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OBJECTIVES: To evaluate the survival and neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants at 18 to 26 months with early hypoxemic respiratory failure (HRF). We also assessed whether African American infants with early HRF had improved outcomes after exposure to inhaled nitric oxide (iNO). METHODS: ELBW infants ≤1000 g and gestational age ≤26 weeks with maximal oxygen ≥60% on either day 1 or day 3 were labeled as "early HRF" and born between 2007 and 2015 in the Neonatal Research Network were included. Using a propensity score regression model, we analyzed outcomes and effects of exposure to iNO overall and separately by race. RESULTS: Among 7639 ELBW infants born ≤26 weeks, 22.7% had early HRF. Early HRF was associated with a mortality of 51.3%. The incidence of moderate-severe NDI among survivors was 41.2% at 18 to 26 months. Mortality among infants treated with iNO was 59.4%. Female sex (adjusted odds ratio [aOR]: 2.4, 95% confidence interval [CI]: 1.8-3.3), birth weight ≥720 g (aOR: 2.3, 95% CI: 1.7-3.1) and complete course of antenatal steroids (aOR: 1.6, 95% CI: 1.1-2.2) were associated with intact survival. African American infants had a similar incidence of early HRF (21.7% vs 23.3%) but lower exposure to iNO (16.4% vs 21.6%). Among infants with HRF exposed to iNO, intact survival (no death or NDI) was not significantly different between African American and other races (aOR: 1.5, 95% CI: 0.6-3.6). CONCLUSIONS: Early HRF in infants ≤26 weeks' gestation is associated with high mortality and NDI at 18 to 26 months. Use of iNO did not decrease mortality or NDI. Outcomes following iNO exposure were not different in African American infants. [ABSTRACT FROM AUTHOR]

The article presents abstracts of studies on pediatrics which include "Neonatal Abstinence Syndrome" by Eric S. Hall et al, "Stool Microbiota and Vaccine Responses of Infants" by M. Nazul Huda et al, and "Socioeconomic Status and Wait Times for Pediatric Surgery in Canada" by Mark Szynkaruk et al.

Nitric oxide, an important signaling molecule with multiple regulatory effects throughout the body, is an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn and hypoxemic respiratory failure. Several randomized controlled trials have evaluated its role in the management of preterm infants ≤34 weeks' gestational age with varying results. The purpose of this clinical report is to summarize the existing evidence for the use of inhaled nitric oxide in preterm infants and provide guidance regarding its use in this population. [ABSTRACT FROM AUTHOR]

OBJECTIVES. Inhaled nitric oxide treatment for ventilated premature infants improves survival without bronchopulmonary dysplasia. However, there has been no information regarding possible effects of this therapy on oxidative stress. We hypothesized that inhaled nitric oxide therapy would not influence concentrations of plasma biomarkers of oxidative stress. PATIENTS AND METHODS. AS part of the Nitric Oxide Chronic Lung Disease Trial, we collected blood samples at specified intervals from a subpopulation of 100 infants of < 1250 g birth weight who received inhaled nitric oxide (20 ppm, weaned to 2 ppm) or placebo gas for 24 days. Plasma was assayed for total protein and for 3-nitrotyrosine and carbonylation by using immunoassays. RESULTS. The demographic characteristics and primary outcome for the infants were representative of the entire group of infants who were in the Nitric Oxide Chronic Lung Disease Trial. For all infants at baseline, before receiving study gas, the concentration of total protein was inversely correlated with the respiratory severity score, and plasma carbonyl was positively correlated with severity score, supporting an association between oxidative stress and severity of lung disease. Infants who survived without bronchopulmonary dysplasia had 30% lower protein carbonylation concentrations at study entry than those who had an adverse outcome. At each of 3 time points (1-10 days) during exposure to study gas, there were no significant differences between control and treated infants for concentrations of plasma protein, 3-nitrotyrosine, and carbonylation CONCLUSIONS. Inhaled nitric oxide treatment for premature infants who are at risk bronchopulmonary dysplasia does not alter plasma biomarkers of oxidative stress, which supports the safety of this therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVES. We hypothesized that inhaled nitric oxide treatment of premature infants at risk for bronchopulmonary dysplasia would not adversely affect endogenous surfactant function or composition. METHODS. As part of the Nitric Oxide Chronic Lung Disease Trial of inhaled nitric oxide, we examined surfactant in a subpopulation of enrolled infants. Tracheal aspirate fluid was collected at specified intervals from 99 infants with birth weights <1250 g who received inhaled nitric oxide (20 ppm, weaned to 2 ppm) or placebo gas for 24 days. Large-aggregate surfactant was analyzed for surface activity with a pulsating bubble surfactometer and for surfactant protein contents with an immunoassay. RESULTS. At baseline, before administration of study gas, surfactant function and composition were comparable in the 2 groups, and there was a positive correlation between minimum surface tension and severity of lung disease for all infants. Over the first 4 days of treatment, minimum surface tension increased in placebo-treated infants and decreased in inhaled nitric oxide-treated infants. There were no significant differences between groups in recovery of large-aggregate surfactant or contents of surfactant protein A, surfactant protein B, surfactant protein C, or total protein, normalized to phospholipid. CONCLUSIONS. We conclude that inhaled nitric oxide treatment for premature infants at risk of bronchopulmonary dysplasia does not alter surfactant recovery or protein composition and may improve surfactant function transiently. [ABSTRACT FROM AUTHOR]

