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Pulmonary Hypertension Secondary to Bronchopulmonary Dysplasia in Very Low Birth Weight Infants (<1,500 g)

기관지 폐 이형성증을 가진 극소 저체중 출생아에서 폐고혈압증

  • Yoo, Hye-Soo (Department of Pediatrics, Ilsan Paik Hospital, Inje University School of Medicine) ;
  • Kim, Myo-Jing (Department of Pediatrics, Dong-A Medical Center, Dong-A University School of Medicine) ;
  • Kang, Ji-Man (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Cha-Gon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Jin-Kyu (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ahn, So-Yoon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Eun-Sun (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Huh, June (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Chang, Yun-Sil (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kang, I-Seok (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Won-Soon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Heung-Jae (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 유혜수 (인제대학교 의과대학 일산백병원 소아과학교실) ;
  • 김묘징 (동아대학교 의과대학 동아대병원 소아과학교실) ;
  • 강지만 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 이차곤 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 김진규 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 안소윤 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 김은선 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 허준 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 장윤실 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 강이석 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 박원순 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 이흥재 (성균관대학교 의과대학 삼성서울병원 소아과학교실)
  • Published : 2011.05.31

Abstract

Purpose: Although infants with bronchopulmonary dysplasia (BPD) are at risk of developing secondary pulmonary hypertension (PH), which is associated with significant morbidity and mortality, little has been reported about the incidence, clinical course and prognosis of PH secondary to BPD in premature infants. This study was done to investigate the incidence, risk factors, clinical course, and the ultimate prognosis of PH developed secondary to BPD in very low birth weight infants (<1,500 g). Methods: Medical records of very low birth weight infant (VLBWI) admitted to Samsung Medical Center NICU from January 2000 to July 2007 were reviewed retrospectively. BPD was defined by Jobe's classification. The diagnosis of pulmonary hypertension was established as velocity of tricuspid valve regurgitation (TR) ${\geq}$3 m/s and a flattening of the intraventricular septum by conducting Doppler echocardiography. Results: The incidence of pulmonary hypertension was 6% in VLBWI with BPD and it developed in moderate to severe BPD. The diagnosis of pulmonary hypertension was made on postnatal 133 days (range 40-224 days) and the risk factors related to developing pulmonary hypertension were severe BPD, small for gestational age and outborn infants. The mortality rate was 57% and especially higher in severe BPD (70%). The time to recovery spent 3 months (range 1-10 months) in survived patients. Conclusion: Based on the results of this research, pulmonary hypertension secondary to BPD in VLBWI related to severity of BPD and had a poor prognosis. We expect that regular long-term echocardiography may be helpful in treating reversible in VLBWI with moderate to severe BPD.

목적: 극소 저체중 출생아에서 폐고혈압증은 기관지 폐 이형성증의 대표적인 심폐관련 합병증으로 높은 사망률과 합병증과 연관되어 있으나, 이에 대한 연구는 드문 실정이다. 이에 본 저자들은 기관지 폐 이형성증을 가진 극소 저체중 출생아에서 폐고혈압증의 유병률, 경과 및 치료뿐 아니라 예후 및 이와 관련된 인자들에 대해 확인해 보고자 하였다. 방법: 2000년 1월부터 2007년 7월까지 성균관대학교 의과대학 삼성서울병원 신생아 집중치료실에 입원한 출생 체중 1,500g 미만 환아 865명 중 28일 이상 산소 치료를 필요로 하였던220명을 대상으로 하였다. 심장 초음파 검사상 삼첨판 역류 속도 3 m/s 이상이 확인되면서, 우심실 비대 혹은 심실 중격이 평형함이 관찰되는 경우를 폐고혈압으로 진단하였으며, 이들을 대조군과 비교하였다. 환아들의 의무기록을 후향적으로 분석하여, 인구학적, 주산기 인자, 합병증, 사망률을 비교하였으며, 폐고혈압증을 가진 환아 중 사망군과 생존군으로 나누어 이들의 특성 및 관련인자를 분석하였다. 결과: 기관지 폐 이형성증을 가진 VLBWI 218명 중 14명(6%)에서 폐고혈압증이 발생하였으며, 모두 중등도 이상의 기관지 폐 이형성증에서 발생하였다. 폐고혈압증은 평균 생후 133일(40-224일)에 진단 받았으며, 중증 기관지 폐 이형성증, 부당 경량아, 외부 환아는 폐고혈압증 발생과 관련된 인자이다. 기관지 폐 이형성증에서 발생한 폐고혈압증의 사망률은 57%이며, 중증 기관지 폐 이형성증은 사망의 중요한 원인이다. 생존한 환아에서 회복되는데 까지 걸리는 시간은 평균 3개월이었다 결론: 극소 저체중 출생아에서 기관지 폐 이형성증과 관련된 폐고혈압증은 높은 사망률 및 합병증을 보이며, 이들의 발생 및 예후는 기관지 폐 이형성증 정도와 연관성이 있다. 이들의 조기진단을 위해 중등도 이상의 기관지 폐 이형성증 환아에서 정기적인 선별검사 및 퇴원 이후에도 장기간 지속적인 추적 관찰이 필요하다.

