江苏省13家医院新生儿严重高胆红素血症现状调查

目的 了解江苏省新生儿严重高胆红素血症的发生情况及诊治、随访等管理情况,为新生儿严重高胆红素血症的预防及规范化管理提供依据。方法 以2018年1~12月江苏省13家医院收治的严重高胆红素血症新生儿为研究对象,回顾性分析患儿的临床资料及随访资料。结果 江苏省13家医院2018年严重高胆红素血症新生儿病例共上报740例,占新生儿科收治病例总数的2.70%（740/27 386）,其中重度高胆红素血症620例（83.8%）,极重度高胆红素血症106例（14.3%）,危险性高胆红血症14例（1.9%）;诊断为急性胆红素脑病共4例（0.5%）。484例（65.4%）新生儿于分娩机构出院后因严重高胆红素血症返回医院住院治疗,中位入院日龄为7 d,其中214例（44.2%）再入院前进行过门诊黄疸随访,第1次门诊中位随访日龄为6 d。住院期间行头颅MRI检查211例（28.5%）,其中85例（40.3%）提示双侧基底节、苍白球T1WI信号偏高;行脑干听觉诱发电位检查238例（32.2%）,其中14例（5.9%）仅一侧通过,7例（2.9%）双侧均未通过。急性胆红素脑病或危险性高胆红素血症患儿（共17例）进行了随访,除1例失访外,均无异常神经系统症状。结论 新生儿严重高胆红素血症在新生儿科住院病人中的占比较高;新生儿从分娩机构出院后黄疸监测及管理需要加强;对并发了严重高胆红素血症的患儿,住院期间相关检查需更完善,出院后均需全面系统地随访。     

新生儿出生早期胆红素监测筛查的研究进展

黄疸是新生儿生后早期入院的主要病因之一。严重的新生儿高胆红素血症可能引起急性胆红素脑病或核黄疸,急性胆红素脑病或核黄疸目前尚缺乏有效治疗。通过监测胆红素水平及时发现需要干预的患儿是新生儿高胆红素血症管理的关键。近年来新生儿出生早期胆红素监测在严重高胆红素血症筛查预防、避免核黄疸发生中起到积极作用,但同时也对如何进行筛查及筛查对干预治疗的利弊、经济效益比等提出新的问题。该文旨在对新生儿期胆红素监测筛查的研究进展进行综述,为指导临床合理开展新生儿胆红素筛查及管理提供依据。     

晚期早产儿高胆红素血症危险因素分析

目的探讨晚期早产儿高胆红素血症的危险因素。方法回顾性分析2011年至2012年收治的211例高胆红素血症晚期早产儿和246例非高胆红素血症晚期早产儿的临床资料,分析可能造成晚期早产儿高胆红素血症的危险因素。结果 211例高胆红素晚期早产儿中27例为重症,晚期早产儿高胆红素血症发生与新生儿相关的因素包括:入院时日龄3 d、出生窒息、小于胎龄儿、头颅血肿或明显产伤淤血、低白蛋白血症、红细胞增多症、感染、溶血病、喂养不耐受、胎粪排泄延迟10个变量;与母亲相关的因素包括:来自农村、妊娠高血压综合征(妊高症)及胎膜早破3个变量。以上变量在高胆红素血症和非高胆红素血症晚期早产儿中的差异均有统计学意义(P0.05)。多因素Logistic回归分析显示,出生窒息、胎粪排泄延迟、低白蛋白血症和母亲妊高症为晚期早产儿高胆红素血症的危险因素(OR=2.35~4.05);母亲妊高症和新生儿溶血病是晚期早产儿发生重度高胆红素血症的危险因素(OR=5.74、73.64)。结论出生窒息、胎粪排泄延迟、低白蛋白血症、溶血病及母亲妊高症是晚期早产儿高胆红素血症发生的高危因素。加强妊高症和新生儿溶血病诊治,可减少晚期早产儿重度高胆红素血症的发生。     

