Early Hypoxic Respiratory Failure in Extreme Prematurity: Mortality and Neurodevelopmental Outcomes

Abstract

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.WHAT'S KNOWN ON THIS SUBJECT: The incidence of early hypoxemic respiratory failure and inhaled nitric oxide therapy are common in preterm infants #26 weeks' gestation. There is limited information regarding developmental outcomes and survival at 18 to 26 months by race outside randomized trials.WHAT THIS STUDY ADDS: In preterm infants #26 weeks' gestation, early hypoxemic respiratory failure is associated with high mortality and severe neurodevelopmental impairment among survivors at 18 to 26 months. Therapy with inhaled nitric oxide did not reduce mortality or severe neurodevelopmental impairment in preterm infants of all races.

Use of Inhaled Nitric Oxide in Preterm Infants: Is There Sufficient Evidence?

“…Infants with early HRF treated with iNO in the neonatal period had 54.1% in-hospital mortality, compared to 44.3% in infants not exposed to iNO [14]. Thus, this study showed that iNO did not decrease mortality or NDI [14].…”

“…Chandrasekharan et al showed that 22.7% of infants ≤ 26 wk GA had early HRF associated with high mortality and neurodevelopmental impairment (NDI) at 18 to 26 mo [14]. Infants with early HRF treated with iNO in the neonatal period had 54.1% in-hospital mortality, compared to 44.3% in infants not exposed to iNO [14]. Thus, this study showed that iNO did not decrease mortality or NDI [14].…”

“…In a large RCT in premature infants (n = 451, < 30 wk), there was no difference in these long-term ND outcomes or evidence of harm with iNO use in preterm infants [10]. In another report, however, infants exposed to iNO had reduced survival to NICU discharge [14]. Chandrasekharan et al showed that 22.7% of infants ≤ 26 wk GA had early HRF associated with high mortality and neurodevelopmental impairment (NDI) at 18 to 26 mo [14].…”

“…In another report, however, infants exposed to iNO had reduced survival to NICU discharge [14]. Chandrasekharan et al showed that 22.7% of infants ≤ 26 wk GA had early HRF associated with high mortality and neurodevelopmental impairment (NDI) at 18 to 26 mo [14]. Infants with early HRF treated with iNO in the neonatal period had 54.1% in-hospital mortality, compared to 44.3% in infants not exposed to iNO [14].…”

Gestational Age-Related Associations between Early-Life Feeding Trajectories and Growth Outcomes at Term Equivalent Age in Very Preterm Infants

“…However, the introduction and advancement of enteral feeding, especially in extremely preterm infants, is often delayed or interrupted because of prematurity-related risks, exposures, and gastrointestinal (GI) morbidities [ 8 , 9 , 10 ]. Risks and exposures, such as sepsis, hypotension and hypoxic respiratory failure requiring mechanical ventilation [ 11 , 12 , 13 , 14 ], and the functional immaturity of GI tracts, may have a significant impact on the feeding progression of preterm infants during the gestational age (GA). In addition, GI morbidities, such as necrotizing enterocolitis (NEC) and non-NEC morbidities, including meconium ileus, spontaneous intestinal perforation or volvulus, may also change the enteral feeding trajectory differently in preterm infants with different GA [ 2 ].…”