Original Article
Early Inhaled Nitric Oxide Therapy in Premature Newborns with Respiratory Failure
N Engl J Med 2006; 355:354-364July 27, 2006
- Abstract
Background
The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain.
Methods
We performed a multicenter, randomized trial involving 793 newborns who were 34 weeks of gestational age or less and had respiratory failure requiring mechanical ventilation. Newborns were randomly assigned to receive either inhaled nitric oxide (5 ppm) or placebo gas for 21 days or until extubation, with stratification according to birth weight (500 to 749 g, 750 to 999 g, or 1000 to 1250 g). The primary efficacy outcome was a composite of death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Secondary safety outcomes included severe intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly.
Results
Overall, there was no significant difference in the incidence of death or bronchopulmonary dysplasia between patients receiving inhaled nitric oxide and those receiving placebo (71.6 percent vs. 75.3 percent, P=0.24). However, for infants with a birth weight between 1000 and 1250 g, as compared with placebo, inhaled nitric oxide therapy reduced the incidence of bronchopulmonary dysplasia (29.8 percent vs. 59.6 percent); for the cohort overall, such treatment reduced the combined end point of intracranial hemorrhage, periventricular leukomalacia, or ventriculomegaly (17.5 percent vs. 23.9 percent, P=0.03) and of periventricular leukomalacia alone (5.2 percent vs. 9.0 percent, P=0.048). Inhaled nitric oxide therapy did not increase the incidence of pulmonary hemorrhage or other adverse events.
Conclusions
Among premature newborns with respiratory failure, low-dose inhaled nitric oxide did not reduce the overall incidence of bronchopulmonary dysplasia, except among infants with a birth weight of at least 1000 g, but it did reduce the overall risk of brain injury. (ClinicalTrials.gov number, NCT00006401.)
Media in This Article
Figure 1
Enrollment of Study Patients.Table 1
Baseline Characteristics of Patients.Article Activity
- Article
Early reports of inhaled nitric oxide therapy showed acute and sustained improvement in oxygenation in term newborns with persistent pulmonary hypertension.1,2 Subsequently, randomized, controlled trials of inhaled nitric oxide in term newborns with persistent pulmonary hypertension confirmed that this selective pulmonary vasodilator improves oxygenation and reduces the need for extracorporeal membrane oxygenation.3,4 Previous studies suggested that inhaled nitric oxide can improve gas exchange in premature newborns with hypoxemia caused by the respiratory distress syndrome or persistent pulmonary hypertension.5-8 Although the Food and Drug Administration (FDA) approved inhaled nitric oxide for use in term newborns, the safety and efficacy of such therapy in premature newborns with respiratory failure remain unproven.
In addition to its effects on gas exchange and pulmonary hypertension, in several laboratory studies, inhaled nitric oxide decreased early lung inflammation and oxidant stress,9-11 maintained surfactant activity,12 and improved lung structure in diverse models of chronic lung disease, known as bronchopulmonary dysplasia.13-15 These findings suggest that inhaled nitric oxide may potentially reduce early lung injury leading to bronchopulmonary dysplasia.16 Whether early treatment with inhaled nitric oxide can attenuate the risk or severity of bronchopulmonary dysplasia in premature infants remains unclear.
Laboratory and clinical studies have suggested that high doses of inhaled nitric oxide may increase the risk of bleeding,17,18 a paramount concern because of the predisposition of premature newborns to intracranial hemorrhage. Although an early multicenter, randomized, controlled trial of low-dose inhaled nitric oxide in premature newborns with severe hypoxemic respiratory failure showed no increased risk of intracranial hemorrhage,8 two recent studies reported contradictory findings regarding the safety and efficacy of such treatment.19,20 One trial showed a decrease in the combined outcome of death or bronchopulmonary dysplasia and severe intracranial hemorrhage or periventricular leukomalacia after treatment with inhaled nitric oxide.19 However, another trial found that inhaled nitric oxide reduced the risk of bronchopulmonary dysplasia only in infants with a birth weight of 1000 g or more and increased the risk of severe intracranial hemorrhage or periventricular leukomalacia in infants with a birth weight below 1000 g.20
We hypothesized that prolonged treatment with low-dose (5 ppm) inhaled nitric oxide would reduce the combined end point of death and bronchopulmonary dysplasia in premature newborns, without increasing the incidence or progression of severe intracranial hemorrhage or periventricular leukomalacia. We also hypothesized that the effect of inhaled nitric oxide therapy may be dependent on the degree of prematurity. We performed a multicenter trial that randomly assigned premature newborns with respiratory distress after stratification by birth weight within the clinical center either to treatment with inhaled nitric oxide or to placebo.
Methods
Organization of the Study and Eligibility Criteria
We conducted the study at 16 centers with clinical experience in inhaled nitric oxide therapy and at a coordinating center. The study was approved by institutional review boards at each institution and by the FDA under an investigational new drug exemption. Criteria for enrollment included a gestational age of 34 weeks or less, birth within the previous 48 hours, respiratory failure requiring endotracheal intubation and mechanical ventilation, and a birth weight of 500 to 1250 g. Exclusion criteria were lethal congenital anomalies or congenital heart disease (including an atrial septal defect larger than 1 cm and a ventricular septal defect larger than 2 mm), active pulmonary hemorrhage, unevacuated pneumothorax, or an expected duration of ventilation of less than 48 hours. Infants were enrolled after written informed consent was obtained from a parent or guardian.
Study Design
Randomization was stratified according to center and birth weight (500 to 749 g, 750 to 999 g, and 1000 to 1250 g), balanced in blocks of two or four within strata on the basis of a planned enrollment of 792 patients. Randomization numbers were linked to masked cylinders of inhaled nitric oxide or placebo study gas identified only by sequence numbers.
After randomization, the ventilator circuit was configured to allow delivery of inhaled nitric oxide at 5 ppm or nitrogen placebo through a shielded INOvent device (INO Therapeutics). This shielding allowed visualization of the set dose of nitric oxide but not the readout of the nitric oxide or nitrogen dioxide analyzers. Study gas was delivered for 21 days or until extubation.
Infants underwent mechanical ventilation with either standard neonatal time-cycled, pressure-limited ventilators (Sensormedics 3100A High Frequency Oscillator, Sensormedics) or high-frequency devices (Infant Star HFV, Infrasonics). The only ventilator prohibited was the Life Pulse High Frequency Ventilator (Bunnell), because of limited information on the accuracy of delivered inhaled nitric oxide concentrations. Ventilation strategies and management were left to the discretion of the neonatologist.
The primary outcome measure was the combined end point of death or bronchopulmonary dysplasia. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen or mechanical ventilation at 36 weeks of postmenstrual age, plus abnormal findings on chest radiography, assessed by a centrally read standardized scoring system.21 Secondary outcomes included grade 3 or 4 intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly.
