新生儿黄疸诊治课件

1、新生儿黄疸诊治 yaoyue28Paediatrics & Child Health 1999;4(2):161-164Reference No. FN98-02Revision in progress May 2007Paediatrics & Child Health 2007;12(5): 1B-12BReference No. FN07-02 Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants 参考文献Hype

2、rbilirubinemia is very common and usually benign in the term newborn infant and the late preterm infant at 35 to 36 completed weeks. Critical hyperbilirubinemia is uncommon but has the potential for causing long-term neurological impairment. Early discharge of the healthy newborn infant, particularl

3、y those in whom breastfeeding may not be fully established, may be associated with delayed diagnosis of significant hyperbilirubinemia. 高胆红素血症很常见，多为良性。危险的高胆红素血症并不常见，但是有潜在的导致长期神经损害的可能。胆红素水平与胆红素脑病发生It is estimated that 60% of term newborns develop jaundice and 2% reach a TSB concentration greater than

4、 340 mol/L(19.8mg/dl). Acute encephalopathy does not occur in full-term infants whose peak TSB concentration remains below 340 mol/L and is very rare unless the peak TSB concentration exceeds 425 mol/L (24.85mg/dl) . Above this level, the risk for toxicity progressively increases. More than three-qu

5、arters of the infants in the United States kernicterus registry (between 1992 and 2002) had a TSB concentration of 515 mol/L(30.1mg/dl) or greater, and two-thirds had a concentration exceeding 600 mol/L(35mg/dl). Even with concentrations greater than 500 mol/L(29.2mg/dl), there are still some infant

6、s who will escape encephalopathy. Kernicterus （核黄疸）:the pathological finding of deep-yellow staining of neurons and neuronal necrosis of the basal ganglia（基底节） and brainstem nuclei（脑干神经元）. Acute bilirubin encephalopathy（急性胆红素脑病） :a clinical syndrome, in the presence of severe hyperbilirubinemia, of

7、lethargy （昏睡）, hypotoniaand（肌张力减低） poor suck, which may progress to hypertonia (with opisthotonos（角弓反张） and retrocollis（颈后倾）) with a high-pitched cry and fever, and eventually to seizures（发作） and coma. Chronic bilirubin encephalopathy（慢性胆红素脑病） :the clinical sequelae of acute encephalopathy with athe

8、toid cerebral palsy（手足徐动症样大脑麻痹）with or without seizures, developmental delay, hearing deficit, oculomotor （眼球运动异常）disturbances, dental dysplasia（牙发育异常） and mental deficiency . Severe hyperbilirubinemia（严重的高胆红素血症） :a total serum bilirubin (TSB) concentration greater than 340 mol/L at any time during

9、the first 28 days of life. Critical hyperbilirubinemia（危险的高胆红素血症）:a TSB concentration greater than 425 mol/L during the first 28 days of life. 具有危险因素人群中患者与非患者之比相当于不具有危险因素人群中患者与非患者之比的倍数 脱水，高渗，呼吸窘迫，水肿，早产，酸中毒，低白蛋白血症，缺氧，抽搐可增加急性脑病的发生率与败血症的关系?All of the reasons for the variable susceptibility of infants a

10、re not known; however, dehydration, hyperosmolarity, respiratory distress, hydrops, prematurity, acidosis, hypoalbuminemia, hypoxia and seizures are said to increase the risk of acute encephalopathy in the presence of severe hyperbilirubinemia ,although reliable evidence to confirm these association

11、s is lacking .In addition, some infants with severe hyperbilirubinemia are found to have sepsis, but both sepsis and hyperbilirubinemia are common in the neonatal period, and sepsis appears to be uncommon in the well-appearing infant with severe hyperbilirubinemia. 黄疸的发生（总体发生情况）Early (days 1-2) - un