Keywords

References

  1. Effer SB, Moutquin JM, Farine D, Saigal S, Nimrod C, Kelly E, et al. Neonatal survival rates in 860 singleton live births at 24 and 25 weeks gestational age. A Canadian multicentre study. BJOG 2002;109:740- 5. https://doi.org/10.1111/j.1471-0528.2002.01067.x
  2. El-Metwally D, Vohr B, Tucker R. Survival and neonatal morbidity at the limits of viability in the mid 1990s: 22 to 25 weeks. J Pediatr 2000;137:616-22. https://doi.org/10.1067/mpd.2000.109143
  3. La Pine TR, Jackson JC, Bennett FC. Outcome of infants weighing less than 800 grams at birth: 15 years' experience. Pediatrics 1995; 96:479-83.
  4. Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH, Cotton RB, et al. Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics 1987;79:26-30.
  5. Gray PH, Burns YR, Mohay HA, O'Callaghan MJ, Tudehope DI. Neurodevelopmental outcome of preterm infants with bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed 1995;73: F128-34. https://doi.org/10.1136/fn.73.3.F128
  6. Danhaive O, Margossian R, Geva T, Kourembanas S. Pulmonary hypertension and right ventricular dysfunction in growth-restricted, extremely low birth weight neonates. J Perinatol 2005;25:495-9. https://doi.org/10.1038/sj.jp.7211299
  7. Gorenflo M, Vogel M, Obladen M. Pulmonary vascular changes in bronchopulmonary dysplasia: a clinicopathologic correlation in short- and long-term survivors. Pediatr Pathol 1991;11:851-66. https://doi.org/10.3109/15513819109065482
  8. Hislop AA, Haworth SG. Pulmonary vascular damage and the development of cor pulmonale following hyaline membrane disease. Pediatr Pulmonol 1990;9:152-61. https://doi.org/10.1002/ppul.1950090306
  9. Kasian GF, Ninan A, Duncan WJ, Bingham WT, Mersal A, Tyrrell MJ, et al. Treatment of pulmonary hypertension with diltiazem in a child with bronchopulmonary dysplasia. Can J Cardiol 1988;4:181- 4.
  10. Parker TA, Abman SH. The pulmonary circulation in bronchopulmonary dysplasia. Semin Neonatol 2003;8:51-61. https://doi.org/10.1016/S1084-2756(02)00191-4
  11. Farquhar M, Fitzgerald DA. Pulmonary hypertension in chronic neonatal lung disease. Paediatr Respir Rev 2010;11:149-53. https://doi.org/10.1016/j.prrv.2010.05.001
  12. Kumar VH, Hutchison AA, Lakshminrusimha S, Morin FC, 3rd, Wynn RJ, Ryan RM. Characteristics of pulmonary hypertension in preterm neonates. J Perinatol 2007;27:214-9.
  13. Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC, et al. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics 2007;120:1260-9. https://doi.org/10.1542/peds.2007-0971
  14. An HS, Bae EJ, Kim GB, Kwon BS, Beak JS, Kim EK, et al. Pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Korean Circ J 2010;40:131-6. https://doi.org/10.4070/kcj.2010.40.3.131
  15. Dhillon R. The management of neonatal pulmonary hypertension. Arch Dis Child Fetal Neonatal Ed. In press 2011.
  16. Hon KL, Cheung KL, Siu KL, Leung TF, Yam MC, Fok TF, et al. Oral sildenafil for treatment of severe pulmonary hypertension in an infant. Biol Neonate 2005;88:109-12. https://doi.org/10.1159/000085646
  17. Tourneux P, Markham N, Seedorf G, Balasubramaniam V, Abman SH. Inhaled nitric oxide improves lung structure and pulmonary hypertension in a model of bleomycin-induced bronchopulmonary dysplasia in neonatal rats. Am J Physiol Lung Cell Mol Physiol 2009;297:L1103-11. https://doi.org/10.1152/ajplung.00293.2009
  18. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723-9. https://doi.org/10.1164/ajrccm.163.7.2011060
  19. Walsh MC, Szefler S, Davis J, Allen M, Van Marter L, Abman S, et al. Summary proceedings from the bronchopulmonary dysplasia group. Pediatrics 2006;117:S52-6.
