موارد شایع در برخورد با زردی نوزادان

2. موارد شایع در برخورد با زردی نوزادان دکتر مجید محمدی زاده فوق تخصص نوزادان عضو هیئت علمی دانشگاه علوم پزشکی اصفهان

3. اهداف آموزشی جلسه • شرکت کنندگان در پایان جلسه: • چرخه تولید و دفع بیلی روبین را مرور کرده باشند • تعریف و سیر زردی فیزیولوژیک را در نوزادان ترم و نزدیک ترم بدانند • انواع زردی مرتبط با شیر مادر و درمان آن را بدانند • فاکتورهای خطر زردی نوزادی را بشناسند • تشخیص زردی نوزاد در روزهای اول تولد پیش از ترخیص از بیمارستان و چگونگی پی گیری آن پس از ترخیص را بدانند • ارزش و موارد کاربرد ترانس کوتانئوس بیلی روبینومتری را در زردی نوزادی بدانند • تشخیص آزمایشگاهی زردی و بررسی های لازم را برای علت زردی بدانند • کلیات درمان زردی را در نوزاد ترم و نزدیک ترم بدانند • اصول حاکم بر فوتوتراپی در منزل را بشناسند • نقش فنوباربیتال در درمان زردی نوزاد را بشناسند

4. neonatal bile pigment metabolism

5. enterohepatic Circulation

6. PHYSIOLOGIC JAUNDICE

8. TERM NEONATE • Physiologic jaundice is characterized by a progressive rise in TSB concentration from approximately 2 mg/dL in cord blood to a mean peak of: • 5 to 6 mg/dLbetween 48 and 120 hours of age in white and African-American babies, with most infants presenting at 72 to 96 hours of age • 10 to 14 mg/dLbetween 72 and 120 hours of age in Asian-American babies • This is followed by a rapid decline to approximately 3 mg/dLby: • the fifth day of life in white and African-American neonates • the seventh to tenth day in Asian-American neonates (phase 1 physiologic jaundice)

9. TERM NEONATE • During the period from the fifth to tenth day of life in white and African-American infants, TSB concentrations decline slowly, reaching the normal adult value of less than 2 mg/dLby the end of that period (phase 2 physiologic jaundice)

10. TERM NEONATE • The epidemiology is dependent, in part, on the prevalence of formula feeding in a population, with lower peak TSB values occurring among the predominantly formula-fed infants

11. PRETERM NEONATE • physiologic jaundice in premature neonates is more severe than in full-term neonates • mean peak TSB concentrations reaches 10 to 12 mg/dLby the fifth day of life • mean peak unconjugatedbilirubin concentrations of 10 to 12 mg/dL may be associated with acute bilirubin encephalopathy or kernicterus in certain high-risk low-birthweight neonates • all degrees of visible jaundice in premature neonates should be monitored closely and investigated fully

12. LATE PRETERM NEONATE • Late preterm gestation is an important risk factor for the development of severe neonatal hyperbilirubinemia and kernicterus • Scrupulous attention to screening for jaundice in the newborn nursery, adequate lactation support, parental education and appropriate postdischarge follow-up should facilitate institution of treatment when clinically indicated

13. POST-TERM NEONATE • nearly all postmature neonates and approximately half of all SGA full-term neonates may be expected to have little or no physiologic jaundice • peak TSB concentrations is less than 2.5 mg/dL

14. Mechanisms for phase 1 physiologic jaundice • It results from the combination of a sixfold increase in the load of bilirubin presented to the liver and a marked deficiency in UGT activity • The very large increase in bilirubin load appears to result from both increased de novo bilirubin synthesis and enteric reabsorption of unconjugatedbilirubin

15. Mechanisms for phase 2 physiologic jaundice • It appears to result from an imbalance in which hepatic uptake of bilirubin remains diminished while the increased bilirubin load presented to the liver persists

