Neonatal Medicine

The Korean Society of Neonatology (대한신생아학회)
권호 표지
DOI QR코드

DOI QR Code

Management of Persistent Pulmonary Hypertension in Preterm Infants

  • Lee, Byong Sop (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2020.09.09
  • Accepted : 2020.10.20
  • Published : 2021.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is a consequence of the failure of a decrease in the elevated pulmonary vascular resistance after birth. Pulmonary vasodilators, including inhaled nitric oxide (iNO), have been the mainstream of targeted therapy for PPHN, but no drugs have been proven to be effective in preterm infants with PPHN. The fetus remains hemodynamically stable despite lower arterial oxygen tension and pulmonary blood flow as compared to full-term newborns. This adaptation is due to the lower oxygen requirement and high oxygen-carrying capacity of fetal circulation. The immature lungs of preterm infants are more vulnerable to reactive oxygen species, and the response of pulmonary vascular dilatation to blood oxygen tension is blunted in preterm infants. Recently, iNO has been reported to be effective in a selected group of preterm infants, such as those with prolonged preterm rupture of membrane-oligohydramnios-pulmonary hypoplasia sequence. PPHN in preterm infants, along with maximum supportive treatment based on fetal physiology and meticulous assessment of cardiovascular function, is in dire need of new treatment guidelines, including optimal dosing strategies for pulmonary vasodilators.

