title: Early Use of Inhaled Nitric Oxide in Preterm Infants: Is there a Rationale for Selective Approach?
abstract: BackgroundInhaled nitric oxide (iNO) is being increasingly used in preterm infants < 34 weeks with hypoxemic respiratory failure (HRF) and/or pulmonary hypertension (PH).ObjectiveTo evaluate the risk factors, survival characteristics, and lung histopathology in preterm infants with PH/HRF.MethodsRetrospective chart review was conducted to determine characteristics of 93 preterm infants treated with iNO in the first 28 days and compared with 930 matched controls. Factors associated with survival with preterm HRF and smooth muscle actin from nine autopsies were evaluated.ResultsPreterm neonates treated with iNO had a higher incidence of preterm prolonged rupture of membrane (pPROM ≥ 18 hours), oligohydramnios and delivered by C-section. In infants treated with iNO, antenatal steroids (odds ratio [OR],3.7; confidence interval [CI], 1.2-11.3;p= 0.02), pPROM (OR, 1.001; CI, 1.0-1.004;p= 0.3), and oxygenation response to iNO (OR, 3.7; CI, 1.08-13.1;p= 0.037) were associated with survival. Thirteen infants with all three characteristics had 100% (13/13) survival without severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL) compared with 48% survival (12/25,p= 0.004) and 16% severe IVH/PVL without any of these factors. Severity of HRF correlated with increased smooth muscle in pulmonary vasculature.ConclusionPreterm infants with HRF exposed to antenatal steroids and pPROM had improved oxygenation with iNO and survival without severe IVH/PVL. Precisely targeting this subset may be beneficial in future trials of iNO.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Women and Children's Hospital of Buffalo, Buffalo, New York.
authors.forename: Praveen
authors.initials: P
authors.lastname: Chandrasekharan
authors.affiliation: Department of Pathology, Women and Children's Hospital of Buffalo, Buffalo, New York.
authors.forename: Rafal
authors.initials: R
authors.lastname: Kozielski
authors.affiliation: Division of Neonatology, Department of Pediatrics, Women and Children's Hospital of Buffalo, Buffalo, New York.
authors.forename: Vasantha H S
authors.initials: VH
authors.lastname: Kumar
authors.affiliation: Division of Neonatology, Department of Pediatrics, Women and Children's Hospital of Buffalo, Buffalo, New York.
authors.forename: Munmun
authors.initials: M
authors.lastname: Rawat
authors.affiliation: Department of Internal Medicine (Cardiology), University at Buffalo, Buffalo, New York.
authors.forename: Veena
authors.initials: V
authors.lastname: Manja
authors.affiliation: Department of Biostatistics, School of Public Health, University at Buffalo, Buffalo, New York.
authors.forename: Changxing
authors.initials: C
authors.lastname: Ma
authors.affiliation: Division of Neonatology, Department of Pediatrics, Women and Children's Hospital of Buffalo, Buffalo, New York.
authors.forename: Satyan
authors.initials: S
authors.lastname: Lakshminrusimha
mesh_terms: D000199:Actins / Q000378:metabolism; D000280:Administration, Inhalation; D016022:Case-Control Studies; D000074042:Cerebral Intraventricular Hemorrhage / Q000209:etiology; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000209:etiology; D005865:Gestational Age; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology; D000860:Hypoxia / Q000209:etiology; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000473:pathology; D007969:Leukomalacia, Periventricular / Q000209:etiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D018579:Patient Selection; D011295:Prenatal Care; D065840:Protective Factors; D011651:Pulmonary Artery / Q000378:metabolism; D011667:Pulmonary Veins / Q000378:metabolism; D012131:Respiratory Insufficiency / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use; D015996:Survival Rate; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000199:Actins; D013256:Steroids; D014665:Vasodilator Agents; D009569:Nitric Oxide; D010100:Oxygen