16. Jaundice Associated with Breast Feeding

17. Jaundice Associated with Breast Feeding • Breast-feeding failure jaundice • Breast milk jaundice

18. PATHOGENESIS OF JAUNDICE ASSOCIATED WITH BREAST-FEEDING

19. Prevention of breast-feeding failure jaundice • encouraging frequent (at least 8 to 12 times per day for the first several weeks) breast feeding • avoiding supplementation with water or glucose solutions • accessing maternal lactation counseling • intensive support of the breast-feeding • mother is necessary, especially in view of early discharge policies in place at many hospitals • both during birth hospitalization and after hospital discharge, the newborn should be closely monitored for weight gain, adequate urination and stool formation, and the development of jaundice

20. Breast milk jaundice • occurs after the first 3 to 5 days of life and may last into the third week of life or beyond • Epidemiologic studies report that 10% to 30% of breast-fed infants in the second to sixth week of life are affected, with some having hyperbilirubinemiainto the third month

21. Interruption of breast feeding is not recommended unless TB concentrations reach levels that might be of danger to the infant • For such diagnosis, it is necessary to confirm that the TB is primarily unconjugated, that thyroid function tests are normal, and that there is no evidence of urinary infection • In the situation in which the infant is thriving and the TB does not reach dangerous levels, it may be prudent to observe the infant

22. DIAGNOSIS

23. Visual assessment • Cutaneousicterus in the newborn is usually not reflected with TSB concentrations of less than 5 mg/dL • As the intensity of jaundice increases, clinical icterus progresses in a caudal direction

24. Visual assessment • Because routine daily TSB determinations are not usually performed on full-term or even premature newborns, careful scrutiny of the nursery population several times a day by experienced personnel is essential to detect infants who are becoming jaundiced • Visual assessment of jaundice, however, is largely subjective, inaccurate, and dependent on observer experience

25. Transcutaneousbilirubinometry • The technique offers an objective measurement of skin color, from which a reading- reflecting the TB- is derived • Two devices, the BiliChek (Philips Childrens Medical Ventures, Monroeville, PA) and JM-103 Jaundice Meter (Konica Minolta/AirShields JM 103 Jaundice Meter, Draeger Medical AG and Co, Lubeck, Germany) are currently commercially available

26. Transcutaneousbilirubinometry • A number of studies have shown that these instruments provide fairly accurate estimates of TB in term and near-term newborn infants of varying races and ethnicities, generally providing values within 2 to 3 mg/dLof the TB, if the TB is less than 15 mg/dL • The technology tends to under-read the actual TB measurement and should be regarded as a screening mechanism rather than an accurate reflection of the TB • The devices have been evaluated as potential predischargescreening tools to identify infants at risk

27. Transcutaneousbilirubinometry • TcB is a measurement of the yellow color of the blanched skin and subcutaneous tissue, not the serum and should be used as a screening tool to help determine whether the TSB should be measured • Although TcBmeasurements provide a good estimate of the TSB level, they are not a substitute for TSB values, and a TSB level should always be obtained when therapeutic intervention is being considered

28. Transcutaneousbilirubinometry • As with any point-of-care test, regular monitoring for appropriate quality assurance by comparison with TSB measurements is necessary

29. Transcutaneousbilirubinometry • The use of TcB screening reduces the number of blood tests for bilirubin determination compared to visual assessment without compromising detection of infants with significant TB values (eg, >75th percentile) • There are significant variations among different instruments. When TcB is used clinically as a substitute for TB, values of new instruments should always be compared to TB performed by the laboratory to ensure good correlation

30. Transcutaneousbilirubinometry • A confirmatory TB should be measured in the following settings : • When TcB exceeds the 75th percentile on the TB nomogram for phototherapy • When the TcB exceeds the 95th percentile on the TcBnomogram • At follow-up after discharge, the TcB >13 mg/dL • When the TcB value is at 70% of the TSB level recommended for the use of phototherapy • When therapeutic intervention is being considered. Therapy should be initiated while awaiting confirmatory results • If the management plan would be altered by considering the TB to be equal to TcB + 3 mg/dL

