《新生儿黄疸诊治》ppt课件

1、2021-9-271新生儿黄疸诊治新生儿黄疸诊治 yaoyue28sina yaoyue28sinaPaediatrics & 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

2、 and late preterm newborn infants 参考文献Hyperbilirubinemia 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

3、of the healthy newborn infant, particularly 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能够。 胆红素程度与胆红素脑病发生胆红素程度与胆红素脑病发生 It is estimated that 60% of term newborns devel

4、op jaundice and 2% reach a TSB concentration greater than 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

5、 for toxicity progressively increases. More than three-quarters 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 great

6、er than 500 mol/L(29.2mg/dl), there are still some infants 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,

7、in the presence of severe hyperbilirubinemia, of 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 seque

8、lae of acute encephalopathy with athetoid cerebral palsy手足徐动症样大脑麻木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

9、340 mol/L at any time during 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. 具有危险要素人群中患者与非患者之比相当于不具有危险要素人群中患者与非患者之比的倍数具有危险要素人群中患者与非患者之比相当于不具有危险要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，抽搐可添加急性脑病的发生率 与败

10、血症的关系? All of the reasons for the variable susceptibility of infants are 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 hyper

11、bilirubinemia ,although reliable evidence to confirm these associations 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 in

12、fant with severe hyperbilirubinemia. 黄疸的发生总体发生情况Early (days 1-2) - uncommon 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 enzy

13、mes - very rare Investigations:Measurement of bilirubin 经皮测并不准确与能否光疗后，皮肤颜色及厚度都有关经皮测并不准确与能否光疗后，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 res

14、ults are more accurate at lower levels of bilirubin, and therefore, use of TcB as a screening 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 d

15、rew attention to the observation that jaundice starts on the head, and extends towards the 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 fo

16、llows: Clinical management of hyperbilirubinemia in infants TABLE 1: Laboratory investigation for hyperbilirubinemia in term newborn infants Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration

17、Blood group with direct antibody test (Coombs test) Hemoglobin and hematocrit determinations Optional (可选择的可选择的) 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

18、albumin or protein concentrations Timed TSB measurements 定时胆红素程度监测，适时干涉定时胆红素程度监测，适时干涉 Umbilical cord blood TSB脐带血胆红素程度并无特异性脐带血胆红素程度并无特异性 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

19、 positive predictive value阳性预测值阳性预测值 is only 4.8% for the term infant, rising to 10.9% in the late preterm infant, and the specificity is very poor Universal hemoglobin assessment 常规脐带血血红蛋白或红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 h

20、emoglobin, routine umbilical cord blood hemoglobin or hematocrit measurement does not aid in the prediction of severe hyperbilirubinemia Blood group and Coombs testing血型及血型及Coombs实实验验 ABO溶血是常见缘由，大部分新生儿黄疸与溶血是常见缘由，大部分新生儿黄疸与ABO溶血有关溶血有关 blood group A or B infants born to a mother with group O blood ABO溶

21、血患儿直抗阳性者比阴性者更需光疗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 DAT-negative 对型血母亲及有高危要素的黄疸患儿进展对型血母亲及有高危要素的黄疸患儿进展DAT检测检测Testing all babies whose mothers are group O doe

22、s 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 risk of needing therapy The results will determine whether they are low risk or high

23、 risk, and may therefore affect the threshold at which therapy would be indicated时间胆红素程度曲线时间胆红素程度曲线 加强光疗的指征曲线Glucose-6-phosphate dehydrogenase deficiency 葡萄糖葡萄糖-6-磷酸脱氢酶缺乏症磷酸脱氢酶缺乏症与严重胆红素血症相关与严重胆红素血症相关Newborns with glucose-6-phosphate dehydrogenase (G6PD) deficiency have an increased incidence of seve

24、re 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 有家族种族高危要素的都应行此检查有家族种族高危要素的都应行此检查Testing for G6PD deficie

25、ncy in babies whose ethnic group or family history suggest an increased risk of G6PD deficiency is advised. 有高危要素男女孩都因检测有高危要素男女孩都因检测Although G6PD deficiency is an X-linked disease, female heterozygotes can have more than 50% of their red cells deficient in the enzyme because of random inactivation o

26、f 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，有溶血病时，G-6-PD程度会被检测过高从而影响诊断程度会被检测过高从而影响诊断It should also be recognized that in the p

27、resence 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 积极进展干涉积极进展干涉G6PD-deficient newborns may require intervention at a lower TSB concentration because they are more likely to progress

28、 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 implicati

29、ons, testing infants at risk is still of value. 建议每项均有建议的等级与研讨的可靠性相建议每项均有建议的等级与研讨的可靠性相关：关： 孕妇孕妇ABO,Rh血型检测及红细胞抗体筛查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 脐血检测脐血检测If the mother was not tested, cord blood from the i