胆红素脑病患儿内在因素及外在高危因素分析

目的探讨新生儿胆红素脑病患儿自身伴发疾病及外在高危因素。方法选择2005年1月至2013年12月本院新生儿科收治的胆红素脑病患儿,记录患儿一般情况、围产期高危因素、伴随疾病及外在高危因素。结果 9年间共收治胆红素脑病患儿52例,胎龄(38.3±2.3)周,出生体重(3 013±483)g,入院日龄(6.7±4.3)天,血清总胆红素(543.6±122.7)μmol/L,血清总胆红素/血浆白蛋白(B/A)比值为(0.96±0.15)。52例胆红素脑病患儿中有明确伴发疾病者44例(占84.6%),其中最常见的伴发疾病是新生儿感染,共30例(57.7%),其次为葡萄糖-6-磷酸脱氢酶缺乏症22例(42.3%),有多重伴发疾病19例(36.5%)。有50例患儿存在外在诱因(96.2%),其中26例患儿家属未按要求进行出院3天后随访;12例患儿产科出院时存在高胆红素血症,但家人拒绝住院治疗;10例患儿出院时黄疸程度不重,在家喂服中药或外洗后导致黄疸加重。结论外在高危因素是新生儿发生胆红素脑病的主要原因,根据调查分析结果针对不同高危因素,对新生儿父母进行黄疸危害的宣传,黄疸治疗方法教育、建立规范的随访时间和及时发现感染是减少新生儿胆红素脑病的主要预防措施。     

美国儿科学会最新新生儿黄疸诊疗指南

大多数新生儿可出现黄疸,大部分新生儿黄疸均较轻微,但由于胆红素毒性,严重高胆红素血症可导致胆红素脑病或核黄疸。为减少严重胆红素血症及胆红素脑症或核黄疸的发生,避免医疗资源的浪费,2004年8月美国儿科学会制定了新的新生儿黄疸诊疗指南。该指南强调了成功母乳喂养、黄疸出现时间、黄疸高危因素评估、严密随访和适时干预的重要性,制定了黄疸干预的流程图,提出了一些新的观点,值得我们借鉴。     

新生儿高胆红素血症再入院的现状和危险因素分析

目的 探讨新生儿高胆红素血症再入院情况及相关危险因素。方法 选择2017年1月至2019年12月新生儿高胆红素血症再入院患儿85例作为研究组,按1：2比例在同期新生儿高胆红素血症未再入院病例中配对随机选取170例作为对照组,分析比较两组患儿的临床资料及再入院的危险因素。结果 研究期间新生儿高胆红素血症再入院率为2.30%,中位再入院间隔天数为5 d。研究组首次出院时总胆红素和间接胆红素水平明显高于对照组（P < 0.05）;首次住院期间蓝光治疗时间长于对照组（P < 0.05）。研究组出生体重、胎龄、首次入院时年龄均低于对照组（P < 0.05）,研究组合并葡萄糖-6-磷酸脱氢酶（G-6-PD）缺乏症比例和合并溶血病比例高于对照组（P < 0.05）。多因素logsitic分析显示,胎龄小、首次入院时年龄小、合并G-6-PD缺乏症是新生儿高胆红素血症再入院的危险因素（分别OR=1.792、1.415、2.829,P < 0.05）。结论 对存在胎龄小、首次入院时年龄小、合并G-6-PD缺乏症等高危因素的高胆红素血症新生儿,应加强住院及出院后管理,防止该病再入院的发生。     

早期干预对新生儿高胆红素血症预后的影响

目的　了解早期干预对新生儿高胆红素血症预后及智力发育情况的影响。方法　选取 2 0 0 1年 9月～ 2 0 0 2年 9月在我院出生后出现黄疸住院新生儿高胆红素血症 4 5例为干预组 ;同期外院出生的高胆红素血症住院患儿 4 0例为对照组。两组均按照我国新生儿黄疸治疗推荐方案进行光疗及药物治疗。干预组予早期干预并在治疗期间给予感知觉、运动及语言训练 ,出院后教会家长 ,定期复查。结果　两组患儿 1岁时身高、体质量、头围无明显差异 ,P均 >0 .0 5。智力发育有明显差异　P <0 .0 1。结论　对新生儿高胆红素血症进行早期干预 ,可促进神经系统发育 ,减少胆红素脑病的发生率 ,有利于早期发现脑瘫。     