  20. Srivastava MC, Ramani GV, Garcia JP, Griffith BP, Uber PA, Park MH. Veno-venous extracorporeal membrane oxygenation bridging to pharmacotherapy in pulmonary arterial hypertensive crisis. J Heart Lung Transplant 2010;29:811-3. https://doi.org/10.1016/j.healun.2010.02.005
  21. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978;92:529-34. https://doi.org/10.1016/S0022-3476(78)80282-0
  22. Maalouf EF, Duggan PJ, Counsell SJ, Rutherford MA, Cowan F, Azzopardi D, et al. Comparison of findings on cranial ultrasound and magnetic resonance imaging in preterm infants. Pediatrics 2001;107:719-27. https://doi.org/10.1542/peds.107.4.719
  23. Wadhawan R, Oh W, Perritt R, Laptook AR, Poole K, Wright LL, et al. Association between early postnatal weight loss and death or BPD in small and appropriate for gestational age extremely low-birthweight infants. J Perinatol 2007;27:359-64. https://doi.org/10.1038/sj.jp.7211751
  24. Westby Wold SH, Sommerfelt K, Reigstad H, Ronnestad A, Medbo S, Farstad T, et al. Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study. Arch Dis Child Fetal Neonatal Ed 2009;94:F363-7. https://doi.org/10.1136/adc.2009.157800
  25. Kim GB. Pulmonary hypertension in infants with bronchopulmonary dysplasia. Korean J Pediatr 2010;53:688-93. https://doi.org/10.3345/kjp.2010.53.6.688
  26. Zellers T, Gutgesell HP. Noninvasive estimation of pulmonary artery pressure. J Pediatr 1989;114:735-41. https://doi.org/10.1016/S0022-3476(89)80129-5
  27. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984;70:657-62. https://doi.org/10.1161/01.CIR.70.4.657
  28. Subhedar NV. Recent advances in diagnosis and management of pulmonary hypertension in chronic lung disease. Acta Paediatr Suppl 2004;93:29-32.
  29. Bentlin MR, Saito A, De Luca AK, Bossolan G, Bonatto RC, Martins AS, et al. [Sildenafil for pulmonary hypertension treatment after cardiac surgery]. J Pediatr (Rio J) 2005;81:175-8.
  30. Hoeper MM, Galiè N, Simonneau G, Rubin LJ. New treatments for pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:1209-16. https://doi.org/10.1164/rccm.200110-028PP
  31. Lee AJ, Chiao TB, Tsang MP. Sildenafil for pulmonary hypertension. Ann Pharmacother 2005;39:869-84. https://doi.org/10.1345/aph.1E426
  32. Zaidi AN, Dettorre MD, Ceneviva GD, Thomas NJ. Epoprostenol and home mechanical ventilation for pulmonary hypertension associated with chronic lung disease. Pediatr Pulmonol 2005;40: 265-9. https://doi.org/10.1002/ppul.20238
  33. Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology 1999;91:307-10. https://doi.org/10.1097/00000542-199907000-00041
  34. Chatterjee K, De Marco T, Alpert JS. Pulmonary hypertension: hemodynamic diagnosis and management. Arch Intern Med 2002;1 62:1925-33.
  35. Murase M, Ishida A. Serial pulsed Doppler assessment of pulmonary artery pressure in very low birth-weight infants. Pediatr Cardiol 2000;21:452-7. https://doi.org/10.1007/s002460010107
  36. Solis A, Harrison G, Shaw BN. Assessing oxygen requirement after discharge in chronic lung disease: a survey of current practice. Eur J Pediatr 2002;161:428-30. https://doi.org/10.1007/s00431-002-0991-z
  37. Abman SH, Accurso FJ, Bowman CM. Unsuspected cardiopulmonary abnormalities complicating bronchopulmonary dysplasia. Arch Dis Child 1984;59:966-70. https://doi.org/10.1136/adc.59.10.966
  38. Abman SH. Monitoring cardiovascular function in infants with chronic lung disease of prematurity. Arch Dis Child Fetal Neonatal Ed 2002;87:F15-8. https://doi.org/10.1136/fn.87.1.F15

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