30、nfant should be sent for evaluation of the blood group and a DAT (Coombs test) 母型血的早期黄疸患儿应做血型鉴定及母型血的早期黄疸患儿应做血型鉴定及DAT检测检测Blood group evaluation and a DAT should be performed in infants with early jaundice of mothers of blood group O. G-6-PD 筛查筛查Selected at-risk infants ( Mediterranean , Middle Easter

31、n, African or Southeast Asian origin) should be screened for G6PD deficiency . 严重的高胆红素血症时应做严重的高胆红素血症时应做G-6-PD检测检测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？怎样减少严重高胆红素血症的发生？HOW CAN THE RISK OF SEVERE HYPERBILIRUBINEMIA BE REDUCE

32、D? Primary prevention of severe hyperbilirubinemia 一级预防一级预防 Breastfeeding support 对于母亲的宣教对于母亲的宣教 Other ineffective interventions Routine use of glycerine suppositories 甘油栓剂甘油栓剂routine glycerine enemas 开赛露，开赛露， L-aspartic acid天天冬氨酸冬氨酸, whey/casein and clofibrate 氯贝丁脂氯贝丁脂 have all been studied in smal

33、l randomized controlled trials (RCTs), but their use has been found to have no effect on clinically important outcomes. Prevention of severe hyperbilirubinemia in infants with hemolysis Phenobarbitone 苯巴比妥苯巴比妥 Tin-mesoporphyrin SnMP 锡中卟啉抑制胆红素合成及活性，锡中卟啉抑制胆红素合成及活性，临床运用未见明显改动临床运用未见明显改动 Prophylactic pho

34、totherapy 预防光疗能否加强光疗见表预防光疗能否加强光疗见表Prevention of severe hyperbilirubinemia in infants with mild or moderate hyperbilirubinemia Phototherapy Interrupting breastfeeding 停顿母乳喂养停顿母乳喂养RCT 未未见明显区别见明显区别 Intravenous immunoglobulin 静丙与免疫要素相静丙与免疫要素相关的溶血关的溶血 Supplemental fluids 补液补液 Agar 琼脂可减少肠壁对未结合胆红素的吸收，没有琼脂可

35、减少肠壁对未结合胆红素的吸收，没有可靠的证据支持可靠的证据支持建议：支持母乳喂养支持母乳喂养A program for breastfeeding support should be instituted in every facility where babies are delivered并不引荐给母乳喂养的婴儿常规补充水或糖水并不引荐给母乳喂养的婴儿常规补充水或糖水Routine supplementation of breastfed infants with water or dextrose water is not recommended 静丙的运用静丙的运用Infants wi

36、th 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 dose of 1 g/kg胆红素程度及高危要素提示能够有发生严重高胆红素血症趋势的时候，即使出院也应追踪胆红素程度及高危要素提示能够有发生严重高胆红

37、素血症趋势的时候，即使出院也应追踪监测胆红素水监测胆红素水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 TcB concentration in most cir

38、cumstances 加强光疗加强光疗Intensive phototherapy should be given according to the guidelines shown in Figure 2 常规光疗常规光疗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光疗中也应继续母乳喂养Breastfeeding should be continued during photot

39、herapy 迅速进展能够需求换血时，应控制补液量迅速进展能够需求换血时，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，监测胆红素程度，有

40、指征时开场做换血预初始治疗，监测胆红素程度，有指征时开场做换血预备补液，静丙备补液，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

41、 of treatment to confirm response. Consideration 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脱水高胆红素血症光疗 I

42、t is important to recognize the relationship between 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. Breastfeedi

43、ng is not contraindicated in the presence of hyperbilirubinemia 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. 没有高危要

44、素的安康足月儿For healthy term newborns without risk factors, 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

45、value for investigating many of the rarer causes 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 pyru

46、vate kinase丙酮酸激酶 deficiency) and metabolic disorders, as well as for hemoglobin electrophoresis and chromosome analysis.假设胆红素程度刚到达换血指征，在换血前应再次检测胆红素程度。严厉掌握换血指征。 Preparation of blood for exchange transfusion may take several hours, during which time intensive phototherapy, supplemental fluids and IVIG

47、 (in case of isoimmunization) should be used. If 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 delay

48、ed. In this way, some exchange transfusions, with 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 in

49、fant with clinical signs of acute bilirubin encephalopathy 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 exch

50、ange transfusion. An infant with clinical signs of acute bilirubin encephalopathy should have an immediate exchange transfusion. 换血指征 Follow-up 随访：随访： Routine newborn surveillance, whether in hospital or after discharge, should include assessment of breastfeeding and jaundice every 24 h to 48 h unti

51、l feeding is established (usually on the third or fourth 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. Communit

52、y services should include breastfeeding support and access 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 multid