新生儿高胆红素血症再入院的现状和危险因素分析

目的 探讨新生儿高胆红素血症再入院情况及相关危险因素。方法 选择2017年1月至2019年12月新生儿高胆红素血症再入院患儿85例作为研究组,按1：2比例在同期新生儿高胆红素血症未再入院病例中配对随机选取170例作为对照组,分析比较两组患儿的临床资料及再入院的危险因素。结果 研究期间新生儿高胆红素血症再入院率为2.30%,中位再入院间隔天数为5 d。研究组首次出院时总胆红素和间接胆红素水平明显高于对照组（P < 0.05）;首次住院期间蓝光治疗时间长于对照组（P < 0.05）。研究组出生体重、胎龄、首次入院时年龄均低于对照组（P < 0.05）,研究组合并葡萄糖-6-磷酸脱氢酶（G-6-PD）缺乏症比例和合并溶血病比例高于对照组（P < 0.05）。多因素logsitic分析显示,胎龄小、首次入院时年龄小、合并G-6-PD缺乏症是新生儿高胆红素血症再入院的危险因素（分别OR=1.792、1.415、2.829,P < 0.05）。结论 对存在胎龄小、首次入院时年龄小、合并G-6-PD缺乏症等高危因素的高胆红素血症新生儿,应加强住院及出院后管理,防止该病再入院的发生。     

Prediction of risk factors of neonatal hyperbilirubinemia

目的 探讨一种无创性、按每小时计的经皮胆红素(TeB)百分位列线图,以预测新生儿高胆红素血症的发生风险.方法 选择2010年1月至2010年3月出生、胎龄≥35周且出生体质量≥2 000 g的健康新生儿679例,测定其出生后152 h内的TcB值.将出生后68 h内对应最高危区域的胆红素测定值作为预测指标,利用以小时为单位的胆红素曲线图评估其高胆红素血症的危险度,利用诊断试验特征曲线(ROC曲线)分析胆红素百分位列线图预测高胆红素血症的发生风险.结果 将679例新生儿7 482个对应不同小时龄的TeB值纳入分析.42例新生儿出生后68 h内的胆红素水平处于高危区,预测高胆红素血症的灵敏度为34.52%,特异度为97.82%;212例新生儿胆红素水平处于高危区和中高危区,预测高胆红素血症的灵敏度为80.95%.特异度为75.80%;213例新生儿胆红素水平处于低危区,预测高胆红素血症的灵敏度为98.81%,特异度为35.63%.以TcB百分位列线图危险区域表示的出院前胆红素水平预测高胆红素血症发生风险的ROC曲线下面积(AUC)为0.846;胎龄与出生68 h内的胆红素水平结合预测高胆红素血症发生风险的ROC曲线下面积(AUC)为0.857;出生后前3 d的生理性体质量下降与出院前胆红素水平结合预测高胆红素血症发生风险的AUC为0.859.结论 根据新生儿出院前胆红素水平结合胎龄、出生后前3天的生理性体质量下降能简单而准确地预测新生儿高胆红素血症的发生风险.     

新生儿高胆红素血症的风险预测

目的探讨一种无创性、按每小时计的经皮胆红素(TcB)百分位列线图,以预测新生儿高胆红素血症的发生风险。方法选择2010年1月至2010年3月出生、胎龄≥35周且出生体质量≥2 000 g的健康新生儿679例,测定其出生后152 h内的TcB值。将出生后68 h内对应最高危区域的胆红素测定值作为预测指标,利用以小时为单位的胆红素曲线图评估其高胆红素血症的危险度,利用诊断试验特征曲线(ROC曲线)分析胆红素百分位列线图预测高胆红素血症的发生风险。结果将679例新生儿7 482个对应不同小时龄的TcB值纳入分析。42例新生儿出生后68 h内的胆红素水平处于高危区,预测高胆红素血症的灵敏度为34.52%,特异度为97.82%;212例新生儿胆红素水平处于高危区和中高危区,预测高胆红素血症的灵敏度为80.95%,特异度为75.80%;213例新生儿胆红素水平处于低危区,预测高胆红素血症的灵敏度为98.81%,特异度为35.63%。以TcB百分位列线图危险区域表示的出院前胆红素水平预测高胆红素血症发生风险的ROC曲线下面积(AUC)为0.846;胎龄与出生68 h内的胆红素水平结合预测高胆红素血症发生风险的ROC曲线下面积(AUC)为0.857;出生后前3 d的生理性体质量下降与出院前胆红素水平结合预测高胆红素血症发生风险的AUC为0.859。结论根据新生儿出院前胆红素水平结合胎龄、出生后前3天的生理性体质量下降能简单而准确地预测新生儿高胆红素血症的发生风险。     

