常；相关性【中图分类号】R722【文献标识码】A【文章编号】10036350（2023）15219104Correlation between hearing screening results and serum bilirubin level in neonates with hyperbilirubinemia.LILi-juan,YANG Yin-tong,QIN Yan.Department of Otolaryngology Head and Neck Surgery,Xian Peoples Hospital(XianFourth Hospital),Xian 710004,Shaanxi,CHINA【Abstract】ObjectiveTo investigate the correlation between hearing screening results and serum bilirubin(SB)level in neonates with hyperbilirubinemia(NHB).MethodsThe clinical data of 320 neonates with NHB whowere admitted to the Department of Otolaryngology Head and Neck Surgery,Xian Peoples Hospital from February2018 to February 2019 were retrospectively analyzed.According to SB level,the neonates were divided into mild tomoderate group(SB342 mol/L,n=96),severe group(342 mol/L427 mol/L,n=76).All neonates underwent preliminary screening by auto auditory brainstem response(AABR)combined with transient evoked otoacoustic emission(TEOAE).Those with unqualified preliminary screeningresults were screened again using 1 000 Hz of tympanic tympanometry.The hearing abnormality rate was comparedamong the three groups and between neonates with jaundice onset time 48 h(n=164)and those with jaundice onsettime 48 h(n=156).The relationship between SB level and hearing screening results was analyzed by Pearson correla-tion analysis.ResultsSB levels in the severe group and the extremely severe group were(401.7420.38)mol/L and(458.5926.25)mol/L,which were significantly higher than(328.6410.27)mol/L in the mild to moderate group,whilethe serum albumin(ALB)level and PH were significantly lower than those in the mild to moderate group,with statistical-ly significant differences(P0.05).The abnormal rates of primary screening and re-screening were the lowest in the mildto moderate group(8.33%),followed by the severe group(21.62%)and then the extremely severe group(34.21%),and theabnormal rate of hearing in the extremely severe group was significantly higher than that in the mild to moderate groupand the severe group,with statistically significant differences(P48 h group(P0.05).Pearson correlation analysis results showed that the abnormal rate of hearing was positively correlated with SB level(r=0.578,P0.05),and negatively correlated with jaundice onset time(r=-0.443,P48 h have a lower rate of hearing abnormalities,and with the increase of SBlevel and the advance of jaundice onset time,the risk of hearing abnormalities in NHB newborns will increase.【Key words】Neonate;Hyperbilirubinemia;Hearing screening;Auto auditory brainstem response;Transientevoked otoacoustic emission;Serum bilirubin;Hearing abnormality;Correlation 论著 doi:10.3969/j.issn.1003-6350.2023.15.014基金项目：陕西省西安市科技计划项目(编号：J201802030)。