31. Transcutaneousbilirubinometry • additional studies are warranted to establish a strong and reliable correlation between TcB and TB: • at levels of 15 mg/dLand higher • during and after phototherapy • in premature or low-birthweightinfants, before its routine use can be advocated

32. Predischarge risk assessment for prediction of subsequent severe hyperbilirubinemia • Combining a predischargemeasurement of TSB or TcBwith clinical risk factors might improve the prediction of the risk of subsequent hyperbilirubinemia • In addition, when interpreted by using the hour-specific nomogram, measurement of TSB or TcB also provides a quantitative assessment of the degree of hyperbilirubinemia • Thisprovides guidance regarding the need (or lack of need) for additional testing to identify a cause of the hyperbilirubinemiaand for additional TSB measurements

33. Risk Factors for Development of Severe Hyperbilirubinemiain Infants of 35 or More Week's Gestation

34. Important Risk Factors for Severe Hyperbilirubinemia

35. Hyperbilirubinemia Neurotoxicity Risk Factors

36. Other Risk Factors for Severe Hyperbilirubinemia to be Considered with the Gestational Age and the Pre-discharge TSB or TcB level

37. Risk designation of term and near-term well newborns based on their hour-specific serum bilirubin values

38. Nomogram of hour-specific transcutaneousbilirubin measurements (mg/dL) for healthy fullterm newborns

39. Predischarge risk assessment for prediction of subsequent severe hyperbilirubinemia • For those infants from whom 2 successive TSB or TcBmeasurements are obtained, it is helpful to plot the data on the nomogramto assess the rate of rise • Hemolysisis likely if the TSB/TcB is crossing percentiles on the nomogram and suggests the need for further testing and follow-up

40. Algorithm providing recommendations for management and follow-up according to predischargebilirubin measurements, gestation, and risk factors for subsequent hyperbilirubinemia

41. Algorithm providing recommendations for management and follow-up according to predischargebilirubin measurements, gestation, and risk factors for subsequent hyperbilirubinemia

42. Algorithm providing recommendations for management and follow-up according to predischargebilirubin measurements, gestation, and risk factors for subsequent hyperbilirubinemia

43. Algorithm providing recommendations for management and follow-up according to predischargebilirubin measurements, gestation, and risk factors for subsequent hyperbilirubinemia

44. Follow up after discharge • It should be noted that, even with a low predischargeTSB or TcB level, the risk of subsequent hyperbilirubinemiais not zero, so appropriate follow-up should always be provided • Most infants discharged at 72 hours should be seen within 2 days of discharge • Earlier follow-up might be necessary for infants who have risk factors for severe hyperbilirubinemia • Those in the lower risk zones with few or no risk factors can be seen later

45. Laboratory Evaluation of the Jaundiced Infant of 35 or More Weeks' Gestation

46. When we search to determine the cause of jaundice • it appears in the 1st 24–36 hr of life • 4 mg/dL or greater in cord blood • serum bilirubin is rising at a rate faster than o.5 mg/dL during a 4-8 hour period • serum bilirubin is rising at a rate faster than 5 mg/dL/24 hr • serum bilirubin is 13-15 mg/dL or greater in full-term infants (especially in the absence of risk factors) or 10 mg/dL or greater in preterm infants • jaundice persists after 10–14 days of life • direct-reacting bilirubin is >2 mg/dL at any time

47. Other factors suggesting a non physiologic cause of jaundice • family history of hemolytic disease • vomiting, lethargy, poor feeding, excessive weight loss, apnea, bradycardia, abnormal vital signs (including hypothermia) • pallor, hepatomegaly, splenomegaly • signs of kernicterus • light-colored stools, dark urine positive for bilirubin • failure of phototherapy to lower bilirubin

48. Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation

49. Guidelines for exchange transfusionin hospitalized infants of 35 or more weeks' gestation

50. HOME PHOTOTHERAPY