NEONATOLOGY

Inhaled nitric oxide may not improve survival of preterm infants

Preterm infants born younger than 29 weeks’ gestational age who were treated for pulmonary hypoplasia with inhaled nitric oxide did not have an increased chance of in-hospital survival, according to findings published in JAMA Pediatrics.

Because blood vessel growth in the lung parallels airway development, pulmonary hypoplasia is often complicated by persistent pulmonary hypertension of the newborn, or PPHN," Kevin R. Ellsworth, MD, from the division of neonatal medicine at the Mayo Clinic, and colleagues wrote. “Pulmonary hypertension is a major contributor to physiologic compromise in these patients, including severe, refractory hypoxemic respiratory failure. To date, to our knowledge, no postnatal therapy has been shown to consistently increase survival in preterm neonates with pulmonary hypoplasia."

To measure the efficacy in which treatment with inhaled nitric oxide within the first week of life improved the survival rate of extremely preterm infants with pulmonary hypoplasia in the hospital, the researchers conducted a cohort study that included information collected from the Pediatrix Medical Group’s Clinical Data Warehouse. This database gathered information from more than 350 U.S. NICUs located in 35 states and Puerto Rico.

To lessen the imbalance of measured covariates between infants receiving inhaled nitric oxide and infants who did not, Ellsworth and colleagues used one-to-one propensity score matching because those in the treatment group were not randomly prescribed the treatment. The first, unmatched group included singleton infants born at 22 to 29 weeks’ gestational age, weighed 400 g or more at birth and received a diagnosis of pulmonary hypoplasia as the catalyst for their respiratory distress. Additionally, these infants had no major anomalies and were discharged between Jan. 1, 2010, and Dec. 31, 2014.

Infants who began treatment with inhaled nitric oxide on a specific day between days 0 and 7 of life were considered exposed by the researchers. Once defined, these infants were matched with a neonate who did not begin inhaled nitric oxide treatment within this time.

Once data were collected and compared, the researchers examined the rate of mortality, which was defined as death of the neonate before transfer or discharge home, any-stage necrotizing enterocolitis, retinopathy of prematurity that required treatment, chronic lung disease and periventricular leukomalacia.

Of the 92,635 preterm neonates included in the cohort study, 0.8% had pulmonary hypoplasia and met inclusion criteria. Of these infants (n = 767), 185 were treated with inhaled nitric oxide. When matched with an unexposed infant, no significant relationship was found between treatment with inhaled nitric oxide and mortality (HR = 0.79; 95% CI, 0.57-1.11).

When the relationship between inhaled nitric oxide use and mortality in infants with and without PPHN was evaluated, no significant association was observed (pulmonary hypoplasia with PPHN: HR = 0.67; 95% CI, 0.45-1.01; pulmonary hypoplasia without pulmonary hypertension of the newborn: HR = 1.11; 95% CI, 0.61-2.02). The researchers noted that these findings may have been affected by ascertainment bias.

The targeted use of inhaled nitric oxide in preterm neonates with pulmonary hypoplasia and PPHN is supported by some organizations, including the American Heart Association, the American Thoracic Society and the Pediatric Pulmonary Hypertension Network,” Ellsworth and colleagues wrote. “This seems rational, given that pulmonary hypoplasia-related PPHN has characteristics that may render it more acutely responsive to inhaled nitric oxide than PPHN that results from parenchymal lung disease. However, an acute clinical response to inhaled nitric oxide may not translate into a survival benefit."

– by Katherine Bortz

(Original citation: Ellsworth KR, et al. JAMA Pediatr. 2018; doi: 10.1001/jama.2018.0761)