Abstract
This study aimed to determine the effect of late-onset sepsis (LOS) on the development of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. A prospective cohort study was performed using data collected from 64 centres registered in the Korean national registry. LOS was defined as a positive blood culture and antibiotics treatment after 72 hours of life and prior to 36 weeks postmenstrual age (PMA). Data on the causative organisms were collected and analysed for respiratory outcomes. Among the 1,434 ELBW infants who survived to 36 weeks PMA, 481 (34%) developed LOS caused by bacteria (n = 405), fungi (n = 28), or both (n = 48). The incidence of BPD was significantly associated with LOS in both the entire cohort and the propensity score-matched cohort. Two or more LOS episodes were a risk factor for BPD. The impact of multiple episodes of LOS on BPD was prominent in infants who received mechanical ventilation for two weeks or less. The estimated odds ratios for BPD and severe BPD were greater with fungal LOS than with bacterial LOS. In conclusion, LOS, particularly complicated by multiple episodes and/or fungi, was a risk factor for BPD in ELBW infants.
Similar content being viewed by others
Introduction
Inflammation in utero and during the postnatal period is one of the key underlying mechanisms in the development of bronchopulmonary dysplasia (BPD)1. The major prenatal factors that modulate foetal lung inflammation include maternal chorioamnionitis and antenatal corticosteroids, although their roles in the development of BPD remain controversial2,3,4. However, a consensus is being formed about the postnatal risk factors for BPD, which share a common mechanism that is characterised by the production of inflammatory cytokines5. These risk factors include respiratory distress syndrome (RDS), invasive mechanical ventilation (IMV), oxygen and sepsis3,6. Several treatment strategies to minimise lung inflammation have been attempted, but the incidence of BPD has remained grossly unchanged over the past two decades7.
Approximately 38% of extremely low birth weight (ELBW; those under 1 kg at birth) infants suffer from late-onset sepsis (LOS)8. The trend of LOS incidence roughly tracks in parallel with that of BPD in large cohort studies9. Thus, LOS could be a promising target for reducing the incidence of BPD in ELBW infants. Several retrospective studies have also reported an association between LOS and BPD in preterm infants2,10,11; however, it is difficult to ascertain the causative role of LOS in the development of BPD. There are several confounders that are linked to LOS and BPD, including prematurity and postnatal steroids. In addition, whether the lung injury is attributable to systemic or local inflammation caused by LOS, or to LOS-associated interventions, such as oxygen and mechanical ventilator therapy, remains unclear.
The severity of inflammation is a matter of interest for the risk assessment of BPD. There are limited data regarding the association between the specific characteristics of LOS and BPD. Among preterm infants who were subjected to neonatal sepsis, approximately 25% experienced two or more episodes of LOS12. However, no previous studies have focussed on the effect of repeated LOS episodes on BPD and its severity. In addition, no studies have thoroughly investigated the impact of different causative organisms on BPD.
The purpose of this study was to determine the causal relationship between LOS and BPD and to address the characteristics of LOS that increase the risk of BPD in ELBW infants by evaluating a nationwide cohort of preterm infants.
Results
During the study period, 2,073 ELBW infants were registered in the Korean Neonatal Network (KNN) registry. Among them, 639 infants were excluded for death prior to 36 weeks postmenstrual age (PMA) (n = 544), major congenital anomalies (n = 44) and positive blood culture results ≤72 hours after birth (n = 51).
Of the 1,434 ELBW infants who fulfilled the inclusion criteria, 481 (33.5%) were diagnosed with LOS. The mean time at diagnosis of the first LOS episode was 27.3 (10–41) days after birth. LOS was caused by either bacteria (n = 405), fungi (n = 28), or both (n = 48). A total of 724 LOS episodes were reported among the 481 infants, and 36.4% (175/481) of the infants experienced multiple episodes, as follows: 2 (n = 120), 3 (n = 344), 4 (n = 49) and 5 (n = 2) episodes. For ELBW infant survivors who experienced bacterial sepsis, the rate of gram-positive and gram-negative bacteria was 84.1% and 15.9%, respectively. Coagulase-negative Staphylococci (CoNS) was the most common organism with an incidence of 40.3% (Table 1).