12、common Haemolytic jaundice (ABO, others) Normal (days 3-10) - very common Uncomplicated Complicated - see below Late (days 14+) Breast milk - common Conjugated jaundice - uncommon Inherited deficiency of glucuronyl transferase enzymes - very rare Investigations:Measurement of bilirubin 经皮测并不准确（与是否光疗

13、后，皮肤颜色及厚度都有关）There are several limitations to TcB measurements: they become unreliable after initiation of phototherapy , and they may be unreliable with changes in skin colour and thickness . However, the results are more accurate at lower levels of bilirubin, and therefore, use of TcB as a screeni

14、ng device is reasonableClinical evaluationKramers RuleRather than estimating the level of jaundice by simply observing the babys skin colour, one can utilise the cephalocaudal progression of jaundice. Kramer drew attention to the observation that jaundice starts on the head, and extends towards the

15、feet as the level rises. This is useful in deciding whether or not a baby needs to have the SBR measured. Kramer divided the infant into 5 zones, the SBR range associated with progression to the zones is as follows:Clinical management of hyperbilirubinemia in infants TABLE 1: Laboratory investigatio

16、n for hyperbilirubinemia in term newborn infants Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombs test) Hemoglobin and hematocrit determinations

17、 Optional (可选择的) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations Timed TSB measurements 定时胆红素水平监测，适时干预Umbilical cord blood TSB（

18、脐带血胆红素水平并无特异性）A TSB concentration greater than 30 mol/L in umbilical cord bloodis statistically correlated with a peak neonatal TSB concentration greater than 300 mol/L, but the positive predictive value（阳性预测值） is only 4.8% for the term infant, rising to 10.9% in the late preterm infant, and the spe

19、cificity is very poor Universal hemoglobin assessment （常规脐带血血红蛋白或红细胞比容测定并不能预测严重高胆红素血症的发生）Although bilirubin is derived from the breakdown of hemoglobin, routine umbilical cord blood hemoglobin or hematocrit measurement does not aid in the prediction of severe hyperbilirubinemia Blood group and Coomb

20、s testing（血型及Coombs试验） ABO溶血是常见原因，大部分新生儿黄疸与ABO溶血有关（ blood group A or B infants born to a mother with group O blood）ABO溶血患儿直抗阳性者比阴性者更需光疗 The need for phototherapy is increased in ABO-incompatible infants who are direct antiglobulin test (DAT direct Coombs test)-positive compared with those who are DA

21、T-negative 对型血母亲及有高危因素的黄疸患儿进行DAT检测Testing all babies whose mothers are group O does not improve outcomes compared with testing only those with clinical jaundice. Therefore, it is reasonable to perform a DAT in clinically jaundiced infants of mothers who are group O and in infants with an elevated ri

22、sk of needing therapy The results will determine whether they are low risk or high risk, and may therefore affect the threshold at which therapy would be indicated时间胆红素水平曲线加强光疗的指征曲线Glucose-6-phosphate dehydrogenase deficiency （葡萄糖-6-磷酸脱氢酶缺乏症）与严重胆红素血症相关Newborns with glucose-6-phosphate dehydrogenase

23、(G6PD) deficiency have an increased incidence of severe hyperbilirubinemiaG6PD deficiency increases the likelihood of requiring exchange transfusion in infants with severe hyperbilirubinemia; therefore, a test for G6PD deficiency should be considered in all infants with severe hyperbilirubinemia 有家族

24、种族高危因素的都应行此检查Testing for G6PD deficiency in babies whose ethnic group or family history suggest an increased risk of G6PD deficiency is advised. 有高危因素男女孩都因检测Although G6PD deficiency is an X-linked disease, female heterozygotes can have more than 50% of their red cells deficient in the enzyme because

25、 of random inactivation of the X chromosome. Females with greater proportions of their red cells affected have an increased risk of severe neonatal hyperbilirubinemia ；therefore, testing of both girls and boys who are at risk is advised 有溶血病时，G-6-PD水平会被检测过高从而影响诊断It should also be recognized that in