Cranial Ultrasonography Studies
Cranial ultrasonography was performed before enrollment (to determine the baseline incidence and severity of intracranial hemorrhage),22 at 7 to 14 days of age, and at more than 30 days of age (to determine the progression of intracranial hemorrhage with treatment and to identify new hemorrhages and periventricular leukomalacia). A diagnosis of incident intracranial hemorrhage in an infant with hemorrhage at baseline required a worsening of the condition over the baseline level. Intracranial hemorrhage was classified according to the most severe grade occurring after baseline, and ultrasonography readings were masked to assignment.
Statistical Analysis
The planned enrollment of 792 infants was based on an estimated reduction of 10 percentage points in the combined end point of death or bronchopulmonary dysplasia in the group that received inhaled nitric oxide, for an incidence of 50 percent, as compared with 60 percent in the placebo group, given a statistical power of 80 percent, with a two-sided alpha of 0.05. Critical values were prespecified for two interim analyses (P=0.001), maintaining the overall type I error for the final data analysis at 0.048. Safety analyses were conducted by the data and safety monitoring board at semiannual meetings and through routine monitoring of all serious adverse events. Significance levels for these analyses were not prespecified, and unadjusted P values are reported for these analyses.
Detailed safety analyses were conducted after 284 infants had been enrolled. At the time of this interim safety analysis, a favorable effect on grade 3 or 4 intracranial hemorrhage was detected in the group that received inhaled nitric oxide. Subsequently, this protective effect was monitored closely. After the Neonatal Network trial of inhaled nitric oxide was prematurely terminated in September 2003, the data and safety monitoring board and National Heart, Lung, and Blood Institute reviewed the safety data and did not recommend stopping the present trial.
Binomial data were analyzed with the use of the chi-square test or Fisher's exact test, where appropriate. Continuous data were compared with the use of Student's t-test or the Wilcoxon test for data that were not normally distributed. Analyses controlling for birth-weight strata, site, and other covariates were conducted with the use of generalized estimating equations based on the ProcGenmod procedure (SAS). The analysis plan adjusted for study site and randomization strata with the use of the Cochran–Mantel–Haenszel test (augmented with more powerful statistical approaches as confirmatory analyses). Generalized estimating equations were used to provide parametric-model adjustment for these design effects. A P value of less than 0.05 was considered to indicate statistical significance for all analyses except for the primary outcome, for which a P value of 0.048 was used to accommodate interim monitoring.
INO Therapeutics provided the study gas, site monitoring after forms were faxed to the coordinating center, and INOvent devices for the trial. The company remained unaware of the results and was not involved in the design of the study, data analysis or interpretation, or the preparation of the manuscript.
Results
Between March 31, 2001, and June 17, 2005, 793 newborns underwent randomization: 398 to receive inhaled nitric oxide and 395 to receive placebo; 384 weighed 500 to 749 g, 280 weighed 750 to 999 g, and 129 weighed 1000 to 1250 g (Figure 1Figure 1
Enrollment of Study Patients.). Of the 4562 newborns who were prospectively screened for this study, 1921 met all eligibility criteria, and 793 were enrolled. The most common reasons for ineligibility included categories of “not intubated” or “expected early extubation” (i.e., within 48 hours). The most common reason for failure to enroll eligible infants was parental refusal (43 percent), followed by failure to obtain consent (20 percent), usually because of logistical issues.There were no significant differences between groups in birth weight, gestational age, sex, race or ethnic group, the use of antenatal corticosteroids, or Apgar scores (Table 1Table 1
Baseline Characteristics of Patients.). More infants in the placebo group were delivered by cesarean section (P=0.03), but there were no significant differences in the rates of chorioamnionitis, preeclampsia, or placental hemorrhage. There were also no significant differences at baseline in ventilator requirements, levels of arterial blood gases, the use of surfactants, or the frequency or severity of intracranial hemorrhage. The median duration of drug treatment was 14 days (range, 0 to 24) in the group that received inhaled nitric oxide and 12 days (range, 0 to 22) in the placebo group.For the overall study population, the combined end point of death or bronchopulmonary dysplasia did not differ significantly between the study groups (71.6 percent in the group receiving inhaled nitric oxide and 75.3 percent in the placebo group, P=0.24) (Table 2Table 2
Incidence of Death or Bronchopulmonary Dysplasia at 36 Weeks of Postmenstrual Age.). However, there was a significant interaction (P<0.001) between birth-weight strata and treatment. Prespecified subgroup analyses according to birth-weight strata showed significant reductions in the combined primary outcome (P=0.004) and in bronchopulmonary dysplasia alone (P=0.001) with inhaled nitric oxide therapy in the group with a birth weight of 1000 to 1250 g; death rates did not significantly differ between the group receiving inhaled nitric oxide and the placebo group in this birth-weight stratum (Table 2). There were no significant differences in the incidence of the combined end point of death or bronchopulmonary dysplasia between groups in the other birth-weight strata.Infants who received low-dose inhaled nitric oxide had a lower incidence of periventricular leukomalacia than did those receiving placebo (5.2 percent vs. 9.0 percent, P=0.048) (Table 3Table 3
Incidence of Primary Outcomes According to Cranial Ultrasonography.). No significant interaction with birth-weight strata was found for periventricular leukomalacia in the overall population. However, there was a significant interaction between birth-weight strata and the combined outcome of severe intracranial hemorrhage or periventricular leukomalacia (P=0.04), with the largest reduction in this outcome with inhaled nitric oxide therapy in the stratum of infants weighing 750 to 999 g (P=0.006). Overall, ventriculomegaly was observed in 5.2 percent of infants in the group that received inhaled nitric oxide and in 8.9 percent of those in the placebo group (P=0.05). However, the interaction with birth-weight strata was not significant in the overall population.We also performed post hoc analyses to examine the effect of race or ethnic group on the combined outcome of death, intracranial hemorrhage, or periventricular leukomalacia and found no significant interaction between race and outcomes after treatment with inhaled nitric oxide (P=0.99). Although nonwhite infants had slightly higher rates of the combined outcome, the effects of inhaled nitric oxide on this combined outcome appeared to be similar in whites and nonwhites (data not shown).