Clinical characteristics and neonatal outcomes were compared between the infants with LOS (LOS group) and those free from LOS (no LOS group). The LOS group had a lower gestational age and birth weight and higher incidences of most neonatal morbidities than the control group. Regarding respiratory morbidities, the LOS group had a higher incidence of BPD, severe BPD, use of corticosteroids and home oxygen therapy as well as a longer duration of IMV support than the control group. The rate of LOS was lower in neonatal intensive care units (NICUs) with 40 or more beds. The associations between LOS and respiratory outcomes including BPD and longer hospital stays were identified with propensity score matching (Table 2).
The ELBW infants who survived to 36 weeks PMA reported BPD and severe BPD incidences of 56.9% and 38.9%, respectively. Compared to the infants without BPD (no BPD group), those diagnosed with BPD (BPD group) had a lower gestational age and birth weight as well as a higher incidence of being male. The BPD group had a higher rate of most major neonatal morbidities than the no BPD group. In the multivariate analysis, lower birth weight, male sex, RDS, treatment for patent ductus arteriosus (PDA), systemic corticosteroids, severe intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP) requiring laser photocoagulation and LOS were risk factors for BPD (Table 3).
We investigated the characteristics of LOS episodes and their impact on respiratory outcomes. After adjusting for potential confounders in the multivariate analysis of the propensity score-matched cohort, two or more episodes of LOS were significantly associated with BPD and severe BPD. As the number of LOS episodes increased, the odds ratios for BPD and severe BPD also increased. The odds ratios for the risk of BPD and severe BPD were greater with fungal LOS than with bacterial LOS. Combined bacterial and fungal LOS had a higher odds ratio than bacterial or fungal LOS in the univariate analysis. However, the significance disappeared when adjusted for the confounding variables including the number of LOS episodes (Table 4).
We investigated the association between multiple episodes of LOS and the respiratory outcomes in the subgroups categorised according to IMV duration. The impact of multiple LOS events on BPD and severe BPD was significant in the infants who received IMV for two weeks or less (Fig. 1).
The incidence of BPD did not differ between the infants with LOS caused by gram-positive bacteria (p = 0.954) and the infants with LOS caused by gram-negative bacteria (p = 0.954). No specific microorganisms, including CoNS (p = 0.452), increased the incidence of BPD relative to other bacteria.
Discussion
Analyses of data from ELBW infants who survived to 36 weeks PMA revealed the following major findings. First, LOS was significantly associated with BPD and severe BPD, and the risk was further augmented by recurrent episodes of LOS. Second, relative to bacterial LOS, fungal LOS carried a greater risk of BPD. Third, there were no specific bacterial species that increased the risk of BPD relative to other bacteria. Our study had several methodological advantages over the aforementioned studies regarding the association between neonatal sepsis and BPD2,3. First, the data included were obtained from a large number of ELBW infants registered in a nationwide cohort. Second, detailed datasets on the episodes of neonatal sepsis in terms of diagnosis time and causative organisms were available. Third, the influence of many prenatal and postnatal variables that are potentially linked to both LOS and BPD were considered and adjusted for by propensity score matching. Notably, our results suggest that LOS acts as a risk factor for BPD, rather than simply being associated with it, in ELBW infants.
Despite a temporal association between the occurrence of LOS and the diagnosis of BPD, the causality between the two factors could not be clarified in practice. As the duration of IMV increases, preterm infants are subjected to both infection and superimposed ventilator-induced lung injury (VILI). As expected, the LOS group experienced a longer duration of IMV even in the propensity-matched cohort; the data on this finding have already been presented in a recent study using the same national cohort13. To determine the direct contribution of LOS to the development of BPD, the outcomes should be compared in study groups with minimal or at least a balanced risk of VILI. However, the design of such a study is not clinically feasible because the infants subjected to LOS inevitably require higher levels of respiratory and other types of supportive care that affect pulmonary outcomes. A few animal studies demonstrated that bacterial infection in the postnatal developing lung, either as a type of septicaemia or lipopolysaccharide injection, stimulates the inflammatory response and subsequent structural change of alveoli that is suggestive of BPD14.
