Development of Periventricular Leukomalacia and Severe Intraventricular Hemorrhage in Very Low Birth Weight Newborns and Relationship with Ventilator Care (Study of Ventilator Care as a Risk Factor of PVL and PV-IVH)

극소저출생체중아의 뇌실주위백질연화증과 중증뇌실출혈의 발생과 인공호흡기 치료와의 상관관계

  • 이학성 (대구파티마병원 소아과) ;
  • 이세규 (대구파티마병원 소아과) ;
  • 김영진 (대구파티마병원 소아과) ;
  • 이상길 (대구파티마병원 소아과)
  • Received : 2005.07.04
  • Accepted : 2005.09.02
  • Published : 2005.12.15

Abstract

Purpose : It has been suggested that changes in cerebral blood flow by ventilator care could be a risk factor in periventricular leukomalacia(PVL) and severe periventricular-intraventricular hemorrhage(PV-IVH). The study aims to assess the relationship between perinatal clinical events, including ventilator care, and the development of PVL and severe PV-IVH; especially, whether ventilator care could be causers of PVL and severe PV-IVH as an individual risk factor. Methods : Among 255 very low birth weight infants who survived in the Fatima neonatal intensive care unit from January 1999 to December 2003, 15 infants with PVL and eight infants with severe PV-IVH were classified as a study group, while 231 infants were enrolled as a control group. The analysis was performed retrospectively with medical records. Results : Twenty four infants were diagnosed with PVL or severe PV-IVH. Asphyxia, recurrent apnea, sepsis, acidosis and ventilator care were significantly increased in the PVL goup. Asphyxia, recurrent apnea, RDS, acidosis and ventilator care were significantly increased in the severe PV-IVH group. Conclusion : Infants with PVL or severe PV-IVH may have multiple perinatal risk factors including asphyxia, recurrent apnea, sepsis, acidosis, RDS and ventilator care. Because most patients with ventilator care have multiple perinatal risk factors, ventilator care does not cause PVL and severe PV-IVH independently. Therefore, incidences of PVL and severe PV-IVH can be decreased by not only gentle ventilation, but also more professional antenatal care.

목 적 : 최근 체계적인 산전 관리 및 다양한 인공호흡기 치료를 비롯한 신생아집중치료술의 발전은 극소저출생체중아 생존율의 많은 향상을 가져왔다. 그러나 극소저출생체중아에서의 허혈성, 저산소성손상의 주된 병변인 뇌실주위백질연화증 및 중증뇌실출혈의 발생 위험성은 여전히 크다. 두 질환에 있어 여러 가지 산전, 산후 위험요소와 더불어 신생아집중치료실에서의 인공호흡기 치료는 뇌혈류의 변화를 유발하는 위험인자로 간주되고 있다. 이에 인공호흡기 치료가 두 질환의 발생에 있어 위험인자로서 작용하는 지를 알아보고자 하였다. 방 법 : 1999년 1월부터 2003년 12월까지 5년간 대구파티마병원에서 출생한 신생아 중에서 신생아집중치료실에 1개월 이상 입원 치료를 받았던 출생체중 1,500 g 미만의 극소저출생체중아 255명을 대상으로 하였다. 이 중 뇌실주위백질연화증 환아 15명 및 중증뇌실출혈 환아 8명, 총 23명을 연구군으로 하였다. 전체 대상 255명 중 인공호흡기 치료를 받았던 환아는 139명이었다. 모든 대상아는 병력지를 기초로 산전 및 산후 병력 및 임상적 특성, 인공호흡기 치료 중 경과를 분석하였고, 뇌초음파검사 결과를 토대로 선별하였다. 결 과 : 전체 255례 중 뇌실주위백질연화증은 16례, 중증뇌실출혈은 8례였고, 출생체중이 작을수록 발생빈도는 더 높았다. 전체 대상 중 인공호흡기 치료병력이 있었던 환아가 139례였고 그 중 15례에서 뇌실주위백질연화증이, 8례에서 중증뇌실출혈이 발생하였다. 반면에, 인공호흡기 치료병력이 없었던 나머지 124례에서는 뇌실주위백질연화증 1례만이 발생하였다. 병력지를 기초로 한 후향적 조사에서 뇌실주위백질연화증과 연관되는 위험인자로서 유의할만한 것은 출생 시 가사(Apgar 점수<5), 무호흡, 인공호흡기 치료병력, 패혈증 및 산혈증이 있었고, 중증뇌실출혈의 경우는 출생 시 가사, 무호흡, 인공호흡기 치료병력, 호흡곤란증후군 및 산혈증이 유의할만 하였다. 인공호흡기 치료를 받았던 139례 중 두 질환군의 경우 이환되지 않았던 환아들에 비해 출생 당시 가사, 산혈증 및 무호흡의 병력이 더 많았고, 인공호흡기 치료 시 고농도의 흡입산소가 필요했던 경우와 장기간의 인공호흡기 치료가 필요했던 경우도 많았다. 결 론 : 다른 연구에서와 같이 본 연구에서도 인공호흡기 치료가 중증뇌실출혈과 뇌실주위백질연화증의 발생과 연관이 있는 것으로 나타났다. 그러나 분만 당시 인공호흡기 치료를 필요로 하는 선행 위험인자를 가지는 경우가 대부분이고, 또한 최근의 인공호흡기 치료기법의 발전으로 인해 인공호흡기 치료 자체가 중증뇌실출혈과 뇌실주위백질연화증의 직접적인 원인이라고 생각되어지지는 않으며 인공호흡기 치료가 요구되어지는 선행질환의 중증도가 더 직접적인 위험요소로 작용할 것으로 추정된다. 결론적으로 적절한 인공호흡기 치료와 더불어 보다 전문적인 산전 관리가 뇌실주위백질연화증 및 중증뇌실출혈의 발생빈도를 줄이는 중요한 수단이 될 것이라고 생각된다.