During the study, there were no significant differences between the groups in the rates of serious adverse events, including air leak, pulmonary hemorrhage, the need for medical or surgical treatment of patent ductus arteriosus, necrotizing enterocolitis, threshold retinopathy of prematurity, or sepsis. There were also no significant differences between groups in the rates of postnatal use of corticosteroids, treatment with respiratory medications at 36 weeks of postmenstrual age (Table 4Table 4
Incidence of Secondary Outcomes.), or in the duration of ventilator therapy or hospitalization. A transient elevation of methemoglobin occurred in two infants in the group receiving inhaled nitric oxide and resolved without specific therapy.Discussion
In this multicenter, randomized, controlled trial of inhaled nitric oxide therapy in premature newborns, we found that low-dose (5 ppm) inhaled nitric oxide therapy, administered within 48 hours after birth for a median of 14 days, did not decrease the overall risk of a composite end point of death or bronchopulmonary dysplasia in infants with birth weights between 500 and 1250 g who required mechanical ventilation. However, inhaled nitric oxide therapy significantly decreased the risk of bronchopulmonary dysplasia and the combined end points by 50 percent and 40 percent, respectively, in premature newborns with birth weights of 1000 to 1250 g. Nitric oxide therapy was associated with a decreased risk of brain injury in the overall population. The risk of serious adverse events was not increased with inhaled nitric oxide therapy in the population overall or within any of the birth-weight strata. These findings suggest that early treatment with low-dose inhaled nitric oxide therapy can safely and effectively improve neurologic and respiratory outcomes in some premature infants.
During the past decade, debate over the safety of inhaled nitric oxide therapy in premature newborns has focused on concern that such treatment might increase the risk of intracranial hemorrhage, predominantly because of the potential adverse effects on platelet adhesion. Our rationale for the use of low-dose inhaled nitric oxide was based on the results of previous laboratory and clinical studies suggesting that this dose could optimize the beneficial vasoactive and antiinflammatory effects while it reduced potential adverse effects on platelet adhesion. Severe intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly are among the most serious consequences of prematurity and the most important predictors of late neurodevelopmental sequelae in premature newborns.23 We found that early, low-dose inhaled nitric oxide decreased the incidence of these abnormalities in the central nervous system, consistent with observations from our pilot trial8 and results of a previous single-center trial by Schreiber et al.19 In contrast to these findings, Van Meurs et al.20 reported that inhaled nitric oxide increased the risk of severe intracranial hemorrhage or periventricular leukomalacia in premature newborns with severe respiratory failure and a birth weight below 1000 g. This conclusion, however, was based on the interpretation of a single cranial ultrasonographic examination at 28 days of age, among a sample smaller than originally planned because of early termination of the study.
Intracranial hemorrhage generally occurs within the first seven days of life, making it difficult to quantify the incidence of hemorrhage that is potentially attributable to inhaled nitric oxide with the use of late cranial ultrasonography studies alone. Indeed, the study by Ballard et al.,24 which appears elsewhere in this issue of the Journal, enrolled patients after the first week of life, and was unable to draw any conclusions about the neuroprotective effect of nitric oxide in the study population. We evaluated the rates of intracranial hemorrhage at baseline, at 7 to 14 days, and at 30 days or later. If we had relied solely on ultrasonography performed at 30 days or later, these results would have suggested an even larger benefit of inhaled nitric oxide (a 38 percent reduction in intracranial hemorrhage). In contrast to our use of 5 ppm of inhaled nitric oxide, Van Meurs et al. treated many infants with 10 ppm of inhaled nitric oxide. It is possible that inhaled nitric oxide in premature newborns acts within a narrow therapeutic range, particularly in the infants with severe respiratory failure whose condition is the least stable.
The precise mechanisms by which inhaled nitric oxide might improve lung function are uncertain. The ability of low-dose inhaled nitric oxide to reduce early neutrophil accumulation in the lung in patients with the acute respiratory distress syndrome may be important, since neutrophils play an important role in the inflammatory cascade, contributing to lung injury and the evolution of bronchopulmonary dysplasia.25-30 In addition, laboratory studies suggest that inhaled nitric oxide therapy modulates lung injury through other means, including the down-regulation of oxidant stress, the production of inflammatory cytokines, and the induction of apoptosis.
We found that low-dose inhaled nitric oxide reduced the incidence of bronchopulmonary dysplasia in infants with a birth weight of 1000 g or more. However, there was no significant reduction in the incidence of bronchopulmonary dysplasia among infants with lower birth weights. The study by Van Meurs et al. also suggested that even brief therapy with inhaled nitric oxide decreased the incidence of bronchopulmonary dysplasia in premature newborns weighing more than 1000 g but not in smaller infants.20 In addition, the study by Schreiber et al., which demonstrated a significant reduction in the combined end point of death and bronchopulmonary dysplasia with inhaled nitric oxide therapy, studied preterm infants with an average birth weight of 992 g.19 In contrast, the average birth weights in our trial and the study by Van Meurs et al. were 792 g and 839 g, respectively. Another important difference between our trial and the study by Van Meurs et al. was the duration of inhaled nitric oxide treatment (a median of 14 days vs. a mean of 76 hours).
Various factors other than inhaled nitric oxide, including the stage of lung development at birth, influence the need for supplemental oxygen at 36 weeks of postmenstrual age. The multifactorial nature of lung injury and repair at the extremes of prematurity may limit the efficacy of any single intervention, and the targeting of 36 weeks of postmenstrual age for an evaluation of the pulmonary reparative capacity of newborns with extremely low birth weights may not be an adequate end point. Longer follow-up is needed to assess whether low-dose inhaled nitric oxide will reduce late pulmonary complications in premature newborns.
Mechanisms through which inhaled nitric oxide therapy might provide neuroprotection in the premature newborn are uncertain and warrant further study. One possibility is that inhaled nitric oxide modulates circulating cells (including neutrophils, monocytes, and platelets) as they transit the pulmonary circulation; the down-regulation of lung-derived cytokines that is induced by inhaled nitric oxide may also reduce the injury of distant organs.31,32 Another possible mechanism may relate to the distal delivery to the central nervous system of nitric oxide or nitric oxide–related metabolites through the systemic circulation through pathways mediated by red cells or proteins.33,34
In conclusion, early, low-dose inhaled nitric oxide did not reduce the risk of bronchopulmonary dysplasia in premature newborns with respiratory failure and a birth weight of 500 to 1250 g, but it did reduce the risk among infants with a birth weight of 1000 g or more and the risk of brain injury in the overall population. Long-term follow-up studies of these infants are ongoing to determine later pulmonary and neurocognitive outcomes of early inhaled nitric oxide therapy.
Supported by grants (NHLBI-UO1-64857 and NHLBI-SCOR-P50-57144) from the National Heart, Lung, and Blood Institute General Clinical Research Centers Program; a grant (M01-RR00069) from the National Center for Research Resources; and by INO Therapeutics.
Drs. Kinsella and Abman report having received consulting fees from INO Therapeutics; and Drs. Auten, Walsh, and Sekar, lecture fees from INO Therapeutics. No other potential conflict of interest relevant to this article was reported.
