Newborn jaundice and kernicterus—health and societal perspectives

Kernicterus, a preventable injury to the brain from severe neonatal jaundice, has re-emerged in the United States as a public and societal health concern. Kernicterus, in its usually recognized form, causes devastating disabilities, including athetoid cerebral palsy and speech and hearing impairment. This condition not only ranks amongst the highest cost per new case (per CDC’s Financial Burden of Disability study, 1992), but also results in profound and uncompromising grief for the family and loss to siblings of healthy, talkative playmates. And for the child with kernicterus (usually remarkably intelligent, but trapped in an uncontrollable body), grief and frustration are enormous. In 2001 national healthcare organizations, including Centers for Disease Control (CDC), the Joint Commission for the Accreditation of Healthcare Organizations (JACHO) and the American Academy of Pediatrics (AAP) issued alerts to all accredited hospitals and public health professionals in the United States that all healthy infants are at potential risk of kernicterus if their newborn jaundice is unmonitored and inadequately treated. The re-emergence of kernicterus in the United States is the result of interacting phenomena including (a) Early hospital discharge (before extent of jaundice is known and signs of impending brain damage have appeared); (b) Lack of adequate concern for the risks of severe jaundice in healthy term and near newborns; (c) An increase in breast feeding; (d) Medical care cost constraints; (e) Paucity of educational materials to enable parents to participate in safeguarding their newborns; and (f) Limitations within in healthcare systems to monitor the outpatient progression of jaundice. A multidisciplinary approach that encompasses both healthcare and societal needs should be evaluated at a national level for practical and easy to implement strategies. An approach that is based on principles of evidence-based medicine, patient-safety and family centeredness is presented in this article. These strategies should also be based on public awareness campaign such that the healthcare providers can attempt to achieve a “Zero Tolerance of Kernicterus” and thereby decrease both childhood disabilities and infant mortality within the community.     

Effect of publication of the "Practice Parameter for the management of hyperbilirubinemia" on treatment of neonatal jaundice

The aim of this study was to evaluate the change in the treatment of neonatal jaundice following introduction of the "American Academy of Pediatrics' Practice Parameter for the management of hyperbilirubinemia in the healthy term newborn". In a historical control observation cohort study, we examined the rate of phototherapy and exchange transfusions among full-term (> or = 37 wk gestation) and near-term (gestational age between 35 and 37 wk and birthweight > 2000 g) infants in two community hospitals. The study included all consecutive infants born during two 15-mo study periods immediately before and after the introduction of the new guidelines. Data were prospectively recorded in a computerized database. The rate of phototherapy significantly decreased in the second study period from 7.9% (514/6499) to 2.9% (251/8650) (p < 0.0001) among full-term infants, and from 20.9% (102/489) to 9.4% (47/502) (p < 0.0001) in near-term infants. The use of exchange transfusion was significantly higher (p < 0.001) in the first compared to the second period: 0.2% (15/6499) vs 0.03% (3/8650). A significant decrease was found when the data from each hospital were analyzed separately. CONCLUSION: A significant decrease in the use of phototherapy and exchange transfusion occurred after the publication of the new practice parameters. This trend was observed for both term and preterm newborns, although the new guidelines were not intended for infants born before term.     

MRI在新生儿核黄疸诊断及随访中的价值

目的探讨MRI在新生儿核黄疸中的应用价值。方法选择21例经临床确诊为核黄疸的足月新生儿进行高场MRI检查。年龄2~11天,平均6.2天。对其中的8例患儿于3个月以后进行随访和复查MRI。MRI采用Philips Intera Achieva 3.0T超导型磁共振扫描系统,扫描图像包括T1 WI、T2 WI和DWI,两名放射科医师采用单盲法分析MR图像。结果①21例核黄疸的足月新生儿中有19例(19/21)T1 WI上双侧苍白球信号对称性增高,2例信号未见改变。②8例核黄疸患儿3个月以后随访和复查MR,其中有6例出现脑后遗改变,均显示T2 WI上双侧苍白球对称性高信号,另外2例信号未见改变,临床症状表现轻微。③上述病例DWI上信号均未见特殊改变。结论MRI T1 WI及T2 WI在本病的诊断及预后判定方面有重要的价值。     

MRI在新生儿核黄疸诊断中的应用

目的 探讨新生儿核黄疸的MRI表现,为临床诊断与随访提供客观的影像学依据. 方法 21例具有典型临床表现的核黄疸患儿在生后接受了头部高场MRI检查,场强为1.5 Tesla,扫描序列包括T1WI,T2WI和DWI,2名不知被检者病史的放射科医师分析MRI 结果.结果 21例新生儿生后2～11天首次MRI检查有19例(约占90.5%)TIWI上双侧苍白球信号对称性增高(其中3例3个月后复查MRI显示T2WI上双侧苍白球对称性高信号),另外2例(约占9.5 %)信号未见改变.上述病例DWI上信号均未见特殊改变. 结论 新生儿期核黄疸主要表现为T1WI上双侧苍白球对称性高信号;后遗症期核黄疸主要表现为T2WI上双侧苍白球对称性高信号;DWI对诊断核黄疸无帮助.     