通讯作者：李丽娟(1986)，女，硕士，主治医师，主要研究方向：耳科学，听力学，眩晕疾病，E-mail：。2191海南医学2023年8月第34卷第15期Hainan Med J,Aug.2023,Vol.34,No.15新生儿听力异常是临床常见的一种先天性缺陷疾病，其致病因素较多，包括宫内感染、药物毒性、遗传及高胆红素血症等，其中高胆红素血症新生儿(neo-natal hyperbilirubinemia，NHB)较为常见，且听力异常率较高1-2。既往研究表明由于新生儿的听觉神经中枢对血清胆红素(serum bilirubin，SB)所产生的部分毒性反应敏感度较高，同时新生儿听觉神经系统尚未发育完全，受到相关刺激时易产生异常，且高水平SB会诱发新生儿胆红素脑病的产生，造成听力损伤，并导致新生儿产生听觉神经后遗症，对新生儿的身心健康造成严重影响3-4。由于部分NHB的早期临床症状较为隐匿，若诊断不及时会对患儿听力及语言发育产生不利影响，而在6个月龄内确诊的NHB患儿在经临床干预后的预后水平较好5。已有研究报道对于听力筛查结果异常患儿需进行密切随访，并及时采取针对性策略进行干预，以降低患儿的听力损伤程度6。为深入探究NHB患儿听力筛查结果与SB水平之间的相关性，本研究采用脑干听觉诱发电位(automatic brainstem re-sponse，AABR)和瞬态耳声发射(transient evoked oto-acoustic emission，TEOAE)及1 000 Hz鼓室声导抗测试进行听力筛查，比较不同SB水平以及黄疸出现时间患儿的听力异常率，以期为临床提供指导。1资料与方法1.1一般资料回顾性分析2018年2月至2019年2月西安市人民医院收治的320例NHB患儿的临床资料，其中男性153例，女性167例；日龄128 d，平均(13.455.23)d；出生体质量2.53.8 kg，平均(2.960.41)kg。纳入标准：(1)符合 NHB 相关诊断标准7；(2)无听力异常家族遗传史；(3)无颅内出血及其他感染情况；(4)临床资料完善。排除标准：(1)近期服用过影响SB水平的药物；(2)患儿母亲孕期服用过存在耳毒性的药物；(3)伴有新生儿窒息；(4)临床诊断为先天畸形。本研究已获得医院伦理委员会批准。1.2方法1.2.1分组方法所有NHB患儿入院后监测SB水平，同时给予患儿蓝光照射等退黄治疗，根据出生 2 周时间内的最高 SB 值作为分组标准，将患儿分为轻中度组(SB342 mol/L)、重度组(342 mol/L427 mol/L)。此外，根据黄疸出现时间分为48 h组及48 h组。1.2.2听力筛查方法对所有新生儿出生后48 h至出院前采用AABR和TEOAE进行联合完成初筛检查，对于初筛未通过的患儿于42 d内采用1 000 Hz鼓室声导抗测试进行双耳复筛。当患儿处于安静状态或自然入睡后，取舒适体位。AABR检查：将仪器探头置于患儿的前额，并将探测器放入耳内，给予刺激开始检测，根据仪器自动分析得到检查结果。TEOAE检查：检查开始前清理患儿外耳道处的分泌物，将仪器探头放置于患儿的外耳道处后开始测试。设置参数如下：每秒叠加刺激80次，刺激强度设为85 dB。由仪器判定是否测试通过。1 000 Hz鼓室声导抗测试：采用中耳分析仪，其中探测音选择1 000 Hz，测试时设定起始压力+200 daPa，同时设定终止压力-400 daPa，速度为100 daPa/s，方向选择从正到负，根据得到的曲线图对筛查结果进行判断，正峰型判定为正常，不确定及负峰型判定为异常。1.3观察指标(1)不同程度黄疸患儿的血清学指标：比较轻中度组、重度组及极重度组患儿的SB、血清白蛋白(serum albumin，ALB)及PH水平；(2)不同程度黄疸患儿的听力筛查结果：比较轻中度组、重度组及极重度组的听力异常率；(3)不同黄疸出现时间患儿的听力筛查结果：比较黄疸出现时间48 h组及48 h组患儿的听力异常率；(4)相关性：分析听力异常率与SB水平及黄疸出现时间的关系。1.4统计学方法应用SPSS 18.0统计软件分析数据。计数资料比较采用2检验；计量资料以均数标准差(x-s)表示，多组间比较采用单因素方差分析，两两间比较采用t检验；采用Pearson相关性分析听力异常率与SB水平及黄疸出现时间的关系。以P0.05)，见表1。2.2不同黄疸出现时间患儿的一般资料比较320例NHB 患儿中164例黄疸出现时间48 h，156例黄疸出现时间48 h。两组不同黄疸出现时间患儿的性别、日龄、体质量及住院时间比较差异均无统计学意义(P0.05)，见表2。2.3不同程度黄疸患儿的血清学指标比较重度组及极重度组患儿的SB水平明显高于轻中度组，ALB水平及PH则明显低于轻中度组，差异均有统计学意义(P0.05)，见表3。表1 不同程度黄疸患儿的一般资料比较例(%)，x-sTable 1Comparison of general information among neonates withdifferent severity of jaundice n(%),x-s例数9614876组别轻中度组重度组极重度组2/F值P值男50(52.08)75(50.68)28(36.84)女46(47.92)73(49.32)48(63.16)4.8540.088日龄(d)13.315.1413.475.2213.585.360.0590.943体质量(kg)3.020.512.980.492.850.372.9860.052住院时间(d)7.022.017.142.066.721.891.1050.332性别2192Hainan Med J,Aug.2023,Vol.34,No.15海南医学2023年8月第34卷第15期2.4不同程度黄疸患儿的听力筛查结果比较轻中度组患儿初筛及复筛的异常率最低，重度组次之，极重度组最高，且极重度组听力异常率高于轻中度组与重度组，差异均有统计学意义(P48 h组，差异有统计学意义(P0.05)，见表5。