Source Information
From the Pediatric Heart Lung Center, University of Colorado School of Medicine, and Children's Hospital — both in Denver (J.P.K., J.D.S., S.H.A.); the University of Alabama at Birmingham, Birmingham (G.R.C., M.B.); Vanderbilt University Medical Center, Nashville (W.F.W.); Utah Valley Regional Medical Center, Provo, Utah (D.R.G.); the University of North Carolina, Chapel Hill (C.L.B.); Magee Women's Hospital, University of Pittsburgh, Pittsburgh (C.H.); the University of Oklahoma, Oklahoma City (K.C.S.); Duke University, Durham, N.C. (R.L.A.); Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia (V.K.B., J.S.G.); the University of Iowa, Iowa City (T.N.G.); Medical University of South Carolina, Charleston (W.M.S.); Loma Linda University, Loma Linda, Calif. (H.C.); Children's Hospital, Minneapolis (R.J.C.); Children's Hospital, St. Paul, Minn. (M.C.M.); St. Joseph's Hospital, Phoenix (D.C.H.); the University of Connecticut, Farmington (M.P.); and the University of Southern California, Los Angeles (S.S.).
Address reprint requests to Dr. Kinsella at the Division of Neonatology, Box B-070, Children's Hospital, 1056 E. 19th Ave., Denver, CO 80218-1088, or at john.kinsella@uchsc.edu.
Other investigators are listed in the Appendix.
Appendix
The following investigators also participated in this study: National Heart, Lung, and Blood Institute — M. Berberich, G. Zheng, N. Geller, C. Hunt; Data and Safety Monitoring Board: University of Rochester Medical Center, Rochester, N.Y. — D. Phelps; Johns Hopkins University, Baltimore — M. Allen; Emmes, Rockville, Md. — S. Carter; New York Academy of Medicine, New York — A. Fleischman; State University of New York, Buffalo — F. Morin; Site Coordinators: University of Colorado Health Sciences Center and Children's Hospital, Denver — S. Moreland, N. Waas, L. Fashaw, D. Rodden, K. Hale, G. Addison, S. Collins, K. Novak, A. Reed, B. Pruckler; Vanderbilt University Medical Center, Nashville — A. Law, S. Steele; Medical University of South Carolina, Charleston — K. Mathis; University of North Carolina, Chapel Hill — B. Gogri, L. Anderson, G. Bose; University of Southern California, Los Angeles — R. Mayoral, B. Jones, H. Chinchilla; Utah Valley Regional Medical Center, Provo, Utah — K. Wood, B. Smith; Duke University Medical Center, Durham, N.C. — K. Auten; Magee Women's Hospital, University of Pittsburgh, Pittsburgh — J. Jones, J. Lisak; Pennsylvania Hospital, Philadelphia — T. Mancini, A. Schwoebel, M. Grous; Children's Hospital of Oklahoma, Oklahoma City — M. McCoy, D. McCann, K. Corff; University of Iowa Hospitals and Clinics, Iowa City — K. Johnson, G. Cress; St. Joseph's Hospital, Phoenix — E. Ramthun; University of Connecticut Health Center, Farmington — K. Jennings; Loma Linda University Medical Center, Loma Linda, Calif. — L. Dalton, L. Machain; Children's Hospitals and Clinics of St. Paul, St. Paul, Minn. — P. Meyers, R. Gertz; Children's Hospitals and Clinics of Minneapolis, Minneapolis — M. Maxwell; Data Coordinating Center: D. Mitchell, W. Gehring, T. Van Duzer, T. Borreck, G. Hansen, C. Bender, C. Daniel.
- References
References
1
Roberts JD ,Polaner DM ,Lang P ,Zapol WM . Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:818-819
CrossRef | Web of Science | Medline2
Kinsella JP ,Neish SR ,Shaffer E ,Abman SH . Low-dose inhalational nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:819-820
CrossRef | Web of Science | Medline3
The Neonatal Inhaled Nitric Oxide Study Group
Full Text | Web of Science | Medline4
Clark RH ,Kueser TJ ,Walker MW , et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. N Engl J Med 2000;342:469-474
Full Text | Web of Science | Medline5
Abman SH ,Kinsella JP ,Schaffer MS ,Wilkening RB . Inhaled nitric oxide in the management of a premature newborn with severe respiratory distress and pulmonary hypertension. Pediatrics 1993;92:606-609
Web of Science | Medline6
Peliowski A ,Finer NN ,Etches PC ,Tierney AJ ,Ryan CA . Inhaled nitric oxide for premature infants after prolonged rupture of the membranes. J Pediatr 1995;126:450-453
CrossRef | Web of Science | Medline7
Subhedar NV ,Shaw NJ . Changes in oxygenation and pulmonary haemodynamics in preterm infants treated with inhaled nitric oxide. Arch Dis Child Fetal Neonatal Ed 1997;77:F191-F197
CrossRef | Web of Science | Medline8
Kinsella JP ,Walsh WF ,Bose CL , et al. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial. Lancet 1999;354:1061-1065
CrossRef | Web of Science | Medline9
Kinsella JP ,Ivy DD ,Abman SH . Inhaled nitric oxide lowers pulmonary vascular resistance and improves gas exchange in severe experimental hyaline membrane disease. Pediatr Res 1994;36:402-408
CrossRef | Web of Science | Medline10
Kinsella JP ,Parker TA ,Galan H ,Sheridan BC ,Halbower AC ,Abman SH . Effects of inhaled nitric oxide on pulmonary edema and lung neutrophil accumulation in severe experimental hyaline membrane disease. Pediatr Res 1997;41:457-463
CrossRef | Web of Science | Medline11
Gutierrez HH ,Nieves B ,Chumley P ,Rivera A ,Freeman BA . Nitric oxide regulation of superoxide-dependent lung injury: oxidant-protective actions of endogenously produced and exogenously administered nitric oxide. Free Radic Biol Med 1996;21:43-52
CrossRef | Web of Science | Medline12
Issa A ,Lappalainen U ,Kleinman M ,Bry K ,Hallman M . Inhaled nitric oxide decreases hyperoxia-induced surfactant abnormality in preterm rabbits. Pediatr Res 1999;45:247-254
CrossRef | Web of Science | Medline13
McCurnin DC ,Pierce RA ,Chang LY , et al. Inhaled NO improves early pulmonary function and modifies lung growth and elastin deposition in a baboon model of neonatal chronic lung disease. Am J Physiol Lung Cell Mol Physiol 2005;288:L450-L459
CrossRef | Web of Science | Medline14
Lin YJ ,Markham NE ,Balasubramaniam V , et al. Inhaled nitric oxide enhances distal lung growth after exposure to hyperoxia in neonatal rats. Pediatr Res 2005;58:22-29
CrossRef | Web of Science | Medline15
Bland RD ,Albertine RH ,Carlton DP ,MacRitchie AJ . Inhaled nitric oxide effects on lung structure and function in chronically ventilated preterm lambs. Am J Respir Crit Care Med 2005;172:899-906