Bilirubin encephalopathy: a study of neuronal subpopulations and neurodegenerative mechanisms in 12 autopsy cases

Bilirubin encephalopathy (BE), which includes acute (kernicterus) and chronic (postkernicteric) forms, results from severe neonatal jaundice. In order to investigate neurodegenerative mechanisms in autopsy cases of BE, we immunohistochemically examined expressions of neurotransmitters, neuropeptides, and calcium-binding proteins in the basal ganglia; and deposition of oxidative products. Expression of tyrosine hydroxylase was reduced in the putamen in cases of acute BE, and in the globus pallidus in cases of acute and chronic postkernicteric BE. Methionine-enkephalin expression was reduced in the external segment of the globus pallidus in cases of acute and chronic postkernicteric BE, and immunoreactivity for substance P was severely altered in both internal and external segments in cases of chronic postkernicteric BE. A decrease in the number of parvalbumin-immunoreactive interneurons in the external segment of the globus pallidus was observed predominantly in cases of acute BE, whereas the number of interneurons immunoreactive for calbindin-D28K was reduced in the putamen in cases of chronic postkernicteric BE. Nuclear immunoreactivity for 8-hydroxy-2'-deoxyguanosine was seen in the putamen in half of the BE cases. These findings indicated that the putamen was impaired in BE and the pallidal external segment was also damaged in the acute form of BE, suggesting that oxidative damage to DNA is implicated in lesions of the basal ganglia.     

胎儿胆红素代谢及其与胎儿结局的关系

胆红素代谢对人体有重要作用,游离型胆红素可自由穿过脂膜和血脑屏障等,产生细胞毒性而引发新生儿核黄疸.胎儿胆红素代谢与成人不同,胎儿期肝脏尚未发育成熟,其体内只有少量胆红素可经肝脏转化为无毒的结合型胆红素,大部分是非结合型胆红素以胆红素-白蛋白复合物的形式溶于血浆中,通过胎盘上的胆红素转运载体运送至母体代谢.当胎儿体内胆...     

血清胆红素水平与胆红素脑病MRI表现的相关性分析

【目的】探讨MRI信号改变与高胆红素血症的严重程度的相关性,为胆红素脑病的早期诊断提供客观依据。【方法】432例重度高胆红素血症新生儿[血清总胆红素（TSB）≥342μmol／L）]在黄疸高峰期后接受头部MRI检查,根据TSB峰值将高胆红素血症患儿分为轻度组（342～427．5μmol／L）,中度组（427．5～513μmol／L）和重度组（≥513μmol／L）,分析MRI T1WI苍白球高信号阳性率与TSB水平的关系,并进行统计学分析。【结果】432例重度高胆红素血症患儿中338例苍白球T1WI呈对称性高信号改变（78．2％）,重度组阳性率最高（94．4％,34／36）,中度组和轻度组阳性率分别为80．5％（95／118）,75．2％（209／278）,黄疸程度与苍白球信号改变有密切关系（X2=7．438,P=0．024）;早期新生儿组苍白球信号改变（82．5％,222／269）明显高于晚期新生儿组（71．2%,116／163）,差异有统计学意义（X2=7．697,P〈0．01）。【结论】MRI T1WI苍白球对称性高信号与高胆红素血症的严重程度及日龄密切相关,是新生儿急性胆红素脑病的重要表现特征。     

Neurological dysfunction induced by bilirrubin

Introduction

“Kernicterus” is a term currently used to describe bilirrubin induced brain injury in the neuro-pathological studies. This is a confusing term and nowadays we prefer bilirrubin encephalopathy or bilirrubin induced neurological dysfunction. The clinical signs vary and it is clearly decreasing in prevalence in developed countries.

Material and methods

We review a series of 7 patients with bilirrubin encephalopathy and variable neurological manifestations, who were seen in the Neuropaediatric Department in the last 10 years. Only one patient died in the neonatal period with hyperbilirubinaemia, sepsis and multi-organ failure.

Results

Diverse aetiological factors were related to hyperbilirubinaemia. All patients had clinical symptoms due to hyperbilirubinaemia. Neuroimaging during the neonatal period showed involvement of the nucleus pallidus, with hyperintensity in T1 in the brain MR scan as the most consistent finding. All the patients who survived developed neurological signs and we try to correlate them with biochemical, clinical, neuroimaging and neurophysiological parameters.

Conclusions

An increase in the number of patients with bilirrubin encephalopathy has been observed over the last few years, and we attempt to find out the causes. The increased survival of the low birth weight newborns, the increase in the immigration population and the use of diagnostic neuroimaging contribute to this increase. It is a great challenge for the neonatologist and for neuropaediatricians to prevent its occurrence and to minimise the effects of bilirrubin encephalopathy.     

MRI成像在新生儿核黄疸诊断中的应用价值

目的 探讨MRI常规序列在新生儿核黄疸的诊断价值.方法 回顾性分析我院2014年5月至2016年8月经临床确诊的35例病理性核黄疸新生儿头颅MRI图像.年龄3~25 d,平均14 d.观察患儿双侧苍白球在T1WI、T2WI、T2FLAIR、DWI及ACD图上的信号变化规律.结果 35例病理性核黄疸新生儿中,26例T1WI上双侧苍白球区表现为对称性高信号;5例T1WI表现为双侧苍白球后部对称性高信号,T2WI、T2FLAIR、DWI及ADC图上未见异常改变;另外4例各序列均未见异常信号;5例病理性核黄疸患儿在随后2~3个月随访、复查中出现脑后遗症改变,均表现为双侧苍白球区T2WI对称性高信号,ADC图上呈稍高信号,T1WI、T2FLAIR及DWI上未见异常信号.结论 MRI常规扫描序列T1WI、T2WI及ADC图分别对新生儿病理性核黄疸急性期及后遗症期的诊断及预后判定具有重要价值.