To the best of our knowledge, no clinical studies have determined the dose-response relationship between the number of LOS episodes and the risk of BPD in preterm infants. In the present study, the odds ratios for BPD and severe BPD increased as the number of LOS episodes increased after adjusting for several confounding variables including chorioamnionitis, RDS, treatment of PDA and postnatal systemic corticosteroids. All of these parameters can alter systemic or local inflammatory responses and thereby affect pulmonary outcomes in preterm infants. For example, infection increases the ductal prostaglandin production and increases the risk of reopening or persistent PDA, which subsequently contributes to the worsening of lung functions due to the increase in pulmonary edema15. Considering the hypothesis of the ‘multiple hit’ model in the pathogenesis of BPD, our finding is not surprising and warrants the need for infection control as a key target for the prevention of BPD5,16. Notably, the association between recurrent LOS and BPD as well as severe BPD was most prominent in the subgroup of infants exposed to the shortest duration of IMV. This implies that recurrent LOS, if complicated during early postnatal days, has a significant impact on the development of BPD, irrespective of the VILI-dependent mechanism.
In the present study, the risk for BPD did not differ between the infants with LOS caused by CoNS and those with LOS caused by other bacteria. This is contrary to the results of a small retrospective study in which CoNS-related sepsis increased the risk for BPD compared to other bacteria; however, our results are in line with the results of another large cohort study3,17. The reason for this discrepancy remains unclear, but it may be due to differences in the study populations, the proportion of causative organisms and the treatment strategies employed. Because neonatal pro-inflammatory responses to CoNS are gestational age-dependent according to an in vivo study18, the differences in prematurity and the time of LOS occurrence might affect the pulmonary outcomes. In a cohort study from the Canadian Neonatal Network, the combined outcome of mortality and BPD was higher in infants with gram-negative bacteria than in those with gram-positive bacteria, but the difference was mainly attributable to the higher mortality in the group with gram-negative infections10.
In accordance with a large cohort study of very low birth weight infants19, fungal LOS was also associated with the risk of BPD, with a greater odds ratio than bacterial LOS. Compared to bacterial infection, fungal infection in rats induces a more severe lung injury characterised by capillary obstruction, interstitial haemorrhage and an elevated lung wet-to-dry ratio20. In a case-control study, candidemia was associated with the duration of IMV and previous bacteraemia, which are presumably the two most significant postnatal risk factors for BPD21. Because the incidence of isolated fungal infection was very limited in the present study, it remains unclear whether fungal LOS itself, mostly caused by systemic candidiasis, conferred a greater risk for BPD than bacterial LOS. Until now, there has been insufficient evidence that fungal prophylaxis reduces the risk of BPD, although a significant reduction of invasive candidiasis was reported in a recent randomised clinical trial22. Although the odds ratios were higher with combined bacterial and fungal LOS than with either bacterial or fungal LOS alone, the significance disappeared when adjusted for confounders including the number of LOS episodes. This suggests that repeated LOS episodes rather than the type of LOS (fungal or bacterial) increase the risk of BPD in preterm infants.
This study has several limitations. First, inherent to the retrospective study design, the treatment or prevention strategies for LOS and BPD may differ across the participating centres. Other treatment strategies that affect the risk of BPD, including fluid management, corticosteroid administration protocol and detailed information on ventilator care, were not available in our registry data. Second, because the main outcome of interest was BPD, the infants who died before 36 weeks PMA were excluded from the analysis. The mortality rate and the time of death following the occurrence of LOS vary depending on the causative organisms23. For example, the exclusion of infants who died from a severe single episode of LOS may result in selection bias in the final data analysis. Third, although adjusted for in the data analysis, the incidence of postnatal corticosteroid use was markedly higher in our study population, which consisted of survivors. This higher incidence of corticosteroid use might have influenced the incidence of LOS and BPD and mortality in an unpredictable direction24,25.
