Pathophysiology, management, and outcome of persistent pulmonary hypertension of the newborn: a clinical review

Mohammed Puthiyachirakkal, Maroun J Mhanna, Mohammed Puthiyachirakkal, Maroun J Mhanna

Abstract

Persistent Pulmonary Hypertension of the Newborn (PPHN) results from the failure of relaxation of the pulmonary vasculature at birth, leading to shunting of non-oxygenated blood from the pulmonary to the systemic circulation. More often, full term and near-term infants are affected, however it is not uncommon to see PPHN in preterm infants who have respiratory distress syndrome. In some infants pulmonary vascular remodeling is present at birth, pointing toward the prenatal onset of the disease process. Regardless of the etiology, PPHN should be diagnosed and treated as soon as possible to avoid hypoxia related short term and long-term morbidities. The mainstay therapy is the treatment of the underlying condition along with several promising therapeutic modalities such as oxygen supplementation, mechanical ventilation, nitric oxide, phosphodiesterase inhibitors, prostaglandins analogs, endothelin receptor antagonists, and extracorporeal membrane oxygenation. The optimal approach to the management of PPHN remains controversial. After discharge from the NICU, infants with PPHN warrant long-term follow up since they are at risk for neurodevelopmental disabilities and chronic health conditions.

Keywords: newborn; outcome; pathophysiology; persistent pulmonary hypertension; treatment.

Figures

Figure 1
Figure 1
Factors affecting the pulmonary vasculature tone. PAF, platelet activating factor; ET1, endothelin-1; ROS, reactive oxygen species; RhoA-ROK, Rho A-Rho kinase; O2, oxygen; CO2, carbon dioxide; NO, nitric oxide; PG, prostaglandins.