Keywords

References

  1. Tarby TJ, Volpe JJ. Intraventricular hemorrhage in the premature infant. Pediatr Clin North Am 1982;29:1077-104 https://doi.org/10.1016/S0031-3955(16)34248-1
  2. Perlman JM. White matter injury in the preterm infant : an important determinant of abnormal neurodevelopmental outcome. Early Human Dev 1998;53:99-120 https://doi.org/10.1016/S0378-3782(98)00037-1
  3. Perlman JM. Intraventricular hemorrhage. Pediatrics 1989; 84:913-4
  4. Hansen NB, Brubakk AM, Bratlid D, William OH, Stonetreet BS. The effects of variation in $PaCO_2$ on brain blood flow and cardiac output in the newborn piglet. Pediatr Res 1984;18:1132-6 https://doi.org/10.1203/00006450-198411000-00015
  5. Calvert SA, Hoskins EM, Fong KW, Forsyth SC. Etiologic factors associated with the development of periventricular leukomalacia. Acta Pediatr Scand 1987;76:254-9 https://doi.org/10.1111/j.1651-2227.1987.tb10456.x
  6. Gresen G, Munck H, Lou H. Severe hypocarbia in preterm infants and neurodevelopmental deficit. Acta Pediatr Scand 1987;76:401-4 https://doi.org/10.1111/j.1651-2227.1987.tb10489.x
  7. Pryds O. Control of cerebral circulation in the high-risk neonate. Ann Neurol 1997;30:321-9 https://doi.org/10.1002/ana.410300302
  8. Perlman JM, Risser R, Broyles RS. Bilateral cystic periventricular leukomalacia in the premature infant : associated risk factors. Pediatrics 1996;97:822-7
  9. Leviton A, Paneth N, Reuss ML. Maternal inefection, fetal inflammatory response, and brain damage in very low birth weight infants. Pediatr Res 1999;46:566-75 https://doi.org/10.1203/00006450-199911000-00013
  10. Perlman JM, Rollins N, Burns D, Risser Rick. Relationship between periventricular intraparenchymal echodensities and germinal matrix-intraventricular hemorrhage in the very low birth weight neonate. Pediatrics 1993;91:474-80
  11. Perlman JM, Rollins N. Surveillance protocol for the detection of intracranial abnormalities in premature neonates. Arch Pediatr Adolesc Med 2000;154:822-6 https://doi.org/10.1001/archpedi.154.8.822
  12. Philip AG, Allan WC, Tito AM, Wheeler LR. Intraventricular hemorrhage in preterm infants : declining incidence in the 1980s. Pediatrics 1989;84:797-801
  13. Perlman JM. White matter injury in the preterm infant : an important determination of abnormal neurodevelopment outcome. Early Hum Dev 1998;53:99-120 https://doi.org/10.1016/S0378-3782(98)00037-1
  14. Strauss A, Kirz D, Mandalou HD, Freeman RK. Perinatal events and intraventricular$_{}$ependymal hemorrhage in the very low-birth weight infant. Am J Obstet Gynecol 1985;151:1022-7 https://doi.org/10.1016/0002-9378(85)90373-4
  15. Jambleton G, Wiggelsworth JS. Origin of intraventricular hemorrhage in the preterm infant. Arch Dis Child 1976;57: 651-5
  16. Volpe JJ. Neonatal intraventricular hemorrhage. N Engl J Med 1981;304:886 https://doi.org/10.1056/NEJM198104093041506
  17. Tavares EC, Correa FF, Viana MB. Risk factors to periventricular- intraventricular hemorrhage in newborns weighing less than 2000 g. J Pediatr 1998;74:17-24 https://doi.org/10.2223/JPED.407
  18. van de Bor M, Verloove-Vanhorick SP, Brand R, Keirse MJ, Ruys JH. Incidence and prediction of periventricular-intraventricular hemorrhage in very preterm infants. J Perinat Med 1987;15:333-9 https://doi.org/10.1515/jpme.1987.15.4.333
  19. Stranak Z, Velebil P, Mechurova A. Influence of antenatal steroids on perinatal mortality and morbidity in extremely low birth weight. Sb Lek 2003;104:345-52
  20. Garland JS, Buck R, Leviton A. Effect of maternal glucocorticoid exposure on risk of severe intraventricular hemorrhage in surfactant-treated preterm infants. J Pediatr 1995;126:272-93-6 https://doi.org/10.1016/S0022-3476(95)70560-0