In conclusion, LOS, particularly if complicated by multiple episodes or fungal infection, increases the risk of BPD in ELBW infants. Our findings suggest that infection control should be a target for the prevention of BPD.
Materials and Methods
Study design
This cohort study used prospectively collected data from 64 NICUs participating in the KNN, a nationwide neonatal registry. Each participating centre recorded the study variables into the KNN data system according to the standardised KNN data manual26. For the present study, eligible infants included preterm infants with a birth weight <1,000 g who were born between 1 January 2013 and 31 December 2015. We excluded infants with major congenital anomalies, death prior to 36 weeks of postmenstrual age (PMA) and positive blood cultures ≤72 hours after birth.
Data collection
Maternal data included hypertension, premature rupture of membrane, diabetes, histological chorioamnionitis and the use of antenatal corticosteroids. The data collected on the infants included sex, gestational age, birth weight, small for gestational age, multiple births, delivery mode, Apgar scores at 1 and 5 minutes, need for resuscitation at birth, the duration of IMV and morbidities, including RDS, PDA, necrotising enterocolitis (NEC), IVH, ROP, BPD and LOS. Data on the duration of hospital stay were also collected. According to the KNN manual of operation, LOS-causative microorganisms included 33 bacterial (Achromobacter, Acinetobacter, Aeromonas, Alcaligenes, Bacteroides, Burkholderia, Campylobacter, Chryseobacterium, Citrobacter, Clostridium, Enterobacter, Enterococcus, Escherichia coli, Flavobacterium, Haemophilus, Klebsiella, Listeria, Moraxella, Neisseria, Pasteurella, Prevotella, Proteus, Providencia, Pseudomonas, Ralstonia, Salmonella, Serratia, coagulase-positive Staphylococcus aureus, CoNS, other Staphylococcus, Stenotrophomonas maltophilia, group B Streptococcus and other Streptococcus) and 2 fungal (Candida and others) classifications.
Definitions
Maternal hypertension included pre-existing hypertension and/or pregnancy-induced hypertension27. Antenatal corticosteroid administration was defined as either completion or incompletion of dexamethasone or betamethasone before delivery. BPD was defined as a requirement for supplemental oxygen or positive pressure support at 36 weeks PMA, with severe BPD defined according to the National Institutes of Health criteria28. An episode of LOS was defined as a positive blood culture result after 72 hours of life for one or more bacteria or fungi that were treated with appropriate antibiotics for five or more days and occurred prior to 36 weeks PMA13,23. A series of samples that were repeatedly positive for the same organism within seven days were considered part of the same episode12. If a different organism was cultured from a subsequent culture, this was considered an additional episode23. Multiple episodes of LOS were defined as two or more sepsis events regardless of the type of pathogen. The association of BPD with specific causative species of LOS was analysed using data from the first LOS episode of each infant. RDS was diagnosed based on typical chest x-ray findings and clinical symptoms requiring mechanical ventilator and/or non-invasive respiratory support after NICU admission. The treatment for PDA included medical treatment with ibuprofen or indomethacin and/or surgical ligation. NEC was confirmed using radiological or surgical findings, and only stage 2 or higher NEC was included for analysis according to Bell’s criteria29. Severe IVH was defined as grade III or IV according to Papile’s criteria30. The variation of care levels and treatment strategies between centres can influence the rates of LOS and BPD. However, data on the NICU level (i.e., level I, II and III) were not available in our KNN registry, and the provision of centre-identification data was not allowed according to KNN regulations31. We used the patient volume of the NICUs as an alternative for the level of NICU. The centres were categorised into three groups based on the number of NICU beds: 1–19 beds were classified as low-volume, 20–39 as mid-volume and 40 or more as high-volume.
