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

Pediatrics. 2020 Oct;146(4):e20193318. doi: 10.1542/peds.2019-3318. Epub 2020 Sep 17.

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.

Trial registration: ClinicalTrials.gov NCT00063063.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • African Americans
  • Apgar Score
  • Birth Weight
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Female
  • Fetal Membranes, Premature Rupture
  • Hospital Mortality
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypoxia / complications*
  • Incidence
  • Infant
  • Infant, Extremely Low Birth Weight
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Male
  • Neurodevelopmental Disorders / diagnosis
  • Neurodevelopmental Disorders / drug therapy
  • Neurodevelopmental Disorders / epidemiology*
  • Neurodevelopmental Disorders / ethnology
  • Nitric Oxide Synthase Type II / administration & dosage
  • Nitric Oxide Synthase Type II / therapeutic use*
  • Patient Discharge
  • Pregnancy
  • Propensity Score
  • Respiratory Insufficiency / drug therapy
  • Respiratory Insufficiency / ethnology
  • Respiratory Insufficiency / etiology
  • Respiratory Insufficiency / mortality*
  • Risk Factors
  • Sex Factors
  • Steroids / therapeutic use

Substances

  • Bronchodilator Agents
  • Steroids
  • Nitric Oxide Synthase Type II

Associated data

  • ClinicalTrials.gov/NCT00063063