  21. Perlman JM, Risser R, Broyles RS. Bilateral cystic periventricular leukomalacia in premature infant : associated risk factors. American Academy of Pediatrics 1996;97:822-7
  22. Volpe JJ. Brain injury in the premature infant-current concepts of pathogenesis and prevention. Biol Neonate 1992;62: 231-42 https://doi.org/10.1159/000243876
  23. Cavazzutti M, Duffy TE. Regulation of cerebral blood flow in normal and hypoxic newborn dogs. Ann Neurol 1982;11: 247-54 https://doi.org/10.1002/ana.410110304
  24. Young RSK, Hernandez MJ, Yagel SK. Selective reduction of blood flow to white matter during hypotention in newborn dogs. A possible mechanism of periventricular leukomalacia. Ann Neruol 1982;12:445-52 https://doi.org/10.1002/ana.410120506
  25. Rice JE III, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 1981;9:131-41 https://doi.org/10.1002/ana.410090206
  26. Bejar RF, Vaucher YE, Benirschke K, Berry CC. Postnatal white matter necrosis in preterm infant. J Perinatol 1992; 12:3-8
  27. Schman RM, Selednik LJ. Periventricular leukomalacia : a one-year autopsy study. Arch Neurol 1980;37:231-5.ms-e https://doi.org/10.1001/archneur.1980.00500530069011
  28. Preds O, Greisen G, Lou H, Friis-Hansen B. Heterogeneity of cerebral vasoreactivity in preterm infants supported by mechanical ventilation. J Pediatr 1989;115:638-45 https://doi.org/10.1016/S0022-3476(89)80301-4
  29. Gannon CM, Wiswell TE, Spitzer AR. Volutrauma, PaCO2 levels, and neurodevelopmental sequelae following assisted ventilation. Clin Perinatol 1998;25:159-75
  30. Okumura A, Hayakawa F, Kato T, Itomi K, Maruyama K, Ishihara N, et al. Hypocarbia in preterm infants with periventricular leukomalacia : the relation between hypocarbia and mechanical ventilation. Pediatrics 2001;107:469-75 https://doi.org/10.1542/peds.107.3.469
  31. Wiswell TE, Graziani LJ, Kornhauser MS, Stanley C, Merton DA, McKee L, et al. Effects of hypocarbia on the development of cystic periventricular leukomalacia in premature infants treated with high-freqeuncy jet ventilation. Pediatrics 1996;98:918-24
  32. Collins MP, Lorenz JM, Jetton JR, Paneth N. Hypocarpnia and other ventilation-related risk factors for cerebral palsy in low birth weight infants. Pediatr Res 2001;50:712-9 https://doi.org/10.1203/00006450-200112000-00014
  33. Graziani LJ, Spitzer AR, Mitchell DG, Merton DA, Stanley C, Robinson N. Mechanical ventilation in preterm infants : neurosonographic and development studies. Pediatrics 1992; 90:515-21
  34. Wung JT. Mechanical ventilation of the newborn. Respiratory care for the newborn. 9th ed. Columbia : Presbyterian Medical Center, 1996:9-33
  35. Wung JT. Continuous positive airway pressure. Respiratory care for the newborn. 9th ed. Columbia : Presbyterian Medical Center, 1996:1-8
  36. Verder H, Robertson B, Greisen G. Surfactant treatment and nasal continuous positive airway pressure for newborn with respiratory distress syndrome. N Engl J Med 1994; 331:1051-64 https://doi.org/10.1056/NEJM199410203311603
  37. Bass WT, Kopelman AE. Central nervous system morbidity. In : Goldsmith JP, Karotkin EH, editors. Assisted ventilation of the neonate. 4th ed. Philadelphia : Saunders, 2003:429-48
  38. Levene MI, Fawer CL, Lamont RF. Risk factors in the development of intraventricular haemorrhage in the preterm neonate. Arch Dis Child 1982;57:410-7 https://doi.org/10.1136/adc.57.6.410
  39. Clark RH. High frequency ventilation. J Pediatr 1994;124: 661-70 https://doi.org/10.1016/S0022-3476(05)81352-6
  40. Mark CM, Stephen JB. High frequency ventilation. Assisted ventilation of the neonate. 3rd ed. Philadelphia : WB Saunders Co, 1996;199-214