중증 고빌리루빈혈증(혈청 빌리루빈 >25 mg/dL)의 발병 원인과 치료 및 예후

Etiology, Management, and Prognosis of Severe Hyperbilirubinemia (Serum Bilirubin Level=25 mg/dL) in Newborn

  • 황종희 (인제대학교 의과대학 일산백병원 소아과) ;
  • 이지현 (성균관대학교 의과대학 소아과학교실) ;
  • 김유진 (성균관대학교 의과대학 소아과학교실) ;
  • 구수현 (성균관대학교 의과대학 소아과학교실) ;
  • 이장훈 (성균관대학교 의과대학 소아과학교실) ;
  • 최창원 (분당서울대학교병원 소아과) ;
  • 장윤실 (성균관대학교 의과대학 소아과학교실) ;
  • 박원순 (성균관대학교 의과대학 소아과학교실)
  • Hwang, Jong Hee (Department of Pediatrics, Ilsan Paik Hospital, College of Medicine, Inje University) ;
  • Lee, Ji Hyun (Department of Pediatrics, College of Medicine, Sungkyunkwan University) ;
  • Kim, Yu Jin (Department of Pediatrics, College of Medicine, Sungkyunkwan University) ;
  • Koo, Su Hyun (Department of Pediatrics, College of Medicine, Sungkyunkwan University) ;
  • Lee, Jang Hun (Department of Pediatrics, College of Medicine, Sungkyunkwan University) ;
  • Choi, Chang Won (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Chang, Yun Sil (Department of Pediatrics, College of Medicine, Sungkyunkwan University) ;
  • Park, Won Soon (Department of Pediatrics, College of Medicine, Sungkyunkwan University)
  • 투고 : 2005.06.01
  • 심사 : 2005.08.01
  • 발행 : 2005.10.15

초록

목 적 : 저자들은 혈청 빌리루빈 25 mg/dL 이상의 중증 고빌리루빈혈증의 발병 원인과 치료 및 예후에 대해 알아보고자 하였다. 방 법 : 1994년 10월부터 2004년 6월까지 성균관대학교 삼성서울병원 신생아 집중치료실에 입원하여 고빌리루빈혈증으로 진단 받은 환아들 중 혈청 빌리루빈치가 25 mg/dL 이상이면서 다른 동반 질환을 가지지 않고 추적관찰이 가능했던 48명을 대상으로 하여 치료 방법에 따라 광선치료군(1군, n=42)과 교환수혈군(2군, n=6)으로 분류하고 인구 통계학적 특징, 발병 시기, 발병 원인 및 치료에 따른 예후의 차이에 대해서 후향적으로 조사하였다. 결 과 : 재태주령은 두 군간(1군; $39{\pm}1$주, 2군; $37{\pm}4$주)에 유의한 차이가 없으며 출생체중은 2군($2,852{\pm}1,085g$)이 1군($3,137{\pm}437g$)에 비해 유의하게 작았으나(P<0.05), 2군에서 820 g의 환아가 포함되어 있어 통계적인 영향을 주었다. 발병 원인으로는 두 군 모두 특발성이 가장 많았으며 황달의 첫 임상적 발현 시기, 첫 혈청 빌리루빈 검사 시기 및 입원 시기는 군간에 유의한 차이가 없었다. 최고 혈청 빌리루빈치는 1군($29{\pm}6mg/dL$)에 비해 2군($45{\pm}16mg/dL$)에서 더 의미 있게 증가하였고(P<0.05), 치료 기간, 치료 후 혈청 빌리루빈의 감소 정도 및 신경학적 예후는 군간에 차이가 없었다. 결 론 : 증증 고빌리루빈혈증의 치료에 있어서 현재의 치료 지침으로도 적절한 치료가 이루어질 수 있으나 조기 진단 및 치료를 위해서는 중증 고빌리루빈혈증의 위험성이 높을 경우 생후 1주일 이내에 황달에 대한 추적 관찰이 필요할 것으로 사료된다.

Purpose : The present study examined the etiology, management, and the difference of prognosis according to methodology of treatment in severe hyperbilirubinemia with total serum bilirubin levels of more than 25 mg/dL. Methods : Medical records of severe hyperbilirubiemia in newborns(serum level=25 mg/dL) admitted to the NICU of Samsung Medical Center between October 1994 and June 2004 were reviewed retrospectively. Infants were grouped according to methodology of treatment : Group I(phototherapy only, n=42), Group II(exchange transfusion, n=6). And In addition, we evaluated the etiology and the difference of prognosis. Results : A total of 48 documented cases of severe hyperbilirubinemia were identified. Birth weight was significantly lower in Group 2($2,852{\pm}1,085g$) compared to Group 1($3,137{\pm}437g$)(P<0.05). There were no significant differences in gestational age, sex, mode of delivery, inborn, age at presentation, and age at first examination and admission between the two study groups. Maximal bilirubin level was significantly higher in Group 2($45{\pm}16mg/dL$) compared to Group 1($29{\pm}6mg/dL$) (P<0.05). But there were no significant differences in neurologic outcome. Conclusion : Our study suggests that the present guidelines for managing hyperbilirubinemia in newborns should be effective but follow-up with the first postnatal week would be necessary for each detection and treatment in the newborn infants with high risk of severe hyperbilirubinemia.