26、the presence of hemolysis, G6PD levels can be overestimated and this may obscure the diagnosis Females in particular can have misleading results on the common screening tests 积极进行干预G6PD-deficient newborns may require intervention at a lower TSB concentration because they are more likely to progress

27、to severe hyperbilirubinemia . Unfortunately, in many centres, it currently takes several days for a G6PD deficiency screening test result to become available. Improving the turnaround time for this test would improve care of the newborn. Because G6PD deficiency is a disease with lifelong implicatio

28、ns, testing infants at risk is still of value. 建议（每项均有建议的等级与研究的可靠性相关）：孕妇ABO,Rh血型检测及红细胞抗体筛查All mothers should be tested for ABO and Rh(D) blood types and be screened for red cell antibodies during pregnancy脐血检测If the mother was not tested, cord blood from the infant should be sent for evaluation of t

29、he blood group and a DAT (Coombs test) 母型血的早期黄疸患儿应做血型鉴定及DAT检测Blood group evaluation and a DAT should be performed in infants with early jaundice of mothers of blood group O. G-6-PD 筛查Selected at-risk infants ( Mediterranean , Middle Eastern, African or Southeast Asian origin) should be screened for

30、G6PD deficiency . 严重的高胆红素血症时应做G-6-PD检测A test for G6PD deficiency should be considered in all infants with severe hyperbilirubinemia When? 怎样减少严重高胆红素血症的发生？HOW CAN THE RISK OF SEVERE HYPERBILIRUBINEMIA BE REDUCED? Primary prevention of severe hyperbilirubinemia 一级预防Breastfeeding support 对于母亲的宣教Other i

31、neffective interventions Routine use of glycerine suppositories （甘油栓剂）routine glycerine enemas 开赛露， L-aspartic acid（天冬氨酸）, whey/casein and clofibrate （氯贝丁脂） have all been studied in small randomized controlled trials (RCTs), but their use has been found to have no effect on clinically important outc

32、omes. Prevention of severe hyperbilirubinemia in infants with hemolysis Phenobarbitone （苯巴比妥） Tin-mesoporphyrin SnMP （锡中卟啉）抑制胆红素合成及活性，临床使用未见明显改变 Prophylactic phototherapy （预防光疗）是否加强光疗见表Prevention of severe hyperbilirubinemia in infants with mild or moderate hyperbilirubinemia Phototherapy Interrupti

33、ng breastfeeding （停止母乳喂养）RCT 未见明显区别 Intravenous immunoglobulin （静丙）与免疫因素相关的溶血 Supplemental fluids （补液） Agar （琼脂）可减少肠壁对未结合胆红素的吸收，没有可靠的证据支持建议：支持母乳喂养A program for breastfeeding support should be instituted in every facility where babies are delivered并不推荐给母乳喂养的婴儿常规补充水或糖水Routine supplementation of breast

34、fed infants with water or dextrose water is not recommended 静丙的使用Infants with a positive DAT who have predicted severe disease based on antenatal investigation or an elevated risk of progressing to exchange transfusion based on the postnatal progression of TSB concentration should receive IVIG at a

35、dose of 1 g/kg胆红素水平及高危因素提示可能有发生严重高胆红素血症趋势的时候，即使出院也应追踪监测胆红素水A TSB concentration consistent with increased risk should lead to enhanced surveillance for development of severe hyperbilirubinemia, with follow-up within 24 h to 48 h, either in hospital or in the community, and repeat estimation of TSB or

36、 TcB concentration in most circumstances 加强光疗Intensive phototherapy should be given according to the guidelines shown in Figure 2 常规光疗Conventional phototherapy is an option at TSB concentrations 35 mol/L to 50 mol/L lower than the guidelines in Figure 2光疗中也应继续母乳喂养Breastfeeding should be continued du