Keywords

References

  1. Martinho S, Adao R, Leite-Moreira AF, Bras-Silva C. Persistent pulmonary hypertension of the newborn: pathophysiological mechanisms and novel therapeutic approaches. Front Pediatr 2020;8:342. https://doi.org/10.3389/fped.2020.00342
  2. 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. https://doi.org/10.1038/sj.jp.7211673
  3. Nakanishi H, Suenaga H, Uchiyama A, Kusuda S; Neonatal Research Network, Japan. Persistent pulmonary hypertension of the newborn in extremely preterm infants: a Japanese cohort study. Arch Dis Child Fetal Neonatal Ed 2018;103:F554-61. https://doi.org/10.1136/archdischild-2017-313778
  4. Jain A, McNamara PJ. Persistent pulmonary hypertension of the newborn: advances in diagnosis and treatment. Semin Fetal Neonatal Med 2015;20:262-71. https://doi.org/10.1016/j.siny.2015.03.001
  5. Barrington KJ, Finer N, Pennaforte T, Altit G. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 2017;1:CD000399.
  6. Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev 2017;1:CD000509.
  7. Van Meurs KP, Wright LL, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, et al. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med 2005;353:13-22. https://doi.org/10.1056/NEJMoa043927
  8. Ha J, Lee EH, Park HK, Choi BM. Clinical status of inhaled nitric oxide treatment in infants with persistent pulmonary hypertension of the newborn in Korea: post-marketing surveillance results. Neonatal Med 2020;27:57-64. https://doi.org/10.5385/nm.2020.27.2.57
  9. Suzuki S, Togari H, Potenziano JL, Schreiber MD. Efficacy of inhaled nitric oxide in neonates with hypoxic respiratory failure and pulmonary hypertension: the Japanese experience. J Perinat Med 2018;46:657-63. https://doi.org/10.1515/jpm-2017-0040
  10. Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, et al. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation 2015;132:2037-99. https://doi.org/10.1161/CIR.0000000000000329
  11. de Waal K, Kluckow M. Prolonged rupture of membranes and pulmonary hypoplasia in very preterm infants: pathophysiology and guided treatment. J Pediatr 2015;166:1113-20. https://doi.org/10.1016/j.jpeds.2015.01.015
  12. Aikio O, Metsola J, Vuolteenaho R, Perhomaa M, Hallman M. Transient defect in nitric oxide generation after rupture of fetal membranes and responsiveness to inhaled nitric oxide in very preterm infants with hypoxic respiratory failure. J Pediatr 2012;161:397-403. https://doi.org/10.1016/j.jpeds.2012.03.008
  13. Rasanen J, Wood DC, Weiner S, Ludomirski A, Huhta JC. Role of the pulmonary circulation in the distribution of human fetal cardiac output during the second half of pregnancy. Circulation 1996;94:1068-73. https://doi.org/10.1161/01.CIR.94.5.1068
  14. Lakshminrusimha S, Saugstad OD. The fetal circulation, pathophysiology of hypoxemic respiratory failure and pulmonary hypertension in neonates, and the role of oxygen therapy. J Perinatol 2016;36 Suppl 2:S3-11. https://doi.org/10.1038/jp.2016.43
  15. Rasanen J, Wood DC, Debbs RH, Cohen J, Weiner S, Huhta JC. Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: a randomized study. Circulation 1998;97:257-62. https://doi.org/10.1161/01.CIR.97.3.257
  16. Berkelhamer SK, Farrow KN. Developmental regulation of antioxidant enzymes and their impact on neonatal lung disease. Antioxid Redox Signal 2014;21:1837-48. https://doi.org/10.1089/ars.2013.5515
  17. Steinhorn RH. Pulmonary vascular development. In: Martin RJ, Fanaroff AA, Walsh MC, editors. Fanaroff and Martin's Neonatal-Perinatal Medicine. 11th ed. Philadelphia: Elsevier, 2020:1306-19.
  18. Porta NF, Steinhorn RH. Pulmonary vasodilator therapy in the NICU: inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents. Clin Perinatol 2012;39:149-64. https://doi.org/10.1016/j.clp.2011.12.006
  19. Lakshminrusimha S, Swartz DD, Gugino SF, Ma CX, Wynn KA, Ryan RM, et al. Oxygen concentration and pulmonary hemodynamics in newborn lambs with pulmonary hypertension. Pediatr Res 2009;66:539-44. https://doi.org/10.1203/PDR.0b013e3181bab0c7
  20. Gonzalez A, Fabres J, D'Apremont I, Urcelay G, Avaca M, Gandolfi C, et al. Randomized controlled trial of early compared with delayed use of inhaled nitric oxide in newborns with a moderate respiratory failure and pulmonary hypertension. J Perinatol 2010;30:420-4. https://doi.org/10.1038/jp.2009.171
  21. Dani C, Corsini I, Cangemi J, Vangi V, Pratesi S. Nitric oxide for the treatment of preterm infants with severe RDS and pulmonary hypertension. Pediatr Pulmonol 2017;52:1461-8. https://doi.org/10.1002/ppul.23843
  22. Baczynski M, Ginty S, Weisz DE, McNamara PJ, Kelly E, Shah P, et al. Short-term and long-term outcomes of preterm neonates with acute severe pulmonary hypertension following rescue treatment with inhaled nitric oxide. Arch Dis Child Fetal Neonatal Ed 2017;102:F508-14. https://doi.org/10.1136/archdischild-2016-312409
  23. Cho JY, Lee BS, Oh MY, Cha T, Jeong J, Jung E, et al. Response to inhaled nitric xxide and clinical outcome in very low birth weight infants with early pulmonary hypertension. Neonatal Med 2020;27:133-40. https://doi.org/10.5385/nm.2020.27.3.133
  24. van Kempen LEM, van Teeffelen AS, de Ruigh AA, Oepkes D, Haak MC, van Leeuwen E, et al. Amnioinfusion compared with no intervention in women with second-trimester rupture of membranes: a randomized controlled trial. Obstet Gynecol 2019;133:129-36. https://doi.org/10.1097/AOG.0000000000003003
  25. Roberts D, Vause S, Martin W, Green P, Walkinshaw S, Bricker L, et al. Amnioinfusion in very early preterm prelabor rupture of membranes (AMIPROM): pregnancy, neonatal and maternal outcomes in a randomized controlled pilot study. Ultrasound Obstet Gynecol 2014;43:490-9. https://doi.org/10.1002/uog.13258
  26. Committee Opinion No. 684 Summary: delayed umbilical cord clamping after birth. Obstet Gynecol 2017;129:232-3. https://doi.org/10.1097/AOG.0000000000001855
  27. Vali P, Lakshminrusimha S. The fetus can teach us: oxygen and the pulmonary vasculature. Children (Basel) 2017;4:67. https://doi.org/10.3390/children4080067
  28. Lakshminrusimha S, Keszler M. Persistent pulmonary hypertension of the newborn. Neoreviews 2015;16:e680-92. https://doi.org/10.1542/neo.16-12-e680
  29. Nair J, Lakshminrusimha S. Update on PPHN: mechanisms and treatment. Semin Perinatol 2014;38:78-91. https://doi.org/10.1053/j.semperi.2013.11.004
  30. Qasim A, Jain SK. Milrinone use in persistent pulmonary hypertension of the newborn. Neoreviews 2020;21:e165-78. https://doi.org/10.1542/neo.21-3-e165
  31. Kelly LE, Ohlsson A, Shah PS. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev 2017;8:CD005 494.
  32. James AT, Bee C, Corcoran JD, McNamara PJ, Franklin O, El-Khuffash AF. Treatment of premature infants with pulmonary hypertension and right ventricular dysfunction with milrinone: a case series. J Perinatol 2015;35:268-73. https://doi.org/10.1038/jp.2014.208
  33. Shivanna B, Gowda S, Welty SE, Barrington KJ, Pammi M. Prostanoids and their analogues for the treatment of pulmonary hypertension in neonates. Cochrane Database Syst Rev 2019;10:CD012963.
  34. Park BY, Chung SH. Treprostinil for persistent pulmonary hypertension of the newborn, with early onset sepsis in preterm infant: 2 case reports. Medicine (Baltimore) 2017;96:e7303. https://doi.org/10.1097/md.0000000000007303