Ethical approval and informed consent
The registration of data in the KNN was approved by the institutional review board of each participating hospital, and all methods were performed in accordance with the relevant guidelines and regulations. Informed consent was obtained from the parents of each infant prior to participation in the KNN registry. This study was approved by the Asan Medical Center Instituitional Review Board.
Statistical analysis
Continuous normally distributed variables were expressed as means and standard deviations or interquartile ranges and were compared with a t-test. Categorical variables were expressed as numbers and percentages and were compared with a χ2 test or Fisher’s exact test as appropriate. To analyse LOS as a risk factor of BPD, propensity score matching was performed including perinatal demographics, clinical characteristics and the number of beds in each participating NICU; LOS and no LOS matched groups were divided, and McNemar’s test, the marginal homogeneity test or a paired t-test were used. A multivariate logistic analysis was used to identify the factors associated with BPD, and the odds ratios were calculated by focussing on LOS. Using the previously prepared propensity score-matched data, the odds ratios of LOS were calculated as a risk factor of BPD and the number of beds and were compared. Statistical analyses were performed using SPSS version 23.0 (IBM Corp, Armonk, NY) and R version 3.1.2. Statistical significance was defined as p < 0.05.
Data availability
The Korean Neonatal Network (KNN) Publication Ethics Policy adheres to the following research data management and access guidelines: All information about patients and participating NICUs is confidential and is only available to individuals who have access for the purposes of the research activities permitted. Access is only allowed for the purpose of collecting data for the first time, and no access for any other purpose is allowed.
References
Balany, J. & Bhandari, V. Understanding the Impact of Infection, Inflammation, and Their Persistence in the Pathogenesis of Bronchopulmonary Dysplasia. Front Med (Lausanne) 2, 90 (2015).
Van Marter, L. J. et al. Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants. J Pediatr 140, 171–176 (2002).
Lahra, M. M., Beeby, P. J. & Jeffery, H. E. Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics 123, 1314–1319 (2009).
Hartling, L., Liang, Y. & Lacaze-Masmonteil, T. Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 97, F8–F17 (2012).
Speer, C. P. Chorioamnionitis, postnatal factors and proinflammatory response in the pathogenetic sequence of bronchopulmonary dysplasia. Neonatology 95, 353–361 (2009).
Stoll, B. J. & Hansen, N. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin Perinatol 27, 293–301 (2003).
Jensen, E. A. & Schmidt, B. Epidemiology of bronchopulmonary dysplasia. Birth Defects Res. A Clin. Mol. Teratol. 100, 145–157 (2014).
Greenberg, R. G. et al. Late-onset sepsis in extremely premature infants: 2000–2011. Pediatr. Infect. Dis. J. 36, 774–779 (2017).
Lapcharoensap, W. et al. The Relationship of Nosocomial Infection Reduction to Changes in Neonatal Intensive Care Unit Rates of Bronchopulmonary Dysplasia. J Pediatr 180, 105–109 e101 (2017).
Shah, J. et al. Risk factors and outcomes of late-onset bacterial sepsis in preterm neonates born at <32 weeks’ gestation. Am. J. Perinatol. 32, 675–682 (2015).
Landry, J. S. & Menzies, D. Occurrence and severity of bronchopulmonary dysplasia and respiratory distress syndrome after a preterm birth. Paediatr. Child Health 16, 399–403 (2011).
Lee, S. M., Chang, M. & Kim, K. S. Blood Culture Proven Early Onset Sepsis and Late Onset Sepsis in Very-Low-Birth-Weight Infants in Korea. J Korean Med Sci 30(Suppl 1), S67–74 (2015).
Choi, Y. B., Lee, J., Park, J. & Jun, Y. H. Impact of Prolonged Mechanical Ventilation in Very Low Birth Weight Infants: Results From a National Cohort Study. J Pediatr 194, 34–39 e33 (2018).