Risk factors for hyperbilirubinemia in breastfed term neonates

Increased breastfeeding was suggested as a contributing factor to significant hyperbilirubinemia. The aim of this study was to identify the risk factors associated with jaundice in exclusively breastfed term neonates. We retrospectively reviewed all consecutively live-born neonates from August 2009 to July 2010 who had complete outpatient department (OPD) follow-up at ≤14 days old. Hyperbilirubinemia was defined as a transcutaneous bilirubin (TcB) value of ≥15 mg/dl. During the study period, there were 718 deliveries, of which 152 neonates were transferred to the special care nursery or neonatal intensive care unit; 566 neonates were discharged from the nursery, and 243 neonates were excluded: 83 did not return to the OPD, 46 were older than 14 days at OPD follow-up, 44 were <37 weeks of gestational age, and 70 had been fed formula. In total, 323 neonates were enrolled and classified into the hyperbilirubinemic (114 neonates) and non-hyperbilirubinemic groups (209 neonates). The gender, gestational age, Apgar score, age at nursery discharge, birth weight, and body weight at nursery discharge and at OPD were comparable between the two groups. TcB values at nursery discharge were positively correlated with TcB values in the OPD. Infants with hyperbilirubinemia exhibited significantly greater body weight loss from birth to the OPD follow-up and significantly less body weight gain from nursery discharge to OPD follow-up. Conclusion High TcB values at nursery discharge and a smaller body weight gain are associated with hyperbilirubinemia in term neonates who are exclusively breastfed.     

Acute, severe bilirubin encephalopathy in a newborn

In recent years, changes in health care practices including the early discharge of newborns have transformed the management of neonatal jaundice into an outpatient problem. At the same time, there has been a resurgence in the incidence of kernicterus. We report the case of a term male infant who presented to our emergency department at 4 days of age with severe jaundice and who subsequently died with autopsy findings of kernicterus. We review the infant's presentation and hospital course, diagnostic and therapeutic interventions, and autopsy findings. In the current era of increased frequency of breast-feeding, shortened hospital stays, and inconsistent follow-up after hospital discharge, emergency department physicians should be alerted to the rare but increasing occurrence of severe hyperbilirubinemia and kernicterus.     

Mandibular distraction in neonates: indications, technique, results

Background

Early discharge of healthy late preterm and full term newborn infants has become common practice because of the current social and economic necessities. Severe jaundice, and even kernicterus, has developed in some term infants discharged early. This study was designed to elaborate a percentile-based hour specific total serum bilirubin (TSB) nomogram and to assess its ability to predict the absence of risk for subsequent non physiologic severe hyperbilirubinaemia before discharge.

Methods

A percentile-based hour-specific nomogram for TSB values was performed using TSB data of 1708 healthy full term neonates. The nomogram's predictive ability was then prospectively assessed in five different first level neonatal units, using a single TSB value determined before discharge.

Results

The 75 ^th percentile of hour specific TSB nomogram allows to predict newborn babies without significant hyperbilirubinemia only after the first 72 hours of life. In the first 48 hours of life the observation of false negative results did not permit a safe discharge from the hospital.

Conclusion

The hour-specific TSB nomogram is able to predict all neonates without risk of non physiologic hyperbilirubinemia only after 48 to 72 hours of life. The combination of TSB determination and risk factors for hyperbilirubinemia could facilitate a safe discharge from the hospital and a targeted intervention and follow-up.     

Glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia

The aim of this article is to investigate the prevalence of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in neonatal hyperbilirubinemia and to compare the clinical presentation and course of G6PD-deficient and normal patients. This study included a total of 624 term neonates with indirect hyperbilirubinemia from March 2001 to September 2004. Birth weight, sex, weight at admission, serum bilirubin at admission, maximum bilirubin, phototherapy duration, duration of hospitalization and the need for exchange transfusion were recorded. Laboratory evaluations included blood group typing of mother and newborn, complete blood count, peripheral blood smear, serum total and direct bilirubin, direct coombs test, reticulocyte count, serum-free T4 and TSH, urine analysis, urinary reducing substance and erythrocyte G6PD level. The analysis of the results indicated that 24 neonates with indirect hyperbilirubinemia were G6PD-deficient. No statistically significant difference was detected between G6PD-deficient and normal groups in relation to the time of onset of jaundice, reticulocyte count, hematocrit level, phototherapy duration and duration of hospitalization. Serum bilirubin at admission, maximum serum bilirubin level and the need for exchange transfusion were higher in G6PD-deficient group. From this study our conclusion is that the G6PD deficiency is a common enzyme defect causing severe indirect hyperbilirubinemia which may result in kernicterus. Early neonatal screening programmes should be instituted in countries where the deficiency is prevalent.     