37、ring phototherapy 迅速进展可能需要换血时，应控制补液量Supplemental fluids should be administered, orally or by intravenous infusion, in infants receiving phototherapy who are at an elevated risk of progressing to exchange transfusion .HOW SHOULD SEVERE HYPERBILIRUBINEMIA BE TREATED? Phototherapy 初始治疗，监测胆红素水平，有指征时开始做换

38、血准备补液，静丙An infant who presents with severe hyperbilirubinemia, or who progresses to severe hyperbilirubinemia despite initial treatment, should receive immediate intensive phototherapy. The bilirubin concentration should be checked within 2 h to 6 h of initiation of treatment to confirm response. Co

39、nsideration of further therapy should commence and preparations for exchange transfusion may be indicated. Supplemental fluids are indicated, and IVIG should be given if not already commencedfor the infant with isoimmunization. Phototherapy脱水高胆红素血症光疗It is important to recognize the relationship betw

40、een dehydration and hyperbilirubinemia. Dehydration may be associated with increased serum bilirubin concentrations and may be exacerbated by phototherapy. All jaundiced infants should be adequately hydrated before and during phototherapy. Breastfeeding is not contraindicated in the presence of hype

41、rbilirubinemia and should be continued. More frequent breastfeedings may be beneficial .Exchange transfusion 光疗失败If phototherapy fails to control the rising bilirubin concentrations, exchange transfusion is indicated to lower TSB concentrations. 没有高危因素的健康足月儿For healthy term newborns without risk fac

42、tors, exchange transfusion should be considered when the TSB concentration is between 375 mol/L(21.9 mg/dL) and 425 mol/L(24.8 mg/dL)(despite adequate intensive phototherapy). 在换血前采血完善相关检查Because blood collected after an exchange transfusion is of no value for investigating many of the rarer causes

43、of severe hyperbilirubinemia, these investigations should be considered before performing the exchange transfusion. Appropriate amounts of blood should be taken and stored for tests such as those for red cell fragility, enzyme deficiency (G6PD or pyruvate kinase丙酮酸激酶 deficiency) and metabolic disord

44、ers, as well as for hemoglobin electrophoresis and chromosome analysis.如果胆红素水平刚达到换血指征，在换血前应再次检测胆红素水平。严格掌握换血指征。 Preparation of blood for exchange transfusion may take several hours, during which time intensive phototherapy, supplemental fluids and IVIG (in case of isoimmunization) should be used. If

45、an infant whose TSB concentration is already above the exchange transfusion line presents for medical care, then repeat measurement of the TSB concentration just before performance of the exchange is reasonable, as long as therapy is not thereby delayed. In this way, some exchange transfusions, with

46、 their attendant risks, may be avoided. Exchange transfusion is a procedure with substantial morbidity that should only be performed in centres with the appropriate expertise under supervision of an experienced neonatologist. 当有急性胆红素脑病的临床表现时应马上换血An infant with clinical signs of acute bilirubin encep

47、halopathy should have an immediate exchange transfusion.建议：Infants with a TSB concentration above the thresholds shown on Figure 3 should have immediate intensive phototherapy, and should be referred for further investigation and preparation for exchange transfusion.An infant with clinical signs of

48、acute bilirubin encephalopathy should have an immediate exchange transfusion. 换血指征 Follow-up 随访：Routine newborn surveillance, whether in hospital or after discharge, should include assessment of breastfeeding and jaundice every 24 h to 48 h until feeding is established (usually on the third or fourt

49、h day of life). All jaundiced infants, especially high-risk infants and those who are exclusively breastfed, should continue to be closely monitored until feeding and weight gain are established and the TSB concentration starts to fall. Community services should include breastfeeding support and acc

50、ess to TSB or TcB testing. Infants with isoimmunization are at risk for severe anemia after several weeks; it is suggested that a repeat hemoglobin measurement be performed at two weeks if it was low at discharge and at four weeks if it was normal .Infants requiring exchange transfusion or those who exhibit neurological abnormalities should be referred to regional multidisci