키워드

참고문헌

  1. Karp WB. Biochemical alteration in neonatal hyperbilirubinemia and bilirubin encephalopathy : a review. Pediatrics 1979;64:361-8
  2. Gourley GR. Bilirubin metabolism and kernicterus. Adv Pediatr 1997;44:173-229
  3. Hansen TW, Bratlid D. Bilirubin and brain toxicity. Acta Paediatr Scand 1986;75:513-22 https://doi.org/10.1111/j.1651-2227.1986.tb10242.x
  4. American Academy of Pediatrics, Steering Committee on Quality Improvement and Management. Classification of recommendation for clinical practice guidelines. Pediatrics 2004; in press
  5. American Academy of Pediatrics, Clinical practice guideline. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004:297-316 https://doi.org/10.1542/peds.114.1.297
  6. Ahn HS. Neonatal jaundice. In : Hong CY, editor. Pediatrics. 8th ed. Daehan Printing & Publishing Co, 2004:342-9
  7. Soorani-Lunsing I, Woltil HA, Hadders-Algra M. Are moderate degrees of hyperbilirubinemia in healthy term neonates really safe for the brain? Pediatr Res 2001;50:701-5 https://doi.org/10.1203/00006450-200112000-00012
  8. Brown AK, Damus K, Kim MH, King K, Harper R, Campbell D, et al. Factors relating to readmission of term and near-term neonates in the first tow weeks of life. J Perinat Med 1999;27:263-75 https://doi.org/10.1515/JPM.1999.037
  9. Newman TB, Xiong B, Gonzales VM, Escobar GJ. Prediction and prevention of extreme neonatal hperbilirubinemia in a mature health maintenance organization. Arch Pediatr Adolesc Med 2000;154:1140-7 https://doi.org/10.1001/archpedi.154.11.1140
  10. Seidman DS, Stevenson DK, Ergaz A, Gale R. Hospital readmission due to neonatal hyperbilirubinemia. Pediatrics 1995;96:727-9
  11. Abulaimoun BM, Eldemerdash AA, Alrifai M, Al-Hathlol K, Al-Tawil KI, Al-Saif SA. Etiologies and presentation of newborns admitted with severe hyperbilirubinemia to a tertiary hospital. Pediatric Academic Societies' Annual meeting; 2004 May 1-4; San Francisco, CA; 2004:301
  12. Harris MC, Bernbaum JC, Polin JR, Zimmerman R, Polin RA. Developmental follow-up of breastfed term and nearterm infants with marked hyperbilirubinemia. Pediatrics 2001;1075-80 https://doi.org/10.1542/peds.107.5.1075
  13. Porter ML, Dennis BL. Hyperbilirubinemia in the term newborn. Am Fam Physician 2002;65:599-606
  14. Kilander A, Michaelsson M, Muller-Eberhand U, Sjoelin S. Hyperbilirubinemia in full-term newborn infants : a follow-up study. Acta Paediatr Scand 1963;52:481-4 https://doi.org/10.1111/j.1651-2227.1963.tb03807.x
  15. Johnson L, Brown AK. A pilot registry for acute and chronic kernicterus in term and near-term infants. Pediatrics 1999;104:736
  16. Newman TB, Maisels MJ. Evaluation and treatment of jaundice in the term newborn : a kinder, gentler approach. Pediatrics 1992;89:809-18
  17. Watchko JF, Oski FA. Bilirubin 20 mg/dL=vigintiphobia. Pediatrics 1983;71:660-3
  18. Grimmer I, Berger-Jones K, Bucher C, Brandl U, Obladen M. Later neurological sequelae of non-hemolytic hyperbilirubinemia of healthy term neonates. Acta Paediatr 1999;88:661-3 https://doi.org/10.1080/08035259950169341
  19. Gurses D, Kilic I, Sahiner T. Effects of hyperbilirubinemia on cerebrocortical electrical activity in newborns. Pediatr Res 2002;52:125-30
  20. Paludetto R, Mansi G, Raidmondi F, Romano A, Crivaro V, Bussi M, et al. Moderate hyperbilirubinemia induces a transient alteration of neonatal behavior. Pediatrics 2002;110:E50 https://doi.org/10.1542/peds.110.4.e50
  21. Gupta AK, Mann SB. Is auditory brainstem response a bilirubin toxicity marker? Am J Otolaryngol 1998;19:232-6 https://doi.org/10.1016/S0196-0709(98)90123-5
  22. Agarwal R, Kaushal M, Aggarwal R, Paul VK, Deorari AK. Early neonatal hyperbilirubinemia using first-day serum bilirubin level. Indian Pediatr 2002;39:724-30
  23. Vohr RB, Karp D, O'Dea C, Darrow D, Coll CG, Lester BM, et al. Behavioral changes correlated with brain-stem auditory evoked responses in term infants with moderate hyperbilirubinemia. J Pediatr 1990;117:288-91 https://doi.org/10.1016/S0022-3476(05)80549-9
  24. Straver B, Hassing MB, Van der Knaap MS, Gemke RJ. Kerincterus in a full-term male infant a few days old. Acta Paediatr Taiwan 2002;43:86-90
  25. Sarici SU, Serdar MA, Korkmaz A, Erdem G, Oran O, Tekinalp G, et al. Incidence, course, and prediction of hyperbilirubinemia in near-term and term newborns. Pediatrics 2004;113:775-80. https://doi.org/10.1542/peds.113.4.775
  26. Ross G. Hyperbilirubinemia in the 2000s : What should we do next? Am J Perinat 2003;20:415-24 https://doi.org/10.1055/s-2003-45385