References

    1. Gao Y, Raj JU. Regulation of the pulmonary circulation in the fetus and newborn. Physiol Rev (2010) 90:1291–33510.1152/physrev.00032.2009
    1. Konduri GG, Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatr Clin North Am (2009) 56:579–60010.1016/j.pcl.2009.04.004
    1. Soll RF. Inhaled nitric oxide in the neonate. J Perinatol (2009) 29(Suppl 2):S63–710.1038/jp.2009.40
    1. Guyatt G, Gutterman D, Baumann M, Addrizzo-Harris D, Hylek E, Phillips B, et al. Grading strength of recommendations and quality of evidence in clinical guidelines. Chest (2006) 129:174–181
    1. Rudolph AM. Distribution and regulation of blood flow in the fetal and neonatal lamb. Circ Res (1985) 57(6):811–2110.1161/01.RES.57.6.811
    1. Steinhorn RH, Farrow KN. Pulmonary hypertension in the neonate. Neoreviews (2007) 8:e14–2110.1542/neo.8-1-e14
    1. Ostrea EM, Villanueva ET, Natarajan G, Herbert G. Persistent pulmonary hypertension of the newborn: pathogenesis, etiology, and management. Pediatr Drugs (2006) 8(3):179–8810.2165/00148581-200608030-00004
    1. Roofthooft MTR, Elema A, Bergman KA, Berger RMF. Patient characteristics in persistent pulmonary hypertension of the newborn. Pulm Med (2011) 2011:858154.
    1. Swarnam K, Soraisham AS, Sindhu S. Advances in the management of meconium aspiration syndrome. Int J Pediatr (2012) 2012:359571.10.1155/2012/359571
    1. Hsieh TK, Su BH, Chen AC, Lin TW, Tsai CH, Lin HC. Risk factors of meconium aspiration syndrome developing into persistent pulmonary hypertension of newborn. Acta Paediatr Taiwan (2004) 45(4):203–7
    1. Abman SH. Abnormal vasoreactivity in the pathophysiology of persistent pulmonary hypertension of the newborn. Pediatr Rev (1999) 20:e103–10
    1. Hernández-Díaz S, van Marter LJ, Werler MM, Louik C, Mitchell AA. Risk factors for persistent pulmonary hypertension of the newborn. Pediatrics (2007) 120(2):e272–8210.1542/peds.2006-3037
    1. Winovitch KC, Padilla L, Ghamsary M, Lagrew DC, Wing DA. Persistent pulmonary hypertension of the newborn following elective cesarean delivery at term. J Matern Fetal Neonatal Med (2011) 24(11):1398–40210.3109/14767058.2010.551681
    1. Woldesenbet M, Perlman JM. Histologic chorioamnionitis: an occult marker of severe pulmonary hypertension in the term newborn. J Perinatol (2005) 25(3):189–9210.1038/sj.jp.7211240
    1. Koren G, Nordeng H. Antidepressant use during pregnancy: the benefit-risk ratio. Am J Obstet Gynecol (2012) 207(3):157–6310.1016/j.ajog.2012.02.009
    1. ‘t Jong GW, Einarson T, Koren G, Einarson A. Antidepressant use in pregnancy and persistent pulmonary hypertension of the newborn (PPHN): a systematic review. Reprod Toxicol (2012) 34(3):293–710.1016/j.reprotox.2012.04.015
    1. Lim K, Sanders A, Brain U, Riggs W, Oberlander TF, Rurak D. Third trimester fetal pulmonary artery Doppler blood flow velocity characteristics following prenatal selective serotonin reuptake inhibitor (SSRI) exposure. Early Hum Dev (2012) 88(8):609–1510.1016/j.earlhumdev.2012.01.004
    1. van Marter LJ, Hernandez-Diaz S, Werler MM, Louik C, Mitchell AA. Nonsteroidal anti-inflammatory drugs in late pregnancy and persistent pulmonary hypertension of the newborn. Pediatrics (2013) 131(1):79–8710.1542/peds.2012-0496
    1. Alano MA, Ngougmna E, Ostrea EM, Jr., Konduri GG. Analysis of nonsteroidal anti-inflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn. Pediatrics (2001) 107(3):519–2310.1542/peds.107.3.519
    1. Curtis J, Kim G, Wehr NB, Levine RL. Group B Streptococcus, phospholipids and pulmonary hypertension. J Perinatol (2011) 31(Suppl 1):S24–810.1038/jp.2010.168
    1. Waites KB, Crouse DT, Philips JB, III, Canupp KC, Cassell GH. Ureaplasma pneumonia and sepsis associated with persistent pulmonary hypertension of the newborn. Pediatrics (1989) 83(1):79–85
    1. Thoresen M. Hypothermia after perinatal asphyxia: selection for treatment and cooling protocol. J Pediatr (2011) 2(Suppl):e45–910.1016/j.jpeds.2010.11.013
    1. Eicher DJ, Wagner CL, Katikaneni LP, Hulsey TC, Bass WT, Kaufman DA, et al. Moderate hypothermia in neonatal encephalopathy: safety outcomes. Pediatr Neurol (2005) 32(1):18–2410.1016/j.pediatrneurol.2004.06.014
    1. Fox WW, Duara S. Persistent pulmonary hypertension in the neonate: diagnosis and management. J Pediatr (1983) 103(4):505–1410.1016/S0022-3476(83)80573-3
    1. Dhillon R. The management of neonatal pulmonary hypertension. Arch Dis Child Fetal Neonatal Ed (2012) 97(3):F223–810.1136/adc.2009.180091
    1. Reynolds EW, Ellington JG, Vranicar M, Bada HS. Brain-type natriuretic peptide in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatrics (2004) 114(5):1297–30410.1542/peds.2004-0525
    1. Vijlbrief DC, Benders MJ, Kemperman H, van Bel F, de Vries WB. B-type natriuretic peptide and rebound during treatment for persistent pulmonary hypertension. J Pediatr (2012) 160(1):111–5.e110.1016/j.jpeds.2011.06.038
    1. Logan JW, Goldberg RN, Cotten CM. Congenital diaphragmatic hernia: a systematic review and summary of best-evidence practice strategies. J Perinatol (2007) 27(9):535–4910.1038/sj.jp.7211794
    1. Lotze A, Mitchell BR, Bulas DI, Zola EM, Shalwitz RA, Gunkel JH. Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. Survanta in Term Infants Study Group. J Pediatr (1998) 132(1):40–710.1016/S0022-3476(98)70482-2
    1. Gadzinowski J, Kowalska K, Vidyasagar D. Treatment of MAS with PPHN using combined therapy: SLL, bolus surfactant and iNO. J Perinatol (2008) 28(Suppl 3):S56–6610.1038/jp.2008.163
    1. Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, et al. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group. Pediatrics (1998) 101(3 Pt 1):325–3410.1542/peds.101.3.325
    1. Kinsella JP. Clinical trials of inhaled nitric oxide therapy in the newborn. Pediatr Rev (1999) 20:e110.
    1. Shivananda S, Ahliwahlia L, Kluckow M, Luc J, Jankov R, McNamara P. Variation in the management of persistent pulmonary hypertension of the newborn: a survey of physicians in Canada, Australia, and New Zealand. Am J Perinatol (2012) 29(7):519–2610.1055/s-0032-1310523
    1. Shah PS, Ohlsson A. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev (2011) 10(8):CD005494.
    1. Steinhorn RH, Kinsella JP, Pierce C, Butrous G, Dilleen M, Oakes M, et al. Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension. J Pediatr (2009) 155(6):841–847.e110.1016/j.jpeds.2009.06.012
    1. Kehat R, Bonsall DJ, North R, Connors B. Ocular findings of oral sildenafil use in term and near-term neonates. J AAPOS (2010) 14(2):159–6210.1016/j.jaapos.2009.12.161
    1. Bassler D, Kreutzer K, McNamara P, Kirpalani H. Milrinone for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev (2010) 10(11):CD007802.
    1. Rao S, Bartle D, Patole S. Current and future therapeutic options for persistent pulmonary hypertension in the newborn. Expert Rev Cardiovasc Ther (2010) 8(6):845–6210.1586/erc.09.186
    1. Nakwan N, Choksuchat D, Saksawad R, Thammachote P, Nakwan N. Successful treatment of persistent pulmonary hypertension of the newborn with bosentan. Acta Paediatr (2009) 98(10):1683–510.1111/j.1651-2227.2009.01386.x
    1. Mohamed WA, Ismail M. A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. J Perinatol (2012) 32(8):608–1310.1038/jp.2011.157
    1. Lazar DA, Cass DL, Olutoye OO, Welty SE, Fernandes CJ, Rycus PT, et al. The use of ECMO for persistent pulmonary hypertension of the newborn: a decade of experience. J Surg Res (2012) 177(2):263–710.1016/j.jss.2012.07.058
    1. Rosenberg AA, Lee NR, Vaver KN, Werner D, Fashaw L, Hale K, et al. School-age outcomes of newborns treated for persistent pulmonary hypertension. J Perinatol (2010) 30(2):127–3410.1038/jp.2009.139
    1. The Neonatal Inhaled Nitric Oxide Study Group Inhaled nitric oxide in term and near-term infants: neurodevelopmental follow-up of the neonatal inhaled nitric oxide study group (NINOS). J Pediatr (2000) 136(5):611–710.1067/mpd.2000.104826
    1. Eriksen V, Nielsen LH, Klokker M, Greisen G. Follow-up of 5- to 11-year-old children treated for persistent pulmonary hypertension of the newborn. Acta Paediatr (2009) 98(2):304.10.1111/j.1651-2227.2008.01065.x

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa