Original Article . . . . . . . . . . . . . . Low-Dose Nitric Oxide Therapy for Persistent Pulmonary Hypertension: 1-Year Follow-up Reese H. Clark, MD Jeryl L. Huckaby, RRT Thomas J. Kueser, MD Marshall W. Walker, MD W. Michael Southgate, MD Jose A. Perez, MD Beverly J. Roy, MD Martin Keszler, MD For the Clinical Inhaled Nitric Oxide Research Group (CINRGI) BACKGROUND: Although inhaled nitric oxide has been shown to reduce the use of extracorporeal membrane oxygenation, there is limited data on its effect on long-term outcomes. OBJECTIVE: The purpose of our study is to report on the 1 year outcome of neonates treated with inhaled nitric oxide compared to a group of neonates who did not receive nitric oxide. METHODS: We have previously reported on the in-hospital outcomes of 248 neonates who were >34 weeks’ gestational age and were randomized to receive low-dose inhaled nitric oxide or placebo. Extracorporeal membrane oxygenation was used in 78 (64%) neonates in the control group and in 48 (38%) neonates in the inhaled nitric oxide group (p ¼ 0.001). We now report on the outcome of neonates followed to 1 year of age. RESULTS: Of the 248 neonates twenty-four (10%) died before 1 year of age. There was no difference in mortality between the two groups (11% in the control group and 9% in the inhaled nitric oxide group). Of the 224 surviving infants, we were able to contact the parents or guardians of 201 (90%) children. There were no intergroup differences in the numbers of patients reported as requiring medications for pulmonary disease (14% in the control group and 14% in the inhaled nitric oxide group) or the need for supplemental oxygen (1% in the control group and 0% in the inhaled nitric oxide group). The number of neonates reported to have an abnormal neurological examination or developmental delay was also similar in both groups (14% in the control group and 19% in the inhaled nitric oxide group). CONCLUSIONS: The use of low-dose inhaled nitric oxide reduces the use of extracorporeal membrane oxygenation without increasing the incidence of adverse outcomes to 1 year of age. Journal of Perinatology (2003) 23, 300 – 303. doi:10.1038/sj.jp.7210908 INTRODUCTION Persistent pulmonary hypertension of the newborn is commonly diagnosed with respiratory failure in neonates. 1–3 It is characterized by pulmonary hypertension and extrapulmonary right-to-left shunting across the foramen ovale and ductus arteriosus. Several studies have shown that inhaled nitric oxide is useful in reducing the use of extracorporeal membrane oxygenation. 1,3–6 However, there are only two other randomized control trials that have reported data on the long-term outcome of neonates treated with inhaled nitric oxide compared to neonates who did not receive treatment. 3,7 The purpose of our study is to report on the 1 year outcome of neonates treated with inhaled nitric oxide compared to a group of neonates who did not receive nitric oxide. METHODS Study Subjects As previously reported, 1 we studied 248 neonates born after more than 34 weeks’ gestation, who were 4 days old or less, required assisted ventilation, and had an oxygenation index ([mean airway pressure  FiO 2  100]/PaO 2 ) of Z25. These neonates were required to have clinical or echocardiographic evidence of pulmonary hypertension without structural heart disease. Neonates Address correspondence and reprint requests to Reese H. Clark, MD, Director of Research, Pediatrix Medical Group, Inc., 1301 Concord Terrace, Sunrise, FL 33323-2825, USA. Pediatrix Medical Group, Inc. (R.H.C.), Sunrise, FL, USA; Egleston Children’s Hospital (J.L.H.) Atlanta, GA, USA; Division of Neonatology (T.J.K.), Carolinas Medical Center, Charlotte, NC, USA; Department of Neonatology (M.W.W.), Greenville Hospital System, Greenville, SC, USA; Medical University of South Carolina (W.M.S.), Charleston, SC, USA; Arnold Palmer Hospital (J.A.P.) Orlando, FL, USA; Department of Pediatrics (B.J.R.), Emory University,Atlanta, GA, USA; and Division of Neonatology (M.K.), Georgetown University Hospital, (m.k.), Washington, DC, USA. Journal of Perinatology 2003; 23:300 – 303 r 2003 Nature Publishing Group All rights reserved. 0743-8346/03 $25 www.nature.com/jp 300