CrossRef | Web of Science | Medline16
Northway WH Jr ,Rosan RC ,Porter DY . Pulmonary disease following respirator therapy of hyaline-membrane disease: bronchopulmonary dysplasia. N Engl J Med 1967;276:357-368
Full Text | Web of Science | Medline17
Hogman M ,Frostell C ,Arnberg H ,Hedenstierna G . Bleeding time prolongation and NO inhalation. Lancet 1993;341:1664-1665
CrossRef | Web of Science | Medline18
George TN ,Johnson KJ ,Bates JN ,Segar JL . The effect of inhaled nitric oxide therapy on bleeding time and platelet aggregation in neonates. J Pediatr 1998;132:731-734
CrossRef | Web of Science | Medline19
Schreiber MD ,Gin-Mestan K ,Marks JD ,Huo D ,Lee G ,Srisuparp P . Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med 2003;349:2099-2107
Full Text | Web of Science | Medline20
Van Meurs KP ,Wright LL ,Ehrenkranz RA , et al. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med 2005;353:13-22
Full Text | Web of Science | Medline21
Toce SS ,Farrel PM ,Leavitt LA ,Samuels DP ,Edwards DK . Clinical and roentgenographic scoring systems for assessing bronchopulmonary dysplasia. Am J Dis Child 1984;138:581-585
Web of Science | Medline22
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;92:529-534
CrossRef | Web of Science | Medline23
Mestan KKL ,Marks JD ,Hecox K ,Huo D ,Schreiber MD . Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med 2005;353:23-32
Full Text | Web of Science | Medline24
Ballard RA ,Truog WE ,Cnaan A , et al. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med 2006;355:343-353
Full Text | Web of Science | Medline25
Ogden BE ,Murphy S ,Saunders GC ,Johnson JD . Lung lavage of newborns with respiratory distress syndrome: prolonged neutrophil influx is associated with bronchopulmonary dysplasia. Chest 1983;83:Suppl 5:31S-33S
Web of Science | Medline26
Merritt TA ,Cochrane CG ,Holcomb K , et al. Elastase and α-1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome: role of inflammation in the pathogenesis of bronchopulmonary dysplasia. J Clin Invest 1983;72:656-666
CrossRef | Web of Science | Medline27
Speer CP ,Ruess D ,Harms K ,Herting E ,Gefeller O . Neutrophil elastase and acute pulmonary damage in neonates with severe respiratory distress syndrome. Pediatrics 1993;91:794-799
Web of Science | Medline28
Brus F ,Van Oeveren W ,Heikamp A ,Okken A ,Oetomo SB . Leakage of protein into lungs of preterm ventilated rabbits is correlated with activation of clotting, complement, and polymorphonuclear leukocytes in plasma. Pediatr Res 1996;39:958-965
CrossRef | Web of Science | Medline29
Auten RL ,Ekekezie II . Blocking leukocyte influx and function to prevent chronic lung disease of prematurity. Pediatr Pulmonol 2003;35:335-341
CrossRef | Web of Science | Medline30
Cannon RO III ,Schechter AN ,Panza JA , et al. Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. J Clin Invest 2001;108:279-287
CrossRef | Web of Science | Medline31
Viscardi RM ,Muhumuza CK ,Rodriguez A , et al. Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr Res 2004;55:1009-1017
CrossRef | Web of Science | Medline32
Haynes RL ,Baud O ,Li J ,Kinney HC ,Volpe JJ ,Folkerth DR . Oxidative and nitrative injury in periventricular leukomalacia: a review. Brain Pathol 2005;15:225-233
CrossRef | Web of Science | Medline33
Pawloski JR ,Hess DT ,Stamler JS . Export by red blood cells of nitric oxide bioactivity. Nature 2001;409:622-626
CrossRef | Web of Science | Medline34
Sugiura M ,McCulloch PR ,Wren S ,Dawson RH ,Froese AB . Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung. J Appl Physiol 1994;77:1355-1365
Web of Science | Medline
- Citing Articles (90)
Citing Articles
1
James M. Greenberg. 2012. Noncardiac Problems of the Neonatal Period. , 261-267.
CrossRef2
Olivia Williams, Graham Hutchings, Corinne Hubinont, Christian Debauche, Anne Greenough. (2012) Pulmonary Effects of Prolonged Oligohydramnios following Mid-Trimester Rupture of the Membranes – Antenatal and Postnatal Management. Neonatology 101:2, 83-90
CrossRef3
Roberta L. Keller, Roberta A. Ballard. 2012. Bronchopulmonary Dysplasia. , 658-671.
CrossRef4
Eric C. Eichenwald. 2012. Care of the Extremely Low-Birthweight Infant. , 390-404.
CrossRef5
K N Farrow, R H Steinhorn. (2012) Sildenafil therapy for bronchopulmonary dysplasia: not quite yet. Journal of Perinatology 32:1, 1-3
CrossRef6
Kristen Tropea, Helen Christou. (2012) Current Pharmacologic Approaches for Prevention and Treatment of Bronchopulmonary Dysplasia. International Journal of Pediatrics 2012, 1-9
CrossRef7
Amir Kugelman, Manuel Durand. (2011) A comprehensive approach to the prevention of bronchopulmonary dysplasia. Pediatric Pulmonology 46:12, 1153-1165
CrossRef8
Robin H. Steinhorn. (2011) Therapeutic approaches using nitric oxide in infants and children. Free Radical Biology and Medicine 51:5, 1027-1034
CrossRef9
Christie J. Bruno, Todd M. Greco, Harry Ischiropoulos. (2011) Nitric oxide counteracts the hyperoxia-induced proliferation and proinflammatory responses of mouse astrocytes. Free Radical Biology and Medicine 51:2, 474-479
CrossRef10
Susan W. Aucott. (2011) Bronchopulmonary Dysplasia: Development and Progression in the Neonatal Intensive Care Unit. Pediatric Allergy, Immunology, and Pulmonology 24:2, 113-118
CrossRef11
Dharmesh M Shah, Martin Kluckow. (2011) Early functional echocardiogram and inhaled nitric oxide: Usefulness in managing neonates born following extreme preterm premature rupture of membranes (PPROM). Journal of Paediatrics and Child Health 47:6, 340-345
CrossRef12
Jason Gien, John P Kinsella. (2011) Pathogenesis and treatment of bronchopulmonary dysplasia. Current Opinion in Pediatrics 23:3, 305-313
CrossRef13
Athena I Patrianakos-Hoobler, Jeremy D Marks, Michael E. Msall, Dezheng Huo, Michael D Schreiber. (2011) Safety and efficacy of inhaled nitric oxide treatment for premature infants with respiratory distress syndrome: follow-up evaluation at early school age. Acta Paediatrica 100:4, 524-528
CrossRef14
Keith J Barrington, Neil Finer, Keith J Barrington. 2010. Inhaled nitric oxide for respiratory failure in preterm infants. .