Objective. Inhaled nitric oxide (iNO) reduces the use of extracorporeal membrane oxygenation (ECMO)/incidence of death in term and near-term neonates with severe hypoxic respiratory failure. We conducted a randomized, double masked, multicenter trial to determine whether administration of iNO earlier in respiratory failure results in additional reduction in the incidence of these outcomes. Methods. Neonates who were born at ≥34 weeks' gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) ≥15 and <25 on any 2 measurements in a 12-hour interval. Infants were randomized to early iNO or to simulated initiation of iNO (control). Infants who had an increase in OI to 25 or more were given iNO as standard therapy. Results. The trial enrollment was halted after 75% of target sample size was reached because of decreasing availability of eligible patients. The 150 infants who were given early iNO and 149 control infants had similar baseline characteristics. Arterial oxygen tension increased by >20 mm Hg in 73% of early iNO and 37% of control infants after study gas initiation. Control infants received standard iNO and deteriorated to OI >40 more often than infants who were given early iNO. The incidence of death (early iNO, 6.7% vs control, 9.4%), ECMO (10.7% vs 12.1%), and their combined incidence (16.7% vs 19.5%) were similar in both groups. Conclusion. iNO improves oxygenation but does not reduce the incidence of ECMO/mortality when initiated at an OI of 15 to 25 compared with initiation at >25 in term and near-term neonates with respiratory failure. [ABSTRACT FROM AUTHOR]

ABSTRACT. Recent reports indicate that inhaled nitric oxide (iNO) causes selective pulmonary vasodilation, increases arterial oxygen tension, and may decrease the use of extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). Despite these reports, the optimal dose and timing of iNO administration in PPHN remains unclear. Objectives. To test the hypotheses that in PPHN 1) iNO at 2 parts per million (ppm) is effective at acutely increasing oxygenation as measured by oxygenation index (OI); 2) early use of 2 ppm of iNO is more effective than control (0 ppm) in preventing clinical deterioration and need for iNO at 20 ppm; and 3) for those infants who fail the initial treatment protocol (0 or 2 ppm) iNO at 20 ppm is effective at acutely decreasing OI. Study Design. A randomized, controlled trial of iNO in 3 nurseries in a single metropolitan area. Thirty-eight children, average gestational age of 37.3 weeks and average age <1 day were enrolled. Thirty-five of 38 infants had echocardiographic evidence of pulmonary hypertension. On enrollment, median OI in the control group, iNO at 0 ppm, (n = 23) was 33.1, compared with 36.9 in the 2-ppm iNO group (n = 15). Results. Initial treatment with iNO at 2 ppm for an average of 1 hour was not associated with a significant decrease in OI. Twenty of 23 (87%) control patients and 14 of 15 (92%) of the low-dose iNO group demonstrated clinical deterioration and were treated with iNO at 20 ppm. In the control group, treatment with iNO at 20 ppm decreased the median OI from 42.6 to 23.8, whereas in the 2-ppm iNO group with a change in iNO from 2 to 20 ppm, the median OI did not change (42.6 to 42.0). Five of 15 patients in the low-dose nitric oxide group required ECMO and 2 died, compared with 7 of 23 requiring ECMO and 5 deaths in the control group. Conclusion. In infants with PPHN, iNO 1): at 2 ppm does not acutely improve oxygenation or prevent clinical deterioration, bu... [ABSTRACT FROM AUTHOR]

