1、THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE新生儿高胆红素血症浙江大学医学院附属儿童医院杜立中2014 兰 州2013新生儿黄疸国际论坛THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE讲课提纲为什么要规范新生儿黄疸的诊治 目前的标准与临床诊治的困惑 中国新生儿黄疸特点AAP的指南我们能完全参考吗？ 急性胆红素脑病现状 保守 vs 积极治疗，哪个更好 ?指南制定的重点方向 用小时胆红素曲线评估 正确地评估高危因素 强调新生儿黄疸的早期筛查和健康宣教
2、强调母乳喂养THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE新生儿高胆红素血症的诊断传统诊断标准 ： （ 足月儿 12mg/dl， 早产儿 15mg/dl）我国足月新生儿血清总胆红素峰值： 1012.1 mg/dl高胆红素血症的负担 :国内 : 25%(34.4%)健康足月儿总胆红素水平大于 13mg/dl美国 : TSB427umol/L(25mg/dl): 1/650-1,000活产婴儿 TSB510umol/L(30mg/dl): 1/10,000THE CHILDRENS HOSPITALZHEJIANG UNIV
3、ERSITY SCHOOL OF MEDICINETHE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINETHE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINETHE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINEAAP指南可以参考的内容相关的定义和处理原则 急性胆红素脑病（ ABE） vs 核黄疸 (临床诊断问题 ) 高胆红素血症定义 : (血清 总 胆红素 ) 显著高胆红素血症 (SHB):TSB
4、胆红素列线图第 95百分位 (17mg)(significant) 严重高胆红素血症 : TSB 20-25 mg/dl (Severe) 极重度高胆红素血症 (EHB):TSB峰值超过 25mg/dL(Extremely) 危险性高胆红素血症 :TSB峰值超过 30mg/dL(Hazardous)强调对出院病人的黄疸筛查和随访 ,提倡母乳喂养THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE我国急性胆红素脑病 /核黄胆现状况研究时段 : 2009.1 2009.12 33家三级医院参加调查 调阅所有出院确诊胆红素脑病或核黄
5、疸患儿的病历资料，记录患儿一般情况、围产期高危因素、伴随疾病、胆红素峰值水平、治疗情况、临床转归等内容结果： 26家医院报告了 343例！胆红素脑病的伴发疾病围产期窒息 35 (10.1%)细菌感染 183 (52.6%)ABO 溶血 104 (29.9%)Rh 溶血 21 (6.0%)G-6-PD 缺陷 33 (9.5%)头颅血肿 31 (8.9%)内脏出血 22 (6.3%)多重因素 149 (42.8%)无明确伴发疾病 31 (8.9%)THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE胆红素脑病的发病估计在没有以人口
6、学为基础的调查的基础上 ,估计实际胆红素脑病发生率是很困难的 中国的出生率 : 1635万 /2012年 3000 家 3级医院 更多的 2级医院 ? 更多的 2级医院 还有很多的胆红素脑病未被认识THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE浙江大学儿童医院数据THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE每年胆红素脑病被诊断病例051015202530351 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
7、19Last 19 years, from 1994 to 2012 (浙江大学儿童医院 )THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE每年胆红素脑病被诊断病例051015202530351 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19Last 19 years, from 1994 to 2012 (浙江大学儿童医院 )THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE每年胆红素脑病被诊断病例05101
8、5202530351 2 3 4 5 6 7 8 9 10Case per year case/1000 admission10 years, from 2003-2012(浙江大学儿童医院 )THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINECharacteristics n=116Gender Male/Female 70/46GA near term / term 16/100Birth weight (g) 3176 453Gestational age (weeks) 38.1 1.6Age at admissio
9、n (days) 5.2 4.3Age at onset of jaundice (days) 2.9 2.0Bilirubin level on admission (mol/L) 442.3 142.4Age at onset of ABE (days) 5.8 3.9Peak bilirubin (mol/L) 486.0 169.4Bilirubin/Albumin ratio (mol/L)/(g/L) 13.3 4.9回顾性调查报 , 2004 to 2011 GA 35 wks 116 例红素脑病(浙江大学儿童医院 )鲍毓 . Hong Kong J Pediatr 2013TH
10、E CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE急性胆红素脑病的原因Bao yu. Hong Kong J Pediatr 2013.18:82-88Causes N (%)Rh incompatibility 7 6.0ABO incompatibility 38 32.8Combined Rh and ABO incompatibility1 0.9G6PD 6 5.2Sepsis or infection 14 12.1Birth trauma 11 9.5Polycythaemia 3 2.6Multiple caus
11、es 3 2.6Unidentified cause 33 28.4THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE胆红素致脑损伤的客观评估THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE胆红素所致脑损伤Acute bilirubin encephalopathy 急性胆红素脑病Chronic bilirubin encephalopathy 慢性胆红素脑病Kernicterus- 核黄疸Bilirubin-induced neurologic dam
12、age 胆红素所致神经损伤Bilirubin-induced neurologic dysfunction (BIND)-胆红素所致神经功能障碍THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE慢性胆红素脑病 (CBE) 指生后第一年已明显的胆红素毒性引起的永久性临床后遗症 CBE =胆红素所致神经损伤 (包括损伤和受伤 ) 核黄疸 - 指胆红素毒性引起的永久性后遗症Pediatrics 2004;114:297-316 CBE =胆红素所致神经损伤 =核黄疸Pediatrics 2004 114:297-316THE CH
13、ILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE胆红素所致的神经功能障碍(BIND)新的名词 指比较隐匿的 (subtle)神经发育功能障碍，而非典型的核黄疸症状经过仔细的评估， BIND常由于胆红素的神经毒性引起BIND-隐匿的 (subtle) 核黄疸THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINEBIND-隐匿的 (subtle) 核黄疸 可以包括下列异常： 感觉和感觉 -运动整合，中枢性听力处理，协调，肌张力 可以导致 :感音障碍失语症听处理紊乱笨拙 和不
14、协调低肌张力共济失调THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE胆红素所致的神经功能障碍(BIND)概念 - BIND (subtle kernicterus) 有争议值得深入研究间接证据提示小脑损伤可能与 BIND有关，特别是早产儿与其他小脑损伤的所致的发育协调紊乱（developmental coordination disorder ， DCD)临床表现有重叠THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE胆红素脑病所致的听力损伤高胆红素血症
15、引起的脑干神经核损害使听力异常 ,包括听力缺失或耳聋听神经病 Auditory neuropathy (AN), 也称为听不同步 auditory dys-synchrony,指 ABR缺失或异常伴正常的内耳测试结果 ,见于高胆红素血症患儿 .在听神经病 ,即使 ABR完全缺失 , 耳蜗微音器反射(cochlear microphonic response) 仍然存在 ,所以人工耳蜗植入有效THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE评估高胆红素血症神经损伤的客观指标典型的急性胆红素脑病的临床表现典型的神经影像改变 (
16、MRI)核黄疸后遗症临床表现T1WI双侧苍白球对称性高信号THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINECoronal T2 weighted MRI at level of basal ganglia on left showing bilateral symmetric high-intensity globus pallidus (GP) signals (arrows) and deep orange staining of GP on coronal section at post-mortem on the
17、rightTHE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE评估高胆红素血症神经损伤的客观指标到目前为止 ,高胆红素血症与一些轻微或隐匿的神经系统异常尚不清楚 ,但应该引起重视 ,包括 :学习障碍 learning disabilities孤独症 autism spectrum disorder多动 ADHD非进行发育延迟 non-progressive developmental delayTHE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE保守 vs 积极治疗THE CHILDRENS HOSPITALZHEJIANG UNIVERSITY SCHOOL OF MEDICINE极低体重儿预防性光疗对极低体重儿预防性光疗可显著降低 NDI Morris BH. NEJM 2008但使 501-750g超低体重儿死亡率增加 5% Morris BH. NEJM 2008早年的 NICHD研究 : 1000g 光疗 , 死亡率增加 19% (Bryla DA. Pediatrics 1986)