2.6听力筛查结果与SB水平及黄疸出现时间的相关性经Pearson相关性分析结果显示，NHB患儿的听力异常率与SB水平呈正相关(r=0.578，P0.05)，与黄疸出现时间呈负相关(r=-0.443，P48 h。比较不同SB水平患儿的血清学指标发现，重度组及极重度组患儿的SB水平明显高于轻中度组，同时ALB水平及 PH 明显低于轻中度组(P0.05)，说明高水平SB患儿会伴随一定程度的低蛋白与酸中毒现象。这是因为高SB水平的患儿由于血脑屏障正常的通透性受到损伤，引起低蛋白及PH降低，从而会进一步加重患儿的听觉相关通路损伤。此外，听力筛查结果显示，轻中度组患儿初筛及复筛的异常率最低，重度组次之，极重度组最高，且极重度组听力异常率明显高于轻中度组与重度组(P48 h 组(P0.05)，经 Pearson 相关性分析结果显示，NHB患儿的听力异常率与SB水平呈正相关，与黄疸出现时间呈负相关(P48 h的患儿听力异常率较低，且随着SB水平的升高，黄疸发生时间的提前，新生儿听力异常的风险会随之增加。这与曾超军等14的研究具有一致表2不同黄疸出现时间患儿的一般资料比较例(%)，x-sTable 2Comparison of general information between neonates with different onset time of jaundice n(%),x-s例数164156组别黄疸出现48 h组黄疸出现48 h组2/t值P值男80(48.78)73(46.79)女84(51.22)83(53.21)4.8540.088日龄(d)13.495.1213.415.060.1410.888体质量(kg)2.940.422.980.510.7670.443住院时间(d)6.801.927.202.051.8020.072性别表3 不同程度黄疸患儿的血清学指标比较(x-s)Table 3Comparison of serum indicator levels among neonates withdifferent severity of jaundice(x-s)组别轻中度组重度组极重度组F值P值例数9614876SB(mol/L)328.6410.27401.7420.38a458.5926.25a950.1610.001ALB(g/L)30.373.2125.393.06a22.172.75a162.6290.001PH7.290.317.140.26a7.020.25a21.1340.001注：与轻中度组比较，aP0.05。Note:Compared with that in mild to moderate group,aP0.05.表4不同程度黄疸患儿的听力筛查结果比较例(%)Table 4Comparison of hearing screening results among childrenwith different severity of jaundice n(%)组别轻中度组重度组极重度组2值P值异常17(17.71)44(29.73)28(36.84)例数9614876正常79(82.29)104(70.27)48(63.16)8.2390.016异常8(8.33)32(21.62)26(34.21)正常9(9.38)12(8.11)2(7.14)听力异常8(8.33)32(21.62)26(34.21)17.5180.001初筛复筛11.6700.003表5不同黄疸出现时间患儿的听力筛查结果比较例(%)Table 5Comparison of hearing screening results between neonateswith different onset time of jaundice n(%)组别黄疸出现48 h组黄疸出现48 h组2值P值例数164156异常54(32.93)35(22.44)正常110(67.07)121(77.56)异常48(29.27)18(11.54)正常6(3.66)17(10.90)15.5500.0014.3830.036初筛复筛2193海南医学2023年8月第34卷第15期Hainan Med J,Aug.2023,Vol.34,No.15性。主要原因在于SB水平过高时，NHB患儿颅内神经元处的突触传递过程会受到影响，使得游离在机体的SB进入患儿脑组织后与突触膜相互结合，进而导致突出膜上的部分酶活性降低，使得神经传导过程延长，且代谢过程被抑制，最终引发患儿听力异常15。因此，建议临床密切监测SB水平的变化情况，并对患儿出现黄疸时及时进行针对性退黄处理，这对治疗NHB以及预防听力损伤具有重要意义。综上所述，轻中度NHB及黄疸发生时间48 h的患儿听力异常率较低，且随着SB水平的升高，黄疸发生时间的提前，新生儿听力异常的风险会随之增加，因此临床上应对高SB水平及黄疸发生较早的NHB患儿提高重视程度，积极采取治疗措施，降低听力损伤程度。参考文献1Shen WS,Han M,Sun ZY,et al.Value of amplitude integratedelectroencephalogram in early brain injury and prognosis of neonatalhyperbilirubinemia J.Maternal and Child Health Care of China,2021,36(21):4955-4957.沈文生,韩明,孙智勇,等.振幅整合脑电图预测高胆红素血症新生儿早期脑损伤和预后的价值J.中国妇幼保健,2021,36(21):4955-4957.2 Li F,Zhang DM.Relationship between changes of serum NSE UCB2-MG and BUN levels in neonates with hyperbilirubinemia andseverity of the disease J.Hebei Medicine,2020,26(11):1789-1792.李芳,张冬梅.高胆红素血症新生儿血清NSE 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