ABSTRACT. Objective. Because of case reports describing hypoxemia on withdrawal of inhaled nitric oxide (I-NO), we prospectively examined this safety issue in newborns with persistent pulmonary hypertension who were classified as treatment successes or failures during a course of I-NO therapy. Methods. Randomized, placebo-controlled, double-masked, dose-response clinical trial at 25 tertiary centers from April 1994 to June 1996. Change in oxygenation and outcome (death and/or extracorporeal membrane oxygenation) during or immediately after withdrawing I-NO were the principal endpoints. Patients (n = 155) were term infants, <3 days old at study entry with echocardiographic evidence of persistent pulmonary hypertension of the newborn. Exclusion criteria included previous surfactant treatment, high-frequency ventilation, or lung hypoplasia. Withdrawal from treatment gas (0, 5, 20, or 80 ppm) started once treatment success or failure criteria were met. Withdrawal of treatment gas occurred at 20% decrements at <4 hours between steps. Results. The patient profile was similar for placebo and I-NO groups. Treatment started at an oxygenation index (OI) of 25 +/- 10 (mean +/- SD) at 26 +/- 18 hours after birth. For infants classified as treatment successes (mean duration of therapy = 88 hours, OI <10), decreases in the arterial partial pressure of oxygen (PaO[sub 2]) were observed only at the final step of withdrawal. On cessation from 1, 4, and 16 ppm, patients receiving I-NO demonstrated a dose-related reduction in PaO[sub 2] (-11 +/- 23, -28 +/- 24, and -50 +/- 48 mm Hg, respectively). For infants classified as treatment failures (mean duration of therapy = 10 hours), no change in OI occurred for the placebo group (-13 +/- 36%, OI of 31 +/- 11 after the withdrawal process); however a 42 +/- 101% increase in OI to 46 +/- 21 occurred for the pooled nitric oxide doses. One death was possibly related to withdrawal of I-NO. Conclusion. For infants classified as treatment su... [ABSTRACT FROM AUTHOR]

Comments on the study concerning the therapeutic effect of inhaled nitric oxide (iNO) on chronic lung disease. Mechanism of action of nitric oxide; Effectiveness of the therapy; Health concerns raised on the use of iNO.

Determines whether inhaled nitric oxide (INO) in term and near-term infants with congenital diaphragmatic hernia (CDH) would reduce the occurrence of death and/or the initiation of extracorporeal membrane oxygenation (ECMO). Study gas administration and monitoring; Study gas weaning; Need for full conventional management of infants before administration of INO.

Examines response to inhaled nitric oxide in newborns with respiratory failure and pulmonary hypertension. Evidence for improved systemic oxygenation in these newborns; Helpfulness of diagnosis and chest radiograph in identifying patients who will have favorable response to this treatment.

Determines the clinical role of inhaled nitric oxide in the treatment of persistent pulmonary hypertension of the newborn (PPHN). Description of the four patterns of response which emerged from this treatment; Decreased sensitivity and differing time course of response in neonates with pulmonary hypoplasia and dysplasia.

Opinion. Comments about the putative benefits and unique hardships of high technology neonatal clinical trials that utilize inhaled nitric oxide (iNO) and high-frequency oscillatory ventilation for persistent pulmonary hypertension of the newborn. Disturbing trend in high technology neonatal clinical research; Future neonatal clinical trials.

Reports on the use of inhaled nitric oxide (NO) therapy in patients with critical hypoxemia during transportation to the Children's Hospital in Denver, Colo. Oxygenation improvement with the onset of NO inhalation; Reduction of pulmonary vascular librium by blending low doses of NO gas with oxygen; Measurement of NO and NO2 concentrations.

Reports on the clinical course of a preterm neonate with respiratory distress and group B streptococcal sepsis who was treated with inhaled nitric oxide because of critical hypoxemia and pulmonary hypertension. Discussion on the mechanism of action of inhaled nitric oxide; Problems that may limit the clinical use of nitric oxide in the treatment of premature infants; Factors that can contribute to high pulmonary vascular resistance in patients with severe diseases.

Opinion. Comments about the ability of inhaled nitric oxide (iNO) to acutely lower pulmonary vascular resistance (PVR). INO therapy as a tool in treating persistent pulmonary hypertension of the newborn; Issues arising from the potential role of iNO therapy in PPHN.

A correction to the article "Inhaled Nitric Oxide in Extremely Premature Neonates With Respiratory Distress Syndrome" that was published in the March 2018 issue is presented.

ABSTRACT. Approval of inhaled nitric oxide by the US Food and Drug Administration for hypoxic respiratory failure of the term and near-term newborn provides an important new therapy for this serious condition. This statement addresses the conditions under which inhaled nitric oxide should be administered to the neonate with hypoxic respiratory failure. [ABSTRACT FROM AUTHOR]

Answers how pediatricians could safely use inhaled nitric oxide (iNO) as a selective pulmonary vasodilator that reduces the use of extracorporeal membrane oxygenation. Reason iNO was not approved for clinical use in 1992; Requirements of the United States Food and Drug Administration; Explanations on why iNO does not promote better health.

Comments on the study that described the role of inhaled nitric oxide in the treatment of neonatal respiratory disorders characterized by pulmonary hypertension. Result of the treatment of neonatal pulmonary hypertensive disorders; Treatment approach used in the study.

A response from the authors is presented concerning the article "Inhaled nitric oxide for persistent pulmonary hypertension of the newborn: The physiology matters!" which was published in a previous issue is presented.

Provides information on inhalational nitric oxide (NO) therapy for persistent pulmonary hypertension (PPHN) of the newborn infant. Background on PPHN; Function of NO; Efficacy of the therapy.

A letter to the editor is presented in response to the article "Inhaled nitric oxide for persistent pulmonary hypertension of the newborn: The physiology matters!" by S.H. Abman and J.P. Kinsella which was published in a previous issue.