CrossRef15
R H Clark, R L Ursprung, M W Walker, D L Ellsbury, A R Spitzer. (2010) The changing pattern of inhaled nitric oxide use in the neonatal intensive care unit. Journal of Perinatology 30:12, 800-804
CrossRef16
ARUL VADIVEL, JUDY L. ASCHNER, GLORIA J. REY-PARRA, JORDAN MAGARIK, HENG ZENG, MARSHALL SUMMAR, FARAH EATON, BERNARD THÉBAUD. (2010) l-Citrulline Attenuates Arrested Alveolar Growth and Pulmonary Hypertension in Oxygen-Induced Lung Injury in Newborn Rats. Pediatric Research 68:6, 519-525
CrossRef17
I Hamon, H Gauthier-Moulinier, E Grelet-Dessioux, L Storme, J Fresson, JM Hascoet. (2010) Methaemoglobinaemia risk factors with inhaled nitric oxide therapy in newborn infants. Acta Paediatrica 99:10, 1467-1473
CrossRef18
Jean-Christophe Mercier, Helmut Hummler, Xavier Durrmeyer, Manuel Sanchez-Luna, Virgilio Carnielli, David Field, Anne Greenough, Bart Van Overmeire, Baldvin Jonsson, Mikko Hallman, James Baldassarre. (2010) Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial. The Lancet 376:9738, 346-354
CrossRef19
Ilene RS Sosenko, Eduardo Bancalari. (2010) NO for preterm infants at risk of bronchopulmonary dysplasia. The Lancet 376:9738, 308-310
CrossRef20
A González, J Fabres, I D'Apremont, G Urcelay, M Avaca, C Gandolfi, J Kattan. (2010) Randomized controlled trial of early compared with delayed use of inhaled nitric oxide in newborns with a moderate respiratory failure and pulmonary hypertension. Journal of Perinatology 30:6, 420-424
CrossRef21
Chris Dewhurst, Hafis Ibrahim, Sylvia Göthberg, Baldvin Jónsson, Nimish Subhedar, . (2010) Use of inhaled nitric oxide in the new born period: results from the European inhaled nitric oxide registry. Acta Paediatrica 99:6, 854-860
CrossRef22
Michael R. Stenger, Melissa J. Rose, Mandar S. Joshi, Lynette K. Rogers, Louis G. Chicoine, John Anthony Bauer, Leif D. Nelin. (2010) Inhaled Nitric Oxide Prevents 3-Nitrotyrosine Formation in the Lungs of Neonatal Mice Exposed to >95% Oxygen. Lung 188:3, 217-227
CrossRef23
Sylvie Joriot-Chekaf, Rony Sfeir, Yvon Riou, Pierre Gressens, Louis Vallée, Régis Bordet, Joseph Vamecq. (2010) Evaluation of inhaled NO in a model of rat neonate brain injury caused by hypoxia–ischaemia. Injury 41:5, 517-521
CrossRef24
M A Posencheg, A J Gow, W E Truog, R A Ballard, A Cnaan, S G Golombek, P L Ballard. (2010) Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites. Journal of Perinatology 30:4, 275-280
CrossRef25
Michele C. Walsh, Anna Maria Hibbs, Camilia R. Martin, Avital Cnaan, Roberta L. Keller, Eric Vittinghoff, Richard J. Martin, William E. Truog, Philip L. Ballard, Arlene Zadell, Sandra R. Wadlinger, Christine E. Coburn, Roberta A. Ballard. (2010) Two-Year Neurodevelopmental Outcomes of Ventilated Preterm Infants Treated with Inhaled Nitric Oxide. The Journal of Pediatrics 156:4, 556-561.e1
CrossRef26
Keith J Barrington, Neil Finer. (2010) Cochrane review: Inhaled nitric oxide for respiratory failure in preterm infants. Evidence-Based Child Health: A Cochrane Review Journal 5:1, 301-336
CrossRef27
Gerald S. Zavorsky, Arlin B. Blood, Gordon G. Power, Lawrence D. Longo, Raul Artal, Emanuel J. Vlastos. (2010) CO and NO pulmonary diffusing capacity during pregnancy: Safety and diagnostic potential. Respiratory Physiology & Neurobiology 170:3, 215-225
CrossRef28
A A Rosenberg, N R Lee, K N Vaver, D Werner, L Fashaw, K Hale, N Waas. (2010) School-age outcomes of newborns treated for persistent pulmonary hypertension. Journal of Perinatology 30:2, 127-134
CrossRef29
Csaba Szabo. 2010. Medicinal Chemistry and Therapeutic Applications of the Gasotransmitters NO, CO, and H 2 S and their Prodrugs. .
CrossRef30
Gi Beom Kim. (2010) Pulmonary hypertension in infants with bronchopulmonary dysplasia. Korean Journal of Pediatrics 53:6, 688
CrossRef31
Prasad Vannemreddy, Christina Notarianni, Krishna Yanamandra, Dawn Napper, Joseph Bocchini. (2010) Is an endothelial nitric oxide synthase gene mutation a risk factor in the origin of intraventricular hemorrhage?. Neurosurgical FOCUS 28:1, E11
CrossRef32
So Young Kim. (2010) Neonatal respiratory distress: recent progress in understanding pathogenesis and treatment outcomes. Korean Journal of Pediatrics 53:1, 1
CrossRef33
Lindsay C. Johnston, Linda W. Gonzales, Richard T. Lightfoot, Susan H. Guttentag, Harry Ischiropoulos. (2010) Opposing regulation of human alveolar Type II cell differentiation by nitric oxide and hyperoxia.. Pediatric Research1
CrossRef34
Win Tin, Thomas E. Wiswell. (2009) Drug therapies in bronchopulmonary dysplasia: debunking the myths. Seminars in Fetal and Neonatal Medicine 14:6, 383-390
CrossRef35
Linda J. Van Marter. (2009) Epidemiology of bronchopulmonary dysplasia. Seminars in Fetal and Neonatal Medicine 14:6, 358-366
CrossRef36
Matthew M. Laughon, P. Brian Smith, Carl Bose. (2009) Prevention of bronchopulmonary dysplasia. Seminars in Fetal and Neonatal Medicine 14:6, 374-382
CrossRef37
TOMMI NOPONEN, ANDERS NORDH, ANSGAR BERG, DAVID LEY, STEFAN R. HANSSON, ERKKI PESONEN, VINETA FELLMAN. (2009) Circulatory Effects of Inhaled Iloprost in the Newborn Preterm Lamb. Pediatric Research 66:4, 416-422
CrossRef38
Matthew W. Foster, Douglas T. Hess, Jonathan S. Stamler. (2009) Protein S-nitrosylation in health and disease: a current perspective. Trends in Molecular Medicine 15:9, 391-404
CrossRef39
RICHARD L. AUTEN, JONATHAN M. DAVIS. (2009) Oxygen Toxicity and Reactive Oxygen Species: The Devil Is in the Details. Pediatric Research 66:2, 121-127
CrossRef40
Anne Greenough, Vadivelam Murthy. (2009) Respiratory problems in the premature newborn. Pediatric Health 3:3, 241-249
CrossRef41
R F Soll. (2009) Inhaled nitric oxide in the neonate. Journal of Perinatology 29, S63-S67
CrossRef42
W. Goździk, J. Albert, P. Harbut, S. Zieliński, S. Ryniak, R. Lindwall, P. Dziegiel, M. Podhorska-Okolow, A. Kübler, C. Frostell. (2009) Prolonged exposure to inhaled nitric oxide transiently modifies tubular function in healthy piglets and promotes tubular apoptosis. Acta Physiologica 195:4, 495-502
CrossRef43
Nandini Arul, G. Ganesh Konduri. (2009) Inhaled Nitric Oxide for Preterm Neonates. Clinics in Perinatology 36:1, 43-61
CrossRef44
Jean-Christophe Mercier, Paul Olivier, Gauthier Loron, Romain Fontaine, Laure Maury, Olivier Baud. (2009) Inhaled nitric oxide to prevent bronchopulmonary dysplasia in preterm neonates. Seminars in Fetal and Neonatal Medicine 14:1, 28-34
CrossRef45
Bryce RH Robinson, Krishna P Athota, Richard D Branson. (2009) Inhalational therapies for the ICU. Current Opinion in Critical Care 15:1, 1-9
CrossRef46
Kushal Y. Bhakta, James M. Adams, Ann R. Stark. 2009. Chronic Lung Disease of Infancy. , 1-27.
CrossRef47
Jeremy D. Marks, Michael D. Schreiber. (2008) Inhaled Nitric Oxide and Neuroprotection in Preterm Infants. Clinics in Perinatology 35:4, 793-807
CrossRef48
Jon O. Lundberg. (2008) Nitric Oxide and the Paranasal Sinuses. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology 291:11, 1479-1484
CrossRef49
John P. Kinsella. (2008) Inhaled nitric oxide in the term newborn. Early Human Development 84:11, 709-716
CrossRef50
Nicolas F.M. Porta, Robin H. Steinhorn. (2008) Inhaled NO in the experimental setting. Early Human Development 84:11, 717-723
CrossRef51
Stephanie S. Miller, William D. Rhine. (2008) Inhaled nitric oxide in the treatment of preterm infants. Early Human Development 84:11, 703-707
CrossRef52
GEORGE R. CONAHEY, GORDON G. POWER, ANDREW O. HOPPER, MICHAEL H. TERRY, LAURA S. KIRBY, ARLIN B. BLOOD. (2008) Effect of Inhaled Nitric Oxide on Cerebrospinal Fluid and Blood Nitrite Concentrations in Newborn Lambs. Pediatric Research 64:4, 375-380
CrossRef53
Xiao Zhang, Gary Cutter. (2008) Bayesian interim analysis in clinical trials. Contemporary Clinical Trials 29:5, 751-755
CrossRef54
Anne Greenough. (2008) Emerging drugs for the prevention of bronchopulmonary dysplasia. Expert Opinion on Emerging Drugs 13:3, 537-546
CrossRef55
Esther Rieger-Fackeldey, Roland Hentschel. (2008) Bronchopulmonary dysplasia and early prophylactic inhaled nitric oxide in preterm infants: current concepts and future research strategies in animal models. Journal of Perinatal Medicine 36:5, 442-447
CrossRef56
ANNE GREENOUGH, VADIVELAM MURTHY. (2008) RESPIRATORY DISTRESS SYNDROME. Fetal and Maternal Medicine Review 19:03,
CrossRef57
Shashank S. Sinha, Sruti Shiva, Mark T. Gladwin. (2008) Myocardial Protection by Nitrite: Evidence That This Reperfusion Therapeutic Will Not Be Lost in Translation. Trends in Cardiovascular Medicine 18:5, 163-172
CrossRef58
Niranjan Kissoon, Peter C. Rimensberger, Desmond Bohn. (2008) Ventilation Strategies and Adjunctive Therapy in Severe Lung Disease. Pediatric Clinics of North America 55:3, 709-733
CrossRef59
N Ambalavanan, K P Van Meurs, R Perritt, W A Carlo, R A Ehrenkranz, D K Stevenson, J A Lemons, W K Poole, R D Higgins. (2008) Predictors of death or bronchopulmonary dysplasia in preterm infants with respiratory failure. Journal of Perinatology 28:6, 420-426
CrossRef60
John Granton, Jakov Moric. (2008) Pulmonary Vasodilators—Treating the Right Ventricle. Anesthesiology Clinics 26:2, 337-353
CrossRef61
Qi Li, Michael Michaud, William Stewart, Michael Schwartz, Joseph A. Madri. (2008) Modeling the neurovascular niche: Murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn. Journal of Neuroscience Research 86:6, 1227-1242
CrossRef62
Eichenwald, Eric C., Stark, Ann R., . (2008) Management and Outcomes of Very Low Birth Weight. New England Journal of Medicine 358:16, 1700-1711
Full Text63
Laura Cerny, John S. Torday, Virender K. Rehan. (2008) Prevention and Treatment of Bronchopulmonary Dysplasia: Contemporary Status and Future Outlook. Lung 186:2, 75-89
CrossRef64
M. Jeeva Sankar, Ramesh Agarwal, Ashok K. Deorari, Vinod K. Paul. (2008) Chronic lung disease in newborns. The Indian Journal of Pediatrics 75:4, 369-376
CrossRef65
Marilee C Allen. (2008) Neurodevelopmental outcomes of preterm infants. Current Opinion in Neurology 21:2, 123-128
CrossRef66
Aparna U. Hoskote, Rosemary A. Castle, Ah-Fong Hoo, Sooky Lum, Sarath C. Ranganathan, Quen Q. Mok, Janet Stocks. (2008) Airway function in infants treated with inhaled nitric oxide for persistent pulmonary hypertension. Pediatric Pulmonology 43:3, 224-235
CrossRef67
Jon O. Lundberg, Eddie Weitzberg, Mark T. Gladwin. (2008) The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nature Reviews Drug Discovery 7:2, 156-167
CrossRef68
P H Su, J Y Chen. (2008) Inhaled nitric oxide in the management of preterm infants with severe respiratory failure. Journal of Perinatology 28:2, 112-116
CrossRef69
Win Tin, Thomas E. Wiswell. (2008) Adjunctive therapies in chronic lung disease: Examining the evidence. Seminars in Fetal and Neonatal Medicine 13:1, 44-52
CrossRef70
J.A. Stockman. (2008) Early Inhaled Nitric Oxide Therapy in Premature Newborns with Respiratory Failure. Yearbook of Pediatrics 2008, 400-402
CrossRef71
P V Gordon, J R Swanson, J T Attridge, R Clark. (2007) Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's criteria?. Journal of Perinatology 27:11, 661-671
CrossRef72
Phillip V Gordon, Andrew C Herman, Marek Marcinkiewicz, Benjamin M Gaston, Victor E Laubach, Judy L Aschner. (2007) A Neonatal Mouse Model of Intestinal Perforation: Investigating the Harmful Synergism Between Glucocorticoids and Indomethacin. Journal of Pediatric Gastroenterology and Nutrition 45:5, 509-519
CrossRef73
L. Gortner, S. Meyer. (2007) Die bronchopulmonale Dysplasie Frühgeborener. Intensivmedizin und Notfallmedizin 44:8, 475-485
CrossRef74
J. A. Madri. (2007) Need MT1-MMP? Just say NO!. Blood 110:8, 2790-2791
CrossRef75
DANIELE TREVISANUTO, NICOLETTA Doglioni, MASSIMO MICAGLIO, VINCENZO ZANARDO. (2007) Feasibility of nitric oxide administration by neonatal helmet-CPAP: a bench study. Pediatric Anesthesia 17:9, 851-855
CrossRef76
Anne Greenough, Atul Sharma. (2007) What is new in ventilation strategies for the neonate?. European Journal of Pediatrics 166:10, 991-996
CrossRef77
Keith J Barrington, Neil Finer, Keith J Barrington. 2007. Inhaled nitric oxide for respiratory failure in preterm infants. .
CrossRef78
John P. Kinsella, Steven H. Abman. (2007) Inhaled Nitric Oxide in the Premature Newborn. The Journal of Pediatrics 151:1, 10-15
CrossRef79
William E Truog. (2007) Inhaled nitric oxide for the prevention of bronchopulmonary dysplasia. Expert Opinion on Pharmacotherapy 8:10, 1505-1513
CrossRef80
Susan R. Hintz, Krisa P. Van Meurs, R. Perritt, W. Kenneth Poole, Abhik Das, David K. Stevenson, Richard A. Ehrenkranz, James A. Lemons, Betty R. Vohr, Roy Heyne, David O. Childers, Myriam Peralta-Carcelen, Anna Dusick, Yvette R. Johnson, Brenda Morris, Robert Dillard, Yvonne Vaucher, Jean Steichen, Ira Adams-Chapman, Ganesh Konduri, Gary J. Myers, Marissa de Ungria, Jon E. Tyson, Rosemary D. Higgins. (2007) Neurodevelopmental Outcomes of Premature Infants with Severe Respiratory Failure Enrolled in a Randomized Controlled Trial of Inhaled Nitric Oxide. The Journal of Pediatrics 151:1, 16-22.e3
CrossRef81
David Sweet, Giulio Bevilacqua, Virgilio Carnielli, Gorm Greisen, Richard Plavka, Ola Didrik Saugstad, Umberto Simeoni, Christian P. Speer, Adolf Valls-i-Soler, Henry Halliday. (2007) European consensus guidelines on the management of neonatal respiratory distress syndrome. Journal of Perinatal Medicine 35:3, 175-186
CrossRef82
K P Van Meurs, S R Hintz, R A Ehrenkranz, J A Lemons, M B Ball, W K Poole, R Perritt, A Das, R D Higgins, D K Stevenson. (2007) Inhaled nitric oxide in infants >1500 g and <34 weeks gestation with severe respiratory failure. Journal of Perinatology 27:6, 347-352
CrossRef83
W Thomas, C P Speer. (2007) Prevention and treatment of bronchopulmonary dysplasia: current status and future prospects. Journal of Perinatology 27, S26-S32
CrossRef84
Robin H Steinhorn, Nicolas FM Porta. (2007) Use of inhaled nitric oxide in the preterm infant. Current Opinion in Pediatrics 19:2, 137-141
CrossRef85
SANDRA M. REES, EMILY J. CAMM, MICHELLE LOELIGER, SARAH CAIN, SANDRA DIENI, DONALD MCCURNIN, PHILIP W. SHAUL, BRADLEY YODER, CATRIONA MCLEAN, TERRIE E. INDER. (2007) Inhaled Nitric Oxide: Effects on Cerebral Growth and Injury in a Baboon Model of Premature Delivery. Pediatric Research PAP,
CrossRef86
Silvia Brunelli, Patrizia Rovere-Querini, Clara Sciorati, Angelo A Manfredi, Emilio Clementi. (2007) Nitric oxide: emerging concepts about its use in cell-based therapies. Expert Opinion on Investigational Drugs 16:1, 33-43
CrossRef87
Charlene Laino. (2006) INHALED NITRIC OXIDE MAY BENEFIT SELECT PRETERM INFANTS, RISK OF BRAIN INJURY LOW. Neurology Today 6:17, 12-13
CrossRef88
Stark, Ann R., . (2006) Inhaled NO for Preterm Infants — Getting to Yes?. New England Journal of Medicine 355:4, 404-406
Full Text89
Ballard, Roberta A., Truog, William E., Cnaan, Avital, Martin, Richard J., Ballard, Philip L., Merrill, Jeffrey D., Walsh, Michele C., Durand, David J., Mayock, Dennis E., Eichenwald, Eric C., Null, Donald R., Hudak, Mark L., Puri, Asha R., Golombek, Sergio G., Courtney, Sherry E., Stewart, Dan L., Welty, Stephen E., Phibbs, Roderic H., Hibbs, Anna Maria, Luan, Xianqun, Wadlinger, Sandra R., Asselin, Jeanette M., Coburn, Christine E., . (2006) Inhaled Nitric Oxide in Preterm Infants Undergoing Mechanical Ventilation. New England Journal of Medicine 355:4, 343-353
Full Text90
Soo-Young Pi, Ki-Soo Kim. (2006) The Disease Spectrum in Premature Infants and the Progress of Pharmacological Treatment. Journal of the Korean Medical Association 49:11, 1003
CrossRef