Bhandari, V. Postnatal inflammation in the pathogenesis of bronchopulmonary dysplasia. Birth Defects Res. A Clin. Mol. Teratol. 100, 189–201 (2014).
Tapia, J. L. et al. Bronchopulmonary dysplasia: incidence, risk factors and resource utilization in a population of South American very low birth weight infants. J Pediatr (Rio J). 82, 15–20 (2006).
Ambalavanan, N. et al. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants. Pediatrics 123, 1132–1141 (2009).
Liljedahl, M., Bodin, L. & Schollin, J. Coagulase-negative staphylococcal sepsis as a predictor of bronchopulmonary dysplasia. Acta Paediatr. 93, 211–215 (2004).
Hartel, C. et al. Characterisation of the host inflammatory response to Staphylococcus epidermidis in neonatal whole blood. Arch Dis Child Fetal Neonatal Ed 93, F140–145 (2008).
Makhoul, I. R. et al. Candidal versus bacterial late-onset sepsis in very low birthweight infants in Israel: a national survey. J. Hosp. Infect. 65, 237–243 (2007).
Lechner, A. J., Ryerse, J. S. & Matuschak, G. M. Acute lung injury during bacterial or fungal sepsis. Microsc Res Tech 26, 444–456 (1993).
Linder, N. et al. Risk factors associated with candidaemia in the neonatal intensive care unit: a case-control study. J Hosp Infect 57, 321–324 (2004).
Benjamin, D. K. Jr. et al. Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial. JAMA 311, 1742–1749 (2014).
Stoll, B. J. et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 110, 285–291 (2002).
Stoll, B. J. et al. Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr 129, 63–71 (1996).
Doyle, L. W. et al. An Update on the Impact of Postnatal Systemic Corticosteroids on Mortality and Cerebral Palsy in Preterm Infants: Effect Modification by Risk of Bronchopulmonary Dysplasia. The Journal of Pediatrics 165, 1258–1260 (2014).
Chang, Y. S., Park, H. Y. & Park, W. S. The Korean Neonatal Network: An Overview. J Korean Med Sci 30(Suppl 1), S3–S11 (2015).
American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 122, 1122–1131 (2013).
Jobe, A. H. & Bancalari, E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163, 1723–1729 (2001).
Bell, M. J. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 187, 1–7 (1978).
Papile, L. A., Burstein, J., Burstein, R. & Koffler, H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 92, 529–534 (1978).
Stark, A. R. American Academy of Pediatrics Committee on Fetus and Newborn. Levels of neonatal care. Pediatrics 114, 1341–1347 (2004).
Acknowledgements
This work was supported by the Korea Centers for Disease Control & Prevention (2016-ER6307-02#). The authors would like to thank Minkyu Han, PhD for assistance with statistical analysis. We also thank the Korean Neonatal Network for providing us with additional materials for data analysis.
Author information
Authors and Affiliations
Contributions
Jung E. and Lee B.S. performed the research, analysed the data and wrote the manuscript. Lee B.S. designed the study. All authors approved the final version of the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Jung, E., Lee, B.S. Late-Onset Sepsis as a Risk Factor for Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants: A Nationwide Cohort Study. Sci Rep 9, 15448 (2019). https://doi.org/10.1038/s41598-019-51617-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-019-51617-8
This article is cited by
-
Microbial signatures in amniotic fluid at preterm birth and association with bronchopulmonary dysplasia
Respiratory Research (2023)
-
Risk factors and machine learning prediction models for bronchopulmonary dysplasia severity in the Chinese population
World Journal of Pediatrics (2023)
-
Longer duration of initial invasive mechanical ventilation is still a crucial risk factor for moderate-to-severe bronchopulmonary dysplasia in very preterm infants: a multicentrer prospective study
World Journal of Pediatrics (2023)
-
Catheter-related bloodstream infections in infants hospitalized in neonatal intensive care units: a single center study
Scientific Reports (2022)
-
Surfactant protein D and bronchopulmonary dysplasia: a new way to approach an old problem
Respiratory Research (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.