How accurate are neonatologists in identifying clinical jaundice in newborns?

This study reevaluates the clinical ability to accurately identifyjaundice in neonates. Three hundred seventy-one term infants were clinically asseseed forjaundice, before discharge home on day 2 to 3 of life. Bilirubin levels obtained at the same time were significantly higher in the newborns clinically diagnosed as beingjaundiced. Our neonatologists were able to diagnose jaundice at clinically low levels, and not to misdiagnose significant hyperbilirubinemia in the majority of the infants. The trained human eye can still discriminate between the jaundiced and nonjaundiced newborn, and clinical impression of jaundice remains a reliable primary screening tool for significant neonatal hyperbilirubinemia.     

Effect of clofibrate in non-hemolytic indirect hyperbilirubinemia in full term neonates

Objective Jaundice is a common clinical problem in neonatal period which may result in brain damage even in healthy full term newborns, when it is severe. The aim of this study was to characterize the therapeutic effect of clofibrate in full term neonates who present with nonhemolytic jaundice. Methods A clinical controlled study was performed on 60 full term neonates who presented with non-hemolytic jaundice. 30 neonates were treated with a single oral dose of clofibrate (100 mg/Kg) plus phototherapy (case group), while 30 neonates received only phototherapy (control group). Both groups were compared in regard to post therapeutic mean total and indirect plasma bilirubin levels, admission duration and the rate of exchange transfusion. Results The reduction rate of total and indirect plasma bilirubin levels were significantly higher in the clofibrate-treated group as compared with the control group (P<0.05). The mean duration of admission was found to be reduced from 2.9 +/− 0.9 days in the control groupl to 2.2 +/− 0.6 days in clofibrate-treated group (P=0.002). The mean plasma total bilirubin level was lower in the clofibrate-treated group. No cases required phototherapy after 48 hour in clofibrate-treated group, while 9 neonates (30%) and 2 neonates (6.7%) required phototherapy after 72 hour and 96 hour respectively in the control group. There was no difference between both the groups for sex, the time of developing jaundice and the rate of exchange transfusion. Conclusion A single dose of clofibrate (100 mg/Kg) alongwith phototherapy is more effective than phototherapy alone in treating non-hemolytic hyperbilirubinemia in term healthy newborn infants.     

Detection of hyperbilirubinemia by skin color measurements in icteric newborn infants at 5 to 14 days of age

The relation between the yellow color of the skin, as read by the Minolta jaundice meter, and total bilirubin concentration, was compared in two groups of newborn infants suspected of having hyperbilirubinemia, but otherwise well. The study group comprised 73 neonates, icteric at the time of discharge from the nursery, and who were seen in the outpatient clinic at 5 to 14 days of age for checkup and blood sampling. The control group consisted of 52 neonates tested for hyperbilirubinemia at 1 to 4 days of age. Additionally, the relation between skin color and conjugated plasma bilirubin concentration was investigated in the study group. No significant differences in meter response to total bilirubin concentration was found between the two groups. The conjugated bilirubin concentration correlated significantly to the yellow skin color. The jaundice meter can be used as a test for hyperbilirubinemia in neonates at 5 to 14 days of age.     

Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation

Jaundice occurs in most newborn infants. Most jaundice is benign, but because of the potential toxicity of bilirubin, newborn infants must be monitored to identify those who might develop severe hyperbilirubinemia and, in rare cases, acute bilirubin encephalopathy or kernicterus. The focus of this guideline is to reduce the incidence of severe hyperbilirubinemia and bilirubin encephalopathy while minimizing the risks of unintended harm such as maternal anxiety, decreased breastfeeding, and unnecessary costs or treatment. Although kernicterus should almost always be preventable, cases continue to occur. These guidelines provide a framework for the prevention and management of hyperbilirubinemia in newborn infants of 35 or more weeks of gestation. In every infant, we recommend that clinicians 1) promote and support successful breastfeeding; 2) perform a systematic assessment before discharge for the risk of severe hyperbilirubinemia; 3) provide early and focused follow-up based on the risk assessment; and 4) when indicated, treat newborns with phototherapy or exchange transfusion to prevent the development of severe hyperbilirubinemia and, possibly, bilirubin encephalopathy (kernicterus).