Clinical characteristics and outcomes in neonates with perinatal acute respiratory distress syndrome in China: A national, multicentre, cross-sectional study

Abstract

Background: Neonatal acute respiratory distress syndrome (NARDS) was defined in 2017 and the epidemiological data remain unknown. Our objective was to explore aetiological factors, clinical characteristics and outcomes in patients with perinatal NARDS.

Methods: A multicentre, prospective, cross-sectional study was performed in 58 tertiary neonatal intensive care units in China from Jan 1, 2018 to June 30, 2019. Neonates diagnosed with NARDS were included. Primary outcomes were aetiological factors, clinical characteristics and outcomes. Binary logistic regression and multivariate cox proportional regression were performed to identify independent predictors for bronchopulmonary dysplasia (BPD) and/or death or single death. This study was registered with ClinicalTrials.Gov, NCT03311165.

Findings: Among 70,013 admitted neonates, the incidence of NARDS was 1.44% (1005). The cumulative incidences were 65.6%, 86.7%, 94.1% within one, two and three days after birth. The median gestational age and birth weight were 36.4 weeks and 2700 g. Three main aetiological triggers included pneumonia (58.1%), asphyxia (24.3%) and early-onset sepsis (EOS) (21.3%). BPD and/or death was observed in 213 (21.2%) infants, consisting 104 (10.3%) BPD and 126 (12.6%) deaths. The numbers of mild, moderate and severe NARDS were 537 (53.4%), 286 (28.4%) and 182 (18.2%). Two or more doses of surfactant was associated with increased mortality as compared with one or less doses of surfactant (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.20-3.10, P = 0.006). Similarity also appeared in the comparison between EOS and non-EOS triggers (OR 1.57, 95% CI 1.06-2.33, P = 0.023).

Interpretation: NARDS incidence was 1.44% and the three main aetiologies were pneumonia, asphyxia and EOS. The cumulative incidences were 65.6%, 86.7%, and 94.1% within one, two and three days after birth. Our results suggested that two or more doses of surfactant increased mortality compared with one or less doses of surfactant.

Funding: The National Clinical Research Center of China and Clinical Medical Study Program of Children's Hospital of Chongqing Medical University (NCRC-2019-GP-13) and Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0197).

Keywords: ARDS, acute respiratory distress syndrome; Acute respiratory distress syndrome; BIPAP, bi-level positive airway pressure; BPD, bronchopulmonary dysplasia; Bronchopulmonary dysplasia; CI, confidence interval; CMV, conventional mechanical ventiation; Epidemiology; GA, gestational age; GDM, gestational diabetes mellitus; HDCP, hypertensive disorder complicating pregnancy; HFOV, high-frequency oscillatory ventilation; ICP, intrahepatic cholestasis of pregnancy; IQR, interquartile range; IV, invasive ventilation; IVF, in vitro fertilization; MAS, meconium aspiration syndrome; Mortality; NARDS, neonatalacute respiratory distress syndrome; NCPAP, nasal continuous positive airway pressure; NHFOV, nasal high-frequency oscillatory ventilation; NIPPV, nasal intermittent positive pressure ventilation; NIV, noninvasive ventilation; NIV-I, intubation after NIV failure; Neonate; OR, odds ratio; PH, pulmonary hemorrhage; PPHN, persistent pulmonary hypertension of newborn; PROM, premature rupture of the membrane; iNO, inhaled nitric oxide.

Conflict of interest statement

No financial disclosure, and the other authors also have no financial disclosures relevant to this article. No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the individuals of this article.

© 2022 The Author(s).

Figures

Fig. 1

Flow chart of studied neonates. ARDS: acute respiratory distress syndrome; NICU: neonatal intensive care unit.

Fig. 2

Changing trends of chest X-rays in neonates with perinatal NARDS. (2A–2C) 30 + 3 weeks. (2A) The chest X-ray at 5 h after birth after the first administration of surfactant with NCPAP; (2B) The chest X-ray before the second administration of surfactant after invasive ventilation on the second day, OI: 22; now the antibiotic was used; (2C) the chest X-ray before extubation on the fifth day. Diagnosis: EOS related NARDS. (2D–2F) 36 + 6 weeks. (2D) the chest X-ray at 10 h after birth after the first administration of surfactant with NCPAP; (2E) the chest X-ray before the second administration of surfactant on the second day, OI: 10; now the antibiotic was used; (2F) the chest X-ray on the third day. Diagnosis: EOS related NARDS. (2G–2J) 30 + 1 weeks. (2G) the chest X-ray at 2 h after birth before the first administration of surfactant with NIPPV, OI:12; (2H) the chest X-ray on the third day, OI: 3; (2I) the chest X-ray on the eighth day; (2J) the chest X-ray on the fifth day, now the antibiotic was used; Diagnosis: LOS related NARDS. (2K–2M) 26 + 3 weeks. (2K) the chest X-ray at 4 h after birth before the first administration of surfactant with NIPPV, OI:16; (2L) the chest X-ray on the second day before extubation, OI: 4; (2M) the chest X-ray on the tenth day, now the antibiotic was used, OI:15. Diagnosis: LOS related NARDS. NCPAP: nasal continuous positive airway pressure; OI: oxygenation index; EOS: early onset sepsis; NARDS: neonatal acute respiratory distress syndrome; NIPPV: nasal intermittent positive pressure ventilation; LOS: late onset sepsis.

Fig. 3

Kaplan–Meier analyses for in-hospital survival for respiratory modes of NIV, NIV-I and IV (Fig 3A) (P = 0.356), mild, moderate and severe NARDS (Fig 3B) (P = 0.032), direct vs indirect insult (Fig 3C) (HR 2.55, 95% CI 1.71–3.58, P < 0.001) and EOS vs non-EOS (Fig 3D) (HR 1.72, 95% CI 1.21–2.91, P = 0.006). ARDS plus RDS vs ARDS (Fig 3E) (HR 0.95, 95% CI 0.64–1.41, P = 0.817) and non-perinatal-onset ARDS vs late-onset ARDS (Fig 3F) (HR 2.89, 95% CI 0.62–6.50, P = 0.259). NIV: noninvasive ventilation; NIV-I: intubation after NIV failure; IV: invasive ventilation; NARDS: neonatal acute respiratory distress syndrome; HR:Hazard ratio; CI:confidence interval; OS: early onset sepsis; ARDS: acute respiratory distress syndrome; RDS: respiratory distress syndrome.