Risk Factors of Neonatal Acute Respiratory Distress Syndrome Based on the Montreux Definition in Neonates with Sepsis: A Retrospective Case–Control Study

Abstract

Objective The aim of the study is to analyze the risk factors for neonatal acute respiratory distress syndrome (NARDS) development based on the Montreux definition among near- and full-term neonates with sepsis and received meropenem.

Study Design This was a single-center, case–control, retrospective trial from January 2019 to June 2020. Newborns of gestational ages (GAs) ≥35 weeks, diagnosed with sepsis and received meropenem were included. Patients who developed NARDS subsequently were defined as the study group (NARDS group), while the others without NARDS were enrolled in the control group (non-NARDS group).

Results Out of 213 eligible neonates, NARDS occurred in 52 (24.4%) cases. In univariate analysis, infants with NARDS had a lower GA and birth weight, but a higher rate of premature birth (p <0.05). The median onset times of sepsis were earlier among neonates with NARDS compared with those without NARDS (1 [1,1] vs. 6 [1,15] days, p <0.001). Neonates with NARDS were more likely to suffer from early-onset sepsis (EOS), persistent pulmonary hypertension of newborns, pulmonary hemorrhage, septic shock, and patent ductus arteriosus (p <0.05). During labor, women whose neonates experienced NARDS were more likely to have a cesarean delivery (67.3 vs. 46.6%, p = 0.009) and likely to receive at least one dose of corticosteroids (21.2 vs. 5.0%, p = 0.001). In multivariable analyses, factors remaining independently associated with NARDS were premature birth, cesarean delivery, EOS, and septic shock. Compared with conventional inflammatory markers for NARDS, procalcitonin (PCT) was correlated with septic neonates who developed NARDS (p = 0.012) but had a low diagnostic value (area under the curve [AUC] = 0.609). C-reactive protein, white blood cells, and PLT did not correlate with morbidity of NARDS (AUC <0.05 and p >0.05).

Conclusion Premature birth, cesarean delivery, EOS, and septic shock were independently associated with NARDS among near- and full-term septic neonates. PCT showed limited predictive value for NARDS.

Key Points

• NARDS is serious and sepsis is proved as a cause for it.

• But rare study suggests the risk factors of NARDS based on the Montreux definition.

• This study may first found the independent risk factors associated with NARDS in septic neonates.

Keywords

neonate - sepsis - acute respiratory distress syndrome - risk factor - Montreux definition

Note

A case–control, retrospective trial to analyze the risk factors for the development of NARDS in near- and full-term neonates with sepsis and received meropenem was performed. The study focused on the risk factors associated with NARDS in near- and full- term septic neonates and compared the predictive value of the conventional inflammatory markers for NARDS. We found that preterm infants, cesarean delivery, EOS and septic shock were the most important independent risk factors associated with NARDS. Conventional inflammatory markers only PCT showed limited predictive value for NARDS.

Authors' Contributions

All authors made substantial contributions to the study and manuscript and meet the criteria for authorship defined in the author instructions:

Y.H. contributed to the study design, acquisition, analysis, and interpretation of the data and the drafting and final approval of the manuscript. X.C. and W.Y. contributed to the acquisition, analysis, and interpretation of the data and the editing of the manuscript. F.W. supervised the project and contributed to the conception and design of the study, and analysis and interpretation of the data. C.L. supervised the project and contributed to the conception and design of the study. H.W. supervised the project and contributed to the conception and design of the study, analysis and interpretation of the data, and critical revision and final approval of the manuscript.

Ethical Approval

This study received ethics approval from the Institutional Review Board of the Children's Hospital of Chongqing Medical University (approval No. 2020/R/225).

Data Availability Statement

The dataset used and/or analyzed during the current study are available from the corresponding author on reasonable request. All data generated or analyzed during this study are included in this published article. Proposals should be submitted to [e-mail].

Publication History

Received: 04 January 2022

Accepted: 24 February 2022

Accepted Manuscript online:
04 March 2022

Article published online:
31 May 2022

• References

• 1 De Luca D, van Kaam AH, Tingay DG. et al. The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity. Lancet Respir Med 2017; 5 (08) 657-666
• 2 Guo JY, Chen L, Shi Y. A single-center retrospective study of neonatal acute respiratory distress syndrome based on the Montreux definition. Zhongguo Dang Dai Er Ke Za Zhi 2020; 22 (12) 1267-1272
• 3 Günther A, Ruppert C, Schmidt R. et al. Surfactant alteration and replacement in acute respiratory distress syndrome. Respir Res 2001; 2 (06) 353-364
• 4 De Luca D, Minucci A, Tripodi D. et al. Role of distinct phospholipases A2 and their modulators in meconium aspiration syndrome in human neonates. Intensive Care Med 2011; 37 (07) 1158-1165
• 5 Jobe AH. “Miracle” extremely low birth weight neonates: examples of developmental plasticity. Obstet Gynecol 2010; 116 (05) 1184-1190
• 6 Merrill JD, Ballard RA, Cnaan A. et al. Dysfunction of pulmonary surfactant in chronically ventilated premature infants. Pediatr Res 2004; 56 (06) 918-926
• 7 Been JV, Rours IG, Kornelisse RF, Jonkers F, de Krijger RR, Zimmermann LJ. Chorioamnionitis alters the response to surfactant in preterm infants. J Pediatr 2010; 156 (01) 10-15.e1
• 8 Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med 2018; 6 (03) 223-230
• 9 Costenaro P, Minotti C, Cuppini E, Barbieri E, Giaquinto C, Donà D. Optimizing antibiotic treatment strategies for neonates and children: does implementing extended or prolonged infusion provide any advantage?. Antibiotics (Basel) 2020; 9 (06) E329
• 10 Pascale R, Giannella M, Bartoletti M, Viale P, Pea F. Use of meropenem in treating carbapenem-resistant Enterobacteriaceae infections. Expert Rev Anti Infect Ther 2019; 17 (10) 819-827
• 11 Bradley JS, Sauberan JB, Ambrose PG, Bhavnani SM, Rasmussen MR, Capparelli EV. Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate. Pediatr Infect Dis J 2008; 27 (09) 794-799
• 12 Wang ZL, Du LZ, Chen YY. et al. Analysis of the characteristics and management of critical values in a newborn tertiary center in China. World J Pediatr 2017; 13 (01) 49-56
• 13 Wang ZL, An Y, He Y. et al. Risk factors of necrotizing enterocolitis in neonates with sepsis: a retrospective case-control study. Int J Immunopathol Pharmacol 2020; 34: 2058738420963818
• 14 Goldstein B, Giroir B, Randolph A. International consensus conference on pediatric sepsis: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6 (01) 2-8
• 15 Davis AL, Carcillo JA, Aneja RK. et al. American College of Critical Care Medicine Clinical Practice Parameters for hemodynamic support of pediatric and neonatal septic shock. Crit Care Med 2017; 45 (06) 1061-1093
• 16 Moresco L, Romantsik O, Calevo MG, Bruschettini M. Non-invasive respiratory support for the management of transient tachypnea of the newborn. Cochrane Database Syst Rev 2020; 4 (04) CD013231
• 17 Schulte W, Bernhagen J, Bucala R. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets—an updated view. Mediators Inflamm 2013; 2013: 165974
• 18 Deshmukh M, Mehta S, Patole S. Sepsis calculator for neonatal early onset sepsis - a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2021; 34 (11) 1832-1840
• 19 Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369 (09) 840-851
• 20 Schouten LR, Veltkamp F, Bos AP. et al. Incidence and mortality of acute respiratory distress syndrome in children: a systematic review and meta-analysis. Crit Care Med